II. Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
- Please summarise this article in your own words
- What is the level of evidence provided by this article?
- What are the criteria required to allow kidney donation in diabteric?
Dear All
Please notice that this study was performed on a deceased kidney transplant patient who received a deceased donor kidney. Some of you got mixed up with living donor transplants.
Please summarise this article in your own words
Small percentage of DM donors have Diabetic Nephropathy (DN), which is mild and in early stages. This DN may stabilize or mildly increase in severity with a small pace.
Diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival
What is the level of evidence provided by this article?
Level IV
What are the criteria required to allow kidney donation in diabetic?
In live kidney donation, donors with well controlled DM on oral hypoglycemics, with no need for insulin and no end-organ damage may donate their kidney after assessing their lifetime risk of cardiovascular events.
They should not have obesity, hypertension or dyslipidemias.
DM is considered a contraindication of kidney donation by living donors. Consideration on the impact of DM on organ allocation in deceased kidney donors is evolving. There have
been various approaches to the allocation of marginal donor kidneys as their utilization has expanded. defined as donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL.
In this study Records of all deceased kidney donors
Ø Place: at the J.C. Walter Transplant Center, The Houston Methodist Hospital,
Ø Time: between January 2006 and December 2014 were reviewed to identify the donors with DM.
Ø Population: Out of 749 donors, 46 (6.1%) had DM.
Ø Action: Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients + Post transplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients.
Ø Result: out of 26 biopsies:
1. DN was not seen in 20 biopsies, even after EM study
2. One biopsy showed no LM changes of DN, but EM showed thickened GBM
3. Five biopsies showed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM
4. None of these biopsies showed class IIb, class III, or class IV lesions.
5. These biopsies also showed other changes, including arterionephrosclerosis (14 biopsies), IFTA >15% of cortical tissue area (8 biopsies), acute tubular necrosis (4 biopsies), myoglobin casts (2 biopsies), incidental IgA nephropathy (1 biopsy), and incidental rare glomerular capillary thrombi, perhaps related to organ preservation (1 biopsy).
Ø Follow-up Biopsies: Among 20 recipients in whom the postperfusion biopsies
showed no DN (class 0), follow-up biopsy was not done in 8. DM was noted in 4 and 5 of these recipients pre- and posttransplant, respectively. Follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 and DN in 3 (class I in 2 and class IIa in 1). For the 9 recipients without DN in follow-upbiopsies, pre- and posttransplant DM were present in 5 and 66 recipients, respectively. For the 3 recipients in whom DN developed in follow-up biopsies, DM was present in 2 recipients before transplantation but developed in all 3 recipients after transplantation.
In summary, DN is noted in a small percentage of diabetic donor kidneys. When this occurs, the DN is often mild and in early stages. After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace. In cases DN is not present in diabetic donor kidneys, DN often does not develop in post-transplant, even in diabetic recipients. This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases with longer follow-up.
Ø Level 3
Ø According to BTS type 2 DM: absence of evidence of target organ damage and having ensured that other cardiovascular risk factors such as obesity, hypertension or hyperlipidaemia are optimally managed, diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of cardiovascular and progressive renal disease in the presence of a single kidney.
Ø In our local Sudan protocol DM is contraindication for donation.
· A common disease turns ESRD secondary to diabetic kidney disease is DM. It is an important factor in renal transplant. According to transplant registry around 8% of deceased donors had DM and up to 40% of the kidneys donated by diabetic donors were rejected. Considering living donors, DM is a contraindicationfor kidney donation.
· Considering organ allocation in deceased kidney donors, the effect of DM on them is studied. The allocation of marginal donor kidneys has had various approaches as their function has become wider. Donors aged =>60, or aged between 50 to 60 years have been included by ECD, having at least 2 out of the 3 risk factors including: history of hypertension- cerebrovascular cause of death- serum creatinine more than 1.5mg/dL. In this method donor having DM is not included as a risk factor. The rejection of donor’s kidneys has been significantly related to DM.
· The outcome of diabetic donors’ transplanted kidneys has been evaluated
by few studies, indicating that kidneys of diabetic donors have can only have small risk for failure or no effect on long-term graft and recipient survival.
· This study discusses diabetic nephropathy (DN) in donated kidneys who were deceased, post-transplantation evolution correlating to DM after the transplantation, and the effect it has on outcome of graft.
· In this study, records of all deceased donors from 2006 to 2014 were reviewed. Fourty-six donors (6.1%) out of 749 had DM. In 26 recipients, post perfusion and post transplantation biopsies were performed and were studied by LM, IF and EM. The diabetic changes were graded as scale 0-Ⅳ. In post perfusion biopsies, DN was not seen in 20 biopsies. One biopsy showed class Ⅰ and five biopsies showed class Ⅱa. In 17 recipients, follow up biopsies were performed. In 5 recipients who had DN on the post perfusion biopsies, one had the same class of DN and in the other 4 patients with class Ⅱa, progressed to class Ⅱb.
· In conclusion, DN is present in a small percentage of diabetic donors. It is often mild and in early stages. DN in may stabilize or have mild increase in severity after donation. So, diabetic kidneys from deceased donors have no significant effect on graft survival.
· The level of evidence is 3.
· In deceased donors, if pre-transplant biopsy showed no more than class Ⅱ DN and no advanced IFTA or glomerulosclerosis or arterosclerosis, it will be allowed. In addition, deceased diabetic donors should be evaluated for albuminuria and BUN and creatinine and if they are ok, it will be allowed.
Introduction:
expanded criteria donor (ECD) defined as donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL.
Donor DM is not included as a risk factor in this scheme. The new Kidney Allocation System implemented in 2014 utilizes the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for posttransplant graft survival.
Donor DM has been an important reason for the discard of donor’s kidneys. Using UNOS data until 2008, Sung et al reported a discard rate of 39%, 57%, and 21% for diabetic donors.
Aim of the study to evaluate status of diabetic nephropathy (DN) in these donated kidneys, its evolution after transplantation in relation to posttransplant DM, and its impact on graft outcome.
· Records of all deceased kidney donors in a single center, were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM.
· Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients.
· Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions.
· The profiles of donors and recipients and their clinical/lab[1]oratory information around the time of transplantation with special attention to those pertinent to the diabetic status, were obtained from hospital medical records, United Network of Organ Sharing registry, and family members.
· For donors, the diagnosis of DM and its estimated duration were made through communication with family members, old medical records, and data from national registries.
· For recipients, the diagnosis criteria included a fasting plasma glucose level of at least 126mg/dL or a random plasma glucose level of at least 200mg/dL and a hemoglobin A1c of at least 6.5%.
Discussion:
Diabetic donor kidneys account for 6.1% of all kidney transplants in study.
The study results may have implications for the utilization of renal biopsy in the decision to accept or discard the donor’s kidneys.
The current study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y).
These biopsies showed significant arterionephrosclerosis, and interstitial fibrosis/tubular atrophy, reflecting the presence of hypertension (in 73% of diabetic donors).
In the most recent kidney donor allocation scheme, which correlates with graft outcome, donor DM is not only one of the 10 evaluated factors, but also carries a heavy scoring weight.
The study suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace. In cases DN is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients. This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases with longer follow-up
What is the level of evidence provided by this article?
level of evidence 3.
What are the criteria required to allow kidney donation in diabetics?
As per BTS:
· Requires very careful evaluation of the risks and benefits.
· Absence target organ damage
· Absence of metabolic abnormalities such as obesity, hypertension or hyperlipidaemia
As per KDIGO:
Donor candidates with type 1 diabetes mellitus should not donate.
Donor candidates with prediabetes or type 2 diabetes should be counseled that their condition may progress over time and may lead to end-organ complications.
Living donors are advised against donating kidneys if they have diabetes mellitus
The Kidney Donor Profile Index, which is based on 10 donor variables, is used by the new Kidney Allocation System introduced in 2014 to determine the risk of post-transplant graft survival. In this rating, Donor DM carries a significant impact
In light of this, a small but significant portion of transplanted kidneys—between 3.5% and 6.5%—come from diabetes donors. Few studies have examined the results of kidney transplants from diabetes donors, but they all agree that diabetic donor kidneys either have no effect on long-term graft or recipient survival or very slightly increase the chance for failure
In the study , diabetic donor kidneys make up 6.1% of all kidney transplants. Similar frequencies (3.5%, 6.4%,) were found in national registry studies
Up to 40% of kidneys from diabetes donors were discarded, and about 8% of deceased donors carry the disease
The degree of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arterial intimal thickness are the main findings that influenced this choice
The contrast between the substantial influence of donor DM on transplant success and the frequent lack of DN in diabetic donor kidneys found in our investigation is quite interesting. It implies that different from the renal tissue damage found in DN, donor DM negatively affects transplant outcome
Acceptance of kidney donors requires the absence of significant proteinuria and intact renal function. Due to the documented progression of DN in native kidneys, donors with DM but without significant clinical symptoms may exhibit minor alterations in their kidney biopsies, as seen in the current investigation
A tiny fraction of diabetic donor kidneys have DN. The DN is frequently moderate and in its early stages when this occurred. After transplantation, DN in diabetic donor kidneys may stabilise or advance slowly with a little worsening of severity. Even in diabetic recipients, DN frequently does not develop after transplant when it is absent in the diabetic donor kidneys. This study raises the possibility that diabetic donor kidneys, with or without DN, may not necessarily have a significant negative impact on transplant survival. However, confirmation of this hypothesis will require a bigger sample size and a longer period of follow-up
retrospective cohort study level 3.
What are the criteria required to allow kidney donation in diabteric?
Not HTN , or obese , no cardiovascular risks , good kidney functions with e GFR > 80
Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
DM is one of the important factors in renal transplantation. According to the 2013 and 2015 scientific Registry of Transplant Recipients Reports, about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors we re discarded. DM is considered a contraindication of kidney donation by living donors. The allocation system has been evolving to include the expanded criteria donors to increase the donor pool.
The first allocation scheme in 1987 introduced the concept of expanded criteria donor (ECD) defiend as donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL. Donor DM is not included as a risk factor in this scheme. The new Kidney Allocation System 2014 utilizes the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for posttransplant graft survival. Donor DM carries a heavyweight in this scoring. Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact on long-term graft or recipient survival or confer only a small risk for failure.
Mostly unknown are the status of diabetic nephropathy (DN) in these donated kidneys, its evolution after transplantation in relation to posttransplant DM, and its impact on graft outcome. The current study aims to address some of these considerations.
MATERIALS AND METHODS
All deceased kidney donors at the J.C. Walter Transplant Centre, The Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM. Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients. Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients. The biopsies are subjected to histopathological examinations.
Postperfusion Renal Transplant Biopsy Findings
The current study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y). However, these biopsies often show significant arterionephrosclerosis, and interstitial !brosis/tubular atrophy, re”ecting the presence of hypertension (in 73% of diabetic donors).
In conclusion, DN is noted in a small percentage of diabetic donor kidneys. When this occurs, the DN is often mild and in early stages. After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace. In cases DN is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients.
Initially, all kidneys from diabetic donors were dispensed at the time of donation. At that time, the criteria for donation were much stricter and involved several clinical situations and pathologies that are tolerated today. From 1987 onwards, with the creation of expanded criteria, some clinical situations (age, hypertension and serum creatinine) were reassessed and donors with these characteristics can now be evaluated positively.
Since 2014 the Kidney Allocation System has been using the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for post-transplant graft survival. In this index, the diabetic patient has an important weight in his score, being almost defining of the reception or not. Despite this fear regarding the use of kidneys from diabetic donors, few studies have evaluated the outcome of kidneys transplanted from this donor profile. And despite this, there seems to be a consensus that kidneys from diabetic donors do not impact the long-term survival of the graft or recipient, or confer only a small risk of failure, even if the status of diabetic nephropathy of these donated kidneys, their evolution after transplantation in relation to post-transplant DM and its impact on graft outcome
This retrospective study analyzed the biopsies of patients who required further follow-up due to a higher risk of rejection or due to changes in renal function, within a population of donors known to be diabetic. Diabetic changes were graded on a scale from 0 to IV, as defined by the Renal Pathology Society.
As a result, from a sample of 26 kidneys, several types of alterations were found in the donation, but only 5 with diabetic nephropathy. During follow-up, some patients died, others had poor creatinine or proteinuria results, but there was no new diagnosis of diabetic nephropathy. Only patients who had diabetes before the reception and after had diabetic nephropathy in the control biopsies.
Thus, even with the Donor Profile Index score allowing the donation of diabetic patients, it seems that the weight attributed to it seems much higher than the actual risk. Other studies involving diabetic and non-diabetic patients listed through standard and expanded criteria, concluded that they concluded that diabetic donors with standard criteria provide better grafts than non-diabetic donors with expanded criteria and worse than diabetic donors with expanded criteria, but the risks of graft loss are all small compared to the ideal situation.
It´s level 03 – case control study.
It is necessary to exclude an increased risk of cardiovascular disease by assessing obesity, hypertension and hyperlipidemia. Subsequently, evaluation of the organ to exclude diabetic nephropathy through biopsy is essential.
DM is contraindication for donation in living donor and around 40 % of deceased donor kidneys are also discarded due to diabetes. Even ECD does not involve diabetic donors. The new kidney allocation system adopted in 2014 depended on evaluating donor profile index based on 10 factors to predict graft survival and presence of donor diabetes has significant score.
The studies evaluating impact of donor diabetes on graft survival were very few, but all found no or small non-significant negative impact.
In this study, the investigators aimed at evaluating the histopathological changes in graft from deceased diabetic donor and their impact on graft survival
They examined 749 deceased donors of them, 46 had diabetes. Renal biopsy was performed post perfusion in 26 diabetic donors and repeated later in the recipients.
Post perfusion biopsy revealed DN in 20 biopsies, one biopsy showed thickened GBM by EM but normal LM examination.
Other pathological findings included arterionephresclerosis , interstitial fibrosis, tubular atrophy, ATN and few cases revealed IgA deposits and glomerular capillaries thrombosis
Regarding graft and patients’ survival
The follow up period was 36-136 months. 4 recipients died with functioning graft due to CV complications while the remaining recipients were alive with functioning graft, one of them lost his graft after 54 months due to interstitial fibrosis
Significant proteinuria and rising S Cr were present in 3 cases, their follow up biopsy revealed PK nephropathy in one, arterionephresclerosis and tubular atrophy in the other two. 23 recipients developed HPN
The result of this study indicates that DM may affect kidney by mechanisms other than DN and thus graft from diabetic donors could be used if pretransplant biopsy was acceptable with no or minimal glomerulosclerosis, interstitial fibrosis and tubular atrophy and that these grafts shouldn’t be discarded only due to donor diabetic history.
II- Level of evidence: II, cohort study.
III-What are the criteria required to allow kidney donation in diabteric
a) In Living donor with diabetes:
b) in deceased donor with diabetes:
if the pre transplant biopsy reveleaded no advanced glomerular sclerosis or tubular atrophy or interstitial fibrosis and no advanced vascular lesions as arteriosclerosis
DM is considered a contraindication of kidney donation by living donors. Consideration on the impact of DM on organ allocation in deceased kidney donors is evolving. There have been various approaches to the allocation of marginal donor kidneys as their utilization has expanded. The rst allocation scheme in 1987 introduced the concept of expanded criteria donor (ECD) dened as donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL. Donor DM is not included as a risk factor in this scheme.
Against this background, diabetic donor kidneys account for a small but signicant percentage of transplanted kidneys ranging from 3.5% to 6.5%. Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure. Although much insight was achieved, all of these studies display some limitations, reecting their retrospective nature utilizing incomplete data from national registries. Mostly unknown are the status of diabetic nephropathy (DN) in these donated kidneys, its evolution after transplantation in relation to posttransplant DM, and its impact on graft outcome. The current study aims to address some of these considerations.
To the best of our knowledge, this is the rst study that comprehensively evaluates the renal changes of diabetic donor kidneys at the time of transplantation and its posttransplant evolution. We found that diabetic donor kidneys account for 6.1% of all kidney transplants in our center.
Finding may have implications for the utilization of renal biopsy in the decision to accept or discard the donor’s kidneys. About 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.Renal changes in pretransplant biopsies are often reported to be the main cause of this discard. Thefi ndings leading to this decision are mostly the severity of glomerulosclerosis, interstitial fibrosis /tubular atrophy, and arterial intimal thickening. Changes referable to DN were not included as a criterion for rejection.
