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Table of Contents
REVIEW ARTICLE
Year : 2017  |  Volume : 11  |  Issue : 3  |  Page : 111-116

Expanding the donor pool for kidney transplantation in India


1 Department of Nephrology and Clinical Transplantation, Institute of Kidney Diseases and Research Center, Dr. H.L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
2 Department of Urology and Transplantation, Institute of Kidney Diseases and Research Center, Dr. H.L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
3 Department of Anesthesia, Institute of Kidney Diseases and Research Center, Dr. H.L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
4 Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Center, Dr. H.L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India

Date of Web Publication20-Dec-2017

Correspondence Address:
Dr. Vivek Balkrishna Kute
Department of Nephrology and Clinical Transplantation, Institute of Kidney Diseases and Research Center, Dr. H.L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_34_17

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  Abstract 


The best and most cost-effective treatment for end-stage renal disease patients is living donor (LD) renal transplantation. It has survival benefit compared to deceased donor (DD) kidney transplant (DDKT) and long-term dialysis and provides a better quality of life. Efficient and effective kidney allocation methods are increasingly necessary to address the problem of organ scarcity. The use of kidney paired donation transplant has increased access to LD kidney transplantation (LDKT) with outstanding results. ABO-incompatible kidney transplantation (KT) and desensitization protocol can expand the donor pool, but as integral to any aggressive immunosuppression protocol, they are associated with increased risk of infection and malignancy. Given the widespread organ shortage, DDKT from donors with sepsis, donors who died from snakebite or acute kidney injury, controlled donation after cardiac death, older donors, can be considered for KT with an acceptable outcome. The acceptable outcome can be achieved with dual KT using kidneys from expanded criteria donors in older population. Dual KT from pediatric donors to adult recipients or from adult marginal DDs is a promising way to expand the donor pool. Carefully selected donor with HIV, HCV, and HBV positivity is not a contraindication for living kidney donation. Careful and meticulous selection of patient and donor is essential for successful outcome. Affordable or free transplantation is other way to increase transplantation rate in developing country. The community support can make transplantation available free to the poor patients under community-government partnership. Various steps should be taken to promote LDKT and DDKT program.

Keywords: Donor pool, living donor transplantation, paired kidney donation, renal transplantation


How to cite this article:
Kute VB, Suresh GK, Patel HV, Shah PR, Modi PR, Shah VR, Rizvi JS, Pal BC, Modi MP, Shah PS, Varyani UT, Wakhare PS, Shinde SG, Ghodela VA, Patel MH, Trivedi VB, Trivedi HL. Expanding the donor pool for kidney transplantation in India. Indian J Transplant 2017;11:111-6

How to cite this URL:
Kute VB, Suresh GK, Patel HV, Shah PR, Modi PR, Shah VR, Rizvi JS, Pal BC, Modi MP, Shah PS, Varyani UT, Wakhare PS, Shinde SG, Ghodela VA, Patel MH, Trivedi VB, Trivedi HL. Expanding the donor pool for kidney transplantation in India. Indian J Transplant [serial online] 2017 [cited 2019 May 23];11:111-6. Available from: http://www.ijtonline.in/text.asp?2017/11/3/111/221187




  Introduction Top


The best and most cost-effective treatment for end-stage renal disease (ESRD) patients is living donor kidney transplantation (LDKT). It has survival benefit compared to deceased donor kidney transplant (DDKT) and long-term dialysis and provides a better quality of life. Every attempt should be made to promote LDKT. Here, we discuss various options to expand living donor (LD) and deceased donor (DD) pool for kidney transplantation (KT).


