2. A 65-year-old male had a previous transplant which failed due to chronic allograft nephropathy (CAN), now has a BMI 40 with massive truncal obesity. He was offered a kidney from his son with 222 mismatch, DSA (B40 with MFI 1645 and Cw15 with MFI 6532), and the flow cytometry crossmatch (FCXM) is negative.
- What do you think about this match?Any problem with it?
- What is effect of BMI of 40 on the outcome of transplant?
- How would you manage this case?
- What is effect of HLA C DSA on the outcome of transplantation?
– 6 mismatches,so high risk of acute rejection
– High BMI >can lead to Anaesthesia complication ,surgical complication ,post operative pneumonia ,atelectasis ,cardiovascular effects ,DVT ,post transplantation DM ,dyslipidemia
– better weight reduction ion :decrease BMI so induction with Thymoglobulin +methyleprednisone ,maintenance with Tacrolimus+MMF and prednisone.
And better ,transplant in those pairs to be avoided as it carries high immunological risk for rejection and hence poor effect on graft survival
And better to go for paired donor exchange
HLA c missmatches affects long term survival of the graft but it is not amajor effect such as DR ,A and B.
– What do you think about this match?Any problem with it?
2- What is effect of BMI of 40 on the outcome of transplant?
3- How would you manage this case?
4- What is effect of HLA C DSA on the outcome of transplantation?
6 mismatches is the case denote he is not his biological son
Increased BMI is well known risk factor associated with unfavorable kidney transplant outcomes and is incorporated for determining transplantation eligibility ,and is an independent risk factor for graft deterioration.
Other risks associated with high BMI are metabolic syndrome, CVS complications, NODM affecting patient survival and quality of life
Obesity related hyperfiltration injury which may have a long term negative impact on graft function
· preoperative weight reduction
· Considering the previous transplant , the patient positive DSAs , we should go for Induction therapy , as long it is with negative FCMXM we can consider Basiliximab.
· 222 mismatch is high level ,it is better to wait for another donor otherwise there is great chance for development of de novo DSA s and AMR early post Tx
· In case of accepting the donor, desensitization protocol is advised with PE, IVIG and Rituximab in addition of maintenance IS including steroids, TAc,&MMF
· Also, DSA monitoring is needed in addition to protocol Biopsy for the first year post Tx
It can lead to poor graft survival ;HLA Cw mismatch is associated with ABMR.
Referencs
– Tran TH, Döhler B, Heinold A, Scherer S, Ruhenstroth A, Opelz G. Deleterious impact of mismatching for human leukocyte antigen-C in presensitized recipients of kidney transplants. Transplantation. 2011 Aug 27;92(4):419-25.
What do you think about this match?Any problem with it?
-Father and son must have single haplotype . There is doubt .
What is effect of BMI of 40 on the outcome of transplant?
– associated with increased risk of hypertension, diabetius and ischemic heat disease.
– difficult to achieve target of immunosuppression.
-high risk of DGF.
– increase risk of surgical complications and infection.
How would you manage this case?
– consultation to dietary on.
– GLP1 for weight reduction.
– avoid herbal or orlistat it will affect drug absorption or trough level .
– discuss until BMI less than 30 .
– post-transplant follow up with DSA within 3 month and at 1 year post-transplant.
What is effect of HLA C DSA on the outcome of transplantation?
– increase risk of early acute rejection with poor graft survival and vascular inflammation.
Considering the fact that the donor is the son, at least 3 matches should be present, however 6 mismatches is the case then he is not his son
Body mass index (BMI) is a known risk factor associated with poor kidney transplant outcomes and is incorporated for determining transplant candidate eligibility. And is considered an independent factor for graft deterioration.
On the other hand other risks associated with high BMI , trunkal obesity may predispose to metabolic syndrome, Cardivascular complications, NODM affecting patient survival and quality of life
Obesity itself may casuse hyperfiltration injury which may have a long term negative impact on graft function
· Advice for weight reduction before surgery
· Considering the previous transplant , the patient positive DSAs , we should go for Induction therapy , as long it is with negative FCMXM we can consider Basiliximab os Alemtuzumab
· 222 mis maches is high level mismatch , if ther is a chance to deny and wait for another donor would be the best option other wise there is a high chnce for denovo DSA s and AMR early post Tx
· If no other way but to accept the donor the desensitization protocol is advised with PE, IVIG, Rituximab
· Mainenace IS: steroids, TAc,MMF
· Frequent monitoring DSA, protocol Biopsy for the first year post Tx
Of clinical significane on graft rejection if added to HLA-B mismatches
The son has not haploid match at least, so may be adopted son not blood related son.
Obesity is associated in some studies with postoperative wound infection and surgical hernias. Most centers would ask the patient to lose weight first before undergoing kidney transplantation.
1- advice the patient to perform Bariatric surgery for weight reduction prior to transplantation.
2- decline the current donor, find a better matched potential donor.
In a study by Tran et al (2011), HLA-C mismatch was associated with poor graft function.
reference:
1- Tran TH, Döhler B, Heinold A, Scherer S, Ruhenstroth A, Opelz G. Deleterious impact of mismatching for human leukocyte antigen-C in presensitized recipients of kidney transplants. Transplantation. 2011 Aug 27;92(4):419-25. doi: 10.1097/TP.0b013e318224c14e. PMID: 21743387.
The donor should be half- haplotype if he is a biologic son. So he is fully mismatched donor with moderate titer of HLA -B DSA and high titer HLA-C and is not an ideal donor in his case.
Q2:
The Era of obesity in kidney transplantation is controversial. Some centers consider these recipients having worse outcome. There is a high incidence of wound healing problems incisional hernia, NODAT, prolonged hospital stay and operation time, DGF and HTN in obese patients. Due to truncal obesity he has increasing cardiovascular and surgical risk. Dietician consultation is necessary. Bariatric surgery before or after TX has same mortality as general population. But there are concerns about malabsorption and alterations in immunosuppression drug levels.
Q3:
This donor is not a desirable one in this case so consider paired kidney exchange and finding a donor without DSA is preferred.
Q4:
Although some controversies but HLA-C DSA can activate complement pathway and is associated with poor transplant outcome.
What do you think about this match? Any problem with it?
His son’s kidney had 2-2-2 mismatches, which is completely mismatched. Usually, son has haploid matches with father, so complete mismatches showed he is not the son of the patient. The patient had DSA towards HLA-B40 with MFI -1645 and Cw15 MFI 6532.
What is effect of BMI of 40 on the outcome of transplant?
Dialysis Outcomes and Practice Patterns Study (DOPPS), the lowest relative risk of death was seen in the group of dialysis patients with a BMI of 30-34.9
Complication’s obesity post transplantation includes
· increased delayed graft function
· wound infection, prolonged hospital stays.
· increased risk of acute rejection and decreased graft survival.
Obesity in the transplant recipient is associated with an increased risk of
· hypertension
· diabetes mellitus
· hyperlipidaemia
· chronic renal failure
· CVD
How would you manage this case?
First, this patient is obese with BMI more than 40, which consistent studies shown that poor graft and patient survival, higher CVD death and development of NODAT. Although patient mortality is better after kidney transplantation than being in dialysis, but the benefit is least observed in BMI more than 40. I would suggest patient to be seen in obesity clinic and evaluate the measures for losing weight.
Bariatric surgery has been proven to be safe and helpful in reducing weight and increasing access to kidney transplantation There is no consensus regarding the optimal timing and the ideal type of bariatric surgery, although sleeve gastrectomy seems to be associated with a reduced risk of postoperative complications. Some studies shown that posttransplant bariatric surgery may result in better graft survival and function but also in a high rate of postoperative complications Not only that, but most centres will also not proceed with transplantation. In our centre, we only accept BMI less than 30 as a criterion for transplantation. But it’s down to each centre and their practices.
Second, this is not the right kidney for transplantation. 6 mismatches and high risk for surgical complications are difficult to convince transplant surgeon to proceed with surgery. I would suggest the patient to look for a better matched kidneys or shall proceed with more suitable deceased donor transplantation or enrol in paired kidney exchange program.
What is effect of HLA C DSA on the outcome of transplantation?
Frohn et al showed that HLA-A/-B mismatch was strongly associated with HLA-C mismatch as a result of linkage disequilibrium. HLA -B mismatch was weakly correlated with rejection probability. Univariate analysis showed HLA-C had is strongly influenced on graft survival. It also showed that B cell mismatches when happened together with HLA-C is associated with independent factor in acute rejection.
Albert et al showed increased incidence of AMR in patient with anti-HLA DSA. Moreover the study showed presence of DSA at day 0 in anti-C group more likely to experience AMR. So,the presence of pretransplantation HLA-C DSA appeared to have higher risk of AMR.
Effect of HLA-C matching on acute renal transplant rejection
HLA-C
· Induces an antibody response and presents peptides similar to HLA-A,B,and DR
· Elevated cytotoxic lymphocytes precursors noticed in otherwise matched bone marrow transplant
HLA Typing
· HLA-A,B mismatched strongly correlated with HLA-C mismatch due to linkage disequilibrium
· HLA-B one mismatched, HLA-C found to have impact in rejection
· No influence of C mismatch was seen in the subgroup of the patients with o additional B mismatches
Graft survival
· Leaning towards better graft survival in HLA-C matched pairs
References
Complete mismatch is associated with higher rates of Delayed graft functions , de novo DSAs and acute rejections, leading to inferior long term graft survival .he is considered high risk and he should be counselled about it
Regarding his BMI , studies reported controversial results about effect of obesity on outcomes of renal transplantation, main effect include wound complications , some studies reported increased incidence of DGF ,others said no difference regarding DGF or graft survival
Johnson DW, Isbel NM, Brown AM, Kay TD, Franzen K, Hawley CM, Campbell SB, Wall D, Griffin A, Nicol DL. The effect of obesity on renal transplant outcomes. Transplantation. 2002 Sep 15;74(5):675-81. doi: 10.1097/00007890-200209150-00015. PMID: 12352885.
I would offer him desensitization in the form of 4 plasma exchanges, IVIG and retuximab then check its effect on Cw15
Then proceed with induction agent thymoglobulin, tacrolimus, MMF and steroids
Effects of HLA C antigens are highly antigenic and can activate both cellular and humoral immune responses , HLAC DSAs are able to recognise donor cells and fix complement and are associated with acute rejections with poor long term graft survival
Frohn C, Fricke L, Puchta JC, Kirchner H. The effect of HLA-C matching on acute renal transplant rejection. Nephrol Dial Transplant. 2001;16(2):355-360.
