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Table of Contents
Year : 2020  |  Volume : 14  |  Issue : 4  |  Page : 313-320

Pediatric kidney transplantation: Long-term outcome of living versus deceased donor program from a single center- A retrospective observational study

1 Department of Pediatric Nephrology and Transplantation, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
2 Department of Nephrology, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
3 Department of Urology, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
4 Department of Anesthesia and Critial Care, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
5 Department of Radiology, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
6 Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India

Date of Submission31-Jul-2020
Date of Acceptance22-Nov-2020
Date of Web Publication30-Dec-2020

Correspondence Address:
Dr. Kinnari B Vala
Department of Pediatric Nephrology and Transplantation, Institute of Kidney Diseases and Research Center and Dr. H L Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_88_20

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Background: Kidney transplantation (KT) is widely accepted as most successful treatment option for patients with end-stage kidney disease (ESKD) for better survival and quality of life for both children as well as adults. Data scarcity on long term outcome of living donor (LD) versus deceased donor (DD) pediatric KT in developing countries prompted us to review our experience. Aims and Objectives: To determine(1) long term graft, (2)patient survival outcome and (3) rejection episodes in LD versus DD pediatric KT in developing country. Patients and Methods: This was a retrospective observational analysis of 151 LD and 37 DD pediatric renal transplants (age ≤18 years) performed at a tertiary care center between 1998 and 2011. This study was under taken to evaluate long term patient and graft survival, rejection episodes and other complications. Demographic details for all patients was retrieved. Kaplan-Meier curves were used for survival analysis. Results: Over a mean follow-up of 4.2 ± 3.61 years, one-, five- and ten- year death-censored graft survival in LDKT was 87.4%, 72.1%, 72.1% and patient survival was 92.5%, 80.9%, 75.1% respectively; 19.8% (n = 30) patients had biopsy proven acute rejection (BPAR) and 17.8% (n = 27) patients died, mainly due to infections (n = 12). In DDKT, over mean follow-up of 3.93 ± 3.5 years, one-, five- and ten-year death-censored graft survival was 90.4%, 86.4% ,73.3% and patient survival was 83.4%, 67.9%, 67.9 %, respectively; 21.6% (n = 8) patients had BPAR and 27% (n =10) patients died, mainly owing to infections (n = 6). Conclusion: LDKT or DDKT in children has acceptable graft function with patient/graft survival over long-term follow-up, encouraging to develop sustained deceased donor program in developing countries. However, infections are major cause of morbidity and mortality.

Keywords: Deceased donor, living donor, outcome, pediatric, renal transplantation

How to cite this article:
Vala KB, Patel HV, Kute VB, Engineer DP, Shah PR, Gera DN, Modi PR, Rizvi JS, Butala B, Mehta S, Mishra VM. Pediatric kidney transplantation: Long-term outcome of living versus deceased donor program from a single center- A retrospective observational study. Indian J Transplant 2020;14:313-20

How to cite this URL:
Vala KB, Patel HV, Kute VB, Engineer DP, Shah PR, Gera DN, Modi PR, Rizvi JS, Butala B, Mehta S, Mishra VM. Pediatric kidney transplantation: Long-term outcome of living versus deceased donor program from a single center- A retrospective observational study. Indian J Transplant [serial online] 2020 [cited 2021 Apr 10];14:313-20. Available from: https://www.ijtonline.in/text.asp?2020/14/4/313/305439

  Introduction Top

Kidney transplantation (KT) is the best treatment for children with end-stage kidney disease (ESKD).[1],[2],[3],[4],[5] Economic constraints in operating an effective maintenance dialysis program leaves KT as the preferred option for ESKD patients in our country.[6],[7],[8],[9] There are many challenges in developing countries for KT in children due to resource limitations, low access to deceased donors (DD), nonadherence, and morbidity and mortality due to infections.[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16] Our pretransplant patients are “more sick” than those in developed countries, presumably related to resource limitations.