  Kidney Paired Donation Increase Living Donor Kidney Transplantation by 25%–35% Top


About 35% of healthy and willing donors are rejected on the grounds of ABO incompatibility and HLA sensitization this leads to increased dialysis duration and its associated increase in morbidity.[1] An effective kidney paired donation (KPD) program should be implemented in each transplantation center. KPD increased LDKT by 25%–35%[2],[3],[4],[5] in the past decade. KPD has all advantages of ABO-compatible LDKT (similar patient, graft survival, cost, and outcome) without long waiting time for DDKT. KPD is more useful in developing countries with poor healthcare insurance, and DDKT is in initial stages. KPD is more suitable transplant option where a directed KT, ABO-incompatible KT (ABOi KT) or cross-match positive pair is not feasible due to costs/infectious complication compatible pairs,[2],[3] nonsimultaneous, extended, altruistic donor chain, domino chain, combination of KPD with ABO incompatible transplantation,[4] or desensitization protocol,[6] international KPD and list exchange are different transplant options to expand the donor pool. LD KPD team can increase access to LDKT at individual centers even in the absence of national KPD program. Hurdles in successful KPD program are the unavailability of computer matching allocation, ABO blood type imbalance, reciprocity, simultaneity, and geography. Transplant centers should work together removing all barriers to successfully implement regional national or even international KPD program to increase donor pool and further optimize potential of KPD to increase transplantation of O group and sensitized patients. KPD should be preferred over ABOiKT or desensitization protocols and donor pool should be increased to reduce the waiting time on dialysis.


  Desensitization Protocols Versus Kidney Paired Donation Top


Desensitization protocols consisted of removal of antibody using standard or double filtration plasmapheresis/immune adsorption and decreased the production of antibody (splenectomy/rituximab/bortezomib) with or without adjunctive therapies such as low- and high-dose intravenous immunoglobulin, can allow for successful transplantation in select recipients. Although the short-term graft and patient survival are acceptable in patients who underwent desensitization protocol, most of the available literature is from a small sample-sized single center experiences. It is the need of time to have multicenter randomized prospective trials to evaluate the efficacy and safety of such desensitization protocols.

ESRD patients who are incompatible with their LD due to positive cross-match and/or donor-specific antibody (DSA) should be first considered for single- or multi-center KPD transplantation. If KPD exchange is not feasible (AB donor, O recipient) and patients are interested in a desensitization protocol, and easy to desensitize (high panel reactive antibody [PRA], low-strength DSA) can be considered with written informed consent about side effects, economic effect, and lack of uniform/safely efficacy of desensitization protocols and existence of DSA after transplantation leading to immune injury and poor long-term graft survival. Patients who have high DSA/PRA values and who are not appropriate candidates for desensitization as well as KPD alone (non-O donor (like AB), O recipient) can be considered for the combination of desensitization and KPD to increase match rate and successful outcome. Those patients who have MFI values of >5000 and a positive complement-dependent cytotoxicity cross match should not be considered for desensitization.[7]


  ABO-Incompatible Kidney Transplantation Top


Data from Japan demonstrated that long-term graft and patient survival of ABOi KT are comparable with those of ABO-compatible KT despite higher rates of acute antibody-mediated rejection in ABOi KT. Higher cost, the risk of infections, lack of uniform access, need of potent immunosuppression, and inferior long-term outcome are the limiting factors for expansion of ABOI KT in developing countries.[7] There is emerging evidence of no long-term difference in graft and patient survivals among the two groups.[8],[9],[10] The baseline ABO antibody titers ≤64 are associated with low risk in ABOi KT. Their use should be limited to O group patients as other non-O group patients can be transplanted with cost-effective KPD with the best long-term outcome.[1],[2]


  Transplant Education and Team Work Top


The prospective transplant education awareness and benefits of LDKT should be increased in general population, patients with diabetes and hypertension, primary care provider for chronic kidney disease patients (Stage 1–3), ESRD patients, and DDKT waitlisted patients, ABO or HLA incompatible pairs. LDKT (preemptive when feasible) should be promoted over DDKT or dialysis. The cost-effective ABO compatible KT with best long-term outcome should be promoted over ABO or HLA incompatible transplant. The primary care providers, physicians, dialysis service providers, medical, and paramedical staff, religious organization, nongovernment organizations should play the vital role in transplant education to all ESRD patients with more focus on patients from rural area.[11]