What do you think about this match? Any problem with it?
This is a high immunological risk with 222 mismatches, DSA positive with a high level.
What is the effect of BMI of 40 on the outcome of transplant?
Obesity is associated with high surgical complications like wound infection, hernia, dehesion, prolonged hospital stay, anaesthesia complication, difficult and prolonged surgery, DGF, AR
These transplanted patients are more liable to DM post-transplantation, hypertension, cardiovascular complication.
How would you manage this case?
· Discus with the patient about the immunological risk, and the better choice to donor exchange or deceased donor
· Counsel him about the obesity risk and the need to reduce his weight before surgery, through exercise, diet advice, drug-like GPL1 agonist, behavioural changes or if these measures fail by bariatric surgery.
(multidisciplinary team cooperation needed. Includes physician, dietician, psychiatrist, psychotherapist, patient,s support group)
· Though cardiac assessment
desensitization
· He needs ATG induction in the second transplant, Maintenance with Talc + MMF+ steroid which better to withdrawn after graft function stabilization
DSA monitoring after transplantation with possible protocol biopsy
What is the effect of HLA C DSA on the outcome of transplantation?
HLA-C DSA associated with increased risk of ABMR
What do you think about this match?Any problem with it?
Yes,it considered high risk due to six antigen mismatch with DSA ; the problem may be early attack of AMR
What is effect of BMI of 40 on the outcome of transplant?
Obesity is one of risk factor in kidney transplant due to it effect in wound healing and risk factor for developing FSGS
How would you manage this case?
This high risk patient so
Induction with ATG and tac ,MMF ,predinsilone as maintenance
What is effect of HLA C DSA on the outcome of transplantation?
The DSA to HLA C considered as high risk for rejection with this high MFI 6532 ; but with negative FCXM we can proceed with induction by lymphocyte depleting agent like ATG with serial follow up by cPRA
●What do you think about this match?Any problem with it?
Yes it is probably high risk there is 6 mismatches
And mfi cw15 more than 2000
Obesity .
●What is effect of BMI of 40 on the outcome of transplant?
It is morbid obese tx as any abdominal surgery it will take longer time with higher incidence of infection
Delayed graft function.
.●How would you manage this case?
We should refer to nutrition specialist and to loose weight and go for sleeve operation ..
Then consider doner it is better to look for another doner .
If nor possible induction with AtGAnd plasma phersis .
●
What is effect of HLA C DSA on the outcome of transplantation?
There is a link between HLA_B. /C
It was found then most of HLA_B mismatches are also HlA _c positive.
Reference
Hand book of transplantation ..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691840/
What do you think about this match?Any problem with it?
Patient and donor has 222 mismatch which means 6 mismatches.
Number of mismatchs gratly affects the graft survival
1 and 2 Mismatchs at HLA-DR were associated with 12% and 15 % Higher risk for graft failure
The patient has anti HLA-B 40 DSA with high MFI 1645 and anti HLA-Cw 15 DSA with high MFI 6532 which was associated with high risk of acute rejection within first year.
So this patient is sensitized by previous transplantation
And has DSA with MFI more than 3000
Also this donor should had half haplotype from his father so he is not biological son.
What is effect of BMI of 40 on the outcome of transplant?
DGF is the most consensual complication observed in obese patients which may be due to longer surgery time required for kidney implantation in obese patients which may predispose to additional complications.
Based on a cohort study done by Y. Foucher et al. report that obesity does not significantly increase the risk of urologic or vascular complications or graft loss, but seems to increase the risk of cardiac and infectious complications and the mortality.they also reported higher risk of death explanations for the increased risk of death with a functioning graft and higher risk of graft failure for the obese group are the higher incidence of NODAT, more serious bacterial infectious diseases and more cardiac complications.
How would you manage this case?
First evaluation of the patient regarding his cardiac condition,presence of any abesity associated conditions as diabetes
I will refer the patient to nutrition team for weight control and consult for gastric sleeve
About the donor i prefer to find another donor with less mismatch especially at DR
If we must proceed with this donor since the FCXM is negative we can proceed aftet detailed information for the patient about the risk
desensitization by plasma exchange
And induction with ATG
With post transplantation Tacrolimus and MMF And early withdrawal of steroids to minimise the risk of diabetes,wound infection.
What is effect of HLA C DSA on the outcome of transplantation?
Thomas Bachelet et al. Study results showed that preformed anti-HLA-Cw and anti-HLA-DP DSA are as deleterious as anti-HLA A/B/DR/DQ DSA
lead to acute rejection , AMR, and graft loss.
It justifies their inclusion in kidney allocation programs and in immunological risk stratification algorithms.
Reference
Heinbokel T, Floerchinger B, Schmiderer A, Edtinger K, Liu G, Elkhal A, et al. Obesity and its impact on transplantation and alloimmunity. Transplantation. 2013;96:10–6.
Y. Foucher, M. Lorent, L. Albano,Renal transplantation outcomes in obese patients:BMC Nephrology volume 22, Article number: 79 (2021) a French cohort-based study
Thomas Bachelet et al. Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation
Transplantation.100(1):159-66.2016 .
What do you think about this match? Any problem with it?
High risk: previous Tx, MM 222, 2 DSAs against B4 (MFI 1645), Cw15 (MFI 6532).
If he is the biological father for his son, it was expected to have at maximum 3 mismatches not 6 mismatches, it seems that he is not the biological father.
What is effect of BMI of 40 on the outcome of transplant?
1-obesity increases risk for anesthesia-related complications, greater incidence of surgical site infections, increased incidence of urinary tract infections, increased susceptibility to incisional hernias, and longer duration of hospitalization.
2-the degree of recipient obesity is directly correlated with increased complications after transplant and longer operative durations, increased incidence of NODAT, hypertension, and cardiovascular complications.5
3-Obesity affects the degradation and bioavailability of immunosuppression drugs particularly rabbit ATG, IL-2 receptor antagonist, and CNI therapies.6
4-there is no solid figure of BMI when to transplant or not, decision is usually varialble between Tx centers.6
How would you manage this case?
a- Regarding transplanatation:
It is high immunological risk case because of previous Tx, MM 222, 2 DSAs against B4 (MFI 1645), Cw15 (MFI 6532). With negative cross match, so we can proceed for this transplantation and immunosuppression for high immunological risk should be used (ATG-àCNI+MMF+Steroids), However I would rather prefer to put this patient on the paired exchange system looking for more matched donors.
No need for Desensitization as cross match is already negative.
If transplantation is done, he will need to have regular follow up of DSAs.
b- Regarding Obesity and High BMI:
This gentleman needs management of obesity on a MDT level which includes dietician, physical therapist, endocrinology specialist (if hormonal issues), and Bariatric surgeon (potential weight losing surgeries). 6
What is effect of HLA C DSA on the outcome of transplantation?
Some studies showed that there is a linkage between HLA- B/C , HLA C mismatches, turned out to be significantly correlated with Acute rejection episodes.HLA-C antibodies are independently associated with high risk of acute rejection and poor graft survival (7).
References:
1-Proc (Bayl Univ Med Cent)v.34(2); 2021 MarPMC7901397.nephro dial transplantation(2001)16:355-360
2- The Renal Association Assessment of the Potential Kidney Transplant Recipient. The Renal Association. 2011. http://www.renal.org/guidelines/modules/assessment-of-the-potential-kidney-transplant-recipient#sthash.fyh0cWpM.dpbs. [Ref list]
3-Lafranca JA, IJermans JN, Betjes MG, Dor FJ. Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis [published correction appears in BMC Med. 2015;13:141]. BMC Med. 2015;13:111. Published 2015 May 12. doi:10.1186/s12916-015-0340-5.
4- Obesity and outcome following renal transplantation.
Gore JL, Pham PT, Danovitch GM, Wilkinson AH, Rosenthal JT, Lipshutz GS, Singer JS
Am J Transplant. 2006 Feb; 6(2):357-63.
5- Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis.
Nicoletto BB, Fonseca NK, Manfro RC, Gonçalves LF, Leitão CB, Souza GC
Transplantation. 2014 Jul 27; 98(2):167-76
6- Bariatric surgery: a systematic review and meta-analysis.
Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K
JAMA. 2004 Oct 13; 292(14):1724-37.
7- Baan CC, Vaessen LM, ten Kate F et al. Rejection of a kidney graft mismatched only for the HLA-C locus and an HLA-BW22 split. Transplantation 1993; 55: 438±439 } {Chapman JR, Taylor C, Ting A, Morris PJ. Hyperacute rejection of a renal allograft in the presence of anti-HLA-Cw5 antibody. Transplantation 1986; 42: 91±93.
In this patient, different factors are related to poor transplant outcomes.
The recipient and donor are 6 HLA mismatch. The patient has anti HLA-B DSA with high MFI (MFI>1000) and anti HLA-C DSA with high MFI (MFI>3000). Although HLA-A, -B and -DR are more polymorphic and they are strongly associated with patient and graft survival, Recent studies have reported that anti–HLA-Cw and anti–HLA-DP DSA could be associated with an increased risk of acute and chronic antibody-mediated rejection (AMR). Studies suggest that preformed anti–HLA-Cw and anti–HLA-DP DSA are as deleterious as anti–HLA A/B/DR/DQ DSAs. In addition, the patient has a history of previous transplantation. One or two HLA-C mismatching was associated with decreased graft survival and acute rejection among those who were presensitized. Especially patients with high levels of pretransplant HLA-C DSA may be more likely to develop ABMR during the first posttransplant year. Therefore, he is highly sensitized recipient.
On the other hand, he has morbid obesity with BMI>40 kg/m2. Morbid obesity (BMI>30 kg/m2) is an important risk factor for renal transplant recipients and by some transplant centers is considered as an exclusion criteria. Some other programs exclude patients with a BMI greater than 35 or 40 kg/m2 from transplantation. Obese kidney transplant recipients have a higher risk of DGF and surgical complications. Obesity is also associated with prolonged post-transplant hospital stay, higher incidence of post-transplant DM and CVD. However, abdominal obesity is a particular concern.
