III. Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression
- Please summarise this article in your own words
- What is the level of evidence provided by this article?
- Please reflect on the guidelines provided above and on your practice.
Dear All
Please read Saja and Mohamed replies.
Thank you All
Do you think this small incidence of proteinuria will affect long-term kidney function?
What do you think about the duration of follow-up in this study?
It is less likely to affect the renal function, reasonable follow up time
Hi Dr. Ben,
Your answer is too short. Any evidence in support of your reply? An average of 7 years of follow-up is NOT enough to project a dependable overall long-term outcome.
Ajay
Thank prof
In one study, five donors with low-grade proteinuria (mean 210 mg in a 24 hr urine
collection) were more likely to have significant proteinuria 20 years or more after
donation (>800 mg/day), although without significant loss of kidney function . A
review of 1,519 living kidney donors in Japan identified eight who developed ESRD
. Of these, only two had pre-donation proteinuria, both of whom developed
cardiovascular disease, hypertension and ESRD 6 and 16 years after donation.
A recent US study among 4,650 living donors found that by 7 years post-donation,
after adjustment for age and sex, greater proportions of black compared with white
donors had chronic kidney disease (12.6% vs 5.6%), proteinuria (5.7% vs 2.6%) or
nephrotic syndrome (1.3% vs 0.1%), suggesting the need for more stringent risk
stratification among black donors .
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
I dont think this proteinuria would affect the long term kidney function , as the drop in GFR of kidney donors,was comparable to that of the aged-matched non donor conterparts.
The duration of the follow was fair to draw a conclusion on this issue, as the average was 7 years(range between 1-25 years)
thanks prof
the long term effect of kidney function from proteinuria depend on the severity of it so small incidence less likely and follow up is accepted
Yes Drs Omar, Malik, Yousuf, Jebur.
I would like to agree with you that small proteinuria is not likely to be associated with the deterioration of renal function.
However, there is enough evidence that persisting microalbuminuria (potentially reversible) in pre-diabetics is associated with a higher incidence of CVS disease. Microalbuminuria is an important risk factor for cardiovascular disease and progressive renal impairment (Diabetologia (2008) 51:714–725)
I must admit that this is a different group of patients but it is worth drawing a parallel. You do not have to agree with me.
Ajay
Even small incidence of proteinuria can affect long term kidney function.
Because this proteinuria could reflect the hyperfiltration incidence
Glomerulars’ changes to take place may need long time exceed the follow up duration in these studies
The difference in proteinuria is not significant and seems not to have any effect on long term donor outcome.
The follow up period is 7 years (1-25) which can be considered reasonable but one cannot be sure what will happen if we follow them up for an average of 15 to 20 years
The presence of proteinuria signifies that there is kidney damage. The amount can give an idea of how fast the kidney function is worsening. If it is less than 500 mg/day, then there is possibility that it may worsen but proper follow-up must be made. Even low amount can lead to graft dysfunction. Once the proteinuria is increasing it will company with hypertension and worsening kidney function. Also, it must be noted that it may be accompanied by a different pathology can be a new glomerulopathy.
So, follow up is important and necessary for better detection and care of the patient.
references:
jasn.asnjournals.org/content/20/12/2490
The study by Carg et al ,2006 : a systematic review ,meta analysis ad meta regression study including more than 5000 donors from 27 countries showed that donation led to small increases in urinary albumin, which increases with time. GFR decreased initially but not followed by accelerated deterioration over subsequent duration of 15 years which cannot be considered enough especially in case of younger age donors.
This small incidence of proteinuria is less likely to affect the long-term kidney function unless donr develops hypertension or diabetes.
The study has given a follow-up of only seven years with lot of heterogeneity among the studies for type and amount of proteinuria.
Only 10 studies out of 48 studies are prospective, which involves recall bias.
Due to this there is lot of data loss of follow-up.
Thus, the level of evidence would be LEVEL 2 as it does not have any high level RCT
I think progression proteinuria depends on good control of Bp, weight reduction, and some times the use of ACEi or ARBs if indicated.
According the duration of follow-up could be not enough, even general population may have progressive proteinuria after many years of follow up
This small incidence of proteinuria is less likely to affect long-term kidney function. But this study had many limitations that makes its results less valuable. In addition, young donors need higher duration of follow-up to indicates harmless donation.
Ø 45 studies from 27 countries followed a total of 5048 donors, review any study where 10 or more healthy adults donated a kidney: proteinuria, or glomerular filtration rate (GFR) was assessed at least 1 year later.
Ø An average of 7 years after donation (range 1–25 years), the average 24 h urine protein was 154 mg/day and the average GFR was 86 ml/min.
Ø In eight studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min (range 0–28%), and 0.2% a GFR less than 30 ml/min (range 0–2.2%).
Ø In controlled studies urinary protein was higher in donors and became more pronounced with time (three studies totalling 59 controls and 129 donors; controls 83 mg/day, donors 147 mg/day, weighted mean difference 66 mg/day, 95% confidence interval (CI) 24–108).
Ø An initial decrement in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging (six studies totalling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6–15; difference not associated with time after donation (P ¼ 0.2)).
Ø Kidney donation results in small increases in urinary protein. An initial decrement in GFR is not followed by accelerated losses over a subsequent 15 years.
Level 5 * not proper meta review
Proteinuria is already quantified in all potential living kidney donors with ACR >30mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation.
But the donor might benefit of more frequent and prolong follow up and check of ACR and eGFR.
Q 1: This article reviews any study about assessment of proteinuria or GFK after one-year post-kidney donations totally. 48 studies and 5048 donors with mean 7 y (1 – 15 y) were studied. That showed mean 24 h proteinuria 154 mg/day and mean GFR 86 ml/mm.
The risk of proteinuria was higher in donors compared to controls with mean difference of 66 mg/day. The pooled risk of albuminuria was 3.9 %. Post donation.
The pooled GFR was 10 ml/min lower than in donors compared to controls but there was no significant difference between the two groups. (p = 0.2)
Male gender was associated with higher proteinuria but donor age or donor’s BP were not associated with that. Approximately 12% of donors had a GFK less than 60 mg/min with f/w but if was not different over that anticipated with normal aging.
· Q 2: level of evidence of this article is one
· Q 3: All donors should be followed up 6 – 8 weeks later and then annually in our center. All donors are advised to avoid nephrotoxic drugs and annually assess for BP, BUN, Cr, U /A, FBS and lipid profile.
Proteinuria and an accelerated loss of kidney function may accompany remaining single nephron hyperfiltration caused by a significant decrease in renal mass
Incidence of proteinuria
42 studies that followed 4793 live donors for an average of 7 years each measured the prevalence of clinical proteinuria following donation (range 2–25 years). There was a lot of variation between the trials . In some studies, the incidence of proteinuria was above 20%, whereas in others, it was less than 5% and the pooled incidence of proteinuria was 12%.
Kidney function after donation
The average decrease in GFR after donation was 26 ml/min (per 1.73 m2) in the 22 studies that addressed it (range 8–50). A postdonation GFR that could be categorised was found in nine trials
Obesity prior to donation, plasma uric acid, and serum cholesterol had no effect on the GFR after donation.
The renal function to donation was similar in black and white donors.
The post-donation GFR or change in GFR were not related to the period after the donation
DISCUSSION
Urinary albumin levels increased somewhat after kidney donation and continued to rise over time. Most people would interpret this as a sign of single nephron hyperfiltration due to a diminished renal mass
Donors had a GFR that was 10 ml/min lower than controls ten years after nephrectomy. Additionally, during follow-up, 12% of donors saw a GFR decrease to less than 60 ml/min
What is the level of evidence provided by this article .?
V
Kidney donation results in small increases in urinary protein. An initial decrement in GFR is not followed by accelerated losses over a subsequent 15 years. Because of this, proteinuria is one of the main predictors of comorbidities after kidney transplantation. The primary questions of this review were: (1) What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min? (2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein? (3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
What we can find as important results:
– There is an increase in proteinuria with increasing donation time, above normal aging
– However, there was no subsequent accelerated loss in GFR above predicted with aging
– Death, renal failure and cardiovascular disease were not systematically evaluated.
– primary studies reported a number of pre-donation prognostic features associated with higher proteinuria or lower post-donation GFR, but which were unproven:
– males had greater increases in proteinuria after donation, but there was no difference in the decrease in GFR.
– neither age nor pre-donation blood pressure were associated with increased proteinuria after donation
– Pre-donation obesity, plasma uric acid and serum cholesterol were not associated with worsening of post-donation GFR.
– in terms of ethnicity, white and black donors were similar in their renal responses after donation.
The main negative point of most of the studies in this analysis was that the majority of the control groups were formed by the general population, that is, a population not as healthy as the donor population.
This is level 01, because is a systematic review, meta-analysis, and meta-regression
This study reflects that conservative donation criteria are very safe for both donors and recipients. It may lead us to reflect that cases of reduced GFR are the result of care that should be reassessed for improvement.
In this review article, the authors examined 48 studies including 5048 donors with mean follow up 7 years to evaluate the effect of kidney donation on development of proteinuria and decrease GFR. There was slight increase in proteinuria in donors (154mg/dl). In eight studies that evaluated post donation sequences revealed mild decrease in GFR in 12% of cases to 30-59ml/min and only 0.2 % of donors experienced marked decrease to < 30 mg/min. While in controlled studies (3 studies), also the donors had mild increase in level of proteinuria up to 147 mg/dl and GFR showed initial decrease but was not complicated by accelerated loss of kidney function. The post donation changes in proteinuria and GFR are attributed to increase single nephron hyperfiltration after nephrectomy that theoretically
Conclusions
Kidney donation leads to slight increase in proteinuria that become obvious with longer time after donation, also there’s decrease in GFR around 1ml/min lower than age controls, this may be related to single nephron hyperfiltration, but it didn’t rest in accelerated kidney function loss.
Risk factors for protienuria:
– Older age at time of donation
– Male donors.
While time since donation ,predonation obesity, dyslidemia and hyperuricemia has no impact on proteinuria development.
Strenght points of this rebview:
· included large number of studies from multiple countries
· Most studies had matched controlls
· Most of the primary authors were contacted.
Weakness points of this review
· Retrospective nature of the study and heterogenicity of the examined population
· No randomised control studies were included.
· · 40%.of donor lost to follow up (Significant percentage)
II- the level of evidence provided by this article
level V
A critical reduction in renal mass may result in remnant single nephron hyperfiltration, with associated proteinuria and an accelerated loss of kidney function.However, the long-term implications of donating a kidney remain uncertain. The primary questions of this review were: (1) What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60ml/min? (2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein? (3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy? Reasons for different estimates in the literature were also explored using meta-regression.
Death, kidney failure, and cardiovascular disease Thirty-three studies described the number of donors who died during follow-up, which ranged from 0 to 16% of the study cohort. In one of these studies, a total of two donors died with kidney failure. A total of 10 donors from eight different studies were living with kidney failure at the time of last assessment.Seven studies described a proportion of donors who developed cardiovascular disease during follow-up, although these events were not systematically assessed.
Incidence of proteinuria
Incidence of proteinuria The incidence of clinical proteinuria after donation was quantified in 42 studies, which followed 4793 living donors an average of 7 years (range 2–25 years). There was significant heterogeneity between the studies (Po0.0001). Some studies reported an incidence of proteinuria over 20%
Risk of proteinuria Three studies compared a total of 129 donors to 59 controls on 24-h urine protein, to determine if increases in proteinuria after donation were above that possibly attributable to normal aging
Kidney function after donation Among the 36 studies of 3529 donors which reported a postdonation serum creatinine or GFR with an estimate of variance, the average time after donation was 6 years, the average serum creatinine was 98 mmol/l (1.11 mg/dl, range 58–119 mmol/l), the average GFR was 86 ml/min (per 1.73m2) (range 64–117).
Risk of reduced kidney function Controlled studies were reviewed to determine if the initial decrement in GFR after nephrectomy was accompanied by subsequent accelerated loss in GFR over that anticipated with normal aging. There was no statistical heterogeneity between those where the average follow-up was at least 5 years after donation (w2 1.49, P¼0.91, I2¼0%) and these results were mathematically pooled
Pre-donation prognostic features Among healthy donors, the primary studies reported a number of prognostic pre-donation features associated with a higher proteinuria or lower GFR after donation. Within donors many of these features clustered together, and multivariate regression was only reported in a minority of studies. Potential true associations may also have gone undetected, as the sample size of many studies was small.
Strengths and weaknesses of this review This review summarized 48 single center studies, and shares similar strengths and weaknesses to a parallel review conducted on hypertension risk in living donors.64 In brief, since the last quantitative review on this topic, we identified 35 new articles.65 Relevant data was rigorously identified and abstracted, articles were translated, information was clarified with a majority of primary study authors, and reasons for diversity in the published literature were explored.
long-term sequelae after donation may be underreported, if transplant centers were reluctant to describe significant morbidity after this perceived iatrogenic event.66 Among the controlled studies proteinuria and GFR were assessed in a similar manner in both donors and controls, with observed differences suggesting a true difference between the groups. However, inconsistent methods of measuring and reporting proteinuria and renal function in the primary studies complicate the interpretation of these results.
Renal sequelae, donor selection, and long-term surveillance The proportion of donors who develop clinical proteinuria appears to be higher than expected in the general population – whereas kidney donation increases urinary protein often within the range considered normal, approximately 10% of donors exceed a threshold of 300 mg/day over a subsequent decade. Similarly, about 12% of donors develop a GFR less than 60 ml/min over this same period.