  Primary Health-Care Providers Improve Living Donor Kidney Transplantation Top


There should be a good relation between transplant team and primary health-care providers who send the ESRD patients for better care and transplantation. The transplant team should actively involve primary health-care providers in donor education, screening, evaluation, and long-term follow-up. All the health-care providers should provide early and intermittent education about benefit and risk of LDKT to potential donors and patients to optimize informed decision making. Recommendations to reduce LDKT disparities and living kidney donation (LKD) differences are removed financial disincentives to LKD, implement culturally tailored, community-based LDKT/LKD educational programming at multiple stages of the transplant referral process. Expand national LD assistance center program to achieve financial neutrality for living kidney donors: (1) Allocate funds for reimbursement of LKD lost wages, and to reduce direct and in direct cost of living kidney donation; (2) pass legislation to offer employment and health insurance to LKD; (3) create a living-donor financial toolkit; (4) research on providing cost-effective LDKT. Preventable deaths due to multiple other causes in India preclude such an initiative from the government in India


  Income Top


The poor economic condition is associated with limited access to LDKT or RRT, noncompliance to medical therapy resulting in higher death rates on the waiting list, and lower rates of LDKT. Many a time, poverty is associated with the lack of access to LDKT despite having healthy willing living kidney donor. The community support can make transplantation available free to the poor patients under community-government partnership using principles of equity, transparency, accountability and development of all facilities under one roof. This resulted in increasing dialysis (1350 dialysis patients in 2009) and transplant activity (544 KT in 2009) in Sindh Institute of Urology and Transplantation, Karachi.[12],[13] Generic drugs, high volume purchase further decreases the cost of drugs.[13] Training more Nephrologists is a more important priority.


  Does Living Kidney Donor Age Matters in Transplant Outcome Top


In KPD allocation donor-recipient pairs (DRPs) expect to have similar age group of the exchange donors. However, it will increase waiting time to achieve of the kidney of similar age group. LD up to 30 years older than their recipients can provide acceptable long-term graft survival.[14],[15],[16] The national registry outcome study showed LD age between 18 and 64 years has minimal effect on long-term graft survival.[17] The Indian study has shown the similar patient and graft survival at 5 years follow–up when the donor-recipient age difference is high. Age alone seems not to be an exclusion criterion to living kidney donation.[18] This information is useful in single-center KPD allocation when donor pool is small. Indirect kidney donation, usually donor age does not seem to be a major barrier, and most transplants are actually parent to son


  Kidney Disease: Improving Global Outcomes Draft Guideline for Care of Living Kidney Donors Top


Donor candidates with diabetes, uncontrolled hypertension (HT) using >2 antihypertensive drugs with evidence of end-organ damage, measured glomerular filtration rate (GFR) <60 ml/min/1.73 m 2, albumin excretion rate (AER) >100 mg/d, body mass index (BMI) ≥40 kg/m 2 and prior or current kidney stones with risk of recurrence should be excluded from donation. The decision to approve donor candidates with measured GFR 60–89 ml/min/1.73 m 2, AER 30–100 mg/d, BMI ≥30–40 kg/m 2, HT that can be controlled to <140/90 mmHg using ≤2 antihypertensive drugs with no evidence of end-organ damage, pre-diabetes and prior or current kidney stones without risk of recurrence should be individualized based on the predicted lifetime incidence of ESRD in relation to the transplant center's acceptance threshold.[17] All potential donors should be advised on lifestyle interventions such as regular exercise adopting a healthy diet, maintaining healthy body weight, and smoking cessation. Obesity, family history of diabetes, metabolic syndrome, history of gestational diabetes or past positive oral glucose tolerance test, younger age, and ethnic minorities are the risk factors for the development of diabetes from prediabetes.[18]


  Need of Organ Donation Awareness Top


The awareness about organ donation is very limited in developing countries. This is one of the reasons for low deceased donation rates in India.[19] The knowledge, attitudes, and practices regarding organ donation was evaluated in 200 selected populations in Ahmedabad India. This study showed that better knowledge and awareness will help in promoting organ donation with use of media, doctors, and religious scholars. Family refusal for the organ donation in majority of cases reflects poor knowledge and thus warrants interventions at community level to increase DDKT. Social, medical, legal, and ethical issues are the key factors in obtaining consent from the relatives of potential DDs.