It is appropriate that high-resolution HLA typing for the donor is performed and if the donor has HLA antigens or their CREGs that the recipient has DSA with high MFI against them, the kidney transplantation will be contraindicated. Even in the absence of unaccepted antigens, because of reasons that I have mentioned, finding another recipient will be the better choice. In addition, weight loss and careful evaluation for cardiovascular risk factors before transplantation are mandatory.
What do you think about this match?Any problem with it?
It is high risk patient due to previous failed transplant and he is sensitized
And this 222 mismatch from the donor which is not his son (may be adopted son )carry high risk of acute rejection and associated with low graft survival
Negative FCXM needs further testing using SAB Technology
.
What is effect of BMI of 40 on the outcome of transplant?
Patiennt BMI of 40 which is morbid obese which associated with high risk of :
-longer hospital stay, higher costs
-increase the risk of wound infection, wound dehiscence
– Delayed graft function (DGF)
-impaired graft survival
-higher incidence of new onset of diabetes after transplantation (NODAT) and increased mortality(3).
How would you manage this case?
Regarding obesity :
Trial of decrease in weight by nutrition specialist through:
*diet , exercise
*GLP1 liraglutide is FDA approved for weight reduction even in non diabetic
*its better to avoid orlistat as it affect cytochrome p450 activity and drug levels
if all lines failed gastric sleeve is indicated…
About the donor:
It is better to find another more matched donor
If we must proceed with this donor :
desensitization by plasma exchange and iv IG
And induction with ATG
Maintenance on triple immunosuppression Tacrolimus and MMF and steroids with early withdrawal of steroids to minimise the risk of diabetes, wound infection.
What is effect of HLA C DSA on the outcome of transplantation?
HLA-C antibodies are independantly associated with high risk of acute rejection and poor graft survival
A lot of risk factors related to this transplantation :
6 mismatches so he is not the biological father for his son
Previouse transplantation
Obesity
Presence of HLA-C DSA
All these factors will affect on the graft function and survival also may cause delay graft function DGF.
The effect of obesity on kidney transplant
WHO define overweight as those people with BMI more than 25 and obese for those with BMI more than 30 ,obese patients already have alot of comorbidities like DM,cardiovascular disease, cancer gallbladder disease and osteoarthritis.
Specifically for those who are candidates for kidney transplant are at higher risks compared to those with normal BMI like wound infection and dehiscen, DGF and graft failure .
Guidelines:
Published European Renal best practice guidelines recommend weight loss in obese patients , KDIGO suggests that weight reduction before surgical procedure doesn’t give much beneficial effects as expected in general population while UK renal association and the kidney health Australia caring for Australians with renal impairment conclude that benefits of kidney transplantation are questionable in potential candidates with BMI more than 40.
References:kidney transplantation in obese patients.(2016,March 24).world journal of transplant, p.135-143.
Obesity and kidney transplantation candidates:how big is too big for transplant.(2012).Am J Nephro,36(6),575-86.
What do you think about this match?Any problem with it?
this son is adopt because of this matching (father and son should have single haplotype match)
What is effect of BMI of 40 on the outcome of transplant?
This patient according to his BMI is classified as very morbid obesity
Few studies addressed the effect of obesity on kidney tranplantation but the main issues are
1) associated with high risk of DGF
2) associated with surgical complications like wound dehiscence and infection
3) associated with increase risk of PTDM , hypertension and ischemic heart diseases
4) difficult to achieve good immunological suppression.
How would you manage this case?
This patient need weight reduction pre-transplant through
1)diet control and exercise and dietitian referral
2) drugs GLP1 liraglutide is FDA approved for weight reduction even in non diabetic patients,also its better to avoid orlistat and herbal drus as it affect cytochrome p450 activity and drug levels
3) laproscopic bariatric surgery roux en y and gastric sleeve but this operation will affect drug absortion and expose patient to risk of malabsorption,2ry oxalosis and hypovitaminosis
Though I will discuss this with the patient that its better to wait until your BMI below 30 to avoid previous risks but no contraindication if he decides to ignore all this and go directly to operation but after extensive cardiac assessment
According to his donor and his immunological risk
As long as flow cytometry crossmatch is negative i will accept this donor without doing desensitization but it’s better to discuss about paired donation and affording him better matching
If not available…go for transportation
day -2 starting of tac 0.1mg/kg and MMF
Biological antibody induction using campth or rATG 3mg/kg and continue of triple conventional immune suppression medications with high trough level tac around 7-10 for the 6m
Post transplant this patient needs
1)Fup DSA in first 3m then at the end of 1st year with protocol biopsy if accepted.
2) strict fracture risk assessment by DEXA scan.
What is effect of HLA C DSA on the outcome of transplantation?
Few studies addressed this issue showed
HLA C DSA associated with risk of early acute rejection , vascular inflammation and poor graft survival specially preformed not donovo.
References
1. Gore JL, Pham PT, Danovitch GM, et al. Obesity and outcome following renal transplantation. Am J Transplant 2006; 6:357.
2. Nicoletto BB, Fonseca NK, Manfro RC, et al. Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis. Transplantation 2014; 98:167.
3. Tzvetanov IG, Spaggiari M, Tulla KA, et al. Robotic kidney transplantation in the obese patient: 10-year experience from a single center. Am J Transplant 2020; 20:430.
4. de Vries AP, Bakker SJ, van Son WJ, et al. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant 2004; 4:1675.
5. Ling M, Marfo K, Masiakos P, et al. Pretransplant anti-HLA-Cw and anti-HLA-DP antibodies in sensitized patients. Hum Immunol 2012; 73:879.
6. Bryan CF, Luger AM, Smith JL, et al. Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C. Clin Transplant 2010; 24:56.
What is effect of BMI of 40 on the outcome of transplant?
Overweight and obesity associated with increased comorbidities after transplantation mainly related to surgical complication like wound infection, hernia ,dehiescnce hematoma ,lymphocele , DGF with increased hospital stay due to sepsis ,in addition to other medical comorbid like increasing rate of PTDM and cardiovascular disease , cancer, OSA , HTN with obesity ,according to the Recent recommendation from KDIOG guideline no contraindication for transplantation because of obesity (as defined by body mass index or waist-to-hip ratio) level (2B)(3) however individualized risk assessment is mandatory especially in the extremes of BMI like 35 and above .
How would you manage this case?
This patient morbidly obese with BMI of 40 associated withincreasedmortality and morbidity as per our local unit protocol any recipient with BMI above 30 he is unfit for kidneytransplantation,he needs proper counselling with dietician endocrine team regarding wt.reduction including diet control and may consider bariatric surgery(open and laparoscopic) Rouxen-Y gastric bypass and laparoscopic sleeve gastrectomy support excellent weight loss (about 50%-60% weight lost at 1year after surgery (1),and based on available evidence this type of surgery not interfere with immunosuppression absorption ,the only concern is on long term the oxalate nephropathy and post operative nutrient deficiencies (1),Like vitamin B12, and zinc deficiencies,Vitamin D deficiencies may emerge and contribute to reduced calcium absorption with secondary hyperparathyroidism (1).
Few case reports address the concern with long term fat malabsorption with associated oxalate nephropathy after bypass surgery .
Pre- transplant Bariatric surgeries With LSG is less invasive with lower morbidity rates (20.5% RYGB vs 6.5% LSG) and comparable degrees of weight loss at 6, 12, and 18 mo, while RYGB appeared to be more efficacious in terms of achieving diabetes remission [4,5).
What is effect of HLA C DSA on the outcome of transplantation
HLA-Cw mismatch is an independent risk for acute rejection if combined with additional B – mismatch and few studies confirm negative effect with HLA- Cw as associated with ABMR (2),
References:
1-Kidney transplantation in obese patients, Minh-Ha Tran, Clarence E Foster, Kamyar Kalantar-Zadeh, Hirohito Ichi, World J Transplant 2016 March 24; 6(1): 135-143.
2-Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation
Thomas Bachelet 1, Charlie Martinez, Arnaud Del Bello, Lionel Couzi, Salima Kejji, Gwendaline Guidicelli, Sébastien Lepreux, Jonathan Visentin, Nicolas Congy-Jolivet, Lionel Rostaing, Jean-Luc Taupin, Nassim Kamar, Pierre Merville.
3-KDIGO guideline 2020.
4- Gehrer S, Kern B, Peters T, Christoffel-Courtin C, Peterli R. Fewer nutrient deficiencies after laparoscopic sleeve gastrectomy (LSG) than after laparoscopic Roux-Y-gastric bypass (LRYGB)-a prospective study. Obes Surg 2010; 20: 447-453 [PMID: 20101473 DOI: 10.1007/s11695-009-0068-4.
5- Chouillard EK, Karaa A, Elkhoury M, Greco VJ. Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy for morbid obesity: case-control study. Surg Obes Relat Dis 2011; 7:500-505 [PMID: 21459682 DOI: 10.1016/j.soard.2011.01.037]
What do you think about this match ?Any problem with it?
1- Complete mismatch 222 the son is missing the father’s haplotype which couldn’t be except for adoption (we have here an ethical point of view to infom the father or not)
2- Complete mismatch increases the immunological risk even with negative crossmatch
What is effect of BMI of 40 on the outcome of transplant?
1-surgical complication and wound complication which predispose to graft loss.
2-Prolonged admission and increase rate of readmission.
3-Decreased graft survival and acute rejection
4-Worse patient and graft survival
5-Increased risk of post-transplant diabetes (2)
How would you manage this case?
– Management of obesity
Only FDA approved for obesity management in patient with advances ckd are
Orlistat
GLP1 agonist
Bariatric surgery
Beside exercise
As regard eligibility to transplant
-According to policy of the center but most centers don’t accept recipient with BMI 35 and more
-According to KDIGO guidelines with level of evidence 2B that patients with BMI 40 and more are less likely to benefit
Assess for other comorbidities if more than two morbidities transplant not proceed
-according to NICE 2018 which recommend against transplant according to BMI alone
As regard his immunological risk state
Paired exchange searching for better mismatch
Induction with ATG
Maintenance with TAC/MMF/steroid/
What is effect of HLA C DSA on the outcome of transplantation?