Living donors whose data were summarized in this review
demonstrated no evidence of hypertension, proteinuria or reduced kidney function before donation. However, in the current era, the eligibility criteria for donation are being extended, and some centers now accept potential donors with a GFR less than 80 ml/min.It is important to consider that many donors may have a genetic predisposition to developing kidney disease, and a total of 10 donors (0.2%, one in 500 donors) in this review were reported to have developed kidney failure requiring dialysis. Thus the acceptance of living donors at potentially higher incremental risk for future adverse events remains contentious.
Finding relevant studies, data abstraction, and statistical analysis We recently published a parallel review on the risk of hypertension after living kidney donation, where methods used in this review are fully described.64 In brief, until November 2005 we screened relevant citations from multiple sources including MEDLINE, EMBASE, and Science Citation Index bibliographic databases. Pairs of reviewers independently evaluated the eligibility of each full-text article, and data was abstracted in duplicate. Studies in languages other than English were translated.
Reasons for diversity in primary study estimates were explored
using univariate and multivariate meta-regression of donor cohorts: mixed models for continuous outcomes (SAS PROC MIXED) and logistic normal random effects models for binary outcomes (SAS PROC NLMIXED). At the study level, the association between the following donor characteristics and outcomes of proteinuria or lower GFR after donation were considered: older age, a higher predonation blood pressure, and a lower pre-donation GFR. We hypothesized that these factors would be associated with increased proteinuria or a lower GFR after donation.
Level 5
Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression
Q1- Please summarise this article in your own words.
this review were designed to answer :
(1)What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min?
(2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
(3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
DISCUSSION
kidney donation resulted in small increases in urinary albumin, which increased with the time after donation. this indicative of single nephron hyperfiltration from a reduced renal mass.
Ten
years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls.
In addition approximately 12% of donors developed a GFR less than 60 ml/min during follow-up. But after the initial decrement in GFR from the nephrectomy, there was no evidence of an accelerated loss in GFR over that anticipated with normal aging.
Renal sequelae , donor selection, and long-term surveillance:
The proportion of donors who develop clinical proteinuria is higher than in the general population
– kidney donation increases urinary protein often within the range considered normal, approximately 10% of donors exceed a threshold of 300 mg/day over a subsequent decade.
– about 12% of donors develop a GFR less than 60 ml/min over this same period.
Although some donors may have been predestined to develop such a GFR even if they had not donated a kidney, a decrement of 10 ml/ min after their nephrectomy likely hastens this event.
Thus the central question remains – what is the prognostic significance of proteinuria or reduced kidney function in this patient population?
In the general population, low GFR and proteinuria may be signs of systemic atherosclerosis, and oth are associated with concurrent metabolic disturbances, future premature mortality, cardiovascular disease, and kidney failure. For this reason some, , consider a GFR of 30–59 ml/min as the pathologic state of stage 3 chronic kidney disease.But kidney donors develop reduced kidney function or low-grade proteinuria through a different mechanism, and their prognostic significance in this segment of the population remains uncertain.
Indeed, donors undergo rigorous evaluation and selection, and their incidence of death is lower than the general population.
Thus, without evidence of adverse health outcomes, small changes in measurements of proteinuria or GFR should not be the sole reason for deterring a practice which benefit recipients, donors, and society.
Living donors in this review demonstrated no evidence of hypertension, proteinuria or reduced kidney function before donation.
However, in the current era, the eligibility criteria for donation are being extended, and some centers now accept potential donors with a GFR less than 80 ml/min.
It is important to consider that many donors may have a genetic predisposition to develop ing
kidney disease, and a total of 10 donors (0.2%, one in 500 donors) in this review were reported to have developed kidney failure requiring dialysis. Thus the acceptance of living donors at potentially higher incremental risk for future adverse events remains complicated.
A decision to proceed in such cases should be made by an experienced transplant team that carefully considers donor and recipient preferences, in conjunction with judicious use of the evidence summarized here for healthy donors. It also remains prudent to counsel all donors, irrespective of their pre-donation health state, on modifiable risk factors which prevent future renal and cardiovascular disease.
Q2- What is the level of evidence provided by this article .?
Level of evidence is 5 .
Q3- Please reflect on the guidelines provided above and on your practice.
It is known that donor are at risk of developing hypertension which occur in about 30% of donors, proteinuria in 10% and reduced GFR rarely . in spite of this the incidence of ESRD in such cases are uncommon. The living kidney donation should be encouraged.
In my center the donors regularly followed up every six month .
Its understood proteinuria can cause progressive renal damage, in this meta analysis which was in 27 countries and more then 5000 donors.
Around 12% of donors developed complications like decrease in eGFR.
Literature reported that there is 5 to 20% incidence of proteinuria post-donation. microalbuminuria risk is around 3.9%. 10 years overall post nephrectomy risk of decrease in eGFR 10ml/minutes/m2 compared to controls.
One big bias was loss of follow up for many donors.
level of evidence II.
We have started transplantation since 2017, we don’t have such evidence yet to follow
Meta-analysis included 48 studies from 27 countries with a total 5048 donors with follow up for 7 years.
They concluded that kidney donation resulted in small increases in urinary albumin, which increases with the time after donation.
In about 10% of donors ,urinary protein exceed a threshold of 300 mg/day over a subsequent decade.
About 12% of donors developed aGFR less than 60 ml/ min . An initial decline in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging .but the study has weak points ( one third of donors were lost to follow up, most studies did not have an internal control group so it is difficult to interpret the results)
Meta-analysis. Level 1 evidence
We have no transplant center
Despite being a meta-analysis study, the quality of the data collected is low, with heterogeneous studies and inconclusive data. The model of the studies surveyed is insufficient to generate robust data, making study level V closer to a narrative review.
The author tried to focus the studies on three questions:
– The proportion of donors who develop proteinuria or GFR < 60mL/min
– If kidney donors had higher proteinuria
– If there is a loss of eGFR after a donation
When cross-referencing information, 48 studies apparently met the criteria, with 5048 donors from 27 countries during the period from 1973 to 2005. These data were dispersed differently in each study, segregating the data according to the findings of their respective Dice.
One-third of patients were lost to follow-up. Most of the studies did not have a control group. Sequelae and complications were apparently underreported. Most studies did not have data linking eGFR, high blood pressure, and proteinuria. Data establishing the strength of these findings were inconclusive.
There is a need for a longer follow-up and a need to better characterize the data suggestive of complications after living kidney donation.
# Introduction:
*A critical reduction in renal mass may result in remnant single nephron hyperfiltration, with associated proteinuria and an accelerated loss of kidney function.
* The primary questions which reviewed by this study were:
(1) What proportion of kidney donors develop proteinuria or (GFR) less than 60 ml/min?
(2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
(3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
# The result
*48 studies from 27 countries followed a total of 5048 donors an average of 7 years, and were published from 1973 to 2005.
*According to the Incidence of proteinuria there was significant heterogeneity between the studies. Some studies reported an incidence of proteinuria over 20% whereas in others the incidence was less than 5%.
*The risk of proteinuria appeared to be increased after donation in each of these three studies.
*The 24-h urine protein was higher in donors compared to controls an average of 11 years
after donation.
*The pooled risk of microalbuminuria after kidney donation was 3.9 (95% CI 1.2–12.6).
*Kidney function after donation is that in these eight studies a mean of 10 years after donation, 40% of donors developed a GFR between 60 and 80 ml/min (per 1.73m2), 12% of donors developed a GFR between 30 and 59 ml/min, and 0.2% a GFR less
than 30 ml/min. These results were no different in a supplementary analysis which only considered those studies where the GFR was measured, rather than estimated from a predictive equation.
# DISCUSSION
*Kidney donation resulted in small increases in urinary albumin, which increased with the time after donation.
*Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls.
*12% of donors developed a GFR less than 60 ml/min during follow-up. However, after the initial decrement in GFR from the nephrectomy.
*There was no evidence of an accelerated loss in GFR over that anticipated with normal aging.
# Strengths and weaknesses of the study
*This review summarized 48 single center studies, and shares similar strengths and weaknesses to a parallel review conducted on hypertension risk in living donors.
*Relevant data was rigorously identified and abstracted, articles were translated, information was clarified with a majority of primary study authors.
*The results from any meta-analysis are inherently limited by the quality of the primary studies.
*One-third donors were lost to follow-up.
*Most of the studies also did not have an internal control group.
*Long-term sequelae after donation may be underreported.
*Inconsistent methods of measuring and reporting proteinuria and renal function in the primary studies complicate the interpretation of these results.
*It was unclear whether donors who developed a low GFR also had concurrent hypertension and proteinuria.
*The level of evidence is level 1 meta analysis.
· Summary
o Effect of donation on hyperfiltration injury that can cause proteinuria, declining GFR and hypertension.
o The current study aimed to evaluate 2 outcomes of living kidney donors:
§ Development and degree of proteinuria in donors compared to none donors.
§ Reduction of GFR < 60mL/min and its progression after initial decrement.
o The current study included 48 studies from different countries from (5040 donors) with median FU duration of 7 years post donation.
o Although 24h urine protein was higher among donors, it was minimal degree proteinuria (average of 148 mg/24h).
o 2.12% of donors developed a GFR between 30 and 59 ml/min and 0.2% had GFR < 30ml/min.
o No evidence of accelerated GFR loss more than that expected with aging process.
o Points of weakness:
§ No RCT or prospective studies included.
§ Relatively small sample size
§ No standardized study design or definition of proteinuria or GFR measurement.
§ Missing data and FU in 31% of the alive donors
· Level of evidence: although it is systemic review (but it included weak studies as retrospective cohort, case control studies, not included any RCT, in addition to small sample size and short duration of FU, so level of evidence may be II.
· Reflect these guidelines in my practice
· Living kidney donation is relatively safe procedure that should continue to help other related and non-related beloved persons to have good quality of life.
· It is proven that it is associated with minimal risk of mortality and CKD development, but relatively small and can be minimized by strict adherence to healthy life style and regular follow up.
· This is a review of 48 studies from 27 countries followed a total of 5048 donors for aan average of 7 years after donation
· It is expected that loss of renal mass after donation may result in proteinuria and progressive loss of kidney function
· This review aim is to answer on the following questions:(inclusion criteria)
1)Estimated proteinuria and GFR in donors post donation
2)If donors have more proteinuria than non-donor controls
3)Comparison between GFR of donors and non-donor controls
RESULTS
Incidence and risk of proteinuria
· There was significant heterogeneity between the studies
· 24 h urine protein increased in donors compared to controls, and proteinuria increased after years of donation (average 11 years)
Risk of reduced kidney function
· The pooled post-donation GFR was 10 ml/min lower in donors compared to controls
· prognostic pre-donation features associated with a higher proteinuria or lower GFR after donation:
– men were reported to have larger increases in proteinuria after donation
– women were reported to have a lower GFR both before and after donation
CONCLUSION
· kidney donation causes a small increase in urinary albumin, which increased with the time after donation
· 10 years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls
· about 12% of donors developed a GFR less than 60 ml/min during follow-up
Weaknesses of this review
· About one-third donors were lost to follow-up.
· Most of the studies did not have an internal control group, making it difficult to interpret the donor results.
· Some donors could have developed certain medical conditions even without donation.
What is the level of evidence provided by this article?
Systematic review, evidence 5
Please reflect on the guidelines provided above and on your practice.
We usually do 24h urine protein, mainly if urine dipstick positive for albumin, or the patient has other risk factor. If 24h urine protein above 500mg per day, we exclude potential donor from donation.
If the patient has DM or HTN and proteinuria even less than 500mg per day we may exclude the donor.
Summary:
It is a systematic review, meta-analysis, and meta-regression of Forty-eight studies (published from 1973 to 2005) from 27 countries followed a total of 5048 donors an average of 7 years and proteinuria, or glomerular filtration rate was assessed.
The pooled incidence of proteinuria was 12%, nine studies which consistently defined proteinuria as >300 mg/ day based on 24 h urine. The pooled incidence of proteinuria among these nine studies which followed a total of 1799 donors for 7 years was 10%.
The 24 hours urine protein was higher in donors compared to controls an average of 11 years after donation in three studies compared a total of 129 donors to 59 controls.
The average time after donation was 6 years, the average serum creatinine was 98 mmol/l this among the 36 studies of 3529 donors.
The pooled post-donation GFR was 10 ml/min lower in donors compared to controls, this in six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min.
Some studies reported the prognostic pre-donation features associated with a higher proteinuria or lower GFR after donation.
Such as proteinuria and low GFR were more common in men than women, older more than younger donors in lower GFR.
The time after donation was not associated with post-donation GFR or change in GFR.
Level of evidence: 1
Reflection on our practice:
We should counsel our kidney donors about risk of proteinuria and we should educate them about importance of long term follow up.
The study intended to find out:
· Proportion of kidney donors develop proteinuria or GFR less than 60 ml/min.
· Kidney donors when compared to healthy non-donor controls to have a higher urinary protein.
· To find out whether kidney donors have accelerated loss of GFR after the initial decrement from their nephrectomy compared to controls
· The is systematic review, meta-analysis, and meta-regression of Forty-eight studies (published from 1973 to 2005) from 27 countries followed a total of 5048 donors an average of 7 years and proteinuria, or GFR was evaluated.
· 11 of the studies were collected data on suitable non-donor controls to determine if increases in urinary protein and reductions in GFR after donation were above that normal decline of aging.
Incidence of proteinuria
· pooled incidence of proteinuria was 12%
· 9 studies which consistently defined proteinuria as >300 mg/ day based on 24 h urine.
· pooled incidence of proteinuria among these 9 studies which (total of 1799 donors followed for 7 years) was 10%.