  Development of Deceased Donor Kidney Transplant Program Top


The successful DDKT program can be started and expanded with the following active steps by the emerging transplant center: Increased awareness in the general population for the organ donation, communication network, participation of physicians and intensive care unit doctors in identification/reporting of potential donors, grief counseling and timely declaration of brain death, aggressive donor management before organ harvesting, dedicated transplant team to harvest the DD organs from potential donor and timely transport of the organs to hospital with the improvement in transportation, adequate hospital infrastructure and support from medical and paramedical staff, transparent DDKT waiting list, positive support from the local government and nongovernmental organizations, KT and medications at the affordable rate to all the patients and at free of cost to the poor patients in the absence of national health-care system.[20],[21],[22]


  Usage of Deceased Donor Organs with Sepsis Top


At the time of organ donation, many potential donors have identified or occult septic focus. Many times, the potential donors are rejected due to anticipated risk of transmission of infection from donor to patients. Many studies have shown acceptable outcome with use of DD organs from infected donors. The careful selection/management of brain-dead DD who died from an infectious cause may have an important role in expanding the donor pool. There should be in-depth evaluation of septic focus, severity of sepsis, and adequacy of antibiotics. The written inform consent from the patients can be obtained about the potential risk and benefit of organs from adequately treated septic donors. The studies have shown that outcome of transplant is similar between organs from infected and noninfected donors with careful selection and management of infected donors before organ harvesting.[23]


  Expanded Criteria Donation and Kidney Transplantation Top


Expanded criteria donors (ECD) form up to 40%–50% of donors in any DDOT program. The patient survival, graft survival is inferior with higher incidence of delayed graft function (DGF), rejection rate and primary nonfunction with an ECD kidney than standard criteria donation (SCD) kidney. The prolonged cold ischemia time (CIT), increased immunogenicity, decreased ability to repair tissue, and decreased nephron mass may contribute to poor outcome with an ECD and older kidney.[24],[25],[26]

The discard rate is significantly more with an ECD kidney than SCD kidney and often attributed to poor organ function and quality; a higher percentage of the glomeruloscerosison the biopsy. The glomeruloscerosis >20% is a common reason for the refusal of an ECD kidney. The refusal also increases CIT. The written informed consent at the time of enrolment on the DDOT waiting list will solve this problem. SRTR data showed that all the age group patients get survival benefit with the use of an ECD kidney than SCD kidney compared to dialysis. However, better outcome can be achieved with the use of an ECD kidney in the older population and avoiding immunologically high-risk patients.

The risks of DGF, immune injury, and graft failure was significantly higher with use of older LDs >65 years compared to transplants from younger donors.[19] The transplant outcome was evaluated from expanded criteria LD and standard criteria donors in the Korean study. The expanded criteria LD has at least one of five criteria (history of HT, body mass index >30 kg/m 2, age ≥60 years, estimated GFR <80 mL/min, and proteinuria or microscopic hematuria).[24],[26] Outcome of the expanded criteria LD group is inferior to the standard criteria group at 1 year after transplantation

Given the widespread organ shortage, with careful selection of donors, DDKT from donors with sepsis,[23] donors who died from snake bite,[27] controlled donation after cardiac death [28] older donors [29] donors with acute kidney injury [30],[31] can be considered for KT with acceptable outcome. The acceptable outcome can be achieved with dual KT using kidneys from ECD in the older population.[32]


  HIV, HCV and HBV Positivity is not a Contraindication for Kidney Transplantation Top


The HIV Organ Policy Equity Act now has made it possible renal transplantation of HIV-positive ESRD patients with organ retrieved from HIV positive living or DD.[33] KT from an HIV-positive donor can be performed for HIV-infected ESRD patients without any history of previous opportunistic infections in the potent ART era when CD4 T-cell count of at least 200/mm 3, and an undetectable HIV RNA level.[34],[35] There was a high frequency of rejection in these patients.