Recent studies proved that DSA against HLA C carry risk of rejection with 1 year survival
After tx
Avoid weight gain
Exercise
regerences
Mohammed Hossain, Alexander Woywodt, Titus Augustin and Videha Sharma (2017). Obesity and listing for renal transplantation: weighing the evidence for a growing problem Clinical Kidney Journal, 2017, vol. 10, no. 5, 703–708doi: 10.1093/ckj/sfx022Advance Access Publication Date: 22 April 2017Editorial CommentDownloaded from https://academic.oup.com/ckj/article/10/5/703/3748295 by guest on 23 December 2021
1-bad mismatch 222 that mean high risk
but it not acceptable as donor is his son
high DSA against HLA C & associated with DSA against HLA B mean high risk of AMR
2-BMI >40 with truncal obesity and previous transplantation make surgery more complicated and high incidence of post surgical complication plus high incidence of DGF ,difficult wound healing , high risk G Anesthesia
3-advice loss of weight (restricted diet or par iatric surgery (if possible) )
-protocol of donor exchange recommended
-advice deceased donor (recipient old age ang sensitized)
-desensitization protocol with (PL ex-start of immunosuppressant before transplantation operation )
-use high risk protocol of induction (ATG) ang maintenance MMF & prograf (try to early withdraw corticosteroid if stable graft)
4-HLA C DSA if accompanied with HLA B DSA lead to high risk of AMR
Regarding the cross match:
There is a high degree of mismatch (222), which is unlikely to be found between a father and son. There is DSA class I with high MFI . Thus high risk Tx.
Obesity :
The prevalence of surgical complications is higher in obese patients( the surgery is more difficult, take longer time and associated with complications such as wound infection, dehiscence and fluid collection).
Increased incidence of delayed graft function in obese patients.
There is controversy about the relationship between obesity and rejection risk,
Tac levels are expected to be relatively higher in obese recipients .
Management:
Weight reduction: nutritional and pharmacological methods and surgical methods( bariatric surgery) .
If a better matching Donor with no DSA’s is available then it would be better but if not it’s still better than dialysis so : Induction with ATG with maintenance therapy with Tac, MMF and steroid with follow up DSA level and protocol biopsy. Desensitization here is not the recommended option as the FCM is –ve .
HLA C DSA:
The presence of HLA-C DSA pre transplant is associated with increased risk of ABMR.
*What do you think about this match?Any problem with it?
Previous transplantation
6 HLA mismatch
Presence of DSA
*What is effect of BMI of 40 on the outcome of transplant?
Obese KT Recipients Outcomes
Short term outcomes
worst short-term outcomes in obese compared to normal weight recipients.
higher prevalence of wound infections and dehiscence
wound complications were associated with an increased length of hospitalization and a higher risk for rehospitalization.
delayed graft function (DGF)
Long term outcomes
Obesity can increase risk of graft loss in obese KT recipients. Obesity can affect kidney haemodynamics, resulting in high renal plasma flow and glomerular filtration rate and increased filtration fraction
Obesity is related to development of hyperfiltration and proteinuria leading to glomerulosclerosis with a consequent reduction in glomerular filtration rate
Obesity is a risk factor for DGF, and DGF increases the risk of kidney fibrosis and graft loss. Endocrine and immunological functions of adipose tissue could account for higher levels of pro-inflammatory cytokines in obese patients, which may mediate glomerular injury and contribute to renal damage
An alternative hypothesis could be that pharmacokinetic abnormalities related with obesity predispose to immunologically mediated graft injury due to sub-therapeutic immunosuppression
• How would you manage this case?
Different strategies for the treatment of obesity
Life style modification
Exercise 30min 5 days per week
Drugs therapy like orcaserin is a selective agonist of the 5-hydroxytryptamine 2C serotonin receptor effective and safe for weight loss, improves glycaemic control, and reduces persistent new or worsening albuminuria and the incidence and worsening of CKD.
Many patients would not be able to achieve weight loss with medical recommendations, and some clinicians may consider bariatric surgery
What is effect of HLA C DSA on the outcome of transplantation?
Increase risk of antibody mediated rejection
Reference
Maria Quero
,Nuria Monteroa,Inés Ramaa, Sergi Codinaa, Carlos Couceiroa Josep M. Cruzadoa,Obesity in Renal Transplantation. Nephron
DOI: 10.1159/000515786.. Published online: May 11, 2021.
References
1-bad match
6 mismatch means high risk of acute rejection and more need of immuno suppression (high risk of malinancy & infection)
DSA with high MFI means high risk of AMR
2-BMI>40 morbid obesity
lead to :difficult operation,long time of healing wound,more surgical comlication, anesthesia complication , high risk of DGF , also mal-adaptive FSGS
3 *desnstization protocol
*loss of weight BMI <30 (diet restriction or pariatric surgery)
*protocol of donor exchange more suitable in this case
4-anti HLA C effect on kidney transplantation not clear but it associated with poor graft survival if accompanied with anti HLA B
1. This is a high immunological risk transplant, considering a previous transplant, 6 mismatches, DSA with high MFI.
2. BMI above 35 kg/m2 limits access to transplantation. Morbid obesity was associated with an increased risk of delayed graft function (DGF), Longer operative times, prolonged hospitalization, wound complications, Higher rates of re-intubation, More frequent intensive care unit admissions, and acute rejection and decreased overall graft survival compared with normal-weight patients. USRDS registry analysis of 51,927 adult kidney transplant patients found a U-shaped association between BMI and death with a functioning graft, and J-shaped association between BMI and allograft survival, and a graded correlation between BMI and DGF.
3. This patient should be encouraged to lose weight. A multidisciplinary approach involving dietary support and supervised exercise programs is ideal to ensure that weight loss is achieved in a healthy manner and to prevent muscle mass loss (sarcopenia), particularly in the dialysis population. For those unable to reach target weight via these means, particularly in the presence of other comorbidities such as hypertension, diabetes mellitus, and sleep apnea, bariatric surgery should be considered. However, the risks associated with bariatric surgery need to be weighed up against the increased mortality risk associated with remaining on dialysis. Moreover, this patient has 222 mismatches, DSA with high MFI, paired exchange donation will be a better option.
4. Santos S et al. found that DSA-Cw is associated with an identical risk of AMR and impact on graft function in comparison with “classical” class I DSA in 12 patients transplanted with DSA exclusively anti-HLA-Cw compared with other patients with preformed DSA anti-HLA-A and/or B. Similarly, Bachelet T et al, reported graft survival to be lower in the Cw/DP, and the preformed anti-HLA-Cw and anti-HLA-DP DSA are as deleterious as anti-HLA A/B/DR/DQ DSA.
References:
· Foucher Y, et al. Outcomes after renal transplantation of obese patients: a French cohort-based study. July 2020
· Santos S, Malheiro J, Tafulo S, Dias L, Carmo R, Sampaio S, Costa M, Campos A, Pedroso S, Almeida M, Martins S, Henriques C, Cabrita A. Impact of preformed donor-specific antibodies against HLA class I on kidney graft outcomes: Comparative analysis of exclusively anti-Cw vs anti-A and/or -B antibodies. World J Transplant. 2016 Dec 24;6(4):689-696.
· Bachelet T, Martinez C, Del Bello A, Couzi L, Kejji S, Guidicelli G, Lepreux S, Visentin J, Congy-Jolivet N, Rostaing L, Taupin JL, Kamar N, Merville P. Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation. Transplantation. 2016 Jan;100(1):159-66.
1- As HLA is inherited as one haplotype from each parent , so with this complete mismatch between the donor and recipient , this donor isn’t his biological son and with this degree of mismatch , the patient will be at a high risk of rejection specially this is his second transplantation
2- There are many obesity related surgical complications as:
General surgical complications :
a- Prolonged operation time .
b- wound infection and dehiscence
c- development of hernia , DVT .
complications related to the graft :
a- Anastomotic and perinephric complications are more common in obese as lymphocele , hematoma , renal artery stenosis
b- obesity is associated with increased risk for AMR , graft dysfunction
c- increased risk of NODM
3- HLA C DSA
Is associated with increased risk of AMR
Although early reports considered HLA C less immunogenic and with lower expression rates on cell surface compared with HLA class A. B and DR. This may be related to instability of HLA C molecules so it was difficult to be detected by old techniques.
But more recent researches proved significant incidence of AMR with HLA C DSA
1- Gill, J S et al. “The survival benefit of kidney transplantation in obese patients.” American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons vol. 13,8 (2013): 2083-90. doi:10.1111/ajt.12331
2- Behzadi AH, Kamali K, Zargar M, Abbasi MA, Piran P, Bastani B. Obesity and urologic complications after renal transplantation. Saudi J Kidney Dis Transpl 2014; 25: 303-308 [PMID: 24625995 DOI: 10.4103/1319-2442.128516]
3- Ditonno P, Lucarelli G, Impedovo SV, Spilotros M, Grandaliano G, Selvaggi FP, Bettocchi C, Battaglia M. Obesity in kidney transplantation affects renal function but not graft and patient survival. Transplant Proc 2011; 43: 367-372 [PMID: 21335224 DOI: 10.1016/j.transproceed.2010.12.022]
4- Takata MC, Campos GM, Ciovica R, Rabl C, Rogers SJ, Cello JP, Ascher NL, Posselt AM. Laparoscopic bariatric surgery improves candidacy in morbidly obese patients awaiting transplantation. Surg Obes Relat Dis 2008; 4: 159-164; discussion 164-165 [PMID: 18294923 DOI: 10.1016/j.soard.2007.12.009]
How would you counsel the patient after transplantation ?
This patient is at high risk of gaining more weight post transplantation. He needs to
1- be motivated to avoid further gaining of weight post transplant.
2- to be warned about the high risk of graft dysfunction and the possibility of having DM, HTN, heart diseases.
3- to be advised regarding life style( avoidance of weight gaining elements and doing regular exercise).
4- Office based intervention are unlikely to be effective , he needs to be included in intensive interventions and in a society of patients with similar issue especially in his first year post transplant.
All these will be better done through a multi-displinary team that include a dietician, endocrinologist, physiotherapist and psychologist.
5- Furthermore, the risk for AMR need to be addressed through protocol biopsies and PRA.
Very balanced answer. Good.
What do you think about this match?Any problem with it?
This is a risky mismatch and is associated with poor graft outcome due to the following:
· there is 6 mismatch which might be due to no biological relationship between the father and the son.
· DSA at both B locus and C locus
· The C DSA have high MFI .