Risk of proteinuria
· The 24-h urine protein was higher in donors, an average of 11 years after donation in 3 studies compared a total of 129 donors to 59 controls
Kidney function after donation
· The average time after donation was 6 years, the average serum creatinine was 98 mmol/l (36 studies of 3529 donors)
· 8 studies a mean of 10 years after donation, 40% of donors developed a GFR between 60 and 80 ml/min, 12% of donors developed a GFR between 30 and 59 ml/min
Risk of reduced kidney function
· pooled post-donation GFR was 10 ml/min lower in donors compared to controls( six studies totaling 189 controls and 239 donors)- controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min
Pre-donation prognostic features.
Studies reported the prognostic pre-donation features associated with a higher proteinuria or lower GFR after donation. Proteinuria and low GFR were more common in men than women. Older donor more has lower GFR than younger donors. The time after donation was not associated with post-donation GFR or change in GFR.
Pre-donation obesity, plasma uric acid, and serum cholesterol were not associated with the post-donation GFR. Black and white donors were similar in their renal response to donation.
Strengths of the analysis
· Large number of studies 48 with 35 new articles
· Information was clarified with most primary study authors
Weakness of the analysis
· Weaknesses points of the review
· One-third donors were lost to follow-up
· Most of the studies don’t have control group
· Long-term sequelae after donation may be underreported
· It was unclear whether donors who developed a low GFR also had concurrent hypertension and proteinuria
Metanalysis -systematic review. LEVEL of evidence: 1
Reflect on your practice:
In our centre, we encourage kidney donation, and we always explain the risk of ESRD which is negligible. Lower eGFR and risk of proteinuria are there, and patient might need long term follow up. Our centre will follow up life long and so far, non-had ESKD.
Level 5
It is supposed that following 50% loss of nephron mass, single nephron hyperfiltration occurs in association with increase in proteinuria and accelerated decrease of GFR.
Questions to be addressed in this review were concerned with incidence of proteinuria and GFR changes
Results form more than 5000 donors from 27 countries revealed small increase of albuminuria increasing with time. GFR decreased initially but not followed by accelerated losses over following 15 years.
Ten years following donation, GFR was 10 ml/ min lower compared with controls. Approximately 12% of donors had GFR less than 60 ml/min .Following initial decrement in GFR ,there was no accelerated loss in GFR.
Strength points included good number of studies from multiple countries ,matching control and reasonable duration of follow up.
·Points of weakness includes retrospection, heterogenicity of studies, controls not followed in all studies and considerable percentage of non compliant donors regarding follow up.
·
-Practical aspect: importance of counselling potential donor regarding small risk of proteinuria and its sequlae.
This meta-analysis reviewed Forty-eight studies from 27 countries followed a total of 5048 donors for about 7 years after donation (range 1–25 years),
the average 24h urine protein was 154mg/day and the average GFR was 86ml/min.
Aiming to evaluate long term effect of kidney donation on proteinuria, decline of GFR.
▪︎Results
*Death, kidney failure, and cardiovascular disease
– number of donors who died during follow-up in 33 studies ranged from 0 to 16% of the study cohort.
In one studiy, two donors died with kidney failure.
-10 donors from eight different studies were living with kidney failure at the time of last assessment.
– Seven studies described a proportion of donors who developed cardiovascular disease during follow-up,although these events were not systematically assessed.
*Incidence of proteinuria
The incidence of clinical proteinuria after donation in 42 studies, followed 4793 living donors an average of 7 years (range 2–25 years). There was significant heterogeneity between the studies .
Some studies reported an incidence of proteinuria was more than 20%
in others the incidence was less than 5%.
The pooled incidence of proteinuria was 12%
after Kidney donation, small increases in proteinuria with an average 24 h urine protein was 154 mg/day which is higher than control.
only 10% of donors developed proteinuria ≻ 300 mg/day.
Three studies compared a total of 129 donors to 59 controls on 24-h urine protein to determine if increases in proteinuria after donation were above that possibly attributable to normal aging
The 24-h urine protein was higher in donors compared to controls an average of 11 years after donation.
*Kidney function after donation
-In 22 studies the average decrement in GFR after donation was 26 ml/min/ 1.73 m2.
(range 8–50).
The average post-donation GFR in these studies did not differ from the remaining studies (88 vs 85 ml/min/1.73 m2.
– in Some studies , 40% of donors developed a GFR between 60 and 80 ml/min 10 years after donation.
-12% of donors developed a GFR between 30 and 59 ml/min and 0.2% a GFR less than 30 ml/min.
DISCUSSION
-kidney donation resulted in small increases in urinary albumin, with the time after donation.
-Whether such hyperfiltration leads to a progressive deterioration in kidney function has been the subject of many debates.
-donors had a GFR 10 ml/ min lower compared to controls 10 years after donation .
12% of donors developed a GFR less than 60 ml/min during follow-up.
– no evidence of an accelerated loss in GFR over that anticipated with normal aging.
systemic Review level of evidence I
Unfortunately we dont have long term follow-up of donors They are followed for the first year only
Introduction
After 50% reduction of nephron mass, expected single nephron hyperfiltration and theoretical increase in proteinuria and accelerated loss of GFR. However, no studies have proven this beyond doubt.
The primary questions of this review were:
(1) What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min?
(2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
(3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
RESULTS
From screening 2886 citations, 262 full-text articles were retrieved, and 62 studies met our criteria for review. Forty-eight studies from 27 countries followed a total of 5048 donors an average of 7 years (median 6, range 1–25 years after donation), and were published from 1973 to 2005.
Thresholds for clinical proteinuria varied and included range from 100-600mg protein per day, or various levels on urinary dipstick. None of the studies, except one, followed the control groups.
The incidence of clinical proteinuria after donation was quantified in 42 studies, which followed 4793 living donors an average of 7 years (range 2–25 years). These studies showed significant heterogenicity. The reported incidence of proteinuria varied between 5-20%. The pooled incidence in those studies consistently defined proteinuria as >300mg/day was 10%. Some of the studies compared the incidence of proteinuria with control groups. Putting in mind significant heterogenicity, they showed significant increase in proteinuria in donors.
Kidney function after donation
Among the 36 studies of 3529 donors which reported a post donation serum creatinine or GFR with an estimate of variance, the average time after donation was 6 years, the average serum creatinine was 98 mmol/l and the average GFR was 86 ml/min. In eight studies with
mean of 10 years after donation:
· 40% of donors developed a GFR between 60 and 80 ml/min
· 12% of donors developed a GFR between 30 and 59 ml/min
· 0.2% a GFR less than 30 ml/min
Risk of reduced kidney function
Controlled studies were reviewed to determine if the initial decrement in GFR after nephrectomy was accompanied by subsequent accelerated loss in GFR over that anticipated with age. The difference was similar across studies, irrespective of the time from donation (P=0.2).
Discussion
Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. In addition, approximately 12% of donors developed a GFR less than 60 ml/min during follow-up. However, after the initial decrement in GFR from the nephrectomy, there was no evidence of an accelerated loss
in GFR over that anticipated with normal aging.
Strengths and weaknesses of this review:
Strengths:
· Large number of studies
· Multiple countries contributed
· Matching control in most of studies.
· Most of the primary authors were contacted.
· Long follow up period.
Weakness:
· Retrospective nature of the study.
· Significant heterogenicity between studies.
· Non is randomised control trial.
· No control follows up in many studies
· Significant percentage of donor lost to follow up reaching 40%.
Level 5
These studies showed slight but statistically significant rise in proteinuria. However, I don’t think this will be clinically significant as the rise was less than 100mg/day. On the other side, these are healthy donor and some studies showed increase cardiovascular risk with little rise in albuminuria even withing the normal range. So counselling the potential donors and telling them about the possible risk, despite being low will continue to be my practice.
Proteinuria has been related with endothethial damages that worse kidney functions if not controlled and also cardiovascular diseases. This article will deal with proteinuria and the reduction kidney function in living kidney donors. The aim of the article was solving the following questions:
1) What is the proportion of donors that develop proteinuria or a GFR less than 60 ml/min?
2) Kidney donor do they have higher proteinuria than those healthy no donor
3) Do donors have accelerated loss of GFR after nephrectomy?
The study comprises of about 48 studies from period of 1973 to 2005 from various countries of a total of 27 countries with about 5048 donors during a period of 7 years. The level of proteinuria and GFR were accessed. Also, there were 11 studies that collected data that were suitable for non-donors’ control to determine if there will be an increase in proteinuria and reduction of GFR.
It was found that the incidence of proteinuria was about 12% from which nine studies found defined proteinuria of greater than 300mg/day. The amount of proteinuria after 7-year period from a population of 1799 was 10%.
It was found that proteinuria was found higher in donors than the control group over a period of 11 years when compared with a total of 129 donors and 59 control.
When it comes to kidney donation, a total of 3529 donors in 36 studies, over 6 years’ period it was found that 98 mmol/L was the average of serum creatinine. However, in an eight study of a period of 10 years after donation that 40% of had a decline in GFR between 60-80 ml/min and 12 % of other donors had a GFR decline of 30-59 ml/min.
It was observed that before donation, obesity, plasma uric acid and serum cholesterol were not associated with post donation GFR and also ethnicity results were similar.
So, one can conclude that kidney donation can result into an increase in urine protein that gradually increase after donation. Based on this fact proper follow up must be done to ensure that it is captured on time and treat accordingly.
In my practice currently there is not kidney transplant, but I am learning to ensure one day I can put things in place and make the right decision. So, t thinks the article is a valid one and take into consideration.
I level of evidence of this article is level5
Please summarise this article in your own word?
Abstract:
Reduction in renal mass may result in remnant single nephron hyper filtration, with
associated proteinuria and an accelerated loss of kidney function.
However, the long-term implications i.e. reduced GFR and proteinuria of donating a
kidney remain uncertain.
RESULTS finding studies
From screening 2886 citations, 262 full-text articles were retrieved, and 62 studies met
our criteria.
Description of studies, methods, donors, controls, and outcome assessment
Forty-eight studies from 27 countries followed a total of 5048 donors an average of 7
years (median 6, range 1–25 years after donation), and were published from 1973 to
2005 .
48 studies, 21% prospectively followed donors in time, 15% had donor outcomes
measured at fixed years.
Average age 41year.
No donors had overt proteinuria before surgery. The aver 95 mg per day.
He average serum creatinine was 81 mmol
He average GFR was 111 ml/min (range 91–132), the average systolic blood pressure
was 121 mmHg (range 107–132), and the average diastolic blood pressure was 77
mmHg (range 75–79).
In all studies control groups were assembled at the time of donor follow-up evaluation.
Incidence of proteinuria
The incidence of clinical proteinuria after donation was quantified in 42 studies, which
followed 4793 living donors an average of 7 years (range 2–25 years).
There was significant heterogeneity between the studies.
Some studies reported an incidence of proteinuria over 20%, whereas in others the
incidence was less than 5%.
The pooled incidence of proteinuria was 12% (95% confidence interval (CI) 8–16%.
The 24-h urine protein was higher in donors compared to controls an average of 11
years after donation (controls 83 mg/day, donors 147 mg/day, weighted mean difference
66 mg/day, and 95% CI 24–108). This difference increased with the time from donation
(Po0.001).
Kidney function after donation:
Among the 36 studies of 3529 donors which reported a post donation serum creatinine
or GFR with an estimate of variance, the average time after donation was 6 years, the
average serum creatinine was 98 mmol/l (1.11 mg/dl, range 58–119 mmol/l), the
average GFR was 86 ml/min (per 1.73 m2.
Risk of reduced kidney function:
The pooled post-donation GFR was 10 ml/min (per 1.73 m2) lower in donors compared
to controls (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors
84 ml/min, weighted mean difference 10 ml/min, and 95% CI 6–15).
Pre-donation prognostic features:
Men more risk of post donation proteinuric than female.
Female and old age more risk of Reduced GFR.
DISCUSSION:
In this quantitative review, kidney donation resulted in small increases in urinary
albumin, which increased with the time after donation.
Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to
controls.
In addition approximately 12% of donors developed a GFR less than 60 ml/min during
follow-up.
Limitation:
. About one-third donors were lost to follow-up.
Most of the studies also did not have an internal control group.
, inconsistent methods of measuring and reporting proteinuria and renal function in the
primary studies complicate the interpretation of these results.
Take home message:
Till prognostic significance of low grade proteinuria or reduced kidney function in some
kidney donors is better understood, we would advocate for a lifetime of annual serum
creatinine and urine protein screening.
Level of evidence v.
Please reflect on the guidelines provided above and on your practice?
Till prognostic significance of low grade proteinuria or reduced kidney function in some
kidney donors is better understood, we would advocate for a lifetime of annual serum
creatinine and urine protein screening.
We continue exclude donor with proteinuria more than ACR >30 mg/mmol, PCR >50
mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day (BTC
guideline)
This a systematic review, meta-analysis and meta regression of 48 studies, 10 of them were prospective studies.
Aim: to answer the following 3 questions:
1- Percentage of kidney donors who develop proteinuria or drop of GFR below 60 ml/min/m2.
2- Is there high incidence of urinary protein excretion in kidney donors compared to healthy non-donor controls?
3- Is there accelerated decline of GFR after among kidney donors after the initial dropped GFR post-donation compared to healthy controls?
Methods:
Review and meta-analysis of 48 studies from 1973 to 2005, from 27 countries, included more than 5000 kidney donors.
Any of the selected studies should have at least more than 10 kidney donors followed up for more than one year when proteinuria and GFR were assessed.
Follow up: average 7 years, range (1-25 years).
Results:
Pooled incidence of proteinuria more than 300 mg/day was 12% which was not related to normal ageing.
Pooled decline of GFR post donation was 10 ml/min/m2.
Men showed higher incidence of proteinuria compared to female kidney donors.
Donor age and pre-donation BP were not risk factors for proteinuria.
There was no gender difference regarding decline in GFR among kidney donors.