Several
studies addressing the outcome of this type of kidney transplant support this trend. Mohan et al
compared 3058 diabetic donors with 90 933 nondiabetic donors and reported that the 10-year graft survival rate were 43% (diabetic + ECD), 55% (diabetic + SCD), 50% (nondiabetic + ECD), and 65% (nondiabetic + SCD), respectively.
Although the optimal outcome of diabetic donor kidney
is perhaps multifactorial, we hypothesize that the good preservation of renal tissue in the presence of DM is 1 significant factor. The current literature is nebulous in this aspect. We could not identify any study evaluating the renal biopsy findings from diabetic donors around the time of transplantation.
In addition, the presence or absence of DN in diabetic donors, as well as the DN class reflecting its severity, does not seem to correlate with the duration of DM. These findings are in keeping with previous native renal biopsy studies in diabetic patients. Although DM is common (10% of adult population in the United States),its involvement of kidney, that is, DN, is less frequent (10%–30% of diabetic patients).
Donors with DM but without significant clinical manifestations, therefore, may show little changes in their kidney biopsies, as shown in the current study, in keeping with the known evolution of DN in native kidneys. It should, however, be emphasized that at least in native kidney, clinicopathologic discrepancy has been noted, as shown by a recent autopsy study in which DN, even of advanced classes, may develop without any clinical manifestations.
The posttransplant evolution of donor kidney DN is of considerable interest for at least 2 major reasons: potential reversibility of the renal changes and high incidence of diabetic donor kidneys transplanted into diabetic recipients. Reversibility of the renal changes characteristic for DN has been evaluated in experimental models. Pugliese et al
noted
that pancreas transplant prevented the development of streptozocin-induced DN in Lewis rats and induced the reverse the DN of 4-month duration, but failed to do so for DN of 8-month duration. Pichaiwong et al
found that advanced
DN in a model of leptin deficiency ob/ob mouse was completely reversed by leptin replacement. However, Steffes et al
reported a failure of pancreas transplant to reverse DN in Lewis rats of 7-month duration.
The current study, although with a limited number of cases, represents the largest study on posttransplant evolution of donor kidney DN. It suggests that DN, at least in early stages, can be stable, or progress albeit rather slowly. These observations, made against some limitations, including the small number of cases (6/26 biopsies), absence of advanced DN, and relatively short follow-up duration, require further confirmatory studies. Factors that impact this evolution have not been elucidated. Nevertheless, posttransplant DM seems to be an important condition, being present in all cases with stable or progressive posttransplant DN
In summary, DN is noted in a small percentage of diabetic
donor kidneys. When this occurs, the DN is often mild and in early stages. After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace. In cases DN is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients. This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases with longer follow-up.
Level 3
II. Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance.
Q1- Please summarise this article in your own words
about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded. DM is considered a contraindication of kidney donation by living donors.
At 1987 the concept of expanded criteria donor (ECD) has been introduced, it is defined as : donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL.
Donor DM has been an important reason for the discard of donor’s kidneys. Sung et al reported a discard rate of 39%, 57%, and 21% for diabetic donors, diabetic donors ofEDC, and diabetic donors of standard criteria donor (SCD), respectively . On the other hand , diabetic donor kidneys accountfor a small but signi!cant percentage of transplanted kidneys ranging from 3.5% to 6.5%.
Of note diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure.
MATERIALS AND METHODS
Records of all deceased kidney donors at the J.C. WalterTransplant Center, The Houston Methodist Hospital,between January 2006 and December 2014 were reviewed to identify the donors with DM.
Post-transplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients. These biopsies are the focus of this study.
DISCUSSION
About 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded. Renal changes in pretransplant biopsies are often reported to be the main cause of this discard.
The current study found that DN is not seen or isonly mild in postperfusion biopsies from donors with DM even of long duration (>10y).
The discrepancy of the signi!cant impact of donor DM on graft outcome and the frequent absence of DN in diabetic donor kidneys noted in this study is of considerable interest. It suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
Diabetic donor kidneys are increasing accepted. Several studies support this trend. Mohan et al compared reported that the 10-year graft survival rate were 43% (diabetic + ECD), 55% (diabetic + SCD), 50% (non diabetic + ECD), and 65% (non diabetic + SCD), respectively. They concluded that SCD diabetic donors provide better grafts than nondiabetic ECD donors and worse than diabetic donors with ECD, but the risks of graft loss are all small compared to the ideal situation.
Cohen et al noted a modest difference in the overall graft survival (10-y survival rateof 37% vs 50%). However, DM in recipient imparts a significant risk for graft loss (25% for diabetic donor/diabetic recipient vs 37% for diabetic donor/nondiabetic recipient or nondiabetic donor/diabetic recipient). In the current study, diabetic donor kidneys enjoy good outcome.
This demonstrates that renal changes characteristic for DN are most often not seen and, when seen, are rather mild in kidneys from diabetic donors.
the presence or absence of DN in diabetic donors, as well as the DN class reflecting its severity, does not seem to correlate with the duration of DM. Although DM is common (10% of adult population in the United States), its involvement of kidney, that is, DN, is less frequent (10%–30% of diabetic patients).
Donors with DM but without significant clinical manifestations, therefore, may show little changes in their kidney biopsies, in keeping with the known evolution of DN in native kidneys. It should, however, be emphasized that at least in native kidney, clinicopathologic discrepancy has been noted, as shown by a recent autopsy study in which DN, even of advanced classes, may develop without any clinical manifestations.
The posttransplant evolution of donor kidney DN is of considerable interest for at least 2 major reasons: potential reversibility of the renal changes and high incidence of diabetic
donor kidneys transplanted into diabetic recipients.
Many studies indicate that reversibility of DN is possible, at least for early lesions and against specific clinical backgrounds.
this study suggests that DN, at least in early stages, can be stable, or progress albeit rather slowly.
Limitation of study : the small number of cases (6/26 biopsies), absence of advanced DN, and relatively short follow-up duration.
conclusion:
DN is noted in a small percentage of diabetic donor kidneys. When this occurs, the DN is often mild and in early stages. After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace. In cases DN is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients. This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires con!rmatory evaluation of a larger number of cases with longer follow-up.
Q2- What is the level of evidence provided by this article?
Level of evidence is 3.
Q3- What are the criteria required to allow kidney donation in diabteric?
The donor should be evaluated carefully
– GUE , urine for micro albumin, ultrasound for kidney , blood urea and serum creatinine should be normal .
– Assessment of other microvascular complication, retinopathy , neuropathy including autonomic neuropathy .
– Donor also need assessment for other cardiovascular complication.
–
Donation with diabetes will make the donor on risk for DKD + risk of NODAT, its contraindication for donation, up to 8 %of deceased donors were diabetic and 40% of donors kidneys were discarded. according to this study the diabetic donors are very low up to 3.5 to 6.5%.
from 2006 to 2014 from two centers they found only 6.1(46) % donors diabetic out of 749 donors.
post transplant biopsy done and graded 0- IV to according to Renal Pathology System.
the diagnostic criteria was fasting atleast126mg/dl, random at least 200mg/dl, HbA1c >6.5%.
They have done total 26 biopsies postperfusion, majority 16 were Hispanic ethnic.
None of them showed class II onward changes, 15 has arteriosclerosis.
however, literature shows there is increased risk of graft loss.
level IV
still we do not entertain diabetic donors.
Level of evidence is IV
Both diagnosed and undiagnosed diabetes mellutes about 9.3% of US population.
Post perfusion renal transplant biopsy finding..
DN not appear in 20 biopsies wit EM
EM showed thickening of glomerular basement membrane
Donor profiles..
Overlapping of duration of diabetes in between diabetic nephropathy classes
Recipient profiles…
It was noted that different diseases developed in between recipient as hypertension diabetes obesity metabolic syndrome has no feed back on diabetic nephropathy
It is found that diabetes in donor reflected on graft outcome by kidney injury with
diabetic rephropatly
About 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
Diabetic donor kidneys account for a small percentage of transplanted kidneys.
This study showed outcome of transplanted kidneys from diabetic donors
Records of all deceased donors at J.C. Walter Transplant Centers between 2006 to 2014 were reviewed to identify donors with DM.
Out of 749 donors , 46 (6.1%) had DM. Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients. Also post transplant biopsy done in them to evaluate renal changes.
20 out of 26 postperfusion biopsies showed no DN even after EM study . Other 6 biopsies showed only class I or IIa DN .these biopsies also showed arterionephrosclerosis , interstitial fibrosis and tubular atrophy.
After follow up ( 36 to136 months) 4 recipients died from cardiovascular complications with functional renal grafts. The remaining 22 recipients were alive with functional graft , only one failed after 54 months
DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration more than 10 years. But the biopsies showed arterionephrosclerosis, interstitial fibrosis and tubular atrophy which may reflect presence of HTN in the donors
Criteria allowed kidney donation from diabetic deceased donors
Absence of significant proteinuria and preserved kidney function
Level B
This is a single-center, retrospective (level III) cohort study between January 2006 and December 2014 that collected data from 749 deceased donors and evaluated donors with kidney disease and post-perfusion clinical and histopathological findings.
Of these findings, 26 donors with diabetes mellitus had 20 biopsies with no findings of diabetic nephropathy, one biopsy with class I basement cell membrane enlargement, and five with class II biopsies. The recipients had a mean age of 57 years, 16 men/10 women, 24 hypertensives, 15 diabetic, and 14 obese. Four died of cardiovascular disease. Of the remaining 22, only one lost a graft due to tubular atrophy and progressive interstitial fibrosis.
Renal biopsy was used, with at least 40% of kidneys from diabetic donors discarded for advanced histopathological findings of tubular atrophy, glomerulosclerosis, and basement membrane enlargement. The small amount of diabetic nephropathy in donors with diagnosed DM is noteworthy.
Previous studies by Mohan et al and Cohen et al suggest that even with diabetic nephropathy there is still a functioning renal mass with good post-transplant clinical response. Diabetic nephropathy usually evolves with proteinuria and worsening renal function, two situations that rule out transplantation independently. These renal changes can be involuted in non-diabetic recipients with clinical and laboratory control.
This study suggests that diabetic patients may be eligible when they do not have impaired renal function or proteinuria. Recipients without diabetes have the best clinical outcome. Despite the small number of cases in the study, the results are consistent with other studies discussed.
diabetic Nephropathy is the leading cause of chronic kidney disease globally, it is as well the leading cause of donor kidneys being discarded. this is because diabetic has a prevalence of 8% of the population and there is a great discrepancy between the clinical information and the histological finding of diabetes nephropathy. also, post-transplant there is a high risk of diabetes and diabetes nephropathy
the study was finding out the graft survival of donors with diabetes in diabetes and nondiabetics patients.
the study took into account the clinical finding of the length of duration of diabetes, level of proteinuria, pre-transplant biopsy findings, and graft survival.
unlike other retrospective studies this study despite its small sample size, it was a prospective non-case-control study.
the main finding was that
the level of evidence is level B
the indication of kidney include
well reserved renal function
absence of protienuria
not more than class ii biopsy finding
· Summary:
· Diabetes in donor is CI in the field of living donor kidney transplantation. However, it was not a cause to discard the kidney in deceased donor kidney transplantation in 1987 and was added recently in 2014.
· The current study is retrospective examination of kidney biopsies from diabetic donors among deceased kidney, examination with L/M, IF and EM (thickness of >430 and 395 nanometers for male and female).
o 4 grades of diabetic nephropathy according to the renal pathology society.
o The post perfusion biopsies revealed: 20 cases with grade 0, 1 case (grade 1), and 5 cases grade IIA.
o The DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10y). However, the biopsies often show Signiant arterionephrosclerosis, and IFTA, indicating the presence of hypertension (in 73% of diabetic donors).
o The data about diabetic donors collected retrospectively from medical records and family members.
o Follow up biopsies were taken (1-6 biopsies for each recipient).
o Diabetic nephropathy to reach advanced stage (presented with renal dysfunction and heavy proteinuria) needs > 10 years.
· Diabetic kidney accounts for 6.1 % of all transplanted kidneys.
· Post perfusion kidney biopsy can be utilized to define when to discard the kidney.
· Reversal of diabetic nephropathy (of 4 months duration) was shown in experimental studies and in few human studies (especially in early stages of (DN).
· The highest risk exists when the recipient also has diabetes (either denovo or present pre transplantation.
· However, DN did not develop in recipients with diabetes (as long as DN did not exist in post perfusion biopsy).
· Level of evidence:
· Criteria to allow kidney donation from cadaveric donor with DM:
o Normal kidney function, No proteinuria
o Pre-transplant biopsy showed no or mild diabetic nephropathy
o The recipient better to be none diabetic
o Counseling of the recipient about the risk of taking a diabetic kidney and obtaining a written consent.
· Criteria required to allow kidney donation in living diabetic donor
o BTS recommend that potential living donors with DM can donate after education about the risk of DM while having single kidney and after addressing all CVD risk, provided that it is controlled and no target end-organ damage
o While Organ Procurement and Transplant Network (OPTN) consider DM as an absolute contraindication for transplantation.
Please summarise this article in your own words
# Introduction
*The objective of the study to conduct the effect of DM donors kidneys in the outcome of the graft survival.
*This is the !rst study that comprehensively evaluates the renal changes of diabetic donor kidneys at the time of transplantation and its posttransplant evolution
*DM is considered a contraindication of kidney donation by living donors. Consideration on the impact of DM on organ allocation in deceased kidney donors is evolving. Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure.
# MATERIALS AND METHODS
Records of all deceased kidney donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM. Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients. Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients.
The biopsies are subjected to light microscopy (LM) and (EM).
# RESULTS
Postperfusion Renal Transplant Biopsy Findings
*Twenty-six postperfusion biopsies were performed from 26 transplanted kidneys from 25 deceased diabetic kidney donors.
* DN was not seen in 20 biopsies, even after EM study.
*One biopsy showed no LM changes of DN, but EM showed thickened GBM (classI).
* Five biopsies showed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM.
*None of these biopsies showed class IIb, class III, or class IV lesions.
*These biopsies also showed other changes, including arterionephrosclerosis , interstitial !brosis and tubular atrophy >15% of cortical tissue area, acute tubular necrosis, myoglobin casts incidental IgA nephropathy (1 biopsy), and incidental rare glomerular capillary thrombi, perhaps related to organ preservation.
# DISCUSSION
Diabetic donor kidneys account for 6.1% of all kidney transplants in our center. This frequency is similar to those derived from national registry studies
*About 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded. Renal changes in pretransplant biopsies are often reported to be the main cause of this discard.
* The DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10#y). However, these biopsies often show signi!cant arterionephrosclerosis, and interstitial fibrosis/
tubular atrophy, refliecting the presence of hypertension (in 73% of diabetic donors).
* The discrepancy of the signi!cant impact of donor DM on graft outcome and the frequent absence of DN in diabetic donor kidneys noted suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
*In the current study, diabetic donor kidneys enjoy good outcome.
*Although the optimal outcome of diabetic donor kidney is perhaps multifactorial, we hypothesize that the good preservation of renal tissue in the presence of DM is 1 significant factor.
*Renal changes characteristic for DN are most often not seen and, when seen, are rather mild in kidneys from diabetic donors. In addition, the presence or absence of DN in diabetic donors, as well as the DN class refliecting its severity, does not seem to correlate with the duration of DM.
# The limitations
*Small number of cases (6/26 biopsies)
* Absence of advanced DN
*Relatively short follow-up duration, require further confirmatory studies.
# What is the level of evidence provided by this article?
*It is retrospective cohort study level 3.
# What are the criteria required to allow kidney donation in diabteric?
* Donor age 60 years old, no end organ faliure, HTN, CVD, normal renal function, eGFR, no proteinuria, normal renal biopsy, and the recipient has no DM.
· about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded
· Donor DM was not included as a risk factor in the first allocation scheme in 1987
· Donor DM was included in the new Kidney Allocation System implemented in 2014
· diabetic donor kidneys account for 3.5% to 6.5% of transplanted kidneys
Aim of the study:
· status of diabetic nephropathy (DN) in donated kidneys,
· its evolution after transplantation in relation to posttransplant DM,
· its impact on graft outcome
MATERIALS AND METHODS
· By revision of records in the transplant centre in The Houston Methodist Hospital, between January 2006 and December 2014, out of 749 deceased kidney donors, 46 (6.1%) had DM
· Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients.
· Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients
· The biopsies were studied by light microscopy, immunofluorescent stains, and Electron microscopy (EM)
· By EM thickened GBM, a diagnostic change of DN, was defined as a thickness of >430 and 395 nanometers for male and female, respectively
RESULTS
Postperfusion Renal Transplant Biopsy Findings
· 26 biopsies were taken from the 26 deceased transplanted kidneys
· DN was not seen in 20 biopsies, even after EM study
· One biopsy showed no LM changes of DN, but EM showed thickened GBM (class I)
· Five biopsies showed DN of class IIa,( mild mesangial sclerosis and hypercellularity, with thickened GBM)
· None of these biopsies showed class IIb, class III, or class IV lesions
· Also these biopsies showed: arterionephrosclerosis (14 biopsies), interstitial fibrosis and tubular atrophy (8 biopsies), ATN (4 biopsies), myoglobin casts (2 biopsies), incidental IgA nephropathy (1 biopsy), and incidental rare glomerular capillary thrombi(1 biopsy)
Follow-up Biopsies
· Follow-up biopsies were done for 17 recipients
· Among 20 recipients with class 0 in postperfusion biopsies, follow-up biopsy was not done in 8. DM was noted in 4 and 5 of these recipients pre- and posttransplant, respectively. Follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 and DN in 3 (class I in 2 and class IIa in 1)
· For the 9 recipients without DN in follow-up biopsies, pre- and posttransplant DM were present in 5 and 66 recipients, respectively
· For the 3 recipients in whom DN developed in follow-up biopsies, DM was present in 2 recipients before transplantation but developed in all 3 recipients after transplantation
CONCLUSION
· Post transplantation DN can be stable in early stages and progress very slowly
· Limitations: small number of cases (6/26 biopsies), absence of advanced DN, and relatively short follow-up duration
· DM present in all cases with stable or progressive posttransplant DN
· De novo DM develops in 4%–25% of kidney transplant recipients and in 6/26 recipients in this study
What is the level of evidence provided by this article?
This is a Retrospective Cohort Study. Level III
What are the criteria required to allow kidney donation in diabetic?
· DM 2
· No HTN
· No obesity
· No complications of DM
· Age above 60
· No other cardiovascular risk
· GFR > 80
Summary:
DN is noted in a small percentage of diabetic donor kidneys. When this occurs, the DN is often mild and in early stages. After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace. In cases DN is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients. This study suggests that diabetic donor kidneys with or without DN may not by itself impart signi!cant adverse effect of graft survival, an observation that requires con!rmatory evaluation of a larger number of cases with longer follow-up.
level of evidence: level 4
Criteria required to allow kidney donation in diabetic:
Living related diabetic donors-contraindicated
Patient should have age greater than 60 with normal renal function i.e.,GFR should b greater than 80ml/min/1.73m2 and without proteinuria.
Its new and interesting topic as we do not have any deceased renal transplantation till now and we exclude any potential donor with DM from donation in our transplantation center .
in this study they evaluate the outcome of transplanted kidneys from diabetic donors .
over view
What is the level of evidence provided by this article?
What are the criteria required to allow kidney donation in diabteric?
thanks
Evidence level: 3
DM is a leading cause of ESR. About 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were excluded.. DM is considered a contraindication of living kidney donation .
Consideration of impact of DM on organ allocation in deceased kidney donors is increasing. There are different approaches to allocation of marginal donor kidneys as their utilization has increased .By definition, ECD included donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/d L. DM is not included as a risk factor in this scheme.DM has been an important cause for discard of donor’s kidneys.
Few studies showed that that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or can cause small risk for failure. This study tries to address incidence of diabetic nephropathy in relation to posttransplant DM, and its impact on graft outcome.
It included 26 recipients. Posttransplant renal biopsies were subjected to light microscopy, Immunofluorescence and EM including measurement of the thickness of the glomerular basement membrane (GBM). Thickened GBM was defined as a thickness of >430 and 395 nanometres for male and female, respectively as marking DN.
DN was found in a small percentage of diabetic deceased donor kidneys. The Diabetic nephropathy is often mild. DN in diabetic donor kidney showed stable or slowly progressive course.. In cases DN changes is absent in diabetic donor kidneys, DN often would not develop following transplantation, even in diabetic recipients.
The study concluded that diabetic donor kidneys with or without DN may not per se have significant adverse effect on graft survival, it that requires further evaluation with larger number of cases and longer follow-up.
This study was conducted retrospectively at J C Walter Transplant centre between January 2006 to December 2014. From 749 deceased donors, 46 (6.1%) had diabetes and post-perfusion biopsy was performed in 26 recipients (from 25 donors) which was staged as per RPS scale for diabetic nephropathy. Post-transplant graft biopsies were also performed in the recipients and followed up 36 to 136 months.
Among post-perfusion biopsies: DN was present in 6 out of the 26 biopsies, with 1 biopsy showing class I changes and 5 biopsies showing class IIa changes. Otherwise, other changes are arterio-nephrosclerosis (14 biopsies), interstitial fibrosis/ tubular atrophy (8 biopsies), acute tubular necrosis (4 biopsies), myoglobin casts (2 biopsies), IgA nephropathy and glomerular capillary thrombi (1 biopsy each).
Donor is at mean age 47 years, males comprise 48% with majority Hispanic, 76% are hypertensive. Recipients are at mean age 57 years, Males are around 61%, majority African Americans, 57% are DM before transplant and hypertension before transplant in 92% of study population. Follow-up biopsies are done for 17 recipients, which about 1-6 biopsies per KTR
Among the 20 patients with no DN changes post-perfusion, biopsy done
5 patients with class IIa DN changes post-perfusion, biopsy showed change to class IIb in one patient and one of the recipients who was not a diabetic pre-transplant became diabetic whereas a other recipients were diabetic pre-transplant.
KTR with class I DN changes post-perfusion did not undergo any follow-up biopsy, although the patient developed DM post-transplant.
Other changes in post-transplant biopsies included arterio-nephrosclerosis (9 biopsies), interstitial fibrosis/ tubular atrophy (8 biopsies), transplant glomerulopathy (2 biopsies), and glomerulitis, severe chronic rejection, chronic AMR( 1 biopsy), and polyomavirus nephropathy (1 biopsy ).
The study found that DN is not seen in majority of post-perfusion biopsies of diabetic donors of even after >10 years, but arterio-nephrosclerosis and IF/TA are significantly seen in those biopsies. DN changes if present, are of mild nature.
Diabetic donor kidneys, when transplanted in a diabetic recipient, may not develop DN at least during the short-term post-transplant period and even if it develops, it is of mild severity. Those with diabetic changes pre-transplant also stabilize or do not worsen much.
What is the level of evidence provided by this article?
Level 3
What are the criteria required to allow kidney donation in diabetic?
Diabetes and deceased kidney donation: Diabetics are not taken as deceased donor in majority of deceased donor transplant programs. Currently more and more studies shows that the graft outcome were similar between diabetic and non-diabetic KTR. These considerations have to applied to increase the donor and procurement rate throughout the world.
Diabetes and living kidney donation:
According to the 2013 and 2015 Scientific Registry of Transplant Recipients Reports, about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
DM is considered a contraindication of kidney donation by living donors.
impact of DM in deceased kidney donors And its effect in graft function and long-term survival is a major concern
The new Kidney Allocation System implemented in 2014 utilizes the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for posttransplant graft survival. Donor DM carries a heavy weight in this scoring.
Sung et al reported a discard rate of 39%, 57%, and 21% for diabetic donors, diabetic donors of EDC, and diabetic donors of standard criteria donor (SCD), respectively.
Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure.
this is the first study that comprehensively evaluates the renal changes of diabetic donor kidneys at the time of transplantation and its posttransplant evolution.
▪︎MATERIALS AND METHODS
This study was done to evaluate post transplantation renal biopsies of Diabetic donors.
Transplantation between 2006 and 2014 were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM.
Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients.
Posttransplantt renal biopsies were also performed in these recipients for evaluating changes of renal functions.
▪︎RESULTS
*Postperfusion Renal Transplant Biopsy Findings:
26 postperfusion biopsies from deceased diabetic donors
all 25 donors had DM with variable durations
-DN was not seen in 20 biopsies, even after EM study
-One biopsy showed no LM changes of DN, but EM showed thickened GBM class I
-Five biopsies showed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM
-None of these biopsies showed class IIb, class III, or class IV lesions.
-4 recipients died of causes other than DN per ser, with functional grafts, other 22 recipients were alive at last follow-up with functional grafts in 21.
-These biopsies also showed other changes , including arterionephrosclerosis , interstitial fibrosis and tubular atrophy >15% of cortical tissue area , acute tubular necrosis , myoglobin casts , incidental IgA nephropathy , and incidental rare glomerular capillary thrombi, perhaps related to organ preservation
-These Findings may have implications for the utilization of renal biopsy in the decision to accept or discard the donor’s kidneys.
-After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace.
-DN often does not develop in posttransplant, even in diabetic recipients.
▪︎In conclusion
-The current study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10y).
However, these biopsies often show signigficant arterionephrosclerosis, and interstitial fibro-sis/tubular atrophy, due to presence of hypertension (in 73% of diabetic donors).
– It is suggested that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
-diabetic donors started to be accepted in many centres
-Several studies addressing the outcome of this type of kidney transplant support this trend.
*Mohan et al compared 3058 diabetic donors with 90,933 nondiabetic donors
They concluded that SCD diabetic donors provide better grafts than nondiabetic ECD donors and worse than diabetic donors with ECD, but the risks of graft loss are all small compared to the ideal situation.
*Cohen et al evaluated 9074 diabetic donors and 152,555 nondiabetic donors and noted a modest difference in the overall graft survival (10-y survival rate of 37% vs 50%).
-it was also found that DM in recipient imparts a significant risk for graft loss (25% for diabetic donor/diabetic recipient vs 37% for diabetic donor/nondiabetic recipient or nondiabetic donor/diabetic recipient).
-Absence of proteinuria and preserved renal function are 2 requirements for kidney donor acceptance.
-Donors with DM but without clinical manifestations, may show little changes in their kidney biopsies, as shown in the current study, in keeping with the known evolution of DN in native kidneys.
-It should, however, be emphasized that at least in native kidney, clinicopathologic discrepancy has been noted, as shown by a recent autopsy study in which DN, even of advanced classes, may develop without any clinical manifestation
These discrepancies also put in focus the potential role of pretransplant biopsy for diabetic donors in at least selected clinical settings.
-The posttransplant evolution of donor kidney DN is of considerable interest for at least 2 major reasons: potential reversibility of the renal changes and high incidence of diabetic donor kidneys transplanted into diabetic recipients.
In summary
This study susuggest that diabetic donor kidneys with or without DN may not by itself impart adverse effect of graft survival, an observation that requires evaluation of a larger number of cases with longer follow-up
What is the level of evidence provided by this article?
This is Retrospective study, III
What are the criteria required to allow kidney donation in diabetic?
Evaluation of Kidney Function, proteinuria is essential before accepting diabetic donors
Careful evaluation of diabetic complications ,cardiovascular risk factors, and target organ damage
renal biopsy would be of great importance to evaluate presence of DN.
risk of development of diabetic nephropathy should be discussed with the donor in case of living donor.
· Please summarise this article in your own words
Introduction:
DM, both diagnosed and undiagnosed, is noted in as many as 9.3% of the US adult population.
8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
It is considered condra indication in living donation, but in deceased donor the situation has changed with the introduction of expanding donor criteria.
MATERIALS AND METHODS
Records of all deceased kidney donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM. Postperfusion biopsy of the transplanted
kidneys were performed in 26 recipients; these biopsies are the focus of this study.
The profiles of donors and recipients and their clinical/laboratory information around the time of transplantation with special attention to those pertinent to the diabetic status, were obtained from hospital medical records, United Network of Organ Sharing registry, and family members. Up to date follow-up, including graft outcome and recipient outcome, was established.
RESULTS
Postperfusion Renal Transplant Biopsy Findings:
· DN was not seen in 20 biopsies (Renal Pathology Society class 0
· One biopsy showed no LM changes of DN, but EM showed thickened GBM (495+/−27 nanometers) (class I)
· Five biopsies showed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM (569+/−51 nanometers)
· None of these biopsies showed class IIb, class III, or class IV lesions
· Other changes seen: including
o Arterionephrosclerosis (14 biopsies)
o Interstitial fibrosis and tubular atrophy >15% of cortical tissue area (8 biopsies),
o Acute tubular necrosis (4 biopsies)
o Myoglobin casts (2 biopsies),
o Incidental IgA nephropathy (1 biopsy)
o Incidental rare glomerular capillary thrombi (1 biopsy).
Donors’ profiles:
By design, all 25 donors had DM with variable durations (unknown in 7, 15 y in 9, 6–10 y in 7, and >10 y in 2)
Mean age 47
16 Hispanic, 5 white, 3 African American, and 1 Asian.
Follow-up Biopsies
Follow-up biopsies (1–6 biopsies /recipient) were done for 17 recipients.
Out of the 20 recipients with no DN on the initial post perfusion biopsies, follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 and DN in 3 (class I in 2 and
class IIa in 1).
DISCUSSION
The findings of this study may change the utilization of diabetic donor kidneys and reduce the discard rate from 40% , knowing that this study found DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10y). It suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN. In the current study, diabetic donor kidneys enjoy good outcome.
Conclusion
This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases with longer follow-up
· What is the level of evidence provided by this article?
Retrospective study, level 3
· What are the criteria required to allow kidney donation in diabetic?
Consideration of a diabetic as a potential donor, as per BTS, requires:
· Thorough evaluation of the risks and benefits of donation and transplantation, for both the donor and recipient.
· Careful search for any evidence of target organ damage
· Assessment of cardiovascular risk factors such as obesity, hypertension, and hyperlipidaemia.
· The age of the donor
· Donor GFR
· Relationship to the potential recipient.
· Exclusion of preexisting diabetic nephropathy, possibly including renal biopsy, the potential risk of development of diabetic nephropathy should be discussed with the potential donor.
Above mentioned requirements are for living donation. For deceased donor with diabetes. We need to find out as much as possible from the history; duration of diabetes, any proteinuria, renal impairment or hypertension. If any of these is present, then pre implantation biopsy will be very useful if possible. To find out grade of diabetic nephropathy if any, degree of nephrosclerosis and interstitial fibrosis and tubular atrophy. Depending on above finding decision will be to take single, dual kidneys or discard it if there is advanced interstitial fibrosis and tubular atrophy.
1- Summary:
Method:
The records of all deceased kidney donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM.
Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients. Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients.
The diabetic changes were graded on a scale of 0–IV, as defined by the Renal Pathology Society: class 0 = no diabetic changes by LM or EM; class I = no obvious LM changes, but a thickening of the GBM by EM; class IIa = mild mesangial expansion by LM; class IIb = marked mesangial expansion by LM; class III = nodular mesangial sclerosis; and class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli. Changes other than DN were also recorded.
RESULTS
Twenty-six postperfusion biopsies were performed from 26 transplanted kidneys from 25 deceased diabetic kidney donors. DN was not seen in 20 biopsies, even after EM study. One biopsy showed no LM changes of DN, but EM showed thickened GBM (class I). Five biopsies showed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM. None of these biopsies showed class IIb, class III, or class IV lesions. These biopsies also showed other changes including arterionephrosclerosis (14 biopsies), interstitial fibrosis and tubular atrophy >15% of cortical tissue area (8 biopsies), acute tubular necrosis (4 biopsies), myoglobin casts (2 biopsies), incidental IgA nephropathy (1 biopsy), and incidental rare glomerular capillary thrombi, perhaps related to organ preservation (1 biopsy).
Recipients’ outcomes:
At follow-up (36–136 mo), 4 recipients died, all of cardiovascular complications, with functional renal grafts.
The remaining 22 recipients were alive with functional grafts in 21 and 1 failed graft 54 months posttransplant probably due to progressive interstitial fibrosis and tubular atrophy. Protein excretion (urine protein/creatinine ratio) was normal in 4; increased, albeit of low levels (0.1–0.83), in 19; and reached high levels in three recipients (1.40, 1.42, and 1.7). The serum creatinine at follow-up of these 3 recipients were 1.8, 8, and 2.7mg/dL, respectively.
The last follow-up transplant biopsies of these recipients showed polyomavirus nephropathy in one and arterionephrosclerosis with interstitial fibrosis and tubular atrophy in all 3, but not DN.