· History of a previous transplant.
What is effect of BMI of 40 on the outcome of transplant?
There are controversial results of studies. But most studies stated the following:
· DGF3
· Reduced patient and graft survival
· Acute cellular rejection
· Problems with drug absorption if bariatric surgery is done
· There will be surgical complications(superficial/deep infections, dehiscence and fluid collections)2
· Increased rate of CVS mortality 4
· NODAT and post transplant weigh gain 5
How would you manage this case?
First I prefer to look for another donor. If we have to proceed with his son as a donor, then we should :
· Pre transplant weight reduction, with collaboration with obesity clinics, through life style modification. If these failed then proceed for laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (RYGB)2
· Do induction with r ATG and maintance with TAC based regimen
· Meticulous follow up for rejection through Protocol biopsy
· Encourage exercise post transplant and follow up with a dietician
What is effect of HLA C DSA on the outcome of transplantation?
HLA-C mismatch is significantly associated with acute rejection in patients with one extra mismatch on the B locus as in this patient (P=0.004). 1
1- Frohn C, Fricke L, Puchta JC, Kirchner H. The effect of HLA-C matching on acute renal transplant rejection. Nephrol Dial Transplant. 2001 Feb;16(2):355-60. doi: 10.1093/ndt/16.2.355. PMID: 11158412
2- Di Cocco, P., Okoye, O., Almario, J., Benedetti, E., Tzvetanov, I.G. and Spaggiari, M. (2020), Obesity in kidney transplantation. Transpl Int, 33: 581-589. https://doi.org/10.1111/tri.13547
3- Gore JL, Pham PT, Danovitch GM, Wilkinson AH, Rosenthal JT, Lipshutz GS, Singer JS. Obesity and outcome following renal transplantation. Am J Transplant. 2006 Feb;6(2):357-63. doi: 10.1111/j.1600-6143.2005.01198.x. PMID: 16426321.
4- Nicoletto BB, Fonseca NK, Manfro RC, Gonçalves LF, Leitão CB, Souza GC. Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis. Transplantation. 2014 Jul 27;98(2):167-76. doi: 10.1097/TP.0000000000000028. PMID: 24911038.
5- Kent PS. Issues of obesity in kidney transplantation. J Ren Nutr. 2007 Mar;17(2):107-13. doi: 10.1053/j.jrn.2006.12.009. PMID: 17321949.
good answer
1- 222 HLA mismatch between father and his son means that the donor is not his son.
2- effects of high BMI on outcome of the graft:
obese patient with high BMI has favorable graft outcome as non-obese patients except for wound complications and cardiovascular risk factors and complications.
David W Johnson 1, Nicole M Isbel, Allison M Brown, Troy D Kay, Kirsten Franzen, Carmel M Hawley, Scott B Campbell, Darryl Wall, Anthony Griffin, David L Nicol. The effect of obesity on renal transplant outcomes.
Transplantation.2002 Sep 15;74(5):675-81.
3-management of this case as follow :
a- offer him paired donor transplantation with better match.
b- if not applicable, will proceed for transplantation after clarification of the complications to the patient, induction will be ATG , conventional therapy Tacrolimus, MMF and steroid. follow up of DSA is mandatory and we may need to repeat crossmatch posttransplant. the possibility of desensitization is available in such highly sensitized patient if crossmatch positive.
4- effect of HLA C DSA on outcome of transplantation
it has deleterious effect on outcome like HLA A/B/DR/DQ DSA
Thomas Bachelet 1, Charlie Martinez, Arnaud Del Bello, Lionel Couzi, Salima Kejji, Gwendaline Guidicelli, Sébastien Lepreux, Jonathan Visentin, Nicolas Congy-Jolivet, Lionel Rostaing, Jean-Luc Taupin, Nassim Kamar, Pierre Merville. Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation. Transplantation. 2016 Jan;100(1):159-66.
How would you counsel the patient after transplantation with all these excellent responses?
For this patient who is already obese and there is a risk of more weight gain post transplant ( due to the improvement in appetite and due to the steroid effect) preventive measures requires multidisciplinary team consist of physician, nutritionist and physical therapist is required, and the use of immunosuppressive protocols with minimum steroid or steroid free regimen if the risk of rejection is low.
Regular follow up for DSA level and protocol biopsy are needed with monitoring of CNI level.
What do you think about this match?Any problem with it?
This patient considers a high-risk recipient for a second transplant.
-The HLA is inherited as a haplotype from the parent so this mismatch is questionable for the son unless he was adopted.
What is effect of BMI of 40 on the outcome of transplant?
-Obese patients benefit from renal transplantation but there are a lot of complications associated with obesity.
-BMI ˃40 is a risk factor for:
1. wound infection in renal transplantation.
2. prolonged operating time and length of staying in hospital.
3. Higher incidence of graft loss due to vascular complication( renal artery thrombosis)
4. delay graft function.
5. Acute rejection.
6. Increased death-censored graft loss.
7. Advancing glomerulosclerosis leads to reduce graft survival.
8. Increase cardiovascular events which lead to reduce patient survival.
How would you manage this case?
-Life style modification (nutrition education, diet, and exercise)
-Orlistat is tolerated in CKD and safe
-Bariatric surgery is superior to nonsurgical in achieving target weight. some studies showed improving transplantation outcomes but it may compromise the absorption and metabolism of immunosuppressive drugs.
-Trial of paired donor exchange if failed proceed with this donor + induction.
-induction with ATG
-Maintenance immunotherapy: Tacrolimus, MMF, prednisolone.
-DSA monitoring.
What is effect of HLA C DSA on the outcome of transplantation?
There is a strong association between HLA-C mismatching and rejection.AntiHLA-C DSA can induce microvascular inflammation, AMAR, and graft loss.
References
1-Heinbokel, Timm; Floerchinger, Bernhard; Schmiderer, Andreas; Edtinger, Karoline; Liu, Guangxiang; Elkhal, Abdallah; Tullius, Stefan G. Obesity and Its Impact on Transplantation and Alloimmunity.Transplantation Journal: July 15, 2013 – Volume 96 – Issue 1 – p 10-16.
2. Jonathan Visentin,lionel Couzi ,Jean-Luc Taupin .Clinical relevance of donor specific antibodies directed at HLA-C :along road to acceptance.12 october 2020.
Do you think Orlistat is an option for such a patent these days?
What is the preferred timing for bariatric surgery?
What do you think about this match?Any problem with it?
So, this is an increased risk of rejection.
What is effect of BMI of 40 on the outcome of transplant?
While obesity is not considered as contraindication to transplantation according to most guidelines, it is associated with lower graft and patient survival, but transplanting an obese patient is better than keeping him on dialysis.
Obesity associated with decrease access to transplantation and long waitlisting time.
The prevalence of surgical complications is higher in obese patients( the surgery is more difficult, take longer time and associated with complications such as wound infection, dehiscence and fluid collection).
Most retrospective studies and meta analysis found a high rate of delayed graft function in obese patients.
There is controversy about the relationship between obesity and rejection risk,
A common challenge in obese patients is the difficulty to achieve adequate exposure of maintenance immunosuppression.
How would you manage this case?
What is effect of HLA C DSA on the outcome of transplantation?
The presence of HLA-C DSA pre transplant is associated with increased risk of ABMR.
References:
of Antibody-Mediated Rejection in Kidney
Transplant Recipients With Anti-HLA-C
Donor-Specific Antibodies Bories
Auber
Auber
Excellent
Thanks
this match is inconsistent with biological son may be adopted, as the entire MHC is inherited as an HLA haplotype in a Mendelian fashion from each parent.
obesity is associated with increased risk of delayed graft function, wound infection and prolonged hospital stay.
some studies showed that it may lead to increased risk of acute rejection and decreased graft survival.
It may lead to hyperfiltration and proteinuria leading to glomerulosclerosis and decrease in GFR
It is associated with increased risk of HTN, DM, hyperlipidemia and CVD as in non-transplant population.
UK renal association suggest that benefits of kidney transplant are doubtful in potential recipients with morbid obesity.
Pre transplant weight loss to decrease peri operative morbidity and mortality.
patients who can’t achieve weight loss with lifestyle, diet and exercise are candidates to bariatric surgery as it has superior efficacy in weight loss than pharmacotherapy which is also understudied in CKD patients)
most common laparoscopic techniques are Roux en Y gastric bypass (associated with malabsorption, oxalate nephrolithiasis, hyperoxaluria and vitamin B12 deficiency)and the sleeve gastrectomy (avoid malabsorption but associated with early gastric leak and stenosis)
It is preferable to find another donor with better match but if not available,
this is considered a high immunological risk (6 mismatches, preformed DSA, previous transplant failed due to chronic allograft nephropathy).
so induction with ATG
triple maintenance therapy with Tacrolimus, mycophenolate and prednisolone
no role for desensitization as the crossmatch is negative.
post transplant close monitoring of DSA
DSA directed at HLA-C antigens are able to induce microvascular inflammation, AMR and graft loss like other class I DSA
SAB assay may detect Anti-denatured HLA antibodies which are clinically irrelevant.
anti-denatured antibodies are more prevalent with anti-HLA-C and are associated with negative FCXM and have lower risk of AMR than anti-native HLA-C DSA but the differentiation between them is difficult.
Dudley C, Harden P. Renal association clinical practice guideline on the assessment of the potential kidney transplant recipient. Nephron Clin Pract. 2011;118(Suppl 1):c209–24.
Glicklich D, Mustafa MR. Obesity in kidney transplantation: Impact on transplant candidates, recipients, and donors. Cardiology in review. 2019 Mar 1;27(2):63-72.
Molnar MZ, Kovesday CP, Mucsi I et al. Higher recipient body mass index is associated with post-transplant delayed kidney graft function. Kidney Int 2011; 80: 218-224 68. Heinbokel T, Floerchinger B, Schmiderer A et al. Obesity and its impact on transplantation and alloimmunity. Transplantation 2013; 96: 10-16.
Lafranca JA, IJermans JN, Betjes MG, Dor FJ. Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis. BMC Med. 2015;13(1):111.
Maggard MA, Shugarman LR, Suttorp M, Maglione M, Sugerman HJ, Livingston EH, et
al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005;142(7):547-59.