The older the donor age, the higher the decline of GFR pre & post donation.
Strengths:
1- Large numbers of studies.
2- Primary authors were contacted and more clarified information was collected.
Weakness:
1- General population control.
2- Underreporting of long term sequalae.
3- 1/3 of donors lost follow up.
Level V
Level of evidence (LOE) Description:
Level I
Evidence from a systematic review or meta-analysis of all relevant RCTs (randomized controlled trial) or evidence-based clinical practice guidelines based on systematic reviews of RCTs or three or more RCTs of good quality that have similar results.
Level II
Evidence obtained from at least one well-designed RCT (e.g. large multi-site RCT).
Level III
Evidence obtained from well-designed controlled trials without randomization (i.e. quasi-experimental).
Level IV
Evidence from well-designed case-control or cohort studies.
Level V
Evidence from systematic reviews of descriptive and qualitative studies (meta-synthesis).
Level VI
Evidence from a single descriptive or qualitative study.
Level VII
Evidence from the opinion of authorities and/or reports of expert committees.
In our center, all living donors are privileged to be followed for life under the renal transplant team for medical issues. Most of them has good health and are being followed yearly by the renal team unless any issues rise, they can contact the transplant clinic and urgent appointment can be arranged
1– Summary of Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression48 studies from 27 candidates for total 5048 donors were included in this Systemic review with a verge of 7 years after donation.
In this study:-
The average of 24 hour protein collection 154 mg /day and average e GFR 86mL/min.
This Study highlight the consequence of nephrectomy are hyperfiltration ,proteinuria and loss of kidney function .
Aim of this study to clarify the portions of kidney donors develop proteinuria or e GFR less than 60mL/min, if the donor had high protein excretion than controls and loss of GFR after nephrectomy
Results
The average age of donors was 41 years.
Average creatinine 81 umoL/L and average e GFR was 11 1mL/min with average BP 121/71 mm Hg
Pre donation using proteins was 95mg Per day.
33 studies mention donor number who died dans follow up (0-16%).
Incidence of proteinuria:
There was significant heterogenetic between study P< 0- 0001 regarding the incidence of proteinuria after donation with studies
The pooled medicine of proteinuria was 12% (95 confidence interval) defined proteinuria > 300 mg/day.
The pooled incidence of protein in 9 studs was 10% (95 CI)
Risk of proteinuria
3 studies compared total of 129 donors to 59 control an 24-h urine protein. The result, that 24h urine was higher in donors compared to control group within11 years after donation.
Risk of reduced Kidney function
The pooled post-donation GFR was 10mL/min(1-7m2) Level in donors compared to controls. The difference some in all studies, irrespective of the Time from donation, donation .
Prognostic feature
Prognostic feature among health donors that result in higher protein or lower GFR.
Potential true association undetected, as the sample size of many study was small.
In the primary studies no gender or age affect GFR before and after donation.
The proportions of female donors , and average pre donation systolic or diastolic blood pressure were not associated with change in GFR or post donation GFR.
Discussion
In this Review, Kidney donation result in small increase in albumin which increase with time.
GFR 10mL/m level compared to control after 10 years. However no evidence of an accerlated loss in GHR donor that anticipated .with normal aging
Limitation of this study:
1. 1/3 of donors were lost to follow up.
2. most of the studies did not have an internal control group.
3. Some of the donor developed certain medical condition.
4. Inconsistent methods of measuring protein and renal function in primary studies complicate the interpertation
2- level of this article is 1.
3-usully in our centre follow up every 6 month for donor postdonation by KFT and 24 hour protien collection but usually most of them lost follow up after one to 2 years
Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression.
Aim of this work is to identify and clarify many issues related to
-Proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min.
-Kidney donors, compared to healthy non-donor controls, relating to have a higher urinary protein.
-Comparing kidney donors to control relating to accelerated loss of GFR after the initial decrement from their nephrectomy.
Methods.
It is a systematic review, meta-analysis, and meta-regression of Forty-eight studies (published from 1973 to 2005) from 27 countries followed a total of 5048 donors an average of 7 years and proteinuria, or glomerular filtration rate (GFR) was assessed.
Eleven of the studies also collected data on suitable non-donor controls to determine if increases in urinary protein and reductions in GFR after donation were above that normal decrement of aging.
Result.
Incidence of proteinuria.
The pooled incidence of proteinuria was 12%, nine studies which consistently defined proteinuria as >300 mg/ day based on 24 h urine. The pooled incidence of proteinuria among these nine studies which followed a total of 1799 donors for 7 years was 10%.
Risk of proteinuria.
The 24-h urine protein was higher in donors compared to controls an average of 11 years after donation in three studies compared a total of 129 donors to 59 controls.
Kidney function after donation.
The average time after donation was 6 years, the average serum creatinine was 98 mmol/l this among the 36 studies of 3529 donors.
In other eight studies a mean of 10 years after donation, 40% of donors developed a GFR between 60 and 80 ml/min , 12% of donors developed a GFR between 30 and 59 ml/min.
Risk of reduced kidney function.
The pooled post-donation GFR was 10 ml/min lower in donors compared to controls, this in six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min.
Pre-donation prognostic features.
Some studies reported the prognostic pre-donation features associated with a higher proteinuria or lower GFR after donation.
Such as proteinuria and low GFR were more common in men than women, older more than younger donors in lower GFR.
The time after donation was not associated with post-donation GFR or change in GFR.
Pre-donation obesity, plasma uric acid, and serum cholesterol were not associated with the post-donation GFR. Black and white donors were similar in their renal response to donation.
Strengths points of the review.
-Large number of studies 48 with 35 new articles.
– Information was clarified with a majority of primary study authors.
Weaknesses points of the review.
– One-third donors were lost to follow-up.
-Most of the studies don’t have control group.
– Long-term sequelae after donation may be underreported.
– It was unclear whether donors who developed a low GFR also had concurrent hypertension and proteinuria.
Summary.
kidney donation resulted in small increases in urinary albumin, which increased with the time after donation but the prognostic significance of low grade proteinuria or reduced kidney function in some kidney donors is better understood, we would advocate for a lifetime of annual serum creatinine and urine protein screening.
LEVEL of evidence: I Metanalysis -systematic review.
Reflect on your practice:
-We should counsel our kidney donors about risk of proteinuria and we should learing them about importance of long term follow up.
Unilateral Nephrectomy may result in remnant single nephron hyperfiltration, with associated proteinuria and an accelerated loss of kidney function.However, the long-term implications of donating a kidney remain uncertain.
Usual questions asked by our potential kidney donors in daily practice is
WHAT WILL HAPPEN TO MY OTHER KIDNEY?
WILL I LOSE MY KIDNEY FUNCTION OVER TIME?
Garg and collaegues in this systemic review have put an effort to answer these questions in a scientific way.They reviewed any study where 10 or more healthy adults donated a kidney, and proteinuria, or glomerular filtration rate (GFR) was assessed at least 1 year later. Data was searched till November 2005.
Total of Forty-eight studies from 27 countries were analysed which followed a total of 5048 donors. An average of 7 years after donation (range 1–25 years),
The average 24 h urine protein was 154 In eight studies which reported GFR in categories
12% of donors developed a GFR between 30 and 59 ml/min (range 0–28%),
0.2% a GFR less than 30 ml/min (range 0–2.2%). In controlled studies urinary protein was higher in donors and became more pronounced with time (three studies totaling 59 controls and 129 donors; controls 83 mg/day, donors 147 mg/day, and the average GFR was 86 ml/min.
An initial decrement in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging
six studies totaling 189 controls and 239 donors; controls 96 ml/min,
donors 84 ml/min,
weighted mean difference 10ml/min,
95% CI 6–15; difference not associated with time after donation.
In this quantitative review, kidney donation resulted in small increases in urinary albumin, which increased with the time after donation which could be sequele or hyperfilteration
Whether such hyperfiltration leads to a progressive deterioration in kidney function has been the subject of many debates.
Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. In addition approximately 12% of donors developed a GFR less than 60 ml/min during follow-up. However, after the initial decrement in GFR from the nephrectomy, there was no evidence of an accelerated loss in GFR over that anticipated with normal aging.
Strengths and weaknesses of this review
Results of any meta-analysis are inherently limited by the quality of the primary studies.
About one-third donors were lost to follow-up.
Most of the studies also did not have an internal control group, making it difficult to interpret the donor results.
Inconsistent methods of measuring and reporting proteinuria and renal function in the primary studies complicate the interpretation
In most studies it was unclear whether donors who developed a low GFR also had concurrent hypertension and proteinuria.
However among the controlled studies proteinuria and GFR were assessed in a similar manner in both donors and controls, with observed differences suggesting a true difference between the groups.
Level of evidence V
Our practice.
A major bulk of our transplant pool has regular follow up and we didn’t find any significant proteinuria apart from few patients where they develop proteinuria due to new onset GN
Proteinuria and reduced kidney function in living
kidney donors: A systematic review, meta-analysis,
and meta-regression
This review answered the following questions:
(1)What proportion of kidney donors develop proteinuria or a
GFR less than 60 ml/min?
(2) Do kidney donors, compared to healthy non-donor controls,
have a higher urinary protein?
(3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
Reasons for different estimates in the literature were also explored using meta-regression.
RESULTS
62 studies met the criteria for the review.
Excluded criteria:
1- Studies which reported hypertension outcomes but not renal outcomes.
2- Donors with HTN, overt proteinuria, or a GFR less than 80 ml/min (per 1.73 m2) before the time of surgery.
Description of studies, methods, donors, controls, and
outcome assessment
Forty-eight studies from 27 countries followed a total of 5048 donors, and were published from 1973 to 2005.
This review identified the donor outcomes.
The average age of donors was 41 years, the average serum creatinine was 81 mmol/l , the average GFR was 111ml/min, the average systolic BP was 121mmHg , and the average diastolic blood pressure was 77mmHg. No donors had overt proteinuria before surgery.
DISCUSSION
kidney donation resulted in small increases in urinary albumin, which increased with the time after donation.. Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. About 12% of donors developed a GFR less than 60 ml/min during follow-up. However, after the initial decrement in GFR from
the nephrectomy, there was no evidence of an accelerated loss
in GFR over that anticipated with normal aging.
Strengths of this review
1.Identified 35 new articles.
2.Relevant data was rigorously identified and abstracted, articles were translated, information was clarified, and reasons for diversity in the published literature were explored.
3.Reasons for mathematically combining certain results were justified.
Weaknesses:
1.Results are limited
2.About one-third donors were lost to follow-up.
3.Most of the studies also did not have an internal control group
4.Some donors would have developed certain medical conditions without donation.
5 Some studies had a control group from the general population and this may have biased towards demonstrating no increased risk of certain medical conditions after donation.
6. Long-term sequelae after donation may be underreported
7. Inconsistent methods of measuring and reporting proteinuria and renal function in the primary studies complicate the interpretation of these results.
8. In most studies it was unclear whether donors who developed a low GFR also had concurrent HTN and proteinuria.
Renal sequelae, donor selection, and long-term surveillance
▪︎Donors who develop clinical proteinuria appears to be higher than expected in the general population
▪︎10% of donors have a urinary protein level of 300 mg/day over a subsequent
decade.
▪︎12% of donors develop a GFR less than 60 ml/min over this same period.
▪︎ In this review the donors have no evidence of HTN, proteinuria or reduced kidney function before donation. However, 10 were reported to have develop kidney failure requiring dialysis.
☆Conclusion:
▪︎The results summarized support the safety of live kidney donation. However, until the prognostic significance of lowgrade proteinuria or reduced kidney function in some kidney donors is better understood, lifetime of annual serum creatinine and urine protein screening is essential.
▪︎ Future research is recommended
Inclusion of racially-diverse, older and genetically unrelated donors, and controls will help define if there are any differential effects of donation among such individuals.
Finally, by assessing definitive outcomes such as death and CVD, the prognostic significance of small increases in urinary protein or reduced kidney function after donation will be better undeunderstood.
☆Level of evidence: 5
The study is a meta-analysis and meta-regression of studies, with minimum 10 subjects and at least 1 year follow-up, assessing proteinuria and GFR in a kidney donor.
48 studies included with 5048 donors from 27 different countries. Average follow-up was of 7 years (1-25 years).
None of the donor had overt proteinuria pre-transplant. Average pre-transplant proteinuria (quantified in 6 studies only) was 95 mg/day. Proteinuria was 154 mg/day in the donor group. Incidence of proteinuria was 12% (10% in 9 studies which clearly defined proteinuria). 24-hour urine protein was higher in donors as compared to controls an average 11 years after donation (147 mg/day versus 86 mg/day).
The average GFR pre-transplant was 111 ml/min, which reduced to 86 ml/min after an average time of 6 years. 40% developed GFR between 60 – 80 ml/min, 12% developed GFR between 30 – 59 ml/min and 0.2% had GFR <30 ml/min 10 years after donation. 6 studies compared donors with controls and found GFR was 10 ml/min lower in the donors irrespective of time from donation.
The pre-donation prognostic factors included:
a) For proteinuria: increased in males, no relation with time after donation, donor age and donor BP at surgery.
b) For Post-donation reduced GFR: older age and female gender, no relation with obesity, uric acid, serum cholesterol, race and time after donation.
The reviewers concluded that kidney donation resulted in small increase in urinary albumin which increased with time. Donors had GFR lower by 10 ml/min but after the initial reduction, any further accelerated loss in GFR not noted.
Limitations of the study: No RCT included. 31% (0-79%) were lost to follow-up. Thresholds for proteinuria as well as methods of assessing GFR varied in different studies. Majority of the studies did not have an internal control group. Only 11 studies compared the donors with non-donors (which were from general population as well as suitable, healthy non-donors) but the follow-up was done prospectively only in one study.