DM was present in 15 recipients before transplantation. After trans[1]plantation, DM persisted in 14, regressed in 1, and developed de novo in 6, for a total of 20 recipients with posttransplant DM. Hypertension noted in 24 recipients pretransplant, was diagnosed in 23 after transplantation.
Follow-up Biopsies (1–6 biopsies /recipient) were done for 17 recipients. Focus was aimed to evaluate the evolution of DN against the background of the DM status of the recipients. Among 20 recipients in whom the postperfusion biopsies showed no DN (class 0), follow-up biopsy was not done in 8. DM was noted in 4 and 5 of these recipients pre- and posttransplant, respectively. Follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 and DN in 3 (class I in 2 and class IIa in 1.
Conclusion:
The current study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y). However, these biopsies often show significant arterionephrosclerosis, and interstitial fibrosis/tubular atrophy. It suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
2- This is a retrospective observational cohort study, level 2 evidence.
3- As per BTS guidelines, Consideration of patients with diabetes as potential kidney donors requires very careful evaluation of the risks and benefits. In the absence of evidence of target organ damage and having ensured that other cardiovascular risk factors such as obesity, hypertension or hyperlipidaemia are optimally managed, diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of cardiovascular and progressive renal disease in the presence of a single kidney. (Not graded).
Dm is important factors in kidney transplant.
Most diabetic deceased donors where discarded.
So it form only 3 -6% of donors kidney, despite this fact studies, shows less impact in
post-transplant graft or recipient survival and small failure rate.
This study address issue of posttransplant diabetic nephropathy incidence and impact on
graft survival.
MATERIALS AND METHODS:
Place of study Walter transplant center.
Study period:
January 2006 and December 2014.
Study population:
46 (6.1%) of 749 donors, had DM.
Biopsy taken for 26 patient.
Histology, immunofluorescent stains, and EM examination done.
Medical records for donors and recipients and their clinical/laboratory information around
the time of transplantation with special attention to those pertinent to the diabetic status.
Posttransplant information gathered include follow up biopsy.
Results:
OF 25 biopsy taken no DN seen in 20.
One biopsy shows thickening Of GBM but no DN.
Five biopsies: showed DN of class IIa, mild mesangial sclerosis and hypercellularity, with
thickened GBM and B).
None of these biopsies showed class IIb, class III, or class IV lesions.
Recipient:
22 recipients were alive with functional grafts in 21 and 1 fail.
Protein excretion (urine protein,) was normal in 4; increased, albeit of low levels (0.1–
0.83), in 19; and reached high levels in three recipients (1.40, 1.42, and 1.7)
. The serum creatinine at follow-up of these 3 recipients were 1.8, 8, and 2.7mg/dL,
respectively.
. DM was present in 15 recipients before transplantation.
After transplantation, DM persisted in 14, regressed in 1, and developed de novo in 6,
for a total of 20 recipients with posttransplant DM. HTN PRESNT IN 24PATEIRNT
POSTARANSPLANT.
Study shows prevalence of 6% similar to other studies.
Discussion:
The current study found that DN is not seen or is only mild in post perfusion biopsies
from donors with DM even of long duration (>10 y).
Diabetic donors frequent used with different outcome, better in SCD than diabetes with
EDC and incidence of graft loss is small. Recipient with diabetes receiving diabetic
donors has high graft loss compared to nondiabetic received diabetic donors.
Conclusion:
DN is noted in a small percentage of diabetic donor kidneys. When this occurs, the DN is
often mild and in early stages. After transplantation, DN in diabetic donor kidneys may
stabilize or progress with a mild increase in severity and at a slow rate.
Limitations:
The small number of cases (6/26 biopsies),
Absence of advanced DN.
Short follow UP.
Level of evidence 111.
What are the criteria required to allow kidney donation in diabetic?
the absence of evidence of target organ damage .
and having ensured that other cardiovascular risk factors such as obesity, hypertension
or hyperlipidemia are optimally managed.
diabetics can be considered for kidney donation after a thorough assessment of the
lifetime risk of cardiovascular .(BTC guideline).
Diabetes is the most common cause of ESRD and considering diabetics for donations is usually contraindicated however does this holds true for deceased donors in view of their biopsy findings at time of transplantation has been addressed in this article by Troung and collaegues.
According to the 2013 and 2015 Scientific Registry of Transplant Recipients Reports, about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
Against this background, diabetic donor kidneys account for a small but significant percentage of transplanted kidneys ranging from 3.5% to 6.5%.There are only Few studies which have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure.
MATERIALS AND METHODS
Records of all deceased kidney donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM. Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients. Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients. The diabetic changes were graded on a scale of 0–IV, as defined by the Renal Pathology Society13: class 0 = no diabetic changes by LM or EM; class I = no obvious LM changes, but thickening of the GBM by EM; class IIa = mild mesangial expansion by LM; class IIb = marked mesangial expansion by LM; class III = nodular mesangial sclerosis; and class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli. Changes other than DN were also recorded. Follow-up biop- sies were evaluated in the same manner.
Twenty-six postperfusion biopsies were performed from 26 transplanted kidneys from 25 deceased diabetic kid- ney donors.DN was not seen in 20 biopsies, even after EM study.This was the first study that comprehensively evaluates the renal changes of diabetic donor kidneys at the time of transplantation and its posttransplant evolution.
The current study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y). However, these biopsies often show significant arterionephrosclerosis, and interstitial fibro- sis/tubular atrophy, reflecting the presence of hypertension (in 73% of diabetic donors). The discrepancy of the significant impact of donor DM on graft outcome and the frequent absence of DN in diabetic donor kidneys noted in this study is of considerable interest. The posttransplant evolution of donor kidney DN is of considerable interest for at least 2 major reasons: potential reversibility of the renal changes and high incidence of diabetic donor kidneys transplanted into diabetic recipients.
This study, though relatively small, suggests that diabetic donor kidneys with or without DN, transplanted into a diabetic recipient, may not develop DN during the posttransplant period at least in short term, or develop into a mild/early form of DN, that by itself may not significantly impact graft outcome.
CONCLUSION
This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival,
EVIDENCE
Retrospective
Level III
CRITERIA TO ALLOW KIDNEY DONATION IN DIABETICS
In case of deceased donor transplant absence of proteinuria or non significant proteinuria with preservation of renal function is the criteria for acceptance.
Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
▪︎This study comprehensively evaluated the renal changes of diabetic donor
kidneys at the time of transplantation and its posttransplant evolution.
Introduction:
Diabetes (DM) is considered a contraindication of kidney donation by living donors and it’s impact on organ allocation in deceased kidney donors is evolving.
Approaches to the allocation of marginal donor kidneys:
1. In 1987 introduced the concept of expanded criteria donor (ECD): donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of HTN, or serum creatinine >1.5mg/dL.
▪︎ Donor DM is not included as a risk factor in this scheme.
2. The new Kidney allocation System (2014) utilizes the Kidney
Donor Profile Index and donor DM carries a heavy weight in the risk score for graft survival .
▪︎Donor DM has been an important reason for the discard of donor’s kidneys. Diabetic donor kidneys account for 3.5% to 6.5% donor kidneys.
Materials and Methods
▪︎All deceased kidney donors records at the J.C. Walter Transplant Center and Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM.
▪︎Out of 749 donors, 46 had DM.
▪︎Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients. ▪︎Posttransplant biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients.
▪︎The biopsies are subjected to LM, IF and EM was done both prospectively and retrospectively, including measurement of the thickness of GBM.
▪︎Systematic examination was performed
The diabetic changes were graded on a scale of 0–IV, as defined by the Renal Pathology Society.
▪︎Changes other than DN were also recorded.
▪︎Follow-up biopsies were evaluated in the same manner.
▪︎The profiles of donors and recipients and their clinical/laboratory information around the time of transplantation with special attention to those pertinent to the diabetic status, were obtained.
▪︎An up-to-date follow-up was established. ▪︎The diagnosis of DM was made for both the donors and recipients.
RESULTS
Postperfusion Renal Transplant Biopsy Findings
▪︎ Twenty-six post perfusion biopsies were performed from 26 transplanted kidneys from 25 deceased diabetic kidney donors.
DN was not seen in 20 biopsies, even after EM study. One biopsy showed no L.M changes, but EM showed thickened GBM. Five biopsies showed DN of class IIa. None
of these biopsies showed class IIb, class III, or class IV lesions.
These biopsies also showed other changes, including arterionephrosclerosis, interstitial fibrosis and tubular atrophy,ATN, myoglobin casts, incidental IgA nephropathy and incidental rare glomerular capillary thrombi.
DISCUSSION
▪︎The finding of this study may have implications for the utilization of renal biopsy in the decision to accept or discard the donor’s kidneys.
▪︎Renal changes in pretransplant biopsies are often reported to bethe main cause of this discard from donation.
The findings leading to this decision are mostly:
1.The severity of glomerulosclerosis
2. Interstitial fibrosis/tubular atrophy
3. Arterial intimal thickening.
▪︎Changes referable to DN were not included as a criterion for rejection.
This study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y).
These observations thus lend support to the validity of the current morphological criteria within the general scheme for organ allocation, which does not include
changes referable to DN.
In most recent kidney donor allocation scheme, donor DM is not only one of the 10 evaluated factors, but also carries a heavy scoring weight.
Donor DM adversely affects graft outcome through mechanisms distinct
from the renal tissue injury seen in DN.
Diabetic donor kidneys are increasing accepted. SCD diabetic donors provide better grafts than nondiabetic ECD donors and worse than diabetic donors with ECD, but the risks of graft loss are all small compared to the ideal situation.
This study hypothesized that: the good preservation of renal tissue in the presence of DM is significant factor.
☆This study demonstrated that:
1. Renal changes characteristic for DN are most often not seen and, when seen, are rather mild in kidneys from diabetic donors.
2. The presence or absence of DN in diabetic donors, as well as the DN class reflecting its severity, does not seem to correlate with the duration of DM.
3. DN, is less frequent in diabetic patients.
Absence of significant proteinuria and preserved renal function are 2 requirements for kidney donor acceptance.
This studty showed that donors with DM but without significant clinical manifestations, may show little changes in their kidney biopsies, in keeping with the known evolution of DN in native kidneys.
Reasons for posttransplant evolution of donor kidney DN:
1. Potential reversibility of the renal changes.
2. High incidence of diabetic donor kidneys transplanted into diabetic recipients.
Strength of the study:
Represents the largest study on posttransplant evolution of donor kidney DN. It suggests that DN, at least in early stages,
can be stable, or progress albeit rather slowly.
Limitation of the study:
1. Small number of cases
2. Absence of advanced DN,
3. Short follow-up duration
4. Rrequire further confirmatory studies.
5. Factors that impact this evolution have not been elucidated.
Summary:
A mild and early stage DN is noted in a small percentage of diabetic donor kidneys. DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace post transplantation.
When DN is not present in diabetic donor kidneys, it often does not develop in posttransplant, even in diabetic recipients.
This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that
requires confirmatory evaluation of a larger number of cases with longer follow-up.
☆Levelof the study: III
DM is considered a contraindication of kidney donation by living donor about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
Donor DM is not included as a risk factor in this scheme. 5,6 The new Kidney Allocation System implemented in 2014 utilizes the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for posttransplant graft survival. Donor DM carries a heavyweight in this scoring. 5-7Donor DM has been an important reason for the discard of donor’s kidneys.
Against this background, diabetic donor kidneys account for a small but significant percentage of transplanted kidneys ranging from 3.5% to 6.5%. 6,9-11 Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure.
The diabetic changes were graded on a scale of 0–IV, as defined by the Renal Pathology Society:
class 0 = no diabetic changes by LM or EM
class I = no obvious LM changes, but thickening of the GBM by EM
class IIa = mild mesangial expansion by LM
class IIb = marked mesangial expansion by LM
class III = nodular mesangial sclerosis
class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli.
Changes other than DN were also recorded. Follow-up biopsies were evaluated in the same manner.
Renal changes in pretransplant biopsies are often reported to be the main cause of this discard. The findings leading to this decision are mostly the severity of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arterial intimal thickening. Changes referable to DN were not included as a criterion for rejection. The current study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y).
The posttransplant evolution of donor kidney DN is of considerable interest for at least 2 major reasons: potential reversibility of the renal changes and high incidence of diabetic donor kidneys transplanted into diabetic recipients.
This study, though relatively small, suggests that diabetic donor kidneys with or without DN, transplanted into a diabetic recipient, may not develop DN during the posttransplant period at least in short term, or develop into a mild/early form of DN, that by itself may not significantly impact graft outcome.
level of evidence IIIb.
DM being the major cause of ESRD worldwide,was considered a contraindication to renal transplantation previously and around 40% patients were discarded because of diabetes ,now KDIGO recommend that few patients with T2 DM who fulfil criteria can donate kidney and 3.5-6.5% of transplanted patients have diabetic donors.Literatire review elucidated less chances of renal failure and no effect on graft and patient survival and outcome in the long run.This study recruited 749 deceased donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital,out of which post perfusion biopsy done in 26 recipients.Results revealed that no diabetic changes observed in 20 cases while rest showed class 1 ,IIa changes with hypertensive change in more than 73% of the cases.
Multiple factors involved in the outcome of diabetic donor patients including severity of proteinuria ,severity of renal impairment, proteinuria severity, with histological changes of DN.
To conclude,early stages of diabetic nephropathy observed in very few patients and there is slow progression to overt diabetic nephropathy post transplantation and no major effects on graft survival.However,more studies needed with large number of population and kidney biopsies and long term follow up.
what is the level of evidence provided by this article?
Level III -retrospective observational study from a single center.
What are the criteria required to allow kidney donation in diabetics?
Living related diabetic donors-contraindicated
Patient should have age greater than 60 with normal renal function i.e.,GFR should b greater than 80ml/min/1.73m2 and without proteinuria.
Renal biopsy features suggestive of mild score .
summary:
DM is a worldwide disease with increasing prevalence globally. The impact of DM on organ allocation in deceased kidney donors is evolving. In UK up to 40% of kidneys from diabetic deceased donors were discarded. In living donor DM is considered contraindication of kidney donation.
Many approaches exist to the allocation of marginal donor kidneys as their use has expanded. In 1987 the first allocation scheme designed with the introduction of expanded criteria donor (ECD) that included donors aged 60 years or older, or aged 50 — 59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine > 1.5mg/dl. In this scheme, DM was not included.
In 2014 new kidney allocation system utilizes Kidney Donor Profile Index based on 10 donor factors to assign a risk score for posttransplant graft survival. Includes DM as important risk.
Diabetic donor kidneys account for a small but significant percentage of transplanted kidneys (3.5% – 6.5%). Diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure according to many studies although; these studies were with some limitations.
The findings of the study may have effect on the decision to accept or discard the diabetic donor’s kidney based on the kidney biopsy. The main changes on pretransplant biopsies leading to discard of the donor’s kidney are mainly related to glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial intimal thickening. DN changes were not included as a criterion for rejection. Current study found that DN is not seen or is only mild in postperfusion biopsies from donor with DM even of long duration (>10 ys). However, these biopsies often show significant arterionephrosclerosis, and interstitial fibrosis/tubular atrophy, reflecting the presence of hypertension (in 73% of diabetic donors).
The study findings support the validity of the current morphological criteria within the general scheme for organ allocation, which does not include changes referable to DN. In most used donor allocation scheme, that correlate with graft outcome, donor DM is not only one of the 10 evaluated factors, but also carries a heavy scoring weight.
This study suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
Diabetic donor kidneys are increasing accepted. Several studies addressing the outcome of this type of kidney transplant support this trend.
Mohan et al, compare diabetic and non-diabetic donor’s kidney. they concluded that SCD diabetic donors provide better grafts than nondiabetic ECD donors and worse than diabetic donors with ECD, but the risks of graft loss are all small compared to the ideal situation.
Cohen et al, study non-diabetic and diabetic donors, noted a modest difference in the overall graft survival. However, DM in recipient imparts a significant risk for graft loss.
The optimal outcome of diabetic donor kidney is determined by multiple factors; this study hypothesizes that good preservation of renal tissue in the presence of DM is the first significant factor.
Although DM is common (10% of adult population in the United States),1 its involvement of kidney, that is, DN, is less frequent.
This study demonstrates that renal biopsy changes of DN are most often not seen and, when seen, they are mild in diabetic donor kidneys. Also; the duration of DM does not correlate with the presence or absence of DN in the donors, as well as the DN class reflecting its severity, does not seem to correlate with the duration of DM.