Visentin J, Guidicelli G, Bachelet T, et al. Denatured class I human leukocyte antigen antibodies in sensitized kidney recipients: prevalence, relevance, and impact on organ allocation. Transplantation. 2014;98(7):738-744
ilippone EJ, Das B, Norin AJ, Ravindranath MH. Optimizing the assessment of pathogenic anti-HLA antibodies. Am J Transplant. 2020;8.
Visentin J, Couzi L, Taupin JL. Clinical relevance of donor‐specific antibodies directed at HLA‐C: A long road to acceptance. HLA. 2021 Jan;97(1):3-14.
Well done
What do you think about this match?Any problem with it?
What is the effect of BMI of 40 on the outcome of transplant?
Obesity is classified according to BMI into
Adverse effects of obesity on transplant outcome may be summarized in the following
So all obese transplant recipients with BMI > 30 should undergo weight loss before transplantation, some centers exclude transplant recipients with morbid obesity BMI > 35 and refer them for assessment for bariatric surgery.
Treatment options
How would you manage this case?
So …
What is effect of HLA C DSA on the outcome of transplantation?
References
1. Gore JL, Pham PT, Danovitch GM, et al. Obesity and outcome following renal transplantation. Am J Transplant 2006; 6:357.
2. Nicoletto BB, Fonseca NK, Manfro RC, et al. Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis. Transplantation 2014; 98:167.
3. Tzvetanov IG, Spaggiari M, Tulla KA, et al. Robotic kidney transplantation in the obese patient: 10-year experience from a single center. Am J Transplant 2020; 20:430.
4. de Vries AP, Bakker SJ, van Son WJ, et al. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant 2004; 4:1675.
5. Ling M, Marfo K, Masiakos P, et al. Pretransplant anti-HLA-Cw and anti-HLA-DP antibodies in sensitized patients. Hum Immunol 2012; 73:879.
6. Bryan CF, Luger AM, Smith JL, et al. Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C. Clin Transplant 2010; 24:56.
7. Gilbert M, Paul S, Perrat G, et al. Impact of pretransplant human leukocyte antigen-C and -DP antibodies on kidney graft outcome. Transplant Proc 2011; 43:3412.
8. Chapman JR, Taylor C, Ting A, Morris PJ. Hyperacute rejection of a renal allograft in the presence of anti-HLA-Cw5 antibody. Transplantation 1986; 42:91.
9. Bachelet T, Couzi L, Guidicelli G, et al. Anti-Cw donor-specific alloantibodies can lead to positive flow cytometry crossmatch and irreversible acute antibody-mediated rejection. Am J Transplant 2011; 11:1543.
10. Tran TH, Döhler B, Heinold A, et al. Deleterious impact of mismatching for human leukocyte antigen-C in presensitized recipients of kidney transplants. Transplantation 2011; 92:419.
11. Aubert O, Bories MC, Suberbielle C, et al. Risk of antibody-mediated rejection in kidney transplant recipients with anti-HLA-C donor-specific antibodies. Am J Transplant 2014; 14:1439.
Thank you for mentioning the role of GLP1 Agonists for weight reduction and referral for bariatric surgery assessment before trasplantaion
This match has 2 problems:
1) a 222 mismatch between biological father-son is not possible as a haplotype match is expected in this case. So it implies that the son is an adopted son.
2) This is a 222 mismatch with presence of DSA and elevated MFI. Although the DSA is high for Cw15 and B40, even presence of anti HLA-C is associated with higher chances of antibody mediated rejection (AMR). (1)
So, this is a high risk transplant.
Patient with obesity undergoing kidney transplant have been shown to have poorer short-term graft outcomes including:
1) Increased wound related complications (wound dehiscence, incisional hernia, prolonged hospital stay and rehospitalization). (2)
2) Increased risk of delayed graft function. (2)
3) Acute rejection increased risk. (3)
Long-term outcomes have also been shown to be affected by obesity:
1) Poorer graft survival. (2,3)
2) No effect on patient survival. (2)
Management includes pre-transplant and post-transplant management.
Prior to transplant:
1) Weight reduction: Data from OPTN/UNOS has not shown any benefit of pre-transplant weight reduction as far as graft and patient survival is concerned. (4) Nevertheless, it would help in reducing short term complications like wound dehiscence, incisional hernia etc. Bariatric surgery has been tried in prospective kidney transplant patients successfully, but a close watch on immunosuppressive trough levels would be required in the post-transplant period due to altered pharmacokinetics of the drugs.
2) Try for a paired kidney transplant: In view of high-risk status (second transplant, presence of DSA and 222 mismatch)
3) If we have to go ahead with the same donor,
Induction with ATG
Maintenance immunosuppression with Tacrolimus, MMF , Steroids
Regular DSA monitoring post-transplant
Protocol biopsy
Post-transplant special emphasis on diet and glycemic control
Role of anti HLA-C antibodies in transplant has been evaluated and it has been shown that patients with high pre-transplant HLA-C DSAs have higher incidence of AMR in first year post-transplant. (1) They have also been shown to be associated with increased incidence of chronic AMR and poor graft survival. (5)
References:
1) Aubert O, Bories MC, Suberbielle C, et al. Risk of antibody-mediated rejection in kidney transplant recipients with anti-HLA-C donor-specific antibodies. Am J Transplant 2014;14:1439-1445.
2) Quero M, Montero N, Rama I, et al. Obesity in renal transplanation. Nephron 2021;145:614-623.
3) Lafranca JA, IJermans JN, Betjes MG, et al. Body mass index and outcome in renal transplant recipients: a systematic review and meta- analysis. BMC Med 2015;13:111.
4) Huang E, Bunnapradist S. Pre-transplant weight loss and survival after kidney transplantation. Am J Nephrol 2015;41:448-455.
5) Visentin J, Bachelet T, Aubert O, et al. Reassessment of the clinical impact of preformed donor-specific anti-HLA-Cw antibodies in kidney transplantation. Am J Transplant. 2020;20:1365–1374.
the patient has poor matching with his son, which increases the risk of rejection and will affect the graft survival.
The median survival for 0 MM was 25 years compared with 20 years for 1 MM, 18 years for 2 MM, 15 years for 3 MM and 12 years for higher MM(1). Allograft loss is primarily due to chronic immune injury and accounts for 50% of allograft losses. There is still a significant risk of rejection even with modern immunosuppression, particularly ABMR which can present with a low-grade indolent course.
HLA haplotypes are inherited in a Mendelian fashion. Statistically, there is a 25% chance that siblings will share the same haplotypes (two-haplotype match), a 50% chance they will share one haplotype (one-haplotype match), and
a 25% chance that neither haplotype will be the same (zero-haplotype match)(2).
-Obesity clearly affects short- and long-term outcomes in obese renal transplant recipients, but losing weight before the transplant poses unique challenges in patients with advanced CKD or on dialysis.
– Obesity and chronic vascular disease are associated with a number of risk factors for hypertension, dyslipidaemia, and diabetes
-The KDIGO guidelines state that, in RT recipients, obesity is associated with cardiovascular events and mortality.
– 7,123 records, included 11 studies (with a total of 305,392 participants) were included in this systematic review This study reported a j-curve relationship between BMI and mortality, with underweight and obesity showing higher all-cause mortality compared with normal BMI-
Obesity also may contribute to allograft loss via its ability to alter drug metabolism.
-high incidence of wound infection and incisional hernia.
What is the effect of HLA C DSA on the outcome of transplantation?
The clinical significance of HLA-C antibodies has been unclear in kidney transplantation HLA-C mismatch significantly correlated with acute renal transplant rejection in pairs with one additional mismatch on the B locus(4).
1-doi: 10.1034/j.1399-3046.2001.00137.x. [PubMed] .
2- Handbook of Kidney transplantation.
3- Obesity in Kidney Transplantation: Impact on Transplant Candidates, Recipients and Donors.Cardiol Rev. 2018 Jun 4.
4-Clin Kidney J. 2012 Jun; 5(3): 254–256.
Published online 2012 Apr 19. doi: 10.1093/ckj/sfs042
What do you think about this match?Any problem with it?
Yes there is a problem 6 mismatch mean that the son is not a biological son he may be adopted.
What is effect of BMI of 40 on the outcome of transplant?
Recipients risk associated with obesity include skin and soft tissue like wound infection and dehiscence, perinephric complications like lymphoceles and hematoma, graft complications like DGF ; rejection; graft survival and patients survival, systemic compliance like sepsis ; recurrent hospital admissions , NODAT and CVD .
How would you manage this case?
First I will refuse this donor and searching for more compatable one
Then advice to decrease weight or doing gastric bybass
checking DSA
Using SAB to define the clinically irrelevant anti-denatured HLA-C DSA from the anti-native HLA-C DSA
Then desensitized the patient with using of ATG for induction and triple is for maintenance with DSA and protocol biopsy follow up
What is effect of HLA C DSA on the outcome of transplantation?
HLA -C mismatches were associated with lower graft survival in HLA-sensitized kidney recipients
Not all anti HLA-C antibodies are clinically relevant,for this SAB must differentiate between the anti denatured HLA-C DSAs and the anti native HLA-C DSAs
Because anti-denatured HLA-C DSA are always associated with negative FCXM and lower risk of ABMR and with better graft survival as compared to anti-native HLA-C DSA
The possibility to transplant reduced with the presence of preformed DSA and positive cross match
Reference:
Clinical relevance of donor specific antibodies directed to HLA-C :a long road to acceptance.
Jonathan visentin.
Kidney transplantation in obese patients
Minh-Ha Tran, Clarence E Foster, […], and Hirohito Ichii
This 6mismatch with high risk of rejection.
Patient has history of graft failure which added to his HLA mismatch.
DSA against B40 of MFI 1645 though not very high (don’t know what center standard)
,still considered a risk in second transplant patient ,as do DSA against CW 15 WHICH
are associated with an identical risk of AMR and impact on graft function in comparison
with “classical” class I DSA.
Extremes of body mass index (BMI) appear to impact survival in kidney transplant
recipients.. Skin and soft-tissue complications, particularly wound infections and
lymphocele formation, are higher among obese patients.
the rate of delayed graft function is also higher, and contributes to longer length of stay
following transplant in this population.
New onset diabetes after transplant also appears to be influenced both by BMI at time
of transplant as well as increasing BMI following transplant.
Obesity in patient over 40 BMI ,Bariatric surgery appears promising to aid in reducing
excess weight both pre- and post-transplant, but further studies are needed.