Level of evidence: Level 5
The authors advocate life-time follow-up of donors with serum creatinine and proteinuria.
In our unit, we emphasize on the importance of renal donor follow-up and advise annual serum creatinine and proteinuria with a general physical examination including BP, FBS and body weight assessment (for BMI). Despite continuous emphasis, the follow-up among the donors is only 60-70%.
kidney donation resulted in small increases in urinary albumin, which increased with the time after donation. Many would consider this indicative of single nephron hyperfiltration from a reduced renal mass. Whether such hyperfiltration leads to a progressive deterioration in kidney function has been the subject of many debates. Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. In addition approximately 12% of donors developed a GFR less than 60 ml/min during follow-up.
Level 5
———————
donor excluded >>>> persistent proteinuria
The subject of this study is identifying
1- if kidney donors develop proteinuria or reduction in GFR less than 60
2 if they have more proteinuria compared to healthy non donor
3- if they have an accelerated GFR loss compared to control group
They review 48 studies form 27 countries with 5048 living donors were followed up 7 years between 1973 and 2005
Population
The average of;
age41 years
Crea 0.8
GFR 111
BPS 120
BPD 77
NO Proteinuria
There are two control groups
Healthy volunteers
Individuals under evaluation as potential donors (with similar age- gender- race….)
The incidence of proteinuria
There is significant heterogeneity of proteinuria incidence between more than 20%in some studies and less than 5% in others
Pooled incidence of proteinuria 12%
The pooled risk of albuminuria 3.9
Kidney function
Average GFR 86
Average GFR reduction after donation was 26
Other studies 40% of GFR was 60- 80
2% of GFR was 30- 59
0.2% of GFR was less than 30
Some limitations
This review summarized 48 single center studies, and shares similar strengths and weaknesses
On average about one-third donors were lost to follow-up.
Most of the studies also did not have an internal control group, making it difficult to interpret the donor results.
In most studies it was unclear whether donors who developed a low GFR also had concurrent hypertension and proteinuria
Level V ( after reading professors notes)
This is not a strong study however we can consider the importance of evaluate living donor very carefully and identifying all accompanied risk factors
In addition, every center should follow a precise guidance in long term care of living donors
Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression:
This article focus on risk of proteinuria and decrease kidney function post donation.
Definition of proteinuria as >300 mg/ day based on 24h urine.
Incidence of proteinuria shows discrepancies between studies, some studies proteinuria is 20% and other studies are less than 5% after donation.
Risk of proteinuria increase after donation within 11 years in comparison to non donor.
Kidney function post donation:
Post donation serum creatinine 1.11 mg/dl or GFR with average 86ml/min, the average time after donation was 6 years.
The average decrement in GFR after donation was 26ml/min.
post-donation GFR was 10 ml/min (per 1.73 m2) lower in donors compared to controls in all studies irrespective to time.
Old age no different than younger in deceased GFR. Male more than female in reduce GFR post donation. Pre-donation obesity, plasma uric acid and serum cholesterol were not associated with the post- donation GFR. Black and white donors were similar in their renal response to donation. The time after donation was not associated with post-donation GFR or change in GFR.
Higher pre-donation blood pressure was associated with a larger decrease in GFR post donation.
kidney donation resulted in small increases in urinary albumin, which increased with the time after donation. It’s may related to single kidney and decrease renal mass.
Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls.
Living donors should undergo good evaluation and selection, and their incidence of death is lower than the general population.
In general population presence of proteinuria and low GFR indicates systemic atherosclerosis and cardiovascular disease and accelerate mortality.
It’s should consider counsel all donors, irrespective of their pre-donation health state, on modifiable risk factors which prevent future renal and cardiovascular disease.
Q2: level I
Q3: Living donor should counseling regarding little increase in proteinuria and decline 10ml/min of GFR post donation.
They need regular fallow up
Please summarise this article in your own words
-This review summarized 48 single center studies, and shares similar strengths and weaknesses from 27 countries followed a total of 5048 donors. An average of 7 years after donation , the average 24 h urine protein was 154mg/day and the average GFR was 86 ml/min.
– The primary questions of this review were:
(1) What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min?
(2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
(3) Do kidney donors compared to controls have an accelerated loss of GFR after
the initial decrement from their nephrectomy?
-In this quantitative review, kidney donation resulted in small increases in urinary albumin, which increased with the time after donation due to single nephron hyperfiltration from a reduced renal mass.
-Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. However, after the initial decrement in GFR from
the nephrectomy, there was no evidence of an accelerated loss in GFR over that anticipated with normal aging.
Limitation of study:
-The results from any meta-analysis are inherently limited by the quality of the primary studies. A bout one-third donors were lost to follow-up. Most of the studies did not have an internal control group, making it difficult to interpret the donor results. A control group often, recruited participants from the general population who may not as fit as donor .
-Results from this quantitative review will be best confirmed by the completion of a large, prospective, multi-center cohort study with representative numbers of donors and appropriate controls followed for extended periods of time.
What is the level of evidence provided by this article?
Level 1
Please reflect on the guidelines provided above and on your practice.
-Proper selection of donor and regular follow up .
Please summarise this article in your own words
To start with, first of all the title of article doesn’t seem to be correct. How can a study be both systematic review and meta analysis. It can be either of them.
This study analysed all the past studies in which 10 or more healthy donors were included and proteinuria and GFR was assessed at least after 1 year post donation. This study tried to answer the following questions:
Description of studies
48 studies were included from 27 countries. A total of 5048 donors included in these studies were followed for an average of 7 years. The key features of included studies were as follows.
Discussion
Strength
Weakness
It was summarised that living kidney donors who develop low grade proteinuria or reduced GFR have a different mechanism acting unlike general population where proteinuria and low GFR is mainly due to associated metabolic disturbances and atherosclerosis.
It seems likely that living donors might be a relatively higher risk of developing renal sequlae but methods of monitoring the same as still unclear.
Since the primary studies included had many weaknesses and had quite heterogeneity, the current study though being a meta analysis does not have a good level of evidence.
It would be level 5 in this case
III. Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression
Please summarise this article in your own words
Introduction
Reduction in renal mass may cause hyper-filtration in the remaining nephrons leading to proteinuria & an accelerated loss of kidney function.
This review aimed to amswer the following:
What proportion of kidney donors develop proteinuria or a GFR < 60 ml/min
Do kidney donors (versus healthy non-donor) have a higher urinary protein?
Do kidney donors have an accelerated loss of GFR after the initial decrement from nephrectomy?
The study
The authors reviewed any study (62 studies met criteria) where 10 or more healthy adults donated a kidney, & proteinuria, or GFR was assessed at least 1 year later.
48 studies from 27 countries followed a total of 5048 donors.
An average of 7 years after donation (range 1–25 years)
The average 24 h urine protein was 154mg/day
The average GFR was 86 ml/min.
In 8 studies which reported GFR, 12% of donors had GFR 30 to 59 ml/min (range 0–28%), & 0.2% a GFR <30 ml/min (range 0–2.2%).
Urinary protein was higher in donors & became more pronounced with time (3 studies,59 controls & 129 donors; controls 83mg/day, donors 147mg/day, weighted mean difference 66mg/day).
Initial GFR decrement post-donation not accompanied by accelerated losses over that expected with normal aging (6 studies,189 controls & 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min). Kidney donation results in small increases in urinary protein.
An initial decrement in GFR is not followed by accelerated losses over a subsequent 15 years.
Death, kidney failure, & CVD
33 studies described the number of donors deaths; it ranged from 0 to 16% during follow up. 2 donors died with kidney failure.
10 donors (from eight different studies) were living with kidney failure at the last follow up.
7 studies described % of donors who developed CVD during follow-up.
Incidence of proteinuria after donation:
42 studies ((4793 living donors followed for 7 years (range 2–25 years)).
Reported incidence of proteinuria ranged from less than 5% to 20%.
Risk of proteinuria
Proteinuria increased after donation (3 studies compared 129 donors to 59 controls on 24-h urine protein).
In 2 of 4 other studies, 24-hurine albumin was 56 mg higher in donors versus controls 14 years post-donation.
2 studies assessed the risk of microalbuminuria in 67 donors & 51 controls at 2 & 13 years after donation; the pooled risk of microalbuminuria was 3.9 (95% CI 1.2–12.6).
Kidney function after donation
Average creatinine was 98 mmol/l (58–119 mmol/l), the average GFR was 86 ml/min(range 64–117)((36 studies, 3529 donors)).
Average decrement in GFR after donation was 26 ml/min (range 8–50)(( 22 studies)).
Risk of reduced kidney function
In controlled studies, the pooled post-donation GFR was 10 ml/min lower in donors versus controls (6 studies, 189 controls & 239 donors; controls 96 ml/min, donors 84 ml/min).
Pre-donation prognostic features associated with a
higher proteinuria or lower GFR after donation:
– Male gender has higher proteinuria.
– No reported association between the time after donation & the amount of proteinuria.
– Neither donor age at the time of surgery, nor pre-donation BP was associated with proteinuria after donation.
– No gender differences in the decrement in GFR after donation.
– Older donors had a lower GFR both before and after donation.
– Pre-donation obesity, plasma uric acid, & serum cholesterol were not associated with the post-donation GFR.
– Black & white donors were similar in their renal response to donation.
– Time after donation was not associated with post-donation GFR or change in GFR.
– A higher pre-donation BP was associated with a larger decrement in GFR(1 study).
Discussion
Kidney donation results in small increases in urinary albumin, which increased with the time after donation.
Ten years after nephrectomy, donors had a GFR 10 ml/min lower compared to controls.
A 12% of donors had a GFR <60 ml/min during follow-up.
After initial decrement in GFR from nephrectomy, there was no evidence of accelerated loss in GFR over that anticipated with normal aging.
Strengths of this review
It is a quantitative review.
Relatively large number of single center studies.
Weaknesses of this review
One-third donors were lost to follow-up.
No internal control group in most of the studies.
Studies with controls, recruited participants from the general population (giving bias towards showing no increased risk of certain medical conditions after donation).
Renal sequelae, donor selection, and long-term surveillance
% of donors who develop proteinuria is higher than expected in the general population.
10% of donors exceed a threshold of 300 mg/day over a subsequent decade; 12% of donors develop a GFR less than 60 ml/min over this same period.
Without evidence of adverse health outcomes, small
changes in proteinuria or GFR should not be the sole reason for denying a practice which benefits , recipients, donors, & society.
Living donors in this review showed no evidence of HTN, proteinuria or reduced kidney function before donation.
Many donors may have a genetic predisposition to developing kidney disease; 10 donors (0.2%) in this review developed kidney failure requiring dialysis.
A decision to proceed in
It is prudent to counsel all on modifiable risk factors which prevent future renal & CVD.
Routine screening (in general population) to detect an elevated serum creatinine or the presence of urine protein is not recommended.
For donors, it is not clear which screening tests should be used, how long they should be followed, & which health care providers should be responsible for such follow-up; until the prognostic significance of low grade proteinuria or reduced kidney function in some kidney donors is better understood, a lifetime of annual serum creatinine and urine protein screening is advocated.
.
===========================
What is the level of evidence provided by this article?
Level V
===========================
Please reflect on the guidelines provided above and on your practice.
Unfortunately, most of the donors in our transplant center are lost for follow up; and more importantly there is a lack of a local database of donors.
High selection & the practice of accepting only the very healthier individuals for donation may, partially, explain the reluctance of donor to show for follow up.
1-Please summarise this article in your own words
The type o the study ;
A systemic review ,meta-analysis and meta regression
The aim o the study ;
The primary questions of this review were:
1-What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min?
2- Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
3- Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
Method;
Bibliographic databases were searched .
The population ;
1-The study group ;
forty-eight studies from 27 countries followed a total of 5048 donors an average of 7 years.
2- The control group;
healthy volunteers, or individuals under evaluation as potential donors, with similar age, sex, race, and / or, height distributions as donors. In all studies control groups were assembled at the time of donor follow-up evaluation.
Inclusion criteria ;
Any study in any language where 10 or more healthy adults donated a kidney, and either proteinuria or GFR was assessed at least 1 year later.
Statistical analysis ;
1-The Q-statistic was used to determine if between study heterogeneity was present, with a P-value of o0.1 considered statistically significant.
2-The i2 –statistic was used to quantify the magnitude of heterogeneity, with value of 0–30%, 31–50% and greater than 50% representing mild, moderate, and notable heterogeneity respectively.
3-Reasons for diversity in primary study estimates were explored using univariate and multivariate meta-regression of donor cohorts: mixed models for continuous outcomes (SAS PROC MIXED) and logistic normal random effects models for binary outcomes (SAS PROC NLMIXED).
The result ;
1-kidney donation resulted in small increases in urinary albumin, which increased with the time after donation.
2-Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. In addition approximately 12% of donors developed a GFR less than 60 ml/min during follow-up.
3- However, after the initial decrement in GFR from the nephrectomy, there was no evidence of an accelerated loss in GFR over that anticipated with normal aging.
Limitation o the study ;
1-one-third donors were lost to follow-up.
2- Most of the studies also did not have an internal control group, making it difficult to interpret the donor results.
.
2-What is the level of evidence provided by this article?
Level I
3-Please reflect on the guidelines provided above and on your practice.
1– living donors are a group who may be at higher risk of renal sequelae, and to prevent future morbidity it remains unclear which renal screening tests should be performed, how long donors should be followed, and which health care providers should be responsible for such follow-up.
2-These guidelines, support the safety of live kidney donation. However, until the prognostic significance of low- grade proteinuria or reduced kidney function in some kidney donors is better understood, we would advocate for a lifetime of annual serum creatinine and urine protein screening.