Historically, living donor kidney transplantation (LDKT) is considered the mainstay of treatment for pediatric transplantation. Recipient and graft survival is superior in pediatric patients receiving a living donor (LD) and the preferred choice by most pediatric nephrologists.[17] Most KT in India takes place from LD. This differs from transplant programs in developed countries where deceased-donor kidney recipients (DDKT) is more popular for children and numbers of LDKT are dropping. With improved medical management, advantages of LDKT over DDKT are narrowing.[18] Data scarcity on long-term outcome of LD versus DD pediatric KT in developing countries prompted us to review our experience. The aim to review our data was to determine (1) long-term graft, (2) patient survival outcome, and (3) rejection episodes in LD versus DD pediatric KT in developing countries. The present paper highlights important challenges in developing countries for successful transplantation and positive outcome for patients despite various restrictions. The rate of pediatric KT has been steadily rising over the past decade. However, because of the lack of national or regional registries, information on the outcome of DD pediatric KT is limited to single-center reports.[8],[19],[20],[21],[22],[23],[24],[25] Here, we report our long-term single-center experience with LD v/s DD pediatric KT.

  Material and Methods Top

This was a retrospective single-center observational analysis of 151 LD and 37 DD pediatric KT (age ≤18 years) performed at a tertiary care institute between June 1998 and December 2011.

Inclusion and exclusion criteria

All pediatric KT performed during above-mentioned period were included. Those who were unwilling to provide informed consent were excluded. None of the patients was lost to follow-up. Those who had sepsis, uncontrolled extra-renal malignancies, irreversible multi-organ failure, severe cardiac and pulmonary dysfunction not corrected by organ transplant, underlying life-threatening disorder not corrected by KT and a recent history of nonadherence to medical care were not offered KT as per the protocol of the institute.

Data for demographics and posttransplant follow-up, including investigations, immunosuppression requirement, rejection episodes, and survival, were retrieved from hospital clinic records.

We encouraged offering LDKT to suitable transplant candidates if donors were readily available. If there was no available LD, patients were enrolled in DDKT waitlist. Year-wise numbers of LDKT is shown below;1998 = 3, 1999 = 11, 2000 = 8, 2001 = 3, 2002 = 6, 2003 = 10, 2004 = 9, 2005 = 7, 2006 = 13, 2007 = 21, 2008 = 17, 2009 = 18, 2010 = 10, 2011 = 15. In DD group, kidneys were allocated according to waiting time. Since 2006, much effort has gone toward giving children the priority for DD transplants. Year-wise number of DDKT is shown below; 1998 = 2, 1999 = 1, 2000 = 2, 2001–2003 = 0, 2004 = 2, 2005 = 3, 2006 = 10, 2007 = 6, 2008 = 2, 2009 = 2, 2010 = 3, 2011 = 4.

Pretransplant evaluation: All children with ESKD were evaluated for etiology of ESKD. The lower urinary tracts were evaluated using a voiding cystourethrogram to detect any abnormality that needed to be corrected before transplantation in patients with a history of congenital abnormalities of the urinary tract or infection (CAKUT).[26] Patients with high-grade vesicoureteric reflux or recurrent urinary infection underwent nephroureterectomy to avoid the development of urosepsis.[27] Children with lower tract uropathies (e.g., posterior urethral valves [PUV], neurogenic bladder) and abnormalities of bladder function were assessed carefully with urodynamic studies. Patients with PUV (38 in LD, 10 in DD group) were all given Oxybyutanin pre and posttransplant period, as per urodynamics were advised CSIC (25 in LD, 6 in DD) and Bladder augmentation was performed if required (2 in LD).

The urinary tract, skin, teeth, and sinuses were carefully examined for signs of infection or site of chronic infection. All children were given minimum of 3 doses of hepatitis B vaccine on addition to the national immunization schedule. However, antibody titers were not monitored due to financial constraints.