Obesity should not constitute an absolute contraindication to transplantation but
individualized risk assessment is necessary.
Transplantation :
will be done with depleting therapy i.e Antithymocyte globulin which lowered the
incidence of AR from 64% to 38% And was beneficial in all presensitized patients.
There was a borderline significant improve in graft survival at 1 year.
Maintenance therapy MMF, CNI plus steroid.
What is effect of HLA C DSA on the outcome of transplantation?
Patients with a high level of pre transplant anti-HLA-C DSAs are likely to develop AMR
during the first year after transplantation.
1- Minh-Ha Tran, Clarence E Foster et al. Kidney transplantation in obese patients.
World J Transplant. 2016 Mar 24; 6(1): 135-143.
2-Sofia Santos, Jorge Malheiro impact of preformed donor-specific antibodies against
HLA class I on kidney graft outcomes: Comparative analysis of exclusively anti-
Cw vs anti-A and/or -B antibodies. World J Transplant. 2016 Dec 24; 6(4): 689–696.
Risk of Antibody-Mediated Rejection in Kidney Transplant Recipients with Anti-HLA-C
Donor-Specific Antibodies.
3-Olivier Aubert M.‐C. Bories et al .Risk of Antibody-Mediated Rejection in Kidney
Transplant Recipients With Anti-HLA-C Donor-Specific Antibodies. American Journal of
Transplantation 14(6) May 2014.
Regarding. His current 6 mismatch indicate That his son adopted. Not his biological son
The patient high immunological risk. As he had previous Tx. Failed due to CAN , 6 mismatched with Preformed DSA
In addition. He is morbidly obese. With BMI 40 ,carry more complications including DGF wound related infection hematoma. Lymphocele
I doubt the transplant surgeon will accept him for surgery. Better to advice Wt reduction first and repeat SAB assay to CPRA. And. Decide further about the need of desensitization prior to Tx. And induction as high immunological risk with
ATG or alemutuzmab followed by triple Maintenance with tacrolimus based and MMF,predisolone with close monitoring for DSAs post transplantation
HLA C DSA. Based. On few studies. Can have negative impact in graft survival
References
1- up to date medicine 2021
2- kidney transplantation guide line 2020
The patient in the mentioned scenario carries a high risk factors for acute and chronic transplant rejection including 6 HLA antigen mismatch and Presence of a donor-specific antibody (DSAs) with negative FCXM.
-Unknown cPRA situation which will determine his options for transplantation.
-Preformed DSAs against HLA B40 with MFI 1645 (below the cut off value of 3000)
-Preformed DSAs against HLA Cw is significant with MFI 6532 (Recently, Bachelet et al in their retrospective and multicentre study showed that anti HLA-Cw DSA have the same effect on graft outcome as DSA against “classical” HLA loci (A, B, DR, DQ), suggesting that anti HLA-Cw should also be considered in transplant allocation. procedures and in immunologic risk stratification of patients).
-Management of this case:
*Perform Luminex SAB: more sensitive to confirm negative cross match
*Wait for better matching or for paired kidney exchange
*If he wants to proceed, he must be induced with lymphocyte depleting agent and plasmapheresis to clear the preformed DSAs.
-The effect of BMI of 40 on the outcome of transplant?
The negative impact of obesity on long term outcome of renal transplant significantly related to cardiovascular diseases, NODAT and peri operation time for wound complications.Other than that obese recipients can achieve excellent long-term patient and graft survivals that are comparable with other nonobese recipients.
References:
Bachelet T, Martinez C, Del Bello A, Couzi L, Kejji S, Guidicelli G, Lepreux S, Visentin J, Congy-Jolivet N, Rostaing L, et al. Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation. Transplantation. 2016;100:159–166.
David W Johnson , Nicole M Isbel, Allison M Brown, Troy D Kay, Kirsten Franzen, Carmel M Hawley, Scott B Campbell, Darryl Wall, Anthony Griffin, David L Nicol: The effect of obesity on renal transplant outcomes
-He is currently highly sensitised after failure of his first transplant
The presence of 222 mismatch means that he isnot his biological son and
Regarding DSA presence with high MFI (B40 with MFI 1645 and Cw15 with MFI 6532)many studies showed that it is associated with a significantly decreased graft survival, even in the case that no AMR
Others claimed that DSA detected in Luminex are irrelevant in patients transplanted in the presence of a negative flow cytometric crossmatch
DSA detectable in solid phase assays are not a contraindication for transplantation but they should be considered a risk factor. (1)
So there is HLA mismatch between them so it is considered a high risk transplant
-obesity directly affects the transplant as it is associated with higher rate of complications, including graft loss and mortality.
Five-year graft survival was assessed by 13 studies, and obesity was associated with graft loss at 5 years
Multiple studies showed that pretransplantation obesity is related to delayed graft function .The impact of obesity on graft loss, death by CVD, and all-cause mortality depends on the transplantation era, on the other hand no association was found between obesity and acute rejection.
Obesity should not solely be an obstacle for a patient to have a kidney transplant.(2)
-Management
He can wait for another matched donor
Otherwise he is considered highly sensitised and have to be desensitised by plasma pharesis ,IVIG and Ritoximab
And then induction by r ATG and maintainence with Tac, MMF and steroids
Counselling for bariatric surgery pretransplanation can be done
– HLA-C should clearly be included in search algorithms as it’s mismatch has an adverse effect on the trasnplanation outcome
A study by Flomenberg N etal suggested that HLA-C exerted an important effects on survival, comparable in magnitude to HLA-A, -B, and -DRB1. it is important that the favorable, independent impact of HLA-C matching on survival be noticed and included in algorithms used for unrelated donor selection.(3)
Reference
1-Roelen D L etal . Detection and clinical relevance of donor specific HLA antibodies: a matter of debate. Transplant international 2012 ;25, 6 (604-610)
2-Nicoletto, Effects of Obesity on Kidney Transplantation Outcomes
Transplantation: July 27, 2014 – Volume 98 – Issue 2 – p 167-176
3- Flomenberg N etal. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome.Blood 2004 Volume 104, Issue 7, Pages 1923-1930
This elderly recipient is sensitized with high HLA mismatch( may be adopted son not his biological sibling), obesity & DSA +ve so he is high risk patient. Seeking for more suitable donor by paired kidney donation program is better than precede with his current donor. If he didn’t find more suitable donor & want to precede with this donor he should desensitized with plasmapheresis+ IVIG, & induction with ATG & maintenance IS MMF, CNI & low dose steroid.
It was found that obesity was associated with poor graft & patient survival due to huge complication of it on transplantation including:
If diet recommendation was not sufficient to reduce weight & BMI, then pre transplant bariatric surgery can reduce the complications of obesity & improve survival, also it was found that post transplant bariatric surgery is safe & effective in reducing weight & complications.
Although HLA-C Ag had low expression & immunogenicity but its expression can be increased during inflammation, so HLA-C DSA was associated with poor graft survival. Routine HLA-C screen is recommended to decrease risk of AMR &chronic rejection.
References:
What do think about this match ? any problem with it ?
The presence of 2 2 2 mismatch means the son is adopted . despite the negative FCMX ,this patient carries a high immunological risk from his previous transplantation , his current 6 HLA mismatch and the presence of DSA .
What is effect of BMI 40 on the outcome of transplant ?
– obesity increases risk of delayed graft function .
-surgical complication including wound infection , dehiscence and lymphocele are reported in obese patient .
– obesity is associated with increased risk of NODAT , hypertension and cardiovascular complication post transplantation .
– immunosuppressant metabolism is affected by obesity .
-some studies reported that graft and patient survival is the same as general population .
How would you mange this case ?
Regarding management of obesity;
Obesity can be managed through a multidisciplinary team approach and the necessity of a multimodal treatment, which includes life-style changes, dietary modification, physical activity, medications and in selected cases surgery. The modern technology with minimally invasive techniques, mainly using robotic platform, reduce the surgical complications rate with comparable graft and patient survival rates to the non-obese population.
Immunosuppressant plan ;
despite the negative FCMX ,this patient carries a high immunological risk from his previous transplantation , his current 6 HLA mismatch and the presence of DSA .
Despite the immunological and obesity risks ,kidney transplantation is not an absolute contra indication and the options of treatment are ;
1-proceed for transplant with immunosuppressant protocol including induction with ATG and maintenance triple TAC ,DSA monitoring and protocol biopsy.
2-pair exchange .
What is effect of HLA C DSA on the outcome of transplant ?
There is significant correlation between HLA-C mismatch and rejection .
Reference;
Transplant International 2020; 33: 581–589ª2019 Steunstichting ESO
Lentine KL, Delos Santos R, AxelrodD, Schnitzler MA, Brennan DC,Tuttle-Newhall JE. Obesity andkidney transplant candidates: how bigis too big for transplantation?Am JNephrol2012;36: 575.
Nicoletto BBFN, Manfro RC,Gonc€Ealves LF, Leit~ao CB, Souza GC.Effects of obesity on kidneytransplantationoutcomes:asystematic review and meta-analysis.Transplantation2014;98: 167.
Humar A, Ramcharan T, Denny R,Gillingham KJ, Payne WD, Matas AJ.Are wound complications after akidney transplant more common withmodernimmunosuppression?Transplantation2001;72: 1920.
Hoznek A, Zaki SK, Samadi DB,et al.Roboticassistedkidneytransplantation: an initial experience.J Urol2002;167: 1604.
Correspondence and offprint request to Dr;Frohn ,institute of immunology and transfusion medicine ,Ratzeburger Alle160 ,D-23538 lubeck ,Germany .@2001 European Renal association –European dialysis and transplant association .
with this DSA would you perform desensitisation besides induction
can you justify your decision.
No. Desensitization is done only if crossmatch is positive. With a negative crossmatch, desensitization is not warranted, but a close watch on DSA levels post-transplant with a protocol biopsy would be prudent so that timely action can be taken.
thanks prof
I would not perform desensitization
no need to do desensitization in cross matched negative patients .
The HLA match between the father and his son will be at least 111 , because the son receive one haplotype from his father and one haplotype from his mother . In this pair the mismatch is 222 which mean that the son is adopted.
Obesity is associated with increased risk of perioperative complications ( wound infections and lymphocele ) and also increase the risk for DGF . also obesity increase the risk of NODAT post transplantation and increase the risk of cardiovascular complications.
