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Table of Contents
ORIGINAL ARTICLE
Year : 2017  |  Volume : 11  |  Issue : 2  |  Page : 55-60

Outcome of live donor kidney transplantation in a Government Hospital of Nepal


1 Department of Nephrology, National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal
2 Department of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication12-Sep-2017

Correspondence Address:
Rajani Hada
Department of Nephrology, National Academy of Medical Sciences, Bir Hospital, Kathmandu
Nepal
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_7_17

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  Abstract 

Background: Live donor kidney transplantation (KT) was started in 2008 in Bir Hospital, a government hospital of Nepal. The present study aims to find out patient and graft outcome, and the factors influencing the graft survival. Methods: It is a retrospective analysis of all KT from December 2008 to May 2013. The immunosuppressive was induction with intravenous methylprednisolone and daclizumab (n = 39) or basiliximab (n = 34) or anti-thymocyte globulin (n = 22) and maintenance with steroid, calcineurin inhibitors (CNIs), and mycophenolate mofetil. All data of recipients and donors were obtained from hospital records. Kaplan–Meier method was used for survival analysis. Results: Totally, ninety-five patients with follow-up duration of 1.5–6.5 years were analyzed. Recipients and donors were disproportionate in age (74.7% vs. 16.8% below 40 years) and gender (87.4% male vs. 77.9% female), respectively. Delayed graft function was observed in 10.5%, and slow graft function in 9.5% of patients with recovery of graft function before discharge in all except two. Within 2 years, 4.2% patients died because of infection and sepsis. Graft loss was observed in 14.7% due to antibody-mediated rejection (noncompliance 50% and unaffordability to treat 21.4%) and recurrent glomerulonephritis (28.6%). Patient survival at 1, 3, and 6.5 years was 97.9%, 95.8%, and 95.8%, respectively. Death noncensored graft survival was 97.9%, 86.2%, and 77.5%, respectively and death censored graft survival was 100%, 90%, and 80.9%, respectively with no influence of induction agents and recipient and donor factors in graft survival. Conclusion: The early and intermediate-term patient and graft outcome is satisfactory and low socioeconomic status related noncompliance is the major cause of graft loss.

Keywords: Graft outcome, graft survival, kidney transplantation, live-donor transplantation, patient outcome, patient survival, transplantation in Nepal


How to cite this article:
Hada R, Prasad N, Baral A, Agrawal RK. Outcome of live donor kidney transplantation in a Government Hospital of Nepal. Indian J Transplant 2017;11:55-60

How to cite this URL:
Hada R, Prasad N, Baral A, Agrawal RK. Outcome of live donor kidney transplantation in a Government Hospital of Nepal. Indian J Transplant [serial online] 2017 [cited 2019 Aug 25];11:55-60. Available from: http://www.ijtonline.in/text.asp?2017/11/2/55/214392


  Introduction Top


Kidney transplantation (KT) is the best as well as the most cost-effective mode of renal replacement therapy (RRT) for end stage renal disease (ESRD) patients with better survival and quality of life compared to dialysis.[1],[2]

With increasing number of ESRD patients and better understanding of transplant immunology, donor pool has expanded from living donor to deceased donor, ideal donor to expanded criteria donor, and ABO/human leukocyte antigen (HLA) compatible to incompatible donors with comparable outcomes.[3]

The outcome of transplantation program in any center is measured from time to time by estimation of patient and graft survival. Living donor transplantation has better immediate and remote graft survival as compared to that of deceased donor transplantation;[4] although graft and patient survival is influenced by several pretransplant factors in donors and recipients and posttransplant complications in recipients such as delayed graft function (DGF), number and severity of rejection episodes, drug toxicity, infections, and other comorbid conditions.[5],[6]

Many developing countries have low rate of KT due to poverty, illiteracy, absence of infrastructure, trained human resources, and appropriate health policies. Moreover, live donor program is predominant in many countries with negligible deceased donor program in some due to religious, cultural, and social constraints and lack of deceased donor act.[7],[8]

Nepal, a developing country with low per capita income as per the World Bank criteria [9] had started ABO compatible legally related live donor KT in 2008 in two tertiary centers in the capital, two decades after the establishment of hemodialysis in the country.[10] So far, the outcome of KT in Bir hospital, the oldest government hospital of Nepal, has not been published and the present study aimed to find out early and intermediate-term patient and graft outcomes, and the factors affecting graft survival in these patients.


  Methods Top


The study was designed as a retrospective analysis of 95 KT recipients who underwent renal transplantation in 4½ years from December 2008 to May 2013. Recipient and donor demography, cause of ESRD, mode and duration of dialysis, blood group, donor recipient relationship, graft functional status, patient survival, and follow-up duration were obtained from hospital records.