Advanced DN is often manifested by impaired renal function and progressively heavy proteinuria, which are reasons for declining kidney donation. This stage is usually associated with sever DN histopathologic findings and significant fibrosis.
Absence of significant proteinuria and preserved renal function are 2 requirements for kidney donor acceptance. Donors with DM but without significant clinical manifestations, therefore, may show little changes in their kidney biopsies, as shown in the current study, in keeping with the known evolution of DN in native kidneys. It should, however, be emphasized that at least in native kidney, clinicopathologic discrepancy has been noted, as shown by a recent autopsy study in which DN, even of advanced classes, may develop without any clinical manifestations.
The posttransplant evolution of donor kidney DN is of considerable interest for at least 2 major reasons: potential reversibility of the renal changes and high incidence of diabetic donor kidneys transplanted into diabetic recipients. The reversibility of DN had been studies by some studies, that Collectively, indicate that knowledge in this area is limited, but suggest that reversibility of DN is possible, at least for early lesions and against specific clinical backgrounds.
This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases
with longer follow-up.
Limitations of the study:
1- the small number of cases (6/26 biopsies).
2- absence of advanced DN.
3- relatively short follow-up duration.
level III
dM kidney donor based on absence f significant biopsy finding
II. Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
Please summarise this article in your own words
Introduction
Almost 8% of deceased donors have DM & 40% of kidneys from diabetic donors are discarded (SRTRR).
DM is a contraindication of kidney donation by living donors.
Donor DM was not a part of the risk factors in the scheme of ECD (1987); however, it is an important factor in KDPI scoring system.
Diabetic donor kidneys are responsible for 3.5% to 6.5% of transplanted kidneys.
Materials & methods
DKD transplants done from 2006 & 2014 were reviewed to identify the donors with DM.
Out of 749 DKDs, (6.1%) had DM.
Biopsy (post-perfusion) of the grafts was done in 26 recipients; post-transplant biopsies were also done for evaluating changes of renal functions or for surveillance in high-risk recipients. This study focuses on these biopsies.
Biopsies studied by LM &IF; EM was done both prospectively & retrospectively, including GBM thickness measurement.
Thickened GBM (diagnostic change of DN), was defined as >430 (males) & 395(females) nanometers. Systematic examination focused on features of DN. Renal Pathology Society grading of diabetic changes were as follows:
– class 0 = no diabetic changes by LM or EM
– class I = no LM changes, but thick GBM by EM
– class IIa = mild mesangial expansion by LM
– class IIb = marked mesangial expansion by LM class III =nodular mesangial sclerosis
– class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli.
Changes other than DN were also recorded.
Follow-up biopsies were dealt with in the same way.
Data of donors (including diagnosis of DM & its duration) & recipients (including diagnosis criteria: FBG at least 126 mg/dL or a RBG at least 200 mg/dL & HbA1c at least 6.5%) were obtained from medical records, UNOS registry, & family members.
Results
A 26 post-perfusion biopsies done from 26 transplanted kidneys from 25 DKDs (2 kidneys from a single donor).
DN was not found in 20 biopsies (even after EM).
In 1 biopsy no LM changes of DN, but thickened GBM on EM.
Class IIa (mild mesangial sclerosis & hypercellularity, with thick GBM)DN in 5 biopsies.
Class IIb, class III, or class IV lesions were not seen in any biopsies.
Other changes in these biopsies included:
– Arterionephrosclerosis (14 biopsies)
– IF/TA (8 biopsies),
– ATN (4 biopsies)
– Myoglobin casts (2 biopsies),
– Incidental IgA nephropathy (1 biopsy)
– Glomerular capillary thrombi (1 biopsy).
Donor Profiles
– Age 18–70 years (mean 47)
– Male/female ratio 12/13
– Ethnicity: 16 Hispanic, 5 white, 3 African American,& 1 Asian
– EDC in 8
– History of HTN in 19
– Obesity (BMI >30) in 11.
All 25 donors had DM; the durations was variable:
– unknown in 7
– 15 y in 9
– 6–10 y in 7
– >10 y in 2.
Recipient Profiles
– Age 33–71 years (mean 57)
– Male/female ratio 16/10
– Ethnicity: 8 Hispanic, 4 white, 11 African American, & 3 Asian.
– Pre-transplantation HTN in 24 & DM in 15 (14 of them having both)
– Obesity (BMI >30) in 8.
– Causes of ESRD:HTN:-10, DM:- 8, HTN & DM:- 3, GN:-2, PKD:-1, & unknown in 2.
– Histocompatibility widely variable
– DGF in 7 (all recovered).
– Thymoglobulin induction in 16
– Maintenance IS included Tac in each recipient with MMF &/or steroid in some.
– Deaths in 4 (all of CV complications with functioning grafts); the remaining 22 were alive with functional grafts in 21 & 1 failed graft 54 months post-transplant ( due to progressive IF/TA).
– UPCR normal in 4; mildly increased in 19; high levels in 3; creatinine at follow-up of these 3 were 1.8, 8, & 2.7 mg/Dl; BKV nephropathy in 1 & arterionephrosclerosis with IF/TA in all 3, but not DN.
– DM: pre-transplantation in 15, persisted post- transplantation in 14, regressed in 1, & de novo in 6.
– HTN: pre-transplant in 24; post-transplant in 23. Several
Follow-up Biopsies (1–6 biopsies /recipient)
Done in 17 (at 5–342 wk, mean 41) to evaluate the evolution of DN.
In 20 with post-perfusion biopsies with no DN (class 0), follow-up biopsy not done in 8.
DM noted in 4 & 5 of these with pre- & post-transplant, respectively.
Follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 & DN in 3.
For the 3 in whom DN developed in follow-up biopsies, DM found in 2 before transplantation but occurred in all 3 after transplantation.
Among the 6 in whom post-perfusion biopsies showed DN, follow-up biopsy not done in 1. follow up biopsies in the other 5, showed no DN of the same class in 3 (class IIa/class IIa) & mild progression in 2 (class IIa/class IIb). Among these 5, pre-transplant DM was present in 4, but developed in all 5 after transplantation.
Other changes in follow up biopsies were:
– Aterionephrosclerosis (9 biopsies)
– IF/TA (8)
– GN (1)
– BKVN (1)
– Severe chronic rejection (1)
– TG(2)
– CAMR(1).
Discussion
DN is not seen or is only mild in post-perfusion biopsies from donors with DM even of long duration (>10#y); however, there often significant arterionephrosclerosis & IF/TA, reflecting the presence of HTN (in 73% of diabetic donors).
In the most recent KAS, donor DM is a factor with a heavy scoring weight.
DKDs are increasingly accepted. Mohan et al reported that SCD diabetic donors provide better grafts than non-diabetic ECD donors & worse than diabetic donors with ECD, but the risks of graft loss are all small compared to the ideal situation.
Cohen et al noted a modest difference in the overall graft survival (10-y survival 37% vs 50%); however, DM in recipient leads to significant risk for graft loss (25% for diabetic donor/diabetic recipient vs 37% for diabetic donor/nondiabetic recipient or nondiabetic donor/diabetic recipient).
In the current study, diabetic donor kidneys enjoy good outcome. Renal changes of DN are most often not seen &, if seen, are mild in kidneys from diabetic donors. The presence or absence of DN in diabetic donors does not correlate with the duration of DM.
Although DM is common, its involvement of kidney, DN, is less frequent (10%–30% of diabetic patients).
Advanced DN is often manifested by impaired renal function and progressively heavy proteinuria, which are reasons for declining kidney donation.
Absence of significant proteinuria & normal renal function are 2 requirements for kidney donor acceptance.
The current study is the largest study on post-transplant evolution of donor kidney DN. It suggests that DN can be stable, or progress (though rather slowly).
Limitations:
– Small number of cases (6/26 biopsies)
– Relatively short follow-up duration.
In summary:
DN is seen in a small % of diabetic donor kidneys.
DN is often mild & in early stages.
Post-transplantation, DN in diabetic donor kidneys
may stabilize or progress with a mild increase in severity.
In cases DN is not present in diabetic donor kidneys, DN often does not develop in post-transplant, even in diabetic recipients.
DN may not by itself cause significant adverse effect of graft survival (needs confirmation by a larger study)
============================
What is the level of evidence provided by this article?
Level III
============================
What are the criteria required to allow kidney donation in diabetic?
– SCD rather than ECD
– Absence of DM in the recipient
– Good renal tissue in the biopsy
– Combined kidney pancreas confers protective effect.
The most diabetic donor excluded from donation and in the past expended donor criteria 1978, excluded age> 60 years or age between 50-59 years with hypertension or cerebrovascular disease and serum creatinine level more than 1.5mg/dl. but risk factor of diabetic donor not included in this criteria
This article focus on impact of diabetic donor in kidney transplan at time of kidney transplant and post transplant.
According to national register studies shows 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
This study done at Walter Transplant Center and Houston Methodist Hospital between 2006-2014 by review all deceased donor for evidence of diabetes and renal biopsy done prospectively and retrospective for features of diabetic nephropathy by light microscopy and electron microscopy and immunoflorescence.
Diagnostic criteria of diabetic nephropathy by renal biopsy is by measurements of basement membrane thickness of >430 and 395 nanometers for male and female, respectively.
Systematic examination was performed with special attention to the features of DN. The diabetic changes were graded on a scale of 0–IV.
class 0 = no diabetic changes by LM or EM.
class I = no obvious LM changes but thickening of the GBM by EM
class IIa = mild mesangial expansion by LM;
class IIb = marked mesangial expansion by LM;
class III = nodular mesangial sclerosis
class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli.
Donor diagnosis in this study from history and review previous medical record donors and data from national registries.
Diagnosis of recipients by blood level of fasting plasma glucose level of at least 126mg/dL or a random plasma glucose level of at least 200mg/dL and a HbA1c at least 6.5%.
The most recipient shows evidence of diabetic nephropathy stage ( 0, Ia, IIa, b) but not seeing III & IV.
one recipient dia from cardiovascular disease and one graft failure shows in biopsy interstitial fibrosis and tubular atrophy.
Several diseases were also noted in these recipients after transplantation, affecting some but not all patients, including hyperparathyroidism, hyperlipidemia, metabolic syndrome, urinary or nonurinary infection, atherosclerosis, obesity, cirrhosis, and gastroesophageal reflux.
In this study diabetic donor kidneys enjoy good outcome.
Diabetic donor kidneys are increasing accepted.
Advanced diabetic nephropathy is manifested by impaired renal function and progressive heavy proteinuria, which are reasons for declining kidney donation.
This stage of DN often requires a long duration of DM >10 y and the renal biopsies tend to show typical changes of DN, often class IIb, III, or IV, together with severe interstitial fibrosis/tubular atrophy and arteriosclerosis/hyalinosis.
The renal changes in the diabetic patients without or with minor clinical manifestation are variable, Absence of significant proteinuria and preserved renal function are 2 requirements for kidney donor acceptance.
This study conducted pre and post transplant evaluation of diabetic nephropathy by renal biopsy to revers and slow progress of early stage of diabetic nephropathy.
Limitations of this study is small number and short duration of fallow up and no cases of advanced diabetic nephropathy.
This high incidence of DM in renal transplant recipients reflects not only the persistence of pretransplant DM, but also de novo DM.
De novo DM develops in 4%–25% De novo DM may be due to several factors, including drug induced by diabetogenic effect of steroid and tacrolimus.
complications of DN may aggravate graft loss and increase incidence of infection and cardiovascular disease.
Q2: Cohort study level 3
Q3: Criteria of diabetes donation:
No renal function impairment and no evidence of proteinuria
no histopathological abnormalities by renal biopsy
Tight blood sugar control and BMI less than 30 Well control of hypertension
II. Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
Diabetes mellitus is the leading cause of kidney failure and it is associated with high cardiovascular disease and an increase in mortality. The article is based on DM and kidney transplants is it advisable to use as a donor or not? so this article is to evaluate the renal changes of DM donors pre-transplantations and post-transplantation.
The study was conducted at the JCA Walser transplant center for a period of 2006 to 2016. The population of the study was about 794 donors of which 46 were DM, biopsy was conducted on 26 patients to see the renal changes as it relates to its functions.
The biopsy was done to evaluate the DN and a grade was given from 0 to 4. Now based on the result obtained it was found that from the 26 biopsies, 20 were free from DM changes. A total of 5 showed light microscope DM changes and 1 showed electron microscope DM changes. In some biopsies, it was noted that some had significant arterio-nephrosclerosis, tubular atrophy, and interstitial fibrosis that is reflective of HTN in the 73 % of DM donors.
During the follow-up of the patients for a period of about 36-136 months, it was found that 4 recipients were deceased the cause of which was cardiovascular complications, with a good functional graft. Of the remaining 22 clients, 21 had functional grafts and 1 had failed graft within 54 months post-transplant likely to be because of interstitial fibrosis and tubular atrophy.
The patients were continuing and were being follow-up with a kidney biopsy, of which, 12 recipients did a biopsy and 9 have no DN class 0, and only 3 had DN class 1 in 2 and class II an in 1. The study concluded that diabetic donors’ DN may stabilize or progress to mild to severe kidney disease. But it must be noted that DM donor kidneys with or without DN may not by itself may not have much adverse effect on graft survival.
The study was a case-control study retrospective and it is level 3,
To have DM kidney donation there must be guidelines and regulations to govern the issues. The criteria for DM donation depends on kidney biopsy, non-diabetic recipient is that there must be minimal DM changes on biopsy, renal function preserved, and no proteinuria and other risk factors that can lead to worsening kidney functions.
Hi Dr Marius Badal,
Getting histopathology of renal biopsy of the cadaveric kidney at 3 am or on weekend is rather an ambitious task in UK.
Ajay
Diabetes is common in adult population and hence its presence in deceased donors’ kidneys needs evaluation to assess its impact on long-term graft and recipient survival.
The study was conducted retrospectively at J C Walter Transplant centre between January 2006 to December 2014. Out of 749 deceased donors, 46 (6.1%) had diabetes and post-perfusion biopsy was performed in 26 recipients (from 25 donors) which was staged as per RPS scale for diabetic nephropathy. Post-transplant graft biopsies were also performed in the recipients. The follow-up ranged from 36 to 136 months.
Post-perfusion biopsies: Diabetic nephropathy was present in 6 out of the 26 biopsies, with 1 biopsy showing class I changes and 5 biopsies showing class IIa changes. Other changes seen included arterio-nephrosclerosis (14 biopsies), interstitial fibrosis/ tubular atrophy (8 biopsies), acute tubular necrosis (4 biopsies), myoglobin casts (2 biopsies), IgA nephropathy and glomerular capillary thrombi (1 biopsy each).
Donor profile: Mean age 47 years, males 48%, majority Hispanic, hypertension in76%
Recipient profile: Mean age 57 years, Males 61%, majority African-Americans, DM before transplant in 57% and hypertension before transplant in 92%
Follow-up biopsies: done for 17 recipients (1-6 biopsies per recipient).
Among the 20 patients with no DN changes post-perfusion, biopsy done in 12: 9 showed no DN changes (5 had DM pre-transplant and one more developed DM later), 1 showed class IIa (did not have DM pre-transplant) and 2 showed class I changes (had DM pre-transplant).
Among the 5 patients with class IIa DN changes post-perfusion, biopsy showed change to class IIb in one patient and one of the recipients who was not a diabetic pre-transplant became diabetic. All the other recipients were diabetic pre-transplant.
The patient with class I DN changes post-perfusion did not undergo any follow-up biopsy, although the patient developed DM post-transplant.
Other changes seen in post-transplant biopsies included arterio-nephrosclerosis (9 biopsies), interstitial fibrosis/ tubular atrophy (8 biopsies), transplant glomerulopathy (2 biopsies), and glomerulitis, severe chronic rejection, chronic AMR and polyomavirus nephropathy (1 biopsy each).
The study found that DN is not seen in majority of post-perfusion biopsies of diabetic donors of even long duration (>10 years), although arterio-nephrosclerosis and IF/TA are significantly present. Even when the DN changes are present, they are of mild nature.
Diabetic donor kidneys, when transplanted in a diabetic recipient, may not develop DN at least during the short-term post-transplant period and even if it develops, it is of mild severity. Those with diabetic changes pre-transplant also stabilize or do not worsen much.