Human leukocyte antigen (HLA) typing and lymphocyte crossmatch were done by conventional serological technique (one lambda predot trays were used for HLA A, B, and DR typing).We routinely perform complement-dependent cytotoxicity cross matches by the serological method using auto dithiothreitol and standard cytotoxicity methods with T and B lymphocytes each, and flow cytometry crossmatch (FCM) was added since 2007. All patients were anti-human globulin-enhanced lymphocytotoxicity crossmatch assay negative with a negative or acceptable FCM pre-KT.

Intra-operative details

Donor nephrectomy was performed by the open or laparoscopic method after consent. Graft placement was performed using an extraperitoneal approach, with the allograft placed in the right iliac fossa, and using an extravesical modified Lich–Gregoir ureteroneocystostomy with or without a stent. Vessel anastomosis was performed by the end to side anastomosis with common iliac vessels in most. Six patients (2 LD, 4 DD) required intraoperative packed red cell transfusion due to significant blood loss. Central Venous Pressure was targeted between 12 and 15 mm of Hg and the mean arterial pressure of donor was achieved in all patients at the time of clamp release.

Immunosuppressive regimen

All patients received induction with methylprednisolone (10 mg/kg intravenously (maximum dose of 500 mg) for 3 days (0, 1, and 2 days) and rabbit-anti-thymocyte globulin (r-ATG) (1.5 mg/kg, single dose) was added in high immunologic risk patients (n = 20) and all DD. Maintenance immunosuppression consisted of prednisolone (2 mg/kg per day [60 mg/m2 per day], with a gradual reduction to approximately 0.12–0.16 mg/kg per day within a 6 month period and continued thereafter, none received alternate day steroid in the first 6 months), a calcineurin inhibitor (CNI) (cyclosporine [CsA] 3–5 mg/kg/day or tacrolimus [Tac], 0.05–0.08 mg/kg/day) administered in two divided doses) ± mycophenolate mofetil (600–800 mg/m2/day in two divided doses) or azathioprine (adjusted for signs of myelosuppression). CNI was replaced by sirolimus in the event of toxicity (n = 10). Doses of CNI were adjusted as per trough levels (C0) by Fluorescence Polarization Immunoassay technology for the first 3 months, and thereafter drug levels were assayed only in the event of graft dysfunction due to financial constraints. CsA dosing was adjusted to achieve target C0 concentrations of 150 and 300 μg/l for the first 3–6 months posttransplant. Long-term trough levels were targeted at 75–125 μg/l. Tac target trough whole blood levels were 5–10 ng/ml during the first 1–3 months posttransplantation and 4–8 ng/ml thereafter. Alternate-day steroid dosing was administered 6–12 months posttransplant to minimize the effect of corticosteroids on growth in the event of steroid toxicity. None of the patients received steroid-free regimens.[28],[29],[30] In this cohort, Tac was used starting from 2004.[31],[32]. All patients received prophylaxis against Pneumocystis carinii pneumonia, Cytomegalovirus, and fungal infections as per recommendations. Those who had PUV received lifelong uroprophylaxis as per case-based scenarios with Cotrimoxazole as the first choice.

Posttransplantation follow-up

All patients were followed at weekly intervals for the first 3 months, every 2 weeks for the next 3 months, monthly for the next 6 months, and at 1–3 monthly intervals thereafter. On every visit, complete blood counts, renal function tests, and urine examination were done, and ultrasound Doppler studies and CNI levels were performed as per requirement.

Diagnosis and treatment of rejection

Graft biopsy was performed in cases of acute graft dysfunction, diagnosed by the modified Banff criteria, and treated accordingly.[29],[30] Rejection was treated with standard anti-rejection therapy. In addition, the maintenance immunosuppression therapy was optimized. Protocol biopsies were not performed. Graft loss was defined as the requirement of maintenance dialysis. They were maintained on dialysis in the setting of allograft failure.