Long term graft survival in obese patients is nearly equal to normal weight patients(1).
Obesity is not a contraindication for kidney transplantation but the patient should be assessed before the transplantation for cardiovascular disease and other metabolic complication for obesity.
This patient had previous failed transplanted kidney so he is already sensitized , the cPRA is not given in the scenario , but he had 2 DSA . Also he has 6 antigen mismatches with the donor . Also his obesity make him at higher risk of DGF. All of the above reasons put the patient in the high immunological risk category.
The FCXM is negative but he had 2 DSA , one against HLA B40 with MFI of 1600 and the other against HLA Cw 15 with MFI of 6000 . we can proceed with transplantation but with high risk of acute AMR and chronic AMR . So paired kidney exchange transplantation will be better option if we found a better match with the patient .
If a better match is not available we can proceed with transplantation with this donor with induction with ATG and triple maintenance immunosuppression .
Preformed antibodies against HLA C antigens is associated with increased incidence of acute AMR and chronic allograft nephropathy and graft loss(2).
References :
(1) Minh-Ha Tran, Clarence E Foster, Kamyar Kalantar-Zadeh, Hirohito Ichii
Kidney transplantation in obese patients
World J Transplant 2016 March 24; 6(1): 135-143 ISSN 2220-3230
(2) Jonathan Visentin | Thomas Bachelet | Olivier Aubert |
Arnaud Del Bello | Charlie Martinez | Frédéric Jambon |
Gwendaline Guidicelli | Mamy Ralazamahaleo | Charlène Bouthemy |
Marine Cargou| Nicolas Congy-Jolivet | Thoa Nong| Jar-How Lee |
Rebecca Sberro-Soussan| Lionel Couzi| Nassim Kamar|
Christophe Legendre| Pierre Merville| Jean-Luc Taupin
Reassessment of the clinical impact of preformed donor specific anti-HLA-Cw antibodies in kidney transplantation Am J Transplant. 2020;20:1365–1374
DOI: 10.1111/ajt.15766
What do you think about this match?Any problem with it?
The HLA matching of 222 is not logical between father and son, as the son should share one haplotype with his biological father. This great mismatch between father and son should raise the idea about adoption. Also the presence of DSA against class I HLA-B and C is questionable. Why a father has preexisting antibodies against son’s antigens.
What is effect of BMI of 40 on the outcome of transplant?
Patient’s truncal obesity and high BMI are features of cushing syndrome which is caused in this case from chronic glucocorticoid use.
Although Obesity is associated with factors that leed to poor graft and patient survival. Obesity is associated with increase risk of hypertension, DMII, DL, CAD, alteration in immunosuppressive drugs metabolism. Obesity per se is not associated with poorer kidney transplant outcomes. Some studies demonstrated that obese patients have increased risk for DGF. However, graft and patient survival is the same as that of the nonobese patient. Findings suggest that transplant contraindications should not be based on absolute BMI thresholds but modified, based on patient characteristics. Although obesity is a risk factor for adverse outcomes, but several studies have demonstrated a survival benefit compared to patients who continue on dialysis.
How would you manage this case?
This patient is at high risk of rejection taking in consideration the results of HLA typing and presence of DSA against HLA-B and Cw. HLA-B40 is an HLA – B broad type. B40 is composed of the B60 and B61 split antigen serotypes. MFI of anti HLA-B 40 is not significantly high, and anti-HLA Cw is associated with late rejection. So we can proceed with this transplantation without desensitization, especially with negative FCXM, but with induction therapy for high risk patients including rATG, and maintenance therapy CNI based, tacrolimus/MMF/steroids.
What is effect of HLA C DSA on the outcome of transplantation?
Anti-HLA-Cw antibodies are found in ≈10%-15% of patients on waiting lists and in 50% of sensitized patients. Preformed anti-HLA-Cw DSA increase the incidence of acute AMR at 2 years and the incidence of chronic AMR at 5 years.
References
Jesse D Schold, Joshua J Augustine , Anne M Huml, Richard Fatica , Saul Nurko , Alvin Wee , Emilio D Poggio . Effects of body mass index on kidney transplant outcomes are significantly modified by patient characteristics.Am J Transplant. 2021 Feb;21(2):751-765
Quero M. Montero N. · Rama I.· Codina · Couceiro C. · Cruzado J.M. Obesity in Renal Transplantation. Nephron 2021;145:614–623
Jonathan Visentin,Thomas Bachelet,Olivier Aubert et al. . Reassessment of the clinical impact of preformed donor-specific anti-HLA-Cw antibodies in kidney transplantation. Am J Transplant. 2020;20:1365–1374.
Lot of effort in the reply but we are not here to establish if the father is real father or not. The question is if we would transplant this kidney or not? Regarding BMI there is no consensus on how big is too big but to my knowledge only Mayo Clinic Rochester accepts recipients>40 BMI . There are multiple meta analyses stating that high BMI recipients have higher DGF rates and inferior outcomes. Immunologically this case is complex but possible but surgically it would be difficult to justify due to risks of survey and predicted inferior survival outweigh the benefit to both donor and recipient.
What do you think about this match?Any problem with it?
What is effect of BMI of 40 on the outcome of transplant?
His BMI of 40 carries more comorbidity to his transplantation surgically and later in the transplant outcome( eg;hyperfiltration injury).
How would you manage this case?
Regarding his BMI :
What is effect of HLA C DSA on the outcome of transplantation?
HLA-C antibodies are independantly associated with high risk of acute rejection and poor graft survival (6).
Referrences :
1- The Renal Association Assessment of the Potential Kidney Transplant Recipient. The Renal Association. 2011. http://www.renal.org/guidelines/modules/assessment-of-the-potential-kidney-transplant-recipient#sthash.fyh0cWpM.dpbs. [Ref list]
2-Lafranca JA, IJermans JN, Betjes MG, Dor FJ. Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis [published correction appears in BMC Med. 2015;13:141]. BMC Med. 2015;13:111. Published 2015 May 12. doi:10.1186/s12916-015-0340-5.
3- Obesity and outcome following renal transplantation.
Gore JL, Pham PT, Danovitch GM, Wilkinson AH, Rosenthal JT, Lipshutz GS, Singer JS
Am J Transplant. 2006 Feb; 6(2):357-63.
4- Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis.
Nicoletto BB, Fonseca NK, Manfro RC, Gonçalves LF, Leitão CB, Souza GC
Transplantation. 2014 Jul 27; 98(2):167-76
5- Bariatric surgery: a systematic review and meta-analysis.
Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K
JAMA. 2004 Oct 13; 292(14):1724-37.
6- Baan CC, Vaessen LM, ten Kate F et al. Rejection of a kidney graft mismatched only for the HLA-C locus and an HLA-BW22 split. Transplantation 1993; 55: 438±439 } {Chapman JR, Taylor C, Ting A, Morris PJ. Hyperacute rejection of a renal allograft in the presence of anti-HLA-Cw5 antibody. Transplantation 1986; 42: 91±93.
The effect of bariatric surgery on dosing and absorption of IS drugs has to be considered
If accepted by surgeons after wt. reduction he is considered a high immunological risk
Please justify your choice of the induction with ATG
Or as well desensitization protocols
the justifications for desensitization are as follows :
Will you accept this match?
yes i will accept this mismtach ?
he may not be his biological father, the son may be adopted.
What is effect of BMI of 40 on the outcome of transplant?
It is well established that compared with their nonobese counterparts, obese (BMI >30 kg/m2 ) and severely obese (BMI >35 kg/m2 ) KT recipients have higher rates of SSI, but similar graft survival.
a lot of complaiction post op including cases of wound infection , lymphocele formation , fascial dehiscence , renal artery stenosis or thrombosis , ureteral stricture , urine leak , and requirement for wVAC therapy
In the general surgery literature, research has shown that SQD depth is a better predictor of developing SSI than BMI.
SQD is a better surrogate of abdominal obesity yet correlates with BMI such that a higher BMI and deeper SQD are associated with a greater risk of wound complications.
How would you manage this case?
from his obesity point of view
transplant surgeons in many centres have cut values in accepting their recipents .
bmi > 35 have a high risk of comapliction as mentioned above,so this pt may be surgically unfit from the surgical point of view .
what is my plan if this pt was rejected from the transplant committe due to morbid obesity?
1- i will reffer him to ditation to help him to reduce weight and if he started to show progress after 3 month i will introduce him again in the committe and let the surgeon decide wether they will accept or not, putting in consideration that mosts studeies showed that enarly 30-40 % will gain weight of transplantion so he will have higher risk to gain more weight after transplantion
2-refferal to endocrionlogist, he may offer him new eras of treatment of obestiy like liragltuide or semaglutide which may hep in reducing weight befor and after kidney trasnplantion( we offerd thisto our pt in our centre)
3-refferal to periatric surgery to decide if he fits crieria for any surgical intervention like sleeve gastrectomy which may feciltate his weight loss pre transplantion.
if this pt was approved by the transplant committe to be transplanted,
a-induction immunsuprrsion
ATG INDUCTION WITH 4-6 MG /KG TOTAL CULMULATIVE DOSE
b-maintinace immunosuppresion
CNI WITH MMF PLUS RAPID STEROID TAPPERING TO LOWES DOSE TO 5 MG MAINTINACE
C-POST OPERTAIVE CARE OF HIS WEIGHT AND COUNSELLING REGARDING THE FFECT OBESITY ON GRAFT SURVIVAL AND PUTTING THE PT AT RISK OF METABOLIC SYNDROME
What is effect of HLA C DSA on the outcome of transplantation?
the potential role of HLA C mismtach in solid organ transplantion has not been exmained systemicaly ,
some studies showed that that there is a linkage desqulibrium between HLA- B/C , HLA C MISMATCHE, TURENED OUT TO BE SIGNIFCANTLY CORRELATED WITH ACUTE TRANPLANT REJECTION EPISODES IN PAIRS WITH ADDITIONAL MISMATCH ON LOCUS B
reffernce
Proc (Bayl Univ Med Cent)v.34(2); 2021 MarPMC7901397
nephro dial transplantion(2001)16:355-360
welldone
considering the 6500 MFI and the controversial role of Cw15 is there a role for desensitisation?
Yes sure, desentization here can be done .with plasmapharesis and iv igg