Level of evidence: Level 3 – Cohort study
Diabetes and deceased kidney donation: Diabetics are not taken as deceased donor in majority of deceased donor transplant programs, although it is not considered a risk factor in criteria of expanded criteria donor.
Diabetes and living kidney donation:
a) A person with Type 1 diabetes is excluded from donation (1).
b) A person with IFG and IGT can donate after counselling and explaining the risks of developing diabetes after donating, and taking care of risk factors like obesity, dyslipidemia and hypertension. They should be counselled regarding life-long precautions with respect to the risk factors like obesity, hypertension etc (2).
c) Those with Type 2 diabetes, and without any target organ damage (by performing kidney biopsy in certain cases), can be taken up as a donor after thorough assessment of lifetime risks of CV disease and ESRD, detailed counselling, and management of risk factors. The donor needs to be emphasized the importance of life-time management of these risk factors and follow-up. As per KDIGO guidelines, older candidates with Type 2 DM having well-controlled glycemia (without insulin use) and no target-organ damage can be taken up for organ donation (2).
References
1) Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, Gallon L, Garvey CA, Guleria S, Li PK, Segev DL, Taler SJ, Tanabe K, Wright L, Zeier MG, Cheung M, Garg AX. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017 Aug;101(8S Suppl 1):S1-S109. doi: 10.1097/TP.0000000000001769. PMID: 28742762; PMCID: PMC5540357.
2) British Transplantation Society. Renal Association Guidelines for Living Donor Kidney Transplantation, 4th ed.; British Transplantation Society: Macclesfield, UK, 2018; Available online: https//bts.org.uk/wp-content/uploads/2018/07/FINAL_LDKT-guidelines_June-2018.pdf (accessed on 18 September 2022).
That is a very good analysis, Dr Amit Sharma.
Getting histopathology of renal biopsy of cadaveric kidney at 3 am or on weekend is rather an ambitious task in UK
Thank you Sir.
Our transplant program is a living donor program, hence we do not have first hand experience of difficulties faced by a deceased donor program.
The aim of this study is to address the impact of diabetic deceased donor on graft and recipient outcome
about 8% of deceased donors have DM
But up to 40% of their kidneys were discarded.
This study from 2006 to 2014
Diabetic donors account 6.1% of all kidney transplants
Diagnosis of DM in donor depends upon family members and old medical DATA
Diagnosis of DM in recipient depends on fasting plasma glucose more than 126 or in random plasma glucose more than 200 or HBA1C more than 6.5
Classification Depending on light and electronic microscopy
0 no DM
I LM normal but EM thickness BM
IIA mild mesangial expansion
IIB marked mesangial expansion
III nodular mesangial sclerosis
IV advanced glomerulosclerosis Global if more than 50%
26 biopsies after renal transplantation
20 no DN
1 class I
5 class II a
There is no class II or class IIII
BUT
arterionephrosclerosis 14
IFTA 8
ATN 4
myoglobin cast 2
IgA nephropathy 1
Glomerular capillary thrombi 1
Results
The presence of DN in recipients was mild or even not seen during 10 years of renal transplantation from DM deceased donors
donor DM impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
Diabetic donor kidneys have either no impact on long-term graft or recipient survival, or confer only a small risk for failure.
Donors with DM but without signicant clinical manifestations, therefore, may show little changes in recipient kidney biopsies,
level III
tow Requirements for kidney donor acceptance
Dear Dr Ghalia,
I like the scientific contents of your write-up. But, it needs to refined:
I would type ‘two requirements for kidney donor acceptance’ rather than ‘tow Requirements for kidney donor acceptance’.
Please type headings and subheadings in bold or underlined to make it easier to read.
. Please summarise this article in your own words
-Diabetes (DM) is an increasingly significant factor in renal transplantation. According to the 2013 and 2015 Scientific Registry of Transplant Recipients Reports, about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
-DM is considered a contraindication of kidney donation by living donors. Consideration on the impact of DM on organ allocation in deceased kidney donors is evolving.
-The first allocation scheme in 1987 introduced the concept of expanded criteria donor (ECD) defined as donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL.
Against this background, diabetic donor kidneys account for a small but significant percentage of transplanted kidneys ranging from 3.5% to 6.5%.
Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all concurring that diabetic donor kidneys have either no impact
on long-term graft or recipient survival, or confer only a small risk for failure.
– 749deceased kidney donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital, between January 2006 and December 2014 were reviewed to identify the donors with DM. 46 donor had DM.
-Post transplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients. These biopsies are the focus of this study.
-Thickened GBM, a diagnostic change of DN, was defined as a thickness of >430 and 395 nanometers for male and female, respectively.
-The diabetic changes were graded on a scale of 0–IV, as defined by the Renal Pathology Society
0 = no diabetic changes by LM or EM .
class I = no obvious LM changes, but thickening of the GBM by EM .
class IIa = mild mesangial expansion by LM.
class IIb = marked mesangial expansion by LM
class III = nodular mesangial sclerosis.
class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli.
– For donors, the diagnosis of DM and its estimated duration were made through communication with family members, old medical records, and data from national registries.
-For recipients, the diagnosis criteria included a fasting plasma glucose level of at least 126 mg/dL or a random plasma glucose level of at least 200 mg/dL and a hemoglobin A1c of at least 6.5%.
-This is the first study that comprehensively evaluates the renal changes of diabetic donor kidneys at the time of transplantation and its post transplant evolution.
– It suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
– Although the optimal outcome of diabetic donor kidney is perhaps multifactorial, the good preservation of renal tissue in the presence of DM is significant factor.
-The study demonstrates that renal changes characteristic for DN are most often not seen and, when seen, are rather mild in kidneys from diabetic donors.
-The presence or absence of DN in diabetic donors, as well as the DN class reflecting its severity, does not seem to correlate with the duration of DM.
-Absence of significant proteinuria and preserved renal function are requirements for kidney donor acceptance.
-Reversibility of the renal changes characteristic for DN has been evaluated in different studies. Abouna et al. reported the absence of DN at 7 months post transplant in both transplanted kidneys from a deceased donor with DM for 17 years and with DN in pretransplant biopsy.
-Post transplant DM seems to be an important condition, being present in all cases with stable or progressive post transplant DN. The high incidence of DM in renal transplant recipients reflects not only the persistence of pretransplant DM, but also de novo DM.
– De novo DM may be due to several factors, including the diabetogenic effect of steroid and tacrolimus, the latter used in all recipients in the current study.
-Recipient DM imparts significantly increased risk of graft loss, and this risk is even more pronounced in cases of diabetic donor kidneys.
-This study, though relatively small, suggests that diabetic donor kidneys with or
without DN, transplanted into a diabetic recipient, may not develop DN during the post transplant period at least in short term, or develop into a mild/early form of DN, that by itself may not significantly impact graft outcome.
– In cases DN is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients.
– This study suggests that diabeticdonor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases with longer follow-up.
What is the level of evidence provided by this article?
Retrospective study.level 3.
What are the criteria required to allow kidney donation in diabetic?
KDIGO-Donor candidates with type 1 diabetes mellitus should not donate.
-The decision to approve donor candidates with prediabetes or type 2 diabetes should be individualized based on demographic and health profile in relation to the transplant program’s acceptable risk threshold.
– Donor candidates with prediabetes or type 2 diabetes
should be counseled that their condition may progress
over time and may lead to end-organ complications.
BTS: All potential living kidney donors must have a fasting plasma glucose level checked. (B1)
– A fasting plasma glucose concentration between 6.1-6.9 mmol/L is indicative of an impaired fasting glucose state and an oral glucose tolerance test (OGTT) should be undertaken. (B1)
-Prospective donors with an increased risk of type 2 diabetes because of family history, a history of gestational diabetes, ethnicity or obesity should also undergo an OGTT. (B1)
-Consideration should be given to the use of a diabetes risk calculator to inform the discussion of potential kidney donation. (B2)
-Consideration of patients with diabetes as potential kidney donors requires very careful evaluation of the risks and benefits. In the absence of evidence of target organ damage and having ensured that other cardiovascular risk factors such as obesity, hypertension or hyperlipidaemia are optimally managed, diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of
cardiovascular and progressive renal disease in the presence of a single kidney. (Not graded)
That is a very good analysis Dr Reem Yunus.
Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
DM is a common disease that causing ESRD secondary to diabetic kidney disease and is a significant factor in renal transplantation.AS per reports for transplantation registry about 8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded. DM is considered a contraindication of kidney donation by living donors.
Consideration on the impact of DM on organ allocation in deceased kidney donors is evolving. There have been various approaches to the allocation of marginal donor kidneys as their utilization has expanded. ECD included donors aged 60 years or older, or aged 50–59 years in the presence of at least 2 of 3 risk factors including cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL. Donor DM is not included as a risk factor in this scheme. Donor DM has been an important reason for the discard of donor’s kidneys.
Few studies have evaluated the outcome of transplanted kidneys from diabetic donors, all claiming that diabetic donor kidneys have either no impact on long-term graft or recipient survival, or can cause only a small risk for failure. The current study aims to address the status of diabetic nephropathy (DN) in deceased donated kidneys, its evolution after transplantation in relation to posttransplant DM, and its impact on graft outcome.
Materials and methods:
The current study evaluated the Postperfusion biopsy of the transplanted kidneys from diabetic deceased donors was performed in 26 recipients. Posttransplant renal biopsies were performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients.
The biopsies are subjected to light microscopy with different stains, Immunofluorescence and EM including measurement of the thickness of the glomerular basement membrane (GBM). Thickened GBM, a diagnostic change of DN, was defined as a thickness of >430 and 395 nanometres for male and female, respectively. The diabetic changes were graded on a scale of 0–IV, as defined by the Renal Pathology Society.
Results and conclusion
Diabetic nephropathy is noted in a small percentage of diabetic deceased donor kidneys. The Diabetic nephropathy is often mild and in early stages. After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow course. In cases DN changes is not present in diabetic donor kidneys, DN often does not develop in posttransplant, even in diabetic recipients.
This study suggests that diabetic donor kidneys with or without DN may not by itself impact significant adverse effect of graft survival, an observation that requires more evaluation of a larger number of cases with longer follow-up.
The level of evidence provided by this article is level III
Thank You, Mohamed
Please summarise this article in your own words
Diabetes mellitus is a very important factor in renal transplantation. Diabetes is one of the contraindication for kidney donation. There is evolving consideration on impact of diabetes on organ allocation in deceased kidney donors. The new allocation system in 2014 uses kidney donor pro index based n 10 donor factors to assign a risk d=score for post transplant survival. Donated kidney from diabetics account for 3.5-6%. Very few studies have evaluated the impact of donation from diabetics.
Methodology
This was a retrospective observational study. It included results of biopsies from diabetic deceased donors which were assessed under light an electron microscopy and IF. Total deceased donors with diabetes was 6.1% ( 46 from 749). Diabetes was diagnosed through medical records, national registry and family communication.
Criteria for diagnosis of diabetes in recipients was-
HBA1c-6.5%
Random sugar at least 200 mg/dl
Fasting sugar 126 mg/dl
After transplant the diabetic nephropathy in donor kidney can be due to reversibility of renal changes and if both donor and recipients are diabetic
Results and conclusions
26 biopsies were done from 25 deceased diabetic donor kidneys ( 2 kidneys from single donor).
20 had no DN. One biopsy showed thickened GM – Class 1. 5 biopsies showed class 11a.
The presence or absence of diabetic nephropathy has no relation with duration of diabetes and is usually not seen or can be seen with minimal presence in graft biopsies from diabetic donors.
Graft with absence of diabetic nephropathy pre transplant are unlikely to develop it after transplant
The diabetic nephropathy after transplant may show minimal progression and graft outcome may not be affected by diabetes in donors as the mechanism can be different than renal insult by diabetes.
Kidney from diabetic donors may not affect over all graft outcomes and may have minimal
Limitations
Short follow up
small number of cases
What is the level of evidence provided by this article?
Retrospective study
Level 111
What are the criteria required to allow kidney donation in diabetics?
Normal renal functions with no proteinuria
eGFR>80 ml/m
No diabetic complications and no Cardiovascular risks
Type 11 Diabetes and age >60 years
I like your write-up Dr Abdul Rahim Khan.
Ajay
Thank you Prof
Please summarise this article in your own words
DM affects almost 10% of general population
The cadaveric diabetic kidney disease only done in 8% of cases , and more than 40% were declined.
The study design :
To clarify the effect of diabetic deceased kidney donor on graft outcome, and recipient survival.
Conducted in single center of kidney transplantation.
Post perfusion kidney transplant biopsy was done in 26 cases studies
Post kidney transplantation kidney biopsy was done in 17 cases studied.
All biopsies examined under light microscopy with different stains, immunofluorescence, and light microscopy (retrospectively or prospectively)- to evaluate GBM thickness (> 430 nanometers in males and 395 nanometers in females)
DN classified according to renal pathology society from 0-IV
0 = no diabetic changes by light microscopy.
I = no microscopic changes but LM thickening of basement membrane.
II = a) mild mesangial expansion by LM, and b) marked mesangial expansion by LM.
III = nodular mesangial sclerosis.
IV = advanced glomerulosclerosis with global sclerosis in > 50% of glomeruli.
Results :
Post perfusion kidney transplant biopsy findings –
DN was not seen in 20 biopsies, even after EM study.
20 biopsies showed no LM neither EM changes.
1 biopsy showed no LM changes of DN, but EM showed thickened GBM (495+/−27 nanometers) (class I).
5 biopsies showed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thick[1]ened GBM (569+/−51 nanometers).
None of these biopsies showed class IIb, class III, or class IV lesions.
Other changes were seen in the biopsies- 14 with arterionephrosclerosis, 8 with interstitial !brosis and tubular atrophy >15% of cortical tissue area, 4 with acute tubular necrosis, 2 with myoglobin casts, 1 with IgA nephropathy, 1 with glomerular capillary thrombi.
Follow-up biopsies – (mean 41 weeks post transplant ) among the 20 recipient whom post perfusion biopsy showed no LM neither EM changes.
12 biopsies showed no DN class 0.
2 biopsies class I
1 biopsy class IIa
8 biopsy were not done due to either deterioration in kidney function or death (4 patients)
In the 5 cases with class IIa DN one case deteriorate to class IIb , other showed the same chnges.
In the 1 no LM changes of DN, but EM showed thickened GBM- biopsy not done.
The study showed the possibility of DN reversal or stabilization of the postperfusion changes and possible resolution and normalization of GBM thickness.
However the discussion showed that diabetic recipients pears increased risk of graft loss and patients survival and increased with receiving kidney from diabetic donor.
Limitations:
Small number of patients.
Absence of advanced DN in evaluated cases.
Short follow-up time.
What is the level of evidence provided by this article?
Individual case control study level of evidence IIIb.
What are the criteria required to allow kidney donation in diabetics?
BTS recommendations:
Consideration s to the use of a diabetes risk calculator to inform the discussion of potential kidney donation. (B2).
Patients with diabetes as potential kidney donors requires very careful evaluation of the risks and benefits. In the absence of evidence of target organ damage and having ensured that other cardiovascular risk factors such as obesity, hypertension or hyperlipidaemia are optimally managed, diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of cardiovascular and progressive renal disease in the presence of a single kidney,(Not graded)
KDIGO 2017 recommendations: Donor candidates with type 1 diabetes mellitus should not donate.
Donor candidates with type 1 diabetes mellitus should not donate.
Donor candidates with prediabetes or type 2 diabetes should be counseled that their condition may progress over time and may lead to end-organ complications.
Organ Procurement and Transplant Network (OPTN): consider DM as an absolute contraindication for transplantation.
Would you consider using kidneys (single or preferably dual) from a cadaveric donor with well-controlled diabetes but with microalbuminuria only?
That is a great question to ponder. I do have much experience but I would think of taking both kidneys since the patient that is the cadaveric kidneys have microalbuminuria and that is showing kidney diseases and the risk of HTN and worsening kidney functions.
Dear Dr Marius Badal, I like your reply. May be you wanted to add ‘not’ after ‘do’.
We have experience with 46 dual transplants in Liverpool.
If this cadaveric donor has only microproteinuria and GP records show that DM has been well-controlled then a single kidney would be fine for transplantation. But if there is one more risk factor such as age or HT then I would use such a donor for dual renal transplant.
Thank you for the nice question and the contribution, i would add also the patient age to be considered in the decision as well if the donor >60 yr old with microalbuminuria i would do dual nephrectomy.