Statistical analysis

All statistical analysis was performed using the Statistical Package for the Social Sciences (version 12.0; SPSS Inc., Chicago, IL, USA). Continuous variables were summarized as mean and standard deviations. Percentages were used to summarize categorical variables. Continuous variables were compared using Student's t-test. Chi-square test or Fisher exact test was used to assess the effect of change in differences in categorical variables. Survivals were examined using Kaplan–Meier analysis and compared using the log-rank test. P < 0.05 were considered significant.

Declaration of patient consent

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity.

Ethics statement

Institute ethics board with IRB board ESR/143/Inst/GJ/2013/RR19 approved this retrospective analysis during the meeting held on July 31, 2020. All protocols as per Declaration of Helsinki were followed.

  Results Top

Recipient and donor characteristics

Demographic data of LD and DD transplantation are shown in [Table 1]. The relation to recipient was mother (n = 100), father (n = 27), brother (n = 2), sister (n = 2), grand-parent (n = 5), extended family members (n = 15), and DD (n = 37). All the recipients/donors were ethnically homogeneous population (Asian). Monthly family income was < Rs. 5000 (50.3%), Rs. 5001–20,000 (39.7%), and >Rs. 20,000 (9.9%). Approximately 70% were on hemodialysis and remaining on peritoneal dialysis. Pretransplantation mean hemoglobin was 8.9 ± 1 g/dl, serum ionized calcium was 0.8 ± 0.09 mg/dL (reference range 1.12–1.32 mg/dL) and serum phosphorus was 5.5 ± 1.9 mg/dL (reference range 2.5–4.5 mg/dL); 69.5% of patients were anemic at the time of transplantation. Posttransplantation at 1 year, mean hemoglobin was 12.1 ± 2.1 g/dl, serum ionized calcium was 1.05 ± 0.09 mg/dL, and serum phosphorus was 4.3 ± 1.2 mg/dL.
Table 1: Comparison of demographic data in live and deceased donor kidney transplantation in our center

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Posttransplant outcome data

Kaplan–Meier analysis for survival is shown in [Figure 1]. Kaplan–Meier analysis for patient and graft survival in LD and DD transplantation is shown in [Figure 2] and [Figure 3], respectively. Comparison of outcome between LD and DD transplantation is shown in [Table 2]. As shown in [Table 2], there was no significant difference in patient survival, graft survival, and acute rejection in LD and DD transplantation. There was no significant difference in graft survival among CAKUT and non CAKUT group also.
Figure 1: Kaplan–Meier analysis for patient and graft survival in living donor transplantation

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Figure 2: Kaplan–Meier analysis for patient survival in living donor and deceased donors transplantation

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Figure 3: Kaplan–Meier analysis for graft survival in living donor and deceased donors transplantation

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Table 2: Comparison of outcome in live and deceased donor kidney transplantation at our center

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Posttransplant patient survival

As shown in [Table 3], in LD total of 17.8% (n = 27) of patients died, mainly due to posttransplant infections (n = 12). Among DD total of 27% (n = 10) of patients died, mainly due to infections (n = 6). Diagnosis of infection was made before dying; patients died in hospital; immunotherapy was reduced on admission/diagnosis of infection. Two patients who died from tuberculosis had reactivation of previous latent infection. Risk factors for posttransplant tuberculosis included allograft rejection occurring <6 months before the onset of TB and rATG administration. Total 18 patients (11 in LD, 7 in DD group) died with functioning graft.
Table 3: Etiology of patient loss in living donor versus deceased donor

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Posttransplant graft survival