Immunosuppression regimen

The immunosuppressive therapy for all patient except diabetics was triple therapy with tacrolimus (0.13 mg/Kg in two divided dosage), mycophenolate mofetil (500 mg BD if weight <50 Kg and 750 mg BD if weight >50 Kg), and steroid. Cyclosporine was used for patients with diabetes. Tacrolimus/cyclosporine and mycophenolate mofetil were started a day before the transplantation. Steroids were started with intravenous methyl prednisolone 500 mg as an induction therapy given just before releasing vascular clamp and oral prednisolone 20 mg from the first postoperative day.

Patients were also given induction immunosuppressive either with IL-2 receptor blockers (daclizumab 50 mg on day 0 and 14 or basiliximab 20 mg on day 0 and 4) or rabbit anti thymocyte globulin (ATG)-thymoglobulin (Sanofi-aventis) on day 0 (1.5 mg/Kg) followed by two more doses (1 mg/Kg) on successive days depending on total leukocyte and platelet count. Daclizumab (n = 39) and basiliximab (n = 34) were given according to availability and ATG (n = 22) was given for a history of previous transplant (n = 1), panel reactive antibody (PRA) >30% (n = 9), Luminex crossmatch (lysate) positive with anti-HLA Class II donor specific antibody and negative complement dependent cytotoxic crossmatch (n = 5) and due to unavailability of IL-2 blocker (n = 7).

First tacrolimus/cyclosporine level estimation was done on the 4th postoperative day. The dose of tacrolimus was adjusted to keep the trough level of 8–10 ng/ml in first 3 months, 6–8 ng/ml in 3–6 months and 5–7 ng/ml afterward and cyclosporine dosage was adjusted to keep trough level of 200–250 μg/dl in first 3 months, 125–200 μg/dl in 3–6 months, and 75–125 μg/dl after 6 months onward. Prednisolone dose was 20 mg daily for 1 month followed by tapering of 2.5 mg every 2 weeks until 5 mg and then continued forever. All patients were also given PCP prophylaxis with cotrimoxazole 490 mg daily for 6 months and cytomegalovirus (CMV) prophylaxis with valganciclovir 450 mg once a day for 90 days to patients with ATG as an induction therapy and KT from CMV D+ to R− patients.

The day of transplantation was considered as the initial event and the day of the last follow-up, day of death of patient and day of graft loss with the need of initiation of maintenance dialysis was considered as the day of final event.

For analyzing the survival rate (patient and graft), Kaplan–Meier probability estimate was used and expressed with 95% confidence interval. Patient survival was calculated from the date of transplant to date of death or last follow-up whereas graft survival was calculated from date of transplant to date of irreversible graft failure signified by the need of maintenance dialysis or date of last follow-up during the period when the graft was still functioning or date of death. Graft survival is calculated both as censored to death with a functioning graft and noncensored to death.


  Results Top


The demography and baseline characteristics of recipient and donor are shown in [Table 1]. The age and gender were disproportionate with recipient being younger (74.7% below 40 years) and of male (87.4%) gender and donors being older (63.2% above 40 years) and of female (77.9%) gender because the most common cause of ESRD was chronic glomerulonephritis (GN) affecting young people and 45.3% donors were parents. All donors were legally related with 66.3% being parents, siblings or children, 28.4% being spouse and remaining were paternal uncle and mother-in-law.
Table 1: Baseline characteristics of recipient and donor

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Pretransplant RRT was maintenance hemodialysis in 89 (93.7%) with duration of dialysis up to 12 months in 80 (89.9%) and continuous ambulatory peritoneal dialysis in 2 (2.1%). Four (4.2%) patients had preemptive transplant. History of blood transfusion was present in more than two-third of patients, and CMV status was positive in all except two who received kidney from CMV positive donor. Blood group was same in 78.9% and compatible in remaining. All the recipients and donors were hepatitis B, hepatitis C, and HIV negative.

Early patient and graft outcome

All patients were discharged with functioning graft and there was no mortality during hospitalization. The early graft function (EGF), final serum creatinine (SCr) at discharge and duration in days for reduction of SCr to <1.5 mg/dl is shown in [Table 2]. All patients had normal SCr at discharge except 2 (2.1%), who never had normal SCr even in follow-up. Among the patients with poor EGF (n = 19), allograft biopsy showed acute tubular necrosis (ATN) in 9, acute cellular rejection (ACR) in 2, and acute interstitial nephritis in 1, donor scarred kidney in 1, and mesangial proliferative GN in 1. Remaining had DVT of femoral vein, uncontrolled sugar, tacrolimus toxicity, ATN, and steroid responsive ACR, as the cause of poor EGF each in one patient.
Table 2: Early graft functional status

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Final patient and graft outcome

Final patient and graft outcome, duration of follow-up, final SCr of patients surviving with graft function (SWGF), etiology of death and graft loss is shown in [Table 3]. Four patients died with a functioning graft, all within 1 year of transplant and due to sepsis. Three of them had an induction with IL-2 blocker and one received ATG for high PRA, and the earliest death was at 2 months due to urosepsis after removal of double J stent.
Table 3: Final patient and graft outcome

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Allograft biopsy showed antibody-mediated rejection (AMR) (n