3- In our practice, we do not accept donor with any evidence of hypertension, proteinuria or reduced kidney function . The donors are followed up every six months and they are requested to do a serum creatinine and a urine albumin creatinine ratio.
Kidney donation result in decreased renal mass leading to increased hyperfiltration in remnant nephrons and may lead to proteinuria and renal impairment but the long-term effect is still not well determined.
This study aims to evaluate the effect of kidney donation on developing proteinuria and renal impairment compared to non-donor controls
The meta-analysis showed that kidney donation is associated with mild increase in albuminuria progressing with time after donation.
During follow up 12% of donors had GFR<60 ml/min and proportion of donors who had GFR <10 ml/min was less than that in controls, however, there was no accelerated decrease in kidney function other than that with normal ageing.
Kidney donors develop proteinuria more than expected in general population, in the first decade 10% of donors have proteinuria >300mg/day and 12% have GFR <60ml/min
The decrease in GFR may occur without donation, but nephrectomy may accelerate GFR reduction.
The prognostic significance of proteinuria and impaired kidney function in kidney donors are not well determined as donors have lower incidence of death than general population as they are carefully evaluated before donation so exclusion of potential donors with no evidence of adverse health outcome due to presence of proteinuria or mild decrease in GFR should be revised.
Accepting donors with marginal criteria is still controversial, as some donors may have genetic predisposition to kidney disease so the decision should be carefully evaluated.
All donors should be counseled about modifiable risk factors which prevent future renal and cardiovascular disease.
Duration of follow up, renal screening tests, the responsible health care provider for follow up are not well defined, however, lifetime annual serum creatinine and urinary protein screening is the safest approach for donors
Limitations:
One third of donors included lost follow up
Most of the included studies didn’t compare donors to control group so couldn’t consider medical conditions that would have develop in donors without donation.
Studies with control group recruited participants from general population and are not as fit as donors and may underestimate the increased risk of certain conditions after donation.
Long-term complications after donation may be underreported.
Few studies included post donation GFR in categories according to modern cutoff points used to assess renal function.
Several studies didn’t report whether the donor with low GFR had also HTN and proteinuria or not.
Level of evidence: 1 (meta-analysis study)
Donors are advised to have regular follow up of GFR and urinary proteins every 6 months after donation.
This meta-analysis addressed the contentious issues of long term post donation sequala.
The deterioration of GFR and proteinuria on long run post donation were assessed , as both were reported in single center studies and anecdotal reports to be adversely affected , imparting an escalating risk of progressing to renal failure.
This meta-analysis considered all studies who include 10 healthy donors and above with average post donation duration of 7 years (range 1 to 25 years).
The consequences of donation are conceptually instigated from reduction of nephron mass with resultant compensatory single nephron hyperfiltration. This adaptive mechanism might provoke wear off and maladaptive glomerular hypertension and hyperfiltration. clinically proteinuria and deteriorating GFR are the markers of this maladaptive process.
The meta-analysis emphasizes on the debates of
1) The incidence of proteinuria and GFR of less than 60 ml/min.in kidney donors.
2) Is the rate of proteinuria in kidney donors is variable from non donor counterparts ?.
3)In comparison to non donor age matched group, was the deterioration of GFR
escalated relentlessly in kidney donors after the initial drop of GFR post operatively.
4) what are the risk factors for deterioration of renal function and proteinuria , and can a schematic selection criteria be formulated depend on that?
48 studies from 27 countries counting 5048 patients were analyzed .
The creatinine , GFR and proteinuria were quantified pre -donation. after donation and then on long term follow up.
Results:
There was a small increase in urinary albumin, might be related to single nephron hyperfiltration.
GFR was 10 % less than counterparts, 10 years after donation.
12% of donors had EGF below 60 ml/min.
the diminution of GFR was comparable to the control population and was not progressing after the initial drop immediately post operatively.
Pre donation risk factors:
Sex , age , obesity and GFR were the main risk factors associated with deterioration of GFR and development of proteinuria.
Level of evidence is 1
In general GFR pre-donation is pre-requisite to accept the donation, similarly obesity is not accepted as donors , elderly people has to be selected carefully as they are featuring significantly higher risk .
Summary
This is meta-analysis with meta-regression review due to differences in estimation from different literatures most of the studies are cohorts retrospective designs some with control group , and small sample size with short FU to such hard outcome , no single RCT included in this review so can’t be level 1 A of evidence may be level 2 A
This study addressed three primary questions
1. What is the percentage of kidney donors develop proteinuria or reduction of GFR < 60mL/min?
2.Do kidney donors have more urinary proteinuria compared to non – donors control group?
3.Look after kidney donors had faster loss of GFR after initial decrement compared to non-donor control?
Results
This review contain 48 studies from different countries from (27 0 with total numbers of donors included of 5040 and median FU of 7 years post donations with the range of (1-24years).
1.24h urine protein was higher in donor group compared to non-donor control (8 studies only) Of average 148mg/24h compared to 83 in control group. However missing data of > 1/3 of the cases ( bias )
2.12% of donors developed a GFR between 30 and 59 ml/min (range 0–28%), and 0.2% had GFR < 30ml/min.
3. An initial decrement in GFR after donation was not go together with accelerated losses over that anticipated with normal aging
Conclusion
Based on this review they conclude that Kidney donation results in trivial increases in urinary protein. An initial decrement in GFR is not followed by accelerated losses over subsequent 15 years of FU. this metanalysis will not change my practise and still we need more studies with more prosepctive design and welmatched homogenous nondonor control group withlonger followup.
limitations
no single RCT included in this meta- analysis , only 21% have aprosepctive cohort and FU with small sample size. others are retrospective design from single centres with heterogeicity in studies designs , data collection and even studies outcome , missing datas including protienuria clinical defintion identified in 67% of the studieswith significant heterogenicity in the incidence of postdonation protienuria, different methodes for assessing GFR and quantification of protuenuria
31% of the alive donors are lost for FU
Thank You Saja for this excellent analysis. In spite of being a meta-analysis, but It is a meta-analysis of week studies (level 3 and level 4) as you pointed. Also, you pointed many limitations of the studies used in the meta-analysis. This gives an indication of the weakness of the whole study.
Remember: Garbage in, Garbage out
Please summarise this article in your own words:
It is known that renal mass reduction resulting in single nephron hyperfiltration results in proteinuria and progressive decline in kidney function.
The study want to figure out this theory in kidney donors after donation of one kidney, so they collected data from 48 articles meets the inclusion criteria, from year 1973- 2005, with 5048 total number of donors.
inclusion criteria was:
Results:
Proteinuria –
The incidence heterogeneity was significant statistically.
The proteinuria increased after donation.
The difference in proteinuria increased with the time from donation.
Kidney function after donation –
The average decrement in GFR after donation is 10 ml/min/1.73m2 compared to control.
10 years after donation, 40% has GFR 60-80 ml/min, 12% developed GFR 30-59 ml/min, and 0.2% a GFR <30 ml/min.( in 8 studies).
The difference was similar across studies irrespective of the time from donation.
Approximately 10% of donors exceed a threshold of 300 mg/d proteinuria, and 12% of donors develop a GFR less than 60ml/min over the same period.
This decline in GFR and proteinuria after donation was not associated with increased risk of systemic atherosclerosis, premature mortality, cardiovascular death, and kidney failure, that was seen in general population, it could be due the different mechanism of proteinuria and GFR decrement in kidney donors, and the donors usually underwent a thorough evaluation and identification of metabolic risk factors and better management.
Predonation risk factors:
Men tend to have proteinuria than women after donation.
Women tend have lower GFR both before and after donation
Donor age , blood pressure , obesity , serum uric acid, and cholestrol not associated with post donation decrement in kidney function.
Limitations:
Conclusion:
counselling all potential donor, irrespective of their predonation health status, on modifiable risk factors is a must, and this could prevent the future renal and cardiovasculart events.
The study support the safety of living kidney donation, and the prognostic significance of low grade proteinuria and GFR decline is better understood. and require annual serum creatinine and urine protein screening for life long.
What is the level of evidence provided by this article?
Level of evidence V – erratic review.
Please reflect on the guidelines provided above and on your practice.
In our practice we follow the KDIGO guide lines for living donor evaluation, we adive the donors to do monitor blood pressure, do urinalysis, FBS and serum creatinine twice yearly, and at least annual lipid profile and to have ideal BMI. Unfortunately most of them lost follow up and small number still following the protocol. – This would make an excellent retrospective pool to study in our center.
Thank You Mohamed
You kindly highlighted the limitations, Well done.
You rated this study as level 5, as an erratic review, I agree with you, it is not a good study.
Remember: Garbage in, Garbage out
This was a systematic review, meta-analysis and meta-regression.
It was trying to answer the following questions:
They had 2886 citations out of which 262 full text articles were reviewed. 62 studies met the study criteria. 2 were excluded as they reported on hypertension outcomes. 12 studies were excluded as they reported composite outcomes.
The final analysis was done on 48 studies from 27 countries which followed a total of 5048 donors over an average period of 7 years and were published from 1973-2005.
Only 10 out of the 48 studies prospectively followed the donors in time, while 15% had donor outcomes measured at fixed year(s) post-donation.
31% of surviving donors eligible to participate in each study were lost to follow up. Only 4 studies described the baseline characteristics of donors lost to follow up.
The average age of the donors pre-transplant was 41 years, with an average serum Cr of 81 mls/min and average GFR of 111 mls/min. No donors had overt proteinuria.
11 of the studies also collected data on suitable non-donor controls to determine if increases in urinary protein and reductions in GFR after donation were above that attributable to normal aging.
The threshold for clinical proteinuria varied widely among studies ranging between > 100 to > 699.
44 studies (91.6%) described the method of GFR estimation which was usually a timed creatinine clearance.
Results
33 studies (68.8%) described the donors who died during follow up which ranged from 0-16%. 2 donors died with ESKD. A total of 10 donors from eight studies were living with kidney failure.
Proteinuria was quantified in 42 studies which followed 4793 living donors for an average of seven years. There was significant heterogeneity between the studies. The pooled incidence of proteinuria was 12%.
3 studies compared a total of 129 donors to 59 controls for 24 hour urine protein excretion to determine if proteinuria after donation was attributable to normal aging. In the pooled analysis, the 24 hour urine protein was higher in the donors compared to controls and the difference increased with time from donation.
Among the 36 studies that reported a post-donation serum creatinine or GFR, the average serum creatinine was 98 micromoles/L and the GFR was 86 mls/min. The average time after donation was 6 years. The average reduction in GFR after donation was 26 mls.min in the 22 studies where it was described.
When compared to healthy donors, the pooled post-donation GFR was 10 mls/min lower in donors compared to controls.
The pre-donation prognostic features for increased proteinuria and reduction in GFR included only gender:
Males had a higher risk of developing proteinuria than women
Women tended to have a lower GFR than men both pre-and post-donation
Conclusion:
Study Limitations:
What is the level of evidence?
This is a systemic review and a meta-analysis, therefore this is level I evidence
Please Reflect On The Guidelines Provided and Your Own Practice
In our practice, we use a GFR pre-donation of > 90 mls/min and no proteinuria. The donors are followed up and every six months they are requested to do a serum creatinine and a urine albumin creatinine ratio. Unfortunately, a number of donors don’t come for follow up after one year. We do see a rise in serum creatinine post-nephrectomy but it stabilizes and reduces overtime.
SUMMARY
It has been observed that uninephrectomy leads to hyperfiltration of the remaining nephrons to compensate and this can simultaneously result in proteinuria. However, very few studies have demonstrated the long-term effect like reduce GFR or proteinuria on a living kidney donor.
This article was set out to answer the following questions
5048 donors were recruited from 48 studies that cut across 27 countries and the median follow up was 6 years. Also, before the surgery, the average age of donors was 41 years, and the average serum creatinine was 81umol/l with GFR at 111mil/min. In addition, 11 of these studies actually collected data on controls that were fit for donation but not allowed to donate their kidney.
The pooled incidence of proteinuria in all the studies was 12% and the 24 hours proteinuria quantification was higher among donors compared to the control group after 11 years of followed up. About 22 studies review the impact on kidney function after donation and found that there is an average reduction of 26ml/min in GFR among the donor group. In the primary studies, women were noticed to have a lower GFR than men even before and after surgery and in some studies, a higher predonation hypertension has effect on lower GFR.
The strengths of this review are first, relevant data were thoroughly searched, second the articles were translated and some of the authors were contacted and the reason for diversity in the various articles were well explored. Among the weakness is, loss of about one third of the donor to follow up, most of the studies did not have an internal control.
In conclusion, this review shows a small increase in the urine albumin after donation and 12% of the donor end up having GFR < 60ml/l after following up and the donors that were reviewed have not prior hypertension, proteinuria of reduce GFR before donation
The level of evidence is 5, because is a narrative review without any design except the one from the different articles that were reviewed
In my centre, a potential donor with persistent proteinuria is not allowed to donate. Unfortunately, most of the donor are usually lost to follow up as we don’t get to see them beyond 2 months except if there is a major complaint that warrant presentation to the hospital
Summary:
Ø Study where 10 or more healthy adults donated a kidney, and proteinuria, or glomerular filtration rate (GFR) was assessed at least 1 year later
Ø Forty-eight studies from 27 countries followed a total of 5048 donors. An average of 7 years after donation (range 1–25 years), the average 24 h urine protein was 154mg/day and the average GFR was 86 ml/min.
Ø In eight studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min (range 0–28%), and 0.2% a GFR less than 30 ml/min (range 0–2.2%).
The primary questions of this review were:
(1) What proportion of kidney donors develop proteinuria or glomerular filtration rate (GFR) less than 60 ml/min?
(2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
(3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy
RESULTS
Finding studies
Ø From screening 2886 citations, 262 full-text articles were retrieved, and 62 studies met our criteria for review.