As shown in [Table 4], etiologies of graft loss (n = 33) in LD group were graft necrosis with thrombosis of graft vessel within 2 weeks after transplantation(n = 4), graft necrosis with thrombosis of graft vessel and HCV positive at 9 months (n = 1), severe acute T + B-cell-mediated rejection and acute tubular necrosis (ATN) leading to graft necrosis with thrombosis of graft vessel at 2 months (n = 1), acute hemolytic-uremic syndrome (HUS) leading to acute cortical necrosis and thrombosis of graft vessel at 1 month (n = 1), CsA-induced thrombotic microangiopathy with patchy cortical necrosis at 5 months (n = 1), CsA toxicity (n = 3), Tac toxicity (n = 2), pyelonephritis (n = 2), mucormycosis of graft with vascular invasion at 11 months (n = 1), de novo anti-GBM at 5 months (n = 1), recurrence of primary IgA nephropathy at 2 years, 2.2 years, 3 years (n = 3), membranoproliferative glomerulonephritis recurrence at 3 years (n = 1), de novo HUS at 1.7 years (n = 1), and chronic rejection (n = 11). The etiologies of graft loss in DD group (n = 6) were vascular graft thrombosis within the first 3 months (n = 1), nonadherence to the immunosuppressive regimen and chronic rejection (n = 5).
Table 4: Etiology of graft loss in living donor versus deceased donor group

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Rejection episodes

As shown in [Table 2] and [Table 5], in LD group total of 19.8% (n = 30) of patients had biopsy proven acute rejection (BPAR). Acute B-cell-mediated rejections were noted in 6.6% (n = 10), acute T-cell-mediated rejections in 4.63% (n = 7), and combined acute T-and B-cell-mediated rejections in 8.6% (n = 13). Majority of BPAR were observed in 1st year and patients responded to anti-rejection therapy. Totally 10.5% (n = 16) patients had chronic rejections which included chronic-B-cell-mediated rejection in 3.31% (n = 5), chronic T-cell mediated in 3.31% (n = 5), and combined T + B-cell mediated in 3.97% (n = 6). ATN (n = 5), CsA toxicity (n = 6), Tac toxicity (n = 4), sirolimus toxicity (n = 2), BK virus nephropathy (n = 1), were other biopsy findings and kidney graft biopsy was unremarkable in 5 cases. In DD group, total of 21.6% (n = 8) patients had BPAR. Acute B-cell-mediated rejections were noted in 5.4% (n = 2), acute T-cell-mediated rejections in 10.8% (n = 4), and combined acute T-and B-cell-mediated rejections in 5.4% (n = 2). Totally, 10.8% (n = 4) patients had chronic rejection.
Table 5: Rejection episodes in living donor versus deceased donor

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None of the patients had posttransplant malignancy in both groups and recurrence of primary disease in the DD group.

  Discussion Top

KT is the best treatment for growth-related issues in children with chronic kidney disease and ESKD.[4],[33],[34],[35] Despite KT being the best available option for children with ESKD, very few centers in India perform more than five transplants a year.[36] The long-term outcomes, including rates of rejection and graft survival, are comparable to centers in developed countries.[35],[37] In addition to late detection and referral, economical constrains, limited access to tertiary care; a poorly developed cadaveric program, and misconceptions about organ donation have been other retarding factors for transplant programs.[24],[38],[39] We have one of the largest centers in our country for KT. Our State Government provides free treatment for kidney disease under School health program to all children up to the age of 18 years. We have reported our long-term single-center experience with DDKT in pediatric recipients.[8]