Please summarize this article in your own words.
Diabetes in potential living donors usually excludes them from donation. but in recent years concept of allocation of marginal donor kidneys has been developed which is called Expanded Criteria Donor (ECD). A new allocation system was developed in 2014 which uses KIDNEY DONOR PROFILE INDEX. this system is based on 10 donor factors which helps to assign risk score for survival of graft post transplantation.
The present study tries to address some of main limitations of the previous studies which are as follows:
Materials and Methods
This is quite interesting, the way the authors have carried out the study
Important outcomes
What is the level of evidence provided by this article?
Its ambispective case control study hence has level 3 evidence
What are the criteria required to allow kidney donation in diabetic?
Absence of proteinuria and normal renal functions are the 2 main requirements for kidney donation from potential donors with DM because such case show minimal changes in kidney biopsy as suggested in present study.
Hi Dr Saini,
A pre-transplant biopsy for a cadveric donor kidney is not easy to arrange at 3 am or on weekends.
I totally agree to it sir but though current study is on cadaveric donor but can be considered on living donors with DM. My quote was for living donors and it seems that per transplant biopsy in living donors with DM will reduce the rejection in donors with DM
Hmmm..
Not an expression one uses in scientific writing, that I have typed my reaction dear Dr Saini. I am not happy with your answer (I am stating it with all the affection and due respect for a colleague like you).
Please reconsider your reply as I type, “Hmmm”.
.
Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance.
Aim of the study is to evaluates the renal changes of diabetic donor kidneys at the time of transplantation and its posttransplant evolution.
Confirmed case of DM and borderline (pre-diabetic ) is considered absolute contraindication for kidney donation, but there is new criteria for deceased kidney donation, trying to increase kidney donation pool from diabetic donors, The new Kidney Allocation System implemented in 2014 utilizes the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for post-transplant graft survival and DM is one of them, Few studies have shown that outcome of transplanted kidneys from diabetic donors is accepted and agreed that diabetic donor kidneys have either no impact on long-term graft or recipient survival.
Material and methods.
This study done on deceased kidney donors from January 2006 and December 2014 at the J.C. Walter Transplant Center, The Houston Methodist were reviewed to identify the donors with DM. Out of 749 donors, 46 (6.1%) had DM.
Post perfusion renal biopsy taken from 26 donors examined by L/M, IF and E/M was done both prospectively and retrospectively, including measurement of the thickness of the glomerular basement membrane (GBM) following diabetic changes as IPS definitions.
All clinical history related to donor diabetic status collected from hospital medical records, United Network of Organ Sharing registry, and family members.
Also recipient followed by clinical status and criteria for diagnosis DM , renal biopsy and following also renal function test.
Result:
Post-perfusion Renal Transplant Biopsy Findings.
Twenty renal biopsies are free of diabetic changes out of 26 renal biopsies done(variable duration of DM), 5 showed L/M diabetic changes(6-10 years history of DM) and 1 showed E/M diabetic changes(1-5 years) but there are biopsies often show significant arterio-nephrosclerosis, and interstitial !bro[1]sis/tubular atrophy, reflecting the presence of hypertension (in 73% of diabetic donors).
Donor Profiles.
EDC in 8; history of hypertension in 19; obesity (body mass index >30) in 11 and all diabetic with variable duration.
Recipient Profiles.
The main cause of ESRD was HTN and DM.
Follow-up (36–136 month) showed 4 recipients died, mainly due to cardiovascular complications, with functional renal grafts. The remaining 22 recipients were alive with functional grafts in 21 and 1 failed graft 54 months post-transplant probably due to progressive interstitial fibrosis and tubular atrophy.
DM was present in 15 recipients before transplantation. After transplantation, DM persisted in 14, regressed in 1, and developed de novo in 6, for a total of 20 recipients with posttransplant DM.
Follow-up Biopsies.
Follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 and DN in 3 (class I in 2 and class IIa in 1).
Conclusion:
DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity, diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival.
level of evidence provided by this article is LEVEL III( retrospective well designed controlled trials without randomization).
What are the criteria required to allow kidney donation in diabetics?
There is no specified standard criteria to allow kidney donation from diabetics in living donation, and considered absolute contraindications in most consensus guidelines but the BTS offers the opinion-based recommendation that “diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of cardiovascular and progressive kidney disease in the presence of a single kidney .
Deceased kidney donation from diabetic still no so clear but mainly depends on risk score for posttransplant graft survival by Kidney Allocation System.
Hi Dr Mohammed Saad,
I quote your reply, ‘there is no specified standard criteria to allow kidney donation from diabetics in living donation.”
My question: is there any need for criteria to be defined for living donor donation from diabetics?
Are we talking about living donors in this study?
Ajay
Thanks ,professor Sharma.
My answer is No(no need for criteria for living kidney donation from diabetics .
In all consensus guidelines, DM is considered absolute contraindications.
Our study here talking about deceased kidney donation which is mainly depends on risk score for post transplant graft survival by KAS as mentioned above .
1-Summary of Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
Few studies have evaluated the outcome of transplant kidney from DM donor ,all concluded no impact on long graft or recipient survival .
The current study aims to evaluate the renal changes of DM donor kidney at time of transplantation and its posttransplant evaluation.
Material and methods
Records of all deceased kidney donors at the J.CA Walser Transplant centre. from 2006 to 2014,
out of 749 donor 46 had DM ,postperfusion biopsy of transplanted kidney was performed in 26 recipients to evaluate changes of renal function .
The biopsy examined for the feature of DN and grate from 0 to 4.
for recipient diagnosis criteria including FBG 126 mg/dl random BG 200 mg /dl and HA1C 6.5.
RESULT
postperfusion renal transplant biopsy finding,26 transplant kidney biopsy from 25 deceased DM donor .
20 biopsy showed no DN but these biopsy showed these changes due to others causes .
The level of histocompatibility were widely variable .
7 recipient has delay graft function all were recoded.
induction with thymoglobulin in 16 recipients ,maintance therapy TAC plus MMF and or steroid in some recipients,
4recipent died all CVS complication with functional renal grafts ..
The remaining 22recipents alive with functioning graft in 21 and 1 failed graft 54 month post transplant due to intestinal fibrosis and tubular atrophy.
Protein excretion (protein /creatinine ratio) was normal in 4 increases of low level in 19 recipients.
And high levels in 3 recipients and serum creatinine at follow up of these 3 recipients were 1.8,8,2.7mg/dl follow up transplant biopsy.
In all recipients they found non DM cause for their graft function deteriorate .
Dm was present in 15 recipient before transplantation after transplantation DM persist in 14 ,regressed in 1 and develop de novo in 6.
Follow up biopsy among 20 recipient with posttransplant biopsy showed no DN.
Follow up in 8 DM was noted in 4 and 5 of the recipients pre and post transplant pre and post transplant, respectively.
12 recipient showed no DN and DN in 3.
Among recipient showed DN and follow up biopsy.
,5 recipients showed no DN of the same class in 3 and mild progression in 2 class2a ,2b.
Postrenal transplant DM in 5 (4 were pretransplant DM).
17 follow up biopsy there were no pathology.
Conclusion
The study found that DN is not seen or is only mild in postperfusion biopsy from donor with DM even of long duration >10years.
This observation may change the morphological criteria for organ allocation and dose not include changes refer to DN .
In this study diabetics donors kidney had good out come ,where 4 recipients died of causes others than DN per se with functional graft ,other 22 recipient alive at last follow up with functional graft .
The absence of significant proteinuria and preserved renal function are 2 require for kidney donor acceptance.
Limited effect of pancreas transplant on DN in the native kidney.
This study suggest that diabetic donor kidney with or without DN may not develop DN and may not impact graft out come
Summary
DN is noted in a small percentage of DM donor kidney .
When this occurs .the DN is often mild and early stages .after transplantation ,DN in diabetic donor kidney may stabilize or progress with a mild increase in severity and at a slow pace.
Absence of DN in DM donor kidney ,DN does not develop in posttransplant even in DM recipients and will not affect graft survival, this observation require confirmatory evaluation of a large number cases with longer 2-What is the level of evidence provided by this article
3-What are the criteria required to allow kidney donation in diabteric?
criteria for donation DM patient ,should has minimal diabetics change(DN) in renal biopsy or no DN. preserved renal function and no proteinuria and no other comorbidity
Yes Dr Manal Malik,
Case-control studies are always retrospective and it is a level 3 evidence, as you state.
8% of deceased donors have DM and up to 40% of kidneys from diabetic donors were discarded.
DM is considered a contraindication of kidney donation by living donors.
The new Kidney Allocation System implemented in 2014 utilizes the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for posttransplant graft survival. Donor DM carries a heavyweight in this scoring.
Materials and methods:
Deceased kidney donors for 9 years between 01/2006 to 12/2014 in 2 hospitals J.C. Walter Transplant Center, The Houston Methodist Hospital.
Aim: Identify donors with DM and assess outcome.
Results: 749 donors, 46 had DM (6.1%).
Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients.
Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients.
DN changes were graded from 0-IV according to renal pathology society definition.
Results:
Postperfusion Renal Transplant Biopsy Findings
26 biopsies:
20-à no LM or EM DN. 5–à Class IIa DN. 1à no LM, but class I EM DN.
Other changes included:
14 biopsies arterio-nephrosclerosis, 8 biopsies IF and TA >15% of cortical tissue area,
4 Biopsies ATN, 2 biopsies myoglobin casts,
One biopsy incidental IgA nephropathy, and
One biopsy incidental rare glomerular capillary thrombi, perhaps related to organ preservation.
Follow-up Biopsies:
Follow-up biopsies (1–6 biopsies /recipient) were done for 17 recipients.
to evaluate the evolution of DN against the background of the DM status of the recipients.
20 recipients: post perfusion biopsy showed no DN, 8 of them didn’t have follow up biopsy. 4 Recipients had DM in pre-transplant biopsy and 5 post- transplant. Follow-up biopsies, done in 12 recipients, showed no DN (class 0) in 9 and DN in 3 (class I in 2 and class IIa in 1).
For the 3 recipients in whom DN developed in follow-up biopsies, DM was present in 2 recipients before transplantation but developed in all 3 recipients after transplantation.
Among the 6 recipients in whom the postperfusion biopsies showed DN, follow-up biopsy was not done in 1.
The follow- up biopsies, done in the other 5 recipients, showed no DN of the same class in 3 (class IIa/class IIa) and mild progression in 2 (class IIa/class IIb.
Among these 5 recipients, pre-transplant DM was present in 4, but developed in all 5 after transplantation.
Donors Profile:
all 25 donors had DM with variable durations (unknown in 7,15y in 9, 6–10y in 7, and>10y in 2).
Absence of significant proteinuria and preserved renal function are 2 requirements for kidney donor acceptance.
Limitations:
included limited number of cases, none of the biopsies showed advanced DN, short follow up duration with no assessment of factors affecting progression of DN.
For living donation:
BTS 2018: DM can be considered for donation after thorough assessment to rule out target organ damage, proteinuria and impaired renal function.
KDIGO 2017:
T1DM; contraindication.
Prediabetes or T2DM: individualized decision.
AST 2015: DM donors are excluded from donation.
For Deceased Donor:
Most centers exclude patient with DM.
some studies showed survival benefits of accepting a diabetic deceased kidney donor.
– Donors with DM but without other significant comorbidities.
– little or no changes in their kidney biopsies
– diabetic-SCD have better graft-survival compared to non-diabetic ECD.
Level III retrospective study
Absence of significant proteinuria and preserved renal function are the two requirements for kidney donor acceptance.
Additional potential criteria include: Pre-transplant biopsy with no or mild DN, non-diabetic recipient, and well education of the recipient.
Hi Dr Hamdy,
What type of retrospective study it is?
Is it longitudinal or cross-sectional?
The aim of the study ;
Is to evaluate the outcome of transplanted kidneys from diabetic donors.
The study area ;
Walter Transplant Center and The Houston Methodist Hospital.
Ethical approval ;
This study is approved by the institutional review board
Population ;
26 transplanted kidneys from 25 deceased diabetic kidney donors (2 kidneys from a single donor).
The method ;
Post transplant renal biopsies were performed in these recipients for evaluating changes of renal functions .
RESULTS;
1-DN is noted in a small percentage of diabetic donor kidneys. When this occurs, the DN is often mild and in early stages.
2- After transplantation, DN in diabetic donor kidneys may stabilize or progress with a mild increase in severity and at a slow pace.
3- In cases DN is not present in diabetic donor kidneys, DN often does not develop in post transplant, even in diabetic recipients.
Conclusion ;
This study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival, an observation that requires confirmatory evaluation of a larger number of cases with longer follow-up.
What is the level of evidence provided by this article?
level of evidence is III as it is a retrospective study
What are the criteria required to allow kidney donation in diabteric?
Absence of significant proteinuria and preserved renal function are the two requirements for kidney donor acceptance .
Hi Dr Ishag,
What type of retrospective study it is?
Is it longitudinal or cross-sectional?
Introduction
This is a very interesting study. The prevalence of diabetes is quite high and we are getting increasing number of deceased donors who were diabetic. Up to 8% of deceased donors have DM and 40% of kidneys from diabetic deceased donors are discarded. The presence of diabetes is a contraindication for living donation. Due to the shortage of organs for donation, there has been increased allocation of marginal donor kidneys. The expanded criteria donor (ECD) was the first criteria used to define marginal donors. It included:
Age > 60 years
or
Age 50-59 years and at least 2 of the following
Donor DM was not included in the criteria
The new kidney allocation system implemented in 2014 utilizes the kidney donor profile based on 10 donor factors to assign a risk score for post-transplant graft survival. Donor DM carries a heavyweight in this system. Due to this a large number of kidneys from diabetic donors are discarded. Only 3.5-6.5% of transplanted kidneys are from diabetic donors. There are very few studies that have looked at the outcomes of transplanted kidneys from diabetic donors.
Methodology
This was an observational survey that looked at all donors utilized from January 2006 to December 2014. They had 749 donors out of which 46 had diabetes (6.1%). 26 kidneys had a post perfusion biopsy (25 donors were utilized – 2 kidneys from one donor).
The biopsies were subjected to routine light microscopy, IF and electron microscopy. The GBM size was measured and a cut off of > 430 nm and > 395 nm were used for males and females respectively to diagnose DM.
The profiles of donors and recipients were and their clinical and laboratory information around the time of transplantation was obtained from the medical records, OPTN registry and from family members.
Information about graft outcome and recipient outcome was obtained.
Results
The mean age of the donors was 47 years. Majority of the donors were hispanics. 76% of the diabetic donors who had biopsies were also hypertensive. 44% were overtly obese.
The mean age of the recipients was 57 years, Majority of the recipients were African Americans. 15 recipients had pre-transplant diabetes and 24 recipients had HTN.
From the 26 biopsies performed, 20 kidneys had no features of Diabetic Nephropathy (DN) on both LM and EM< one biopsy had only GBM thickening on EM and 5 biopsies showed class IIa DN.
In the follow-up period (36 months 136 months), 4 recipients had died, all due to cardiovascular complications with functional renal grafts.
21 out of 22 recipients who were alive had functional grafts while only one had a failed graft 54 months post-transplant due to IF/TA.
The follow-up transplant biopsies of the 20 diabetic kidneys with no DN did not reveal DN.
6 patients developed post-transplant DM. 3 recipients had high levels of proteinuria
Only 2 out of the six donor kidneys with DN had progression of the Diabetic Nephropathy.
Discussion
The study shows that DN is only found in a small percentage of donors. Early DN in diabetic kidney donors can be stable or progresses very slowly and does impact graft survival. A study by Mohan et al showed that graft survival for SCD with Diabetes was higher than ECD with diabetes and non-diabetic ECD.
The authors conclude by acknowledging that this was a small study population but the data should prompt a much larger study as this study shows that using diabetic kidney donor with or without DN does not impact graft survival
What is the level of evidence provided by this study?
Level III
What are the criteria required to allow kidney donation in diabetic?
The potential diabetic donor should undergo extensive evaluation. There should be no signs of target organ damage, no associated HTN, CVD, proteinuria and a normal eGFR. If there is a family history of diabetes and CKD, then the donor should be excluded.
The donor should not be overweight or obese
He should undergo rigorous counseling
Hi Dr Bagha,
You state that ‘normal eGFR’ is a pre-requisite for cadaveric kidney usage. Would you use cadaveric kidneys from those who have ARF grade 1 or 2?