Description of studies, methods, donors, controls, and outcome assessment:
Ø 48 studies, 21% prospectively followed donors in time.
Ø 15% had donor outcomes measured at fixed year(s) post-donation.
Ø 91% defined how proteinuria was measured.
Ø 96% defined how renal clearance was measured.
Ø 67% provided a definition of clinical proteinuria.
Ø 90% described the total number of donors from which the participating sample was drawn
In all studies control groups were assembled at the time of donor follow-up evaluation
Forty-one studies described the method of urine protein quantification, which usually was a timed (i.e. 24 h) urine. Other methods included a random urine protein, dipstick, a timed urine albumin, a random urine albumin to creatinine ratio34 and a first am urine albumin concentration.56 Thresholds for clinical proteinuria varied, , or various levels on urinary dipstick
31% of surviving donors eligible to participate in each study were lost to follow-up (range 0–79%).
Forty-four studies described the method of GFR estimation, which usually was a timed urine creatinine clearance. Other methods included the use of inulin or radioisotopes,
or a predictive equation for GFR. Ten studies only described a serum creatinine result. In 61% of studies the reported GFR was standardized to 1.73m2 of body surface area.
Before surgery:
1-donors age was 41 years
.2- the average serum creatinine was 81 mmol/l
3-GFR was 111 ml/min
.4- systolic blood pressure was 121mmHg
5-diastolic blood pressure was 77mmHg 6
6–. No donors had overt proteinuria before surgery
Controls
healthy volunteers, , with similar age, sex, race, and / or, height distributions as donors. In all studies control groups were assembled at the time of donor follow-up evaluation. With the exception of a single study,39 none appeared to follow controls prospectively from the time of donor surgery
Death, kidney failure, and cardiovascular disease
Thirty-three studies described the number of donors who died during follow-up, which ranged from 0 to 16% of the study cohort
Incidence of proteinuria:
incidence of proteinuria was 12% (95% confidence interval (CI) 8–16%).
The pooled risk of micro albuminuria after kidney donation was 3.9 (95% CI 1.2–12.6)
Kidney function after donation:
The average post-donation GFR in these studies did not differ from the remaining studies (88 vs 85 ml/min (per 1.73m2).
Risk of reduced kidney function:
The pooled post-donation GFR was 10 ml/min (per 1.73m2) lower in donors compared to controls (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, and 95% CI 6–15). The difference was similar across studies, irrespective of the time from donation (P=0.2).
Pre-donation prognostic features:
There was no gender differences in the decrement in GFR after donation.
Strengths of this review:
1-This review summarized 48 single center studies.
2-Relevant data was rigorously identified and abstracted, articles were translated, information was clarified with a majority of primary study authors.
3- reasons for diversity in the published literature were explored.
Weakness of this review :
1-one-third donors were lost to follow-up.
2-Most of the studies also did not have an internal control group, making it difficult to interpret the donor results.
3-long-term squeal after donation may be underreported,
4-Among the controlled studies protein uria and GFR were assessed in a similar manner in both donors and controls, with observed differences suggesting a true difference between the groups
5-inconsistent methods of measuring and reporting protein uria and renal function in the primary studies complicate the interpretation of these results.
The level of evidence provided by this article: level 5
Please reflect on the guidelines provided above and on your practice.:
Persistent protein urea and low GFR ,excluded from donation
ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation. (C2)
Please summarise this article in your own words :
What is the level of evidence provided by this article?
Please reflect on the guidelines provided above and on your practice :
The meta-analysis addressed the development of proteinuria, and the GFR changes after kidney donation compared to healthy non-donor control.
Any study where 10 or more healthy adults donated a kidney, and proteinuria, or GFR was assessed at least 1 year later. Bibliographic databases were searched until November 2005.
2886 citations were screened, 262 full-text articles were retrieved, and 62 studies met criteria for review. 48 studies from 27 countries followed a total of 5048 donors. An average of 7 years after donation (range 1–25 years),
Controls were healthy volunteers, or individuals under evaluation as potential donors, with similar age, sex, race, and / or, height distributions as donors.
Pre-donation:
The average GFR was 111 ml/min.
No donors had overt proteinuria before surgery.
Average SBP 121 and DBP 77
The method of protein measurements and the threshold for clinical proteinuria varied.
44 studies described the method of GFR estimation, variable.
Incidence of proteinuria
The pooled incidence of proteinuria was 12%
Proteinuria appeared to be increased after donation in 3 studies, the 24-h urine protein was higher in donors compared to controls an average of 11 years after donation (controls 83 mg/day, donors 147 mg/day), and became more pronounced with time.
The pooled risk of microalbuminuria after kidney donation was 3.9
Kidney function after donation
The average GFR was 86 ml/min.
The average decrement in GFR after donation was 26 ml/min (per 1.73m2)
In eight studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min and 0.2% a GFR less than 30 ml/min.
Risk of reduced kidney function
An initial decrement in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6–15; difference not associated with time after donation (P.0.2)
Pre-donation prognostic features
Men were reported to have larger increases in proteinuria after donation
There was no reported association with proteinuria post- donation in the following: the time after donation and the amount of proteinuria at last follow-up, donor age at the time of surgery, nor pre-donation blood pressure.
There was no association in the decrement in GFR after donation with the following; gender differences, older donors, pre-donation obesity, plasma uric acid, and serum cholesterol, race difference, and the time after donation was not associated with post-donation GFR or change in GFR.
Limitations:
The results are inherently limited by the quality of the primary studies.
There was significant heterogeneity between the studies
About one-third donors were lost to follow-up.
No control group in most of the studies, making it difficult to interpret the donor results. Those studies, often, recruited participants from the general population. Such individuals are not as fit as donors, which may have biased towards demonstrating no increased risk of certain medical conditions after donation The long-term sequelae after donation may be underreported
The inconsistent methods of measuring and reporting proteinuria and renal function in the primary studies.
Level 2a systematic review with heterogenous cohort.
Potential donors with eGFR less than 80 generally excluded. Those with abnormal ACR or PCR, confirmed by 24 h urine protein if abnormal will be excluded.
Donors followed annually with BP, renal function/ eGFR and UPCR.
Please summarise this article in your own words
Post donation the remnant nephron cell mass will decrease and this can lead to hyperfilteration and proteinuria with ultimately renal damage.
Primary questions in this review
Proportion of kidney donors developing proteinuria or eGFR less than 60ml/min
Kidney donors have higher urine protein than non donors??
Do kidney donors as compared to controls have accelerated loss of GFR
In this review total donors from 48 studies and 27 countries were included. Total donors were 5048.
24 hours urinary proteins and GFR were assessed after 1-25 years with average at 7 years
Findings
Proteinuria
24 hour urine protein was at 154 mg/day. This was slight higher than controls
Proteinuria > 300 mg/day was seen in 10% donors.
GFR
GHR was lower than controls after 10 years. On average the GFR was 86 ml/min.
<30 ml/min was seen in 0.2% and 30-59 ml/min was seen inn 12%.
Conclusion
Renal donation is associated with slight increase in proteinuria bit not associated with long term reduction of GFR.
Post donation there should be annual screening for proteinuria and Creatinine check.
What is the level of evidence provided by this article?
Level of evidence 111
Please reflect on the guidelines provided above and on your practice.
I will take detailed medical history and also review full investigations. I will take into consideration the effect of kidney donation on donor in term of cardiovascular risks and kidney disease.
Our department does not accept kidney donation if eGFR is less than 80
we do regular follow up with history, blood pressure, fasting glucose and assessment of proteinuria.
– The decrease in renal mass can lead to remnant
single nephron hyperfiltration, with proteinuria
and rapid decline of the kidney function.
This study discussed the effect of kidney donation on proteinuria and GFR .
This study evaluated 48 studies that followed a total of 5048 donors for an average of 7 years.
Before donation the average age of donors was 41 years , the average serum creatinine was 81 mmol/l and the average GFR was 111 ml/min , the average systolic BP was 121 mmHg , and the average diastolic BP was 77 mmHg ,the average pre-donation urinary protein was 95 mg per day in 6 studies also some studies compared them with matched controls.
33 studies mentioned the donors who died whom was 0-16%, 2 died out of renal failure and 10 lived with renal failure, others suffered cardiovascular diseases.
The incidence of proteinuria occurrence post donation is variable but some studies stated it to be >20% while others stated it to be 5%.
3 studies compared proteinuria in donors to controls revealing that proteinuria can increase after donation as the 24-h urine protein was higher in donors compared to controls for an average of 11 years post donation which increased with time as well.
Other study published that the pooled risk of
microalbuminuria after kidney donation was 3.9.
22 studies noticed that the average decrease in GFR after donation was 26 ml/min.
8 studies showed that within mean of 10 years after donation, 40% of donors developed a GFR between 60 -80 ml/min, 12% of donors developed a GFR between 30 -59 ml/min , and 0.2% a GFR <30 ml/min (per 1.73 m2).
Also studies showed that post-donation GFR was 10 ml/min / 1.73 m2 less in donors compared to controls.
Pre-donation prognostic features with higher proteinuria or lower GFR after donation included possible male gender while others mentioned that female gender was associated with lower GFR .
Duration , blood pressure and age of donor did not corelate in some studies while others stated that older donor age was associated with lower GFR and one study mentioned that HTN was associated with decrease in GFR .
Pre-donation obesity, plasma uric acid and serum cholesterol were not associated with the postdonation GFR.
Discussion
This quantitative review showed that kidney donation can lead to increased proteinuria with time due to hyper filtration occurring due to decreased renal mass, meanwhile accelerated decrease in GFR over that anticipated with normal aging was not noticed.
Weakness and strength of this article
This study included 48 single center studies.
Important data was analysed exploring variability in published information.
Meta-analysis results were limited by the quality of the primary studies with lost donors in the follow up and some studies did not include an internal control group.
Another drawback is that some studies included controls from general population whom could be less healthy than donors revealing biased results of the comorbidity liability in donors.
Methods of assessing and recording proteinuria and GFR were variable rendering evaluation complicated.
For general population, low GFR and proteinuria can be signs of systemic atherosclerosis, with subsequent metabolic disturbances, premature mortality, cardiovascular disease, and renal failure.
Kidney donors experience low GFR or low-grade proteinuria through different mechanism, and their prognostic importance is uncertain ,in fact small decline in GFR and mild increase of proteinuria must not be an obstacle in front of donation.
This review did not include ECD , other donors whom developed ESRD in this study could possibly be having genetic liability to develop renal diseases.
The decision of accepting living donor with high possible risk is mandatory to be done through expert MDT assessment , informing the donor of all the possible long term hazards.
As long as living kidney donors are at higher risk of renal drawbacks , long term follow up is needed on the other hand the specific renal screening tests are not well established.
It is recommended to have lifelong follow up of those donors till the prognostic importance of proteinuria and low GFR are noticed.
– Level of evidence is level III as it involved retrospective primary studies
– Donors with mild proteinuria or with mild reduced GFR can be enrolled as ECD and furtherly assessed and different aspects have to be evaluated by MDT before deciding to include or decline them.
Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression
Summary of the Article
This is a systematic review meta-analysis and meta-regression of 262 full-text articles and 62 studies after fulfilling the required criteria for the study. Reasons for different estimates in the literature were explored using meta-regression.
In the general population, low GFR and proteinuria may be signs of systemic atherosclerosis, and both are associated with concurrent metabolic disturbances, future premature mortality, cardiovascular disease, and kidney failure. kidney donors develop reduced kidney function or low-grade proteinuria through a different mechanism, and their prognostic significance in this segment of the population remains uncertain.
The primary questions of this review were:
1) What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min?
2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein?
3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
The Study’s Outcome
1. There is small increase in proteinuria after kidney donation with tendency to progress over time which was explained by single nephron hyperfiltration after reduced renal mass.
2. The proportion of donors who develop clinical proteinuria appears to be higher than expected in the general population – whereas kidney donation increases urinary protein often within the range considered normal, approximately 10% of donors exceed a threshold of 300 mg/day over a subsequent decade.
3. Ten years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls. 12% of donors developed a GFR less than 60 ml/min during follow-up. Although some donors may have been predestined to develop such a GFR even if they had not donated a kidney, a decrement of 10 ml/ min after their nephrectomy likely hastens this event. However, after the initial decrement in GFR from the nephrectomy, there was no evidence of an accelerated loss in GFR over that anticipated with normal aging.
4. Donors undergo rigorous evaluation and selection, and their incidence of death is lower than the general population.
5. A lifetime of annual serum creatinine and urine protein screening would be advocated until the prognostic significance of low-grade proteinuria or reduced kidney function in some kidney donors is better understood.
Suggestions raised by the study
1. Without evidence of adverse health outcomes, small changes in measurements of proteinuria or GFR should not be the sole reason for deterring a practice which benefits recipients, donors, and society.
2. It is important to consider that many donors may have a genetic predisposition to developing kidney disease, and a total of 10 donors (0.2%, one in 500 donors) in this review were reported to have developed kidney failure requiring dialysis.
3. Results from this quantitative review will be best confirmed by the completion of a large, prospective, multi-center cohort study with representative numbers of donors and appropriate controls followed for extended periods of time.
The Strength of the study
1. This review summarized 48 single center studies.
2. Relevant data was rigorously identified and abstracted, articles were translated, information was clarified with a majority of primary study authors.
3. Reasons for diversity in the published literature were explored.
4. Reasons for mathematically combining certain results were justified.
Limitations of the study
1. About one-third donors were lost to follow-up.
2. Most of the studies did not have an internal control group, making it difficult to interpret the donor results.
3. The long-term sequelae after donation may be underreported.
4. The inconsistent methods of measuring and reporting proteinuria and renal function in the primary studies complicate the interpretation of these results. For example, only a few studies reported post-donation GFR in categories consistent with modern cutoff points used to assess renal function.