[Table 6] shows outcome of pediatric KT from individual centers in India. Sinha et al.[20] concluded that their results affirm that despite the scarcity of resources and frequent infections, the long-term outcome of pediatric KT is highly satisfactory. Gulati et al.[22] reported that CsA discontinuation (n = 12) due to financial constraints and/or noncompliance remain the most important reasons for suboptimal outcome in their study. The incidence of pediatric graft failure due to nonadherence is 10%–15%.[40],[41],[42],[43],[44],[45] Several studies have shown a high incidence of nonadherence particularly among adolescents and young adults.[40],[41],[42],[43],[44],[45] In our study, the limitations of our ability to detect posttransplant nonadherence was that it was determined by the personal assessment of drug intake by transplant team and parents. It was very difficult to measure the nonadherence accurately, and diagnosis was often selective (e.g., at the time of graft dysfunction/rejection/irregular follow-up). Comparing 3-year allograft survival from the latest The Organ Procurement and Transplantation Network/The Scientific Registry of Transplant Recipients data report between living and DD (transplanted 2012 and 2013), graft survival was 95.1 and 89.2%, respectively. The 5-year graft survival was 88.5% in living versus 81.8% in deceased transplants from 2010 to 2011 and 10-year graft survival was 45.8 vs. 30.5% in transplants from 2006 to 2007.[35],[46],[47] At our center, a higher incidence of graft failure in the LD group likely due to more rejections, higher graft vessel thrombosis and more CNI toxicity as compared to the DD group. Despite the incidence of BPAR almost similar in LD and DD groups (21 and 21%), there were no AR episodes in DD and only 3 had AR in LD children beyond 12 months, likely due to the effect of ATG (100% use in DD and 13% in LD).
Table 6: Outcomes of pediatric renal transplantation from individual centers in India

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Although initial results from steroid-avoidance protocols are encouraging, there is still a lack of long-term data from large, prospective randomized trials and there are not enough data to determine the optimal steroid-avoidance protocol for pediatric KT recipients.[28],[29],[30] We did not use steroid-avoidance protocols.

As per NAPRTCS data, percent patient survival estimates for recipients of index LD kidneys were 98.5 ± 0.2, 96.2 ± 0.3 and 92.7 ± 0.6 percent versus recipients of DD allografts 97.5 ± 0.2, 93.8 ± 0.4 and 88.0 + 0.8 percent at 1, 5, and 10 years posttransplant, respectively. Infection was the cause of death in 168 patients (28.4% of deaths).[18] However, major causes of death after transplantation are CVD, infection and malignancy, variously reported as 30%–36% for CVD, 24%–56% for infection and 11%–20% for malignancy.[48],[49],[50] Two other important factors that contribute to death are nonadherence to medications or treatment withdrawal and obesity.[26],[27],[40],[41],[42],[43] The major causes of death were infections in our study, similar to the experience by other studies in India.[20],[21],[22],[23],[24],[37] Infections are a common cause of morbidity and mortality after transplantation in Asia and account for half the deaths in posttransplant patients in India.[50] The high infection rate despite judicious use of immunosuppressive agents and infection prophylaxis is not specific to the pediatric population, but it is common in the transplantation setting in our country.[50] It is possible that unhygienic living conditions, delayed presentation and diagnosis, tropical climate, presence of dormant endemic infections, in addition to economic constraints for treatment in the majority of patients, may have contributed to the high infection rate, similar to experience by other studies.[20],[21],[22],[23],[24],[37],[51],[52]

Preemptive transplantation is the preferred modality in children because it is associated with better long-term outcome in terms of growth, development, quality of life, and mortality and stability in the social life of patients and their families.[17] Despite these advantages, preemptive transplantation is still not achieved in majority of children with ESKD in most of the centers of the world because patients present in CKD stage-5 with the insufficient preparatory time required for transplantation, small size, comorbidity, nonadherence to medical therapy, family instability or other factors.[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]

To our knowledge, this is the largest study of LDKT outcome in children from India with long-term follow-up and comparison with DDKT. Our reports add to current knowledge to encourage DD kidney transplants in pediatric recipients. However, prospective data with a larger sample size, which caters more than one center will be needed to confirm our analysis. By increasing the donor pool, choosing the right donor, encouraging preemptive transplants by giving extra points to pediatric recipients, and registering them on the basis of GFR, using infant donors; will improve the pediatric DD KT program.

Limitations of the study

Relatively small number of patients and single centre nature of the study are the limitations of the study.

  Conclusions Top

LDKT or DDKT in children has acceptable graft function with patient/graft survival over long-term follow-up, encouraging to develop sustained DD program in developing countries. However, infections are a major cause of morbidity and mortality.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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