I am raising a very important practical issue here.
Ajay
Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance
Summary of the Article
In this retrospective study, at the J.C. Walter Transplant Center and the Houston Methodist Hospital; records of all deceased kidney donors in the period from January 2006 and December 2014 were reviewed to identify the donors with DM(Out of 749 donors, 46 (6.1%) had DM).
In 26 recipients, graft biopsy pre- and post-transplantation was performed post-perfusion.
The biopsies are subjected to:
a) light microscopy (LM) including; H&E, PAS, Masson’s trichrome and methenamine silver stains.
b) Immunofluorescent stains; including IgG, IgA, IgM, C3, C4, C1q, kappa light chain, lambda light chain, and C4d.
c) Electron microscopy (EM); was done both prospectively and retrospectively.
d) Biopsies were graded according to the grades of the Renal Pathology Society:
i. class 0 = no diabetic changes by LM or EM.
ii. class I = no obvious LM changes, but thickening of the GBM by EM.
iii. class IIa = mild mesangial expansion by LM.
iv. class IIb = marked mesangial expansion by LM.
v. class III = nodular mesangial sclerosis.
vi. class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli.
e) Changes other than DN were also recorded.
f) Follow-up biop- sies were evaluated in the same manner.
Study’s Methods and Results
Postperfusion Renal Transplant Biopsy Findings:
a) Twenty-six postperfusion biopsies were performed from 26 transplanted kidneys from 25 deceased diabetic kidney donors (2 kidneys from a single donor).
b) DN was not seen in 20 biopsies, even after EM.
c) One biopsy revealed only EM changes; thickening of the GBM(RPS class I).
d) Five biopsies showed DN changes, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM(RBS class IIa).
e) None of these biopsies showed class IIb, class III, or class IV lesions.
f) Other changes; arterionephrosclerosis (14 biopsies), interstitial fibrosis and tubular atrophy >15% of cortical tissue area (8 biopsies), acute tubular necrosis (4 biopsies), myoglobin casts (2 biopsies), incidental IgA nephropathy (1 biopsy), and incidental rare glomerular capillary thrombi, perhaps related to organ preservation (1 biopsy).
Follow-up Biopsies
a) Follow-up biopsies (1–6 biopsies /recipient) were done to evaluate the evolution of DN against the background of the DM status of the recipients.
b) Among 20 recipients(RPS; class 0), biopsy was not done in 8, while 12 recipients showed DN class 0 in 9, DN class I in 2 and DN class IIa in 1.
c) Other significant changes in follow- up biopsies included; arterionephrosclerosis (9 biopsies), interstitial fibrosis and tubular atrophy >25% of cortical tissue (8), glomerulitis (1), polyomavirus nephropathy (1), severe chronic rejection (1), transplant glomerulopathy (2), and chronic antibody-mediated rejection(1).
Study’s Outcome
a) The study’s findings may have implications for the utilization of renal biopsy in the decision to accept or discard the donor’s kidneys.
b) The study found that DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration (>10 y).
c) Biopsies showed significant arterio-nephrosclerosis, and interstitial fibro- sis/tubular atrophy, may reflect the presence of hypertension (in 73% of diabetic donors).
d) Study’s observations supported the validity of the current morphological criteria within the general scheme for organ allocation, which does not include changes referable to DN.
e) The discrepancy of the significant impact of donor DM on graft outcome and the frequent absence of DN in diabetic donor kidneys noted in this study is of considerable interest. It suggests that donor DM adversely impacts graft outcome through mechanisms distinct from the renal tissue injury seen in DN.
f) There are comparable studies concluded that SCD diabetic donors provide better grafts than nondiabetic ECD donors and worse than diabetic donors with ECD, but the risks of graft loss are all small compared to the ideal situation.
g) The study demonstrated that the presence or absence of DN in diabetic donors, as well as the DN class reflecting its severity, does not seem to correlate with the duration of DM.
h) Absence of significant proteinuria and preserved renal function are 2 requirements for kidney donor acceptance.
i) Several studies have suggested that pancreas/islet transplantation did confer protective effects, including attainable glycemic control, attenuated diabetic vascular complications, and better renal transplant survival.
j) The study suggests that diabetic donor kidneys with or without DN may not by itself impart significant adverse effect of graft survival.
What is the level of evidence provided by this article?
Retrospective study
Level of evidence grade III
What are the criteria required to allow kidney donation in diabetic?
a) Absence of significant proteinuria.
b) Preserved renal function.
You state that ‘preserved renal function’ is a prerequisite for cadaveric kidney usage. Would you use cadaveric kidneys from those who have ARF grade 1 or 2?
I am raising a very important practical issue here.
Ajay
-DM is a contraindication for living candidates to donate
Due to the effect of DM on the kidney , it’s donation in deceased donors is emerging as marginal donors.
Expanded criteria donor (ECD) are donors aged 60 years or older, or aged 50–59 years with at least 2 of 3 risk factors involving cerebrovascular cause of death, history of hypertension, or serum creatinine >1.5mg/dL.
The new Kidney Allocation System in 2014 utilized the Kidney Donor Profile Index based on 10 donor factors to assign a risk score for post transplant graft survival.
Diabetic donor kidneys represent a significant percentage of transplanted kidneys even if accounting for a small number
Studies revealed that diabetic kidney donors have either no impact on long-term graft or recipient survival but those studies have their limitations.
Methods
46 candidates of deceased kidney donors at the J.C. Walter Transplant Center, The Houston Methodist Hospital, had DM,26 underwent posttransplant renal biopsies through 9 consecutive years. Biopsies were subjected to LM,IF ,EM, grading the DN as per the Renal pathology society .The medical data of the donors and the recipients were collected from the medical records.
Results
DN was not detected in 20 of the posttransplant renal biopsies even with EM ,one showed thicked BM with EM and 5 revealed DN of class IIa, characterized by mild mesangial sclerosis and hypercellularity, with thickened GBM .
The other biopsy findings were arterionephrosclerosis , interstitial fibrosis, tubular atrophy,ATN ,incidental Ig A nephropathy.
Donors had variable DM durations, 24 recipients were hypertensive and 15 were diabetics while 14 of them had both and 8 were obese.
ESRD etiology was variable and HLA compatibility was variable too.
16 recipients had induction with thymoglobulin, and maintenance immunosuppression included tacrolimus in each recipient with mycophenolate and/or steroid in some cases.
With follow up 4 recipients died rendered to cardiovascular causes having functioning graft, one graft failed with interstitial fibrosis and tubular atrophy,21 had a functioning graft.
15 recipients had DM pre transplantation ,persisted in 14, regressed in 1, and newly developed in 6,out of 20 cases other co morbides diseases were detected post transplant but did not have an effect on the DN.
Follow-up biopsies for 12 recipients, showed no DN in 9 and DN in 3 (class I in 2 and class IIa in 1) DM was detected in 2 recipients before transplantation and developed in all 3 recipients post transplantation.
Other significant changes in these followup biopsies included arterionephrosclerosis , interstitial fibrosis and tubular atrophy >25% of cortical tissue , glomerulitis , polyomavirus nephropathy ,severe chronic rejection , transplant glomerulopathy , and chronic antibody-mediated rejection.
Discussion
Renal changes in pretransplant biopsies were the main cause of declining diabetic donors including the severity of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arterial intimal thickening.
This study noticed that DN wasnot detected or is only mild in postperfusion biopsies from diabetic donors
even of long duration ,on the other hand those biopsies revealed hypertensive related renal changes .
Donor DM has negative effect on graft outcome in a different mechanism from the renal tissue injury noticed in DN.
Diabetic donors acceptance is increasing and this is supported by multiple study results.
Mohan et al published that that SCD diabetic donors grafts are better than nondiabetic ECD donors and worse than diabetic donors with ECD.
It was determined that good conservation of renal tissue with DM is an important factor.
DN changes are not frequent and if seen are mild also DM duration doesnot correlate with DN severity.
Renal biopsies tend to show DN, after long duration , more than 10 y including class IIb, III, or IV, together with
severe interstitial fibrosis/tubular atrophy and arteriosclerosis/hyalinosis.
The development of donor kidney DN posttransplant is important due to the potential reversibility of the renal changes and high incidence of diabetic donor kidneys transplanted into diabetic recipients.
A study done to evaluate the effect of pancreatic transplant of DM type I patients on DN ,and it concluded that DN can be reversible even in cases of initial advanced DN (RPS class III) at 10 years but was not changed at 5 years.
This study demonstrated that diabetic donor kidneys with or without DN, transplanted into a diabetic recipient, was possible not to develop DN during the posttransplant period at least in short term.
This study limitations included small number of cases with early stages of DN and follow up for short period of time.
The current study and other studies spotlight on the fact that DN changes are possibly to be reversible post transplant particularly in early stages mean while further studies are needed in this aspect.
-level of evidence is III as it is a retrospective study
-Criteria for allowing kidney donation in diabetics should include precise evaluation of risk and benefits .
In absence of target organ damage ,and cardiovascular risk factors as HTN ,obesity are well treated those candidates can be considered after thorough investigations including assessment of long term risk of cardiovascular and progressive renal affection with a single kidney.
Reference
Dr Roberto Cacciola presentation
Hi Dr Doaa,
What type of retrospective study it is?
Is it longitudinal or cross-sectional?
SUMMARY
Introduction
One of the reasons of not accepting a kidney for transplantation is if is from and individual with diabetic nephropathy, and a scientific registry of 2013 – 2015 reports 8% of disease donor are diabetic and up to 40% of them were rejected from kidney transplantation. However, some studies that has evaluated the outcome of kidney from a diabetic found no negative impact on the graft after transplantation.
Materials and Methods
Results
Conclusion
DN is seeing among few percentages of kidney donors and usually at early stage without significant negative impact on the function of the graft even after the transplantation as the DN in the graft may either stabilizes or progress slowly in the recipients.
The Level of Evidence is 3
Criterial for Kidney Donation in Diabetic.
Generally, potential donors with DM are not allowed to donate, the following criterial can be followed:
Then after excluding the above, the possibility of development of DN should be explained to the donor, and if he is still motivated to go ahead then he or she can be accepted for donation.
Hi Dr Issac,
There is some misunderstanding here, as I quote your statement, ” possibility of development of DN should be explained to the donor” .
Are we talking about living donors in this study?
Would we ever use a living donor with DM?
Diabetic donor kidneys account for a small but significant percentage of transplanted kidneys ranging from 3.5% to 6.5%. Few studies have evaluated the outcome of transplanted kidneys from diabetic donors and results are mixed.
Aim of the study:
To review renal biopsy findings from diabetic kidney Donors at Time of Transplantation and their significance.
Material and method:
– All diabetic deceased kidney donors between January 2006 and December 2014 were reviewed
– Out of 749 donors, 46 (6.1%) had DM. Postperfusion biopsy of the transplanted kidneys was performed in 26 recipients.
– Posttransplant renal biopsies were also performed in these recipients for evaluating changes of renal functions or for surveillance in high-risk recipients
-Systematic examination of renal biopsy was done both prospectively and retrospectively was performed with special attention to the features of DN.
The diabetic changes grades, as defined by the Renal Pathology Society:
class 0 = no diabetic changes by LM or EM
class I = no obvious LM changes, but thickening of the GBM by EM
class IIa = mild mesangial expansion by LM
class IIb = marked mesangial expansion by LM
class III = nodular mesangial sclerosis
class IV = advanced diabetic glomerulosclerosis with global sclerosis in >50% of glomeruli.
RESULTS
Postperfusion Renal Transplant Biopsy Findings :
Total of 26 biopsy were done
– DN was not seen in 20 biopsies, even after EM
– One biopsy class I
– Five biopsies class IIa.
– Class III, IV ,V were not seen.
– Other changes including arterionephrosclerosis (14 biopsies), IFTA >15% (8 biopsies), ATN (4 biopsies), myoglobin casts (2 biopsies), incidental IgA nephropathy (1 biopsy), and incidental rare glomerular capillary thrombi (1 biopsy).
DM was present in 15 recipients before transplantation. After transplantation, DM persisted in 14, regressed in 1, and developed. De novo in 6, for a total of 20 recipients with posttransplant DM.
DN is noted in a small percentage of diabetic donor kidneys
DN is not seen or is only mild in postperfusion biopsies from donors with DM even of long duration >10y.
DN, at least in early stages, can be stable, or progress albeit rather slowly.
The study showed that diabetic donor kidneys with or without DN, transplanted into a diabetic recipient, may not develop DN during the posttransplant period at least in short term, or develop into a mild/early form of DN, that by itself may not significantly impact graft outcome.
Level III
For living donor:
KDIGO 2017 :
T1DM; contraindication.
Prediabetes or T2DM, donation decisions should be individualized based on demographic and health profile data and should be counseled that their condition may progress over time and may lead to end-organ complications.
BTS 2018;
Diabetic can be considered as potential kidney donors after after a thorough assessment of the lifetime risk of cardiovascular and progressive renal disease in the presence of a single kidney. In the absence of evidence of target organ damage; no albuminuria, normal renal function ( eGFR age/ gender reference)
AST 2015 :preclude diabetic donor.
OPTN; DM is considered an exclusion to donation.
For Deceased Donor:
Most centers exclude patient with DM. In response to donor organ shortage and the long waiting list specially in diabetic donor, some studies showed survival benefits of accepting a diabetic decease kidney donors.
– Donors with DM but without other significant comorbidities.
– little or no changes in their kidney biopsies
– SCD; Mohan et al showed diabetic-SCD have better graft-survival compared to non-diabetic ECD
I like your discussion, logical approach, and conclusions, Dr Hadeel Badawi.
this is an interesting study, was conducted to evaluate the severity of diabetic nephropathy and the other pathological changes in allograft biopsies of diabetic deceased donors’ kidneys and its progression post transplantation elucidating on the related confounding factors. The histopathological changes were addressed right post transplantation or after allograft perfusion. then on regular planned biopsies. {up to 6 sessions}
26 diabetic deceased donors were identified, and the diabetic Nephropathy classification was scored for each allograft biopsy as follow:
class 0: no changes.
class 1: normal light microscopy , but EM revealed thickening of the glomerular basement membrane.
IIa: mild mesangeal expantion
IIb :marked mesangeal expantion.
III: mesangeal nodular sclerosis.
VI:diffuse glomerulo-sclerosis.
Other finding were arterionephrosclerosis.
Interstitial fibrosis, tubular arophy..
The 26 diabetic deceased donors kidenys biopsies were tested according to the above-mentioned criteria as follows:
1] 20 patients, No Diabetic nephropathy DN was found.
2] 1 kidney biopsy showed class I DN
3] 5 biopsies revealed class IIa DN.
Arterionephrosclerosis was spotted in 14 biopsies IFTA in 8 biopsies. The 26 diabetic deceased donors were additionally hypertensive 19 patients, and 11 obese. with varied duration of diab etes between more than 15 years and 5 years. Some recipients attracted DM post transplantation.
The intriguing point in this group of patients is that DN is inconspicuous or non-existent in the majority of patients of variable duration DM, In the contrary, arterionephrosclerosis was more prevalent and linked to renal outcome.
In order to examine the progression of status of the diabetic transplanted kidneys, protocol biopsies were performed on those patients.
characteristics of recipients:
15 Recipients’ patients were having DM before transplantation, 14 persistent and 6 de novo DM culminating in 20 patients with post-transplant DM, creatinine and proteinuria were tested regularly.
Protocol biopsies findings were predominantly reflecting arterionephrosclerosis and IFTA , transplant glomerulopathy and polyoma nephropathy. Of those biopsies showed DN, post perfusion, mere one case progressed to class IIb DN, rest of the cases
Important messages reflected by this study:
1]Diabetic nephropathy is not commonly uncounted in diabetic deceased donors.
2]progression of disease post transplantation is rare.
3] diabetic deceased donors can be included in extended criteria donation ECD to enlarge deceased donors’ pool.
4]Other confounding factors including hypertension and obesity might have an influence on the outcome of transplanted kidneys.
Its prospective level 2 evidence.
proposed criteria to include DN donors:
1]No proteinuria
2]normal renal function or mildly impaired in marginal donors.
3]Kidney biopsy revealed 0- Ia class DN
4]other co-morbid conditions have addressed and treated promptly, particularly Obesity and hypertension to be
If the donor is marginal due to mild changes, what are the options, dear Dr Jebur?