5. In most studies it was unclear whether donors who developed a low GFR also had concurrent hypertension and proteinuria.
What is the level of evidence provided by this article?
This is a systematic review and meta-analysis
Level of evidence grade I
Please reflect on the guidelines provided above and on your practice.
In our practice, we don’t proceed or accept a potential kidney donor with proteinuria or low GFR.
The provided review article with level of evidence 5, included forty-eight studies from 27 countries followed a total of 5048 donors an average of 7 years (median 6, range 1–25 years after donation), and were published from 1973 to 2005.
The primary questions of this review were: (1) What proportion of kidney donors develop proteinuria or a glomerular filtration rate (GFR) less than 60 ml/min? (2) Do kidney donors, compared to healthy non-donor controls, have a higher urinary protein? (3) Do kidney donors compared to controls have an accelerated loss of GFR after the initial decrement from their nephrectomy?
– Before surgery, over all studies, the average age of donors was 41 years
– Average serum creatinine was 81 mmol/l
– Average GFR was 111 ml/min (range 91–132),
– Average systolic blood pressure was 121 mmHg (range 107–132), and
– Average diastolic blood pressure was 77 mmHg (range 75–79).
– No donors had overt proteinuria before surgery
The incidence of clinical proteinuria after donation was quantified in 42 studies, which followed 4793 living donors an average of 7 years.
Results
– Kidney donation resulted in small increases in urinary albumin, which increased with the time after donation-154 mg/day which is higher than control
– Albuminuria was attributed to a single nephron hyperfiltration from a reduced renal mass.
– 10 years after nephrectomy, donors had a GFR that was 10 ml/ min lower compared to controls.
– Approximately 12% of donors developed a GFR less than 60 ml/min during follow-up.
In conclusion, patients with normal albumin excretion in the pretransplant period are at low risk to develop proteinuria post kidney donation, No evidence of an accelerated loss in GFR over that anticipated with normal aging.
method:
We looked at any trial in which at least 10 healthy persons donated a kidney and either proteinuria or the glomerular filtration rate (GFR) was measured at least one year after the donation.
A total of 5048 donors were tracked by 48 studies that came from 27 different nations. After an average of seven years (the range is one to twenty-five years), the average amount of protein in the donor’s urine for 24 hours was 154 mg/day, and the average GFR was 86 ml/min. In the eight studies that reported GFR in categories, 12% of donors produced a GFR that was between 30 and 59 ml/min (range: 0–28%), while 0.2% of donors developed a GFR that was less than 30 ml/min (range: 0–2.2%). Urinary protein was found to be higher in donors in controlled studies, and this difference became more pronounced over time (three studies with a total of 59 controls and 129 donors; controls had an average of 83 mg/day, while donors had an average of 147 mg/day; the weighted mean difference was 66 mg/day, and the 95% confidence interval (CI) ranged from 24–108).
Results:
An initial decrease in GFR after donation was not followed by accelerated losses beyond those anticipated with normal aging (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6–15; difference not associated with time after donation (P less than 0.2)). Donating a kidney leads to negligible elevations in the amount of protein found in the urine. After an initial decrease in GFR, there is not a significant acceleration in loss during the ensuing 15 years. In subsequent research, we will be able to get more accurate estimations and identify those donors who have the lowest risk of developing a long-term morbidity.
Level of evidence:
· This is a systemic review and meta-analysis; hence level of evidence is 1.
Please reflect on the guidelines provided above and on your practice.
I think the close monitoring of proteinuria post donation is very important at regular interval.
we are reviewing our donors ever 3 month in the first year then every 6 month ,then yearly.
the Alb/creatinine and Pro/creatinine shiuld be routinely assessed.
Dear colleagues and fellows,
Many of you have labeled this publication as level 1 evidence just by reading the words meta-analysis or met-regression.
Level 1A evidence is a meta-analysis of well-conducted RCTs.
Are these RCTs?
Are these studies, included in the analysis, uniform type? Many of them are just follow-up studies without controls.
There is an expression used GIGO for meta-analysis or systematic reviews. Apologies for using GIGO, a swear word; garage in, garbage out.
In other words, a meta-analysis is as good as the weakest link in that study. Please go back and review and let us know what level of evidence this publication is.
Ajay
As per Oxford criteria its level V of evidence from systematic reviews of descriptive and qualitative studies (meta‐synthesis) can not be level 1 as its not contain even single RCTtrail.
Proteinuria and reduced kidney function in living kidney donors; A systemic review, metanalysis, and meta regression.
A significant reduction in nephron mass post donation, may be a result in a single kidney hyperfiltration and the associated development of proteinuria and reduced kidney function.
This was the results of multiple studies done in this field, However, 48 studies done in 27 countries, followed a total of 5048 donors, average of 7 years, from 1973 to 2005.
All donors before surgery data was;
Control group.
41 studies, describes methods of urinary proteinuria, quantification methods, as 24 hrs, other was spot samples, where some were, by dipstick.
Threshold of proteinuria, were variables between studies, ( >100, >150, >200, >300, >500, >600 mg/g.
44 studies, describes, methods of GFR estimation, some using urinay Cr Cl, some with inulin, and other with radioisotopes, while some using predicted equation, and 61% reports GFR to standard 1.73m2.
Death, kidney failure, and CVD;
33 studies describe No. of donors who died during follow up.
2 donors died because of kidney failure, range between 0-16%.
10 donors live with kidney failure.
Proteinuria;
Described in 42 studies followed 4793 live donors, with variable level of proteinuria described by dtudies, with pooled incidence of proteinuria was 12% , but studies described level of 10%.
Risk of proteinuria;
3 studies compare a total of 129 donors, to 59 controlls on 24 Hrs urinary protienuria, found that proteinuria increased post donation.
24 Hrs proteinuria were higher in donors compared to controll group, with median follow up of 11 Yrs.
4 studies contain 146 donors compared to 105 control, describes urinary albuminuria; 2 of the studies, urinary albuminurea, was 56 mg higher than control, other 2 studies obsrve that risk of microalbuminuria post donation and found that 67 donors vs 51 control at 2nd and 13 yrs post donation, found that pooled risk of microalbuminuria post donation was 3.9.
kidney function after donation; 36 studies, involve 3529 donors reported post donation Cr and GFR, for 6 yrs, average Cr was 98 micro mol/l, and average GFR was 86 ml.min, with variables among studies, found that the risk of pooled data post donation GFR was 10 ml/min lower in donors compared to control; 96 ml/min in control, with 84 ml/min in donors.
discussion ;
In this quantitative review, kidney donation resulted in small increase in uACR, which increasing with time post donation.
This may be explained by hyperfilteration from reduce nephron mass.
10 yrs post donation kidney has decrease GFR by 10 ml/min compared to control, 12% of donors develop reduce GFR < 60 ml/min.
Renal sequele , donors selection;
Long term surveillance, found that proportion of donors develop clinical proteinuria was higher than expected, where as kidney donation associated with increase urinary protein excretion , 10% of donors exceed threshold of 300 mg/dl over decades.
12% of donors develop GFR < 60 ml/minwithin the same period.
live donation data which summarized in this review , results in no evidence of HTN , proteinuria, and reduced kidney function before donation , some centers accept GFR < 80 ml/min, some donors have genetic predisposition to develop kidney failure, 10% develop ESKD necessitating dialysis.
Level of Evidence ((I)).
In our facility where primary selection of coupled D/R selection prepared , donors with high risk index ; donor with reduce GFR, proteinuria 24 hrs > 150 mg/g, underwent specific masures to re esimate the donor inluding history , retesting and imaging , family running renal diseases and chronic dieases associated with proteinuria , matched with age of donor .
Persistant high level of proteinuria and/or reduce renal function in form of Crcl or eGFR, may be excluding from donation , unless there is corrected factor that involve in cause such abnormality.
Well done,Kamal
Please summarise this article in your own words
– A critical reduction in renal mass may result in remnant single nephron hyper filtration, with associated proteinuria and an accelerated loss of kidney function.
-However, the long-term implications of donating a kidney remain uncertain.
The primary questions of this review were:
1-What proportion of kidney donors develop proteinuria or a
glomerular filtration rate (GFR) less than 60 ml/min?
2-Do kidney donors, compared to healthy non-donor controls,
have a higher urinary protein?
3-Do kidney donors compared to controls have an accelerated loss of GFR after
the initial decrement from their nephrectomy?
– 48 studies from 27 countries followed a total of 5048 donors.
-An average of 7 years after donation (range 1–25 years), the
average 24 h urine protein was 154 mg/day and the average
GFR was 86 ml/min.
-In 8 studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min (range 0–28%), and 0.2% a GFR less than 30 ml/min
(range 0–2.2%).
-The average age of donors was 41 years .
-The average serum creatinine was 81 mmol/L.
-The average GFR was 111 ml/min.
-The average systolic blood pressure was 121 mmHg.
– The average diastolic blood pressure was 77 mmHg.
– No donors had overt proteinuria before surgery.
### Controls were healthy volunteers, or potential donors, with similar age, sex, race, and / or, height distributions as donors.
– The method in 41 studies is ( 24 h urine protein ) and Other is random , a timed urine albumin, a random urine albumin to creatinine ratio.
– (44) studies described the method of GFR estimation, which usually was a timed urine creatinine clearance.
Incidence of proteinuria
– The pooled incidence of proteinuria was 12%.
-The 24-h urine protein was higher in donors compared to controls an average of 11 years after donation.
– This difference increased with the time from donation.
Risk of proteinuria
– 3 studies compared a total of 129 donors to 59 controls
on 24-h urine protein, to determine if increases in proteinuria after donation were above that possibly attribute- to normal aging.
– Proteinuria appeared to be increased after donation in each of these three studies, although the CIs were wide.
The 24-h urine protein was higher in donors compared to controls an average of 11 years-
after donation (controls 83 mg/day, donors 147 mg/day,
weighted mean difference 66 mg/day, and 95% CI 24–108).
(4) studies compared a total of 146 donors to 105 controls on 24-h urine albumin.-
– There was evidence of extreme statistical heterogeneity between
these studies; thus results were not mathematically pooled (w2
57.4, Po0.00001, I2 ¼ 95%).
-In 2 of the 4r studies, 24-h urine albumin was approximately 56 mg higher in donors-
compared to controls 14 years after donation.
Kidney function after donation
– 36 studies of 3529 donors reported a post donation serum creatinine or GFR with an estimate of variance, the average time after donation was 6 years
– The average serum creatinine was 98 mmol/l
– The average GFR was 86 ml/min (per 1.73 m)
– The average decrement in GFR after donation was 26 ml/min(per 1.73 m2)
-The average post-donation GFR.
After 10 years of donation
– 40% of donors developed a GFR between 60 and 80 ml/min (per 1.73 m2)
-12% of donors developed a GFR between 30 and 59 ml/min (per 1.73 m2) ** 0.2% a GFR less than 30 ml/min (per 1.73 m2 )
Risk of reduced kidney function
-The average follow-up was at least 5 years after donation.
-The pooled post-donation GFR was 10 ml/min (per 1.73 m2) lower in donors compared to controls.
Pre-donation prognostic features
– Men were reported to have larger increases in proteinuria after donation
– N0 reported association between the time after donation and the amount of proteinuria at last follow-up.
– Neither donor age at the time of surgery, nor pre-donation blood pressure was associated with proteinuria after donation.
– Compared to men, women were reported to have a lower GFR both before and after donation.
– There was no gender differences in the decrement in GFR after donation.
– older donors demonstrated a lower GFR both before and after donation
– The decrement in GFR after donation in older donors is similar to younger
– Pre-donation obesity, uric acid, and cholesterol were not associated with the post-donation GFR decreased .
– Black and white donors were similar in their renal response to donation.
Limitaion of study
– Results are influenced by the quality of the primary studies.
– One-third donors were lost to follow-up.
-Most of the studies also did not have an internal control group, making it difficult to interpret the donor results.
-A proportion of donors would have developed certain medical conditions even if they had not donated a kidney.
– A control group often, recruited participants from the general population. ** long-term sequelae after donation may be underreported, if transplant centers were
reluctant to describe significant morbidity after this perceived iatrogenic event.
-In most studies it was unclear whether donors who developed a low GFR also
had concurrent hypertension and proteinuria
Strengths in the study
Among the controlled studies proteinuria and GFR were assessed in a similar manner in both donors and controls, with observed differences suggesting a true difference between the groups.
Renal sequelae, donor selection, and long-term surveillance
– Donors undergo rigorous evaluation and selection, and their
incidence of death is lower when compared to general population.
– Living donors in this review demonstrated no evidence of hypertension, proteinuria or reduced kidney function before donation.
– Some donors may have a genetic predisposition to developing kidney disease
routinely screening the general population.
– Living donors are at higher risk of renal sequelae
– It is unclear which renal screening tests and how long donors should be followed, and which health care providers for follow up to prevent the morbidity after donation
-We advocate for annual serum creatinine and urine protein screening
What is the level of evidence provided by this article?
– Level eivdence I meta-analysis
Please reflect on the guidelines provided above and on your practice.
In our hospital :-
1-Dipistic urine analysis at least 2 time
2- Urine analysis sample
3- Urine collection for 24 h
4- Spot urine (ACR+PCR )
###Spot urine test as albumin:creatinine ratio >30mg/mmol or protein:creatinine ratio >45mg/mmol.
-Proteinuria may be increased by a factor of 2-3 times by strenuous exercise or fever.
-We exclude patients with proteinuria >300 mg/day,while others use a lower threshold of >150 mg/day.
Thank you Mahmoud