  The Use of Kidneys from Donors with HCV Infection Top


2008 Kidney Disease: improving Global Outcomes guidelines suggested that HCV-positive kidneys should be allocated to only HCV RNA-positive recipients.[36] HCV-positive patients have better graft survival and shorter waiting time on DDKT wait list when they accept kidney from HCV positive donor compared to HCV negative donor.[37] The combination of direct-acting antiviral agents (DAA) has shown high efficacy and good safety after KT. DAA reduces the risk of HCV transmission in the presence of viral replication in the donor at the time of transplantation. Current era of safe and effective interferon-free combination of DAA, the use of kidneys from HCV positive donors may be considered in HCV negative patients in cases of urgent medical need where the benefit is deemed to outweigh the risks. In all such cases, the recipient should receive specific counseling and be well-informed about the risk of HCV transmission, complications of long-term dialysis and benefits of KT. Interferon-free oral antiviral agents increase access to KT for HCV positive patients.


  The Use of Kidneys from Donors with HBV Infection Top


HBsAg(−) negative patients have similar graft and patient survival rates, acute rejection rates, and graft functions when they accept kidney from HBsAg(+) donor compared to HBsAg(−) donor.[38] KT without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia (HBV DNA polymerase chain reaction negative) to HBsAg(−) recipients with anti-HBs titer >100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.[39] The safe and effective oral antiviral therapy will further decreases risk of HBV transmission, active hepatitis, and other liver complications


  List Exchange Top


In an LD list exchange program, LD in ABO or HLA incompatible pair donates a kidney to the DDKT waitlist patient, and in return, the incompatible patient gets top priority on the DDKT waitlist. The legal permission from the transplant human organ act from the local area is mandatory. DD kidneys can be used to initiate nonsimultaneous LDKT chain.[40] However, it will increase waiting time for O group patients who are at disadvantaged even in KPD. List exchange can be restricted to non-O blood group and highly sensitized DRP excluding O group patients.[41] In a high volume LDKT program, all A and B blood group DRP without sensitization can be transplanted with KPD within reasonable waiting time.[5] The graft half-life of LD kidney is significantly better than DD kidney (21.6 vs. 13.8 years).[42] It supports that A and B group patient and donor are not required to participate in list exchange. Incompatible pairs are more willing to participate in LD KPD compared to list exchange where the intended recipient will receive a DD kidney rather than a kidney from LD.[43] This could be the reason for restricting the expansion of LD-DD list exchange in the last decade all over the world. The highly sensitized, elderly, and diabetic patients may be considered to get benefit from accepting DD kidney of lower quality as compared to LD kidney early after ESRD, whereas younger, non-O group patients benefit from receiving better quality LD kidney even with prolong pretransplant dialysis duration.[44] DD in list exchange should be standard criteria donor. In list exchange, every attempt should be made to improve the quality of DD organ (CIT minimization, carefully exclude infections or expanded criteria donation) to improve the long-term survival. The frozen section biopsy should be used to validate the quality of DD kidney. More studies are required to address this issue to balance principal of utility and justice of KT.

The national and international transplant community should help the emerging transplant center to expand the cost-effective KT program.


  Conclusion Top


A study has LDKT is the best and cost-effective treatment for ESRD patients compared to DDKT and long-term dialysis. Every attempt should be made to promote LDKT. The prospective transplant education awareness and benefits of LDKT should be increased. The acceptable outcome can be achieved with careful selection of donor and recipient. The community support can make transplantation available at affordable rate/free of cost to the poor patients under community-government partnership. Various steps should be taken to promote LDKT, DDKT program and transplant education.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Introduction
Kidney Paired Do...
Desensitization ...
Transplant Educa...
Primary Health-C...
Income
Does Living Kidn...
Kidney Disease: ...
Need of Organ Do...
Development of D...
Expanded Criteri...
List Exchange
Conclusion
The Use of Kidne...
The Use of Kidne...
ABO-Incompatible...
Usage of Decease...
HIV, HCV and HBV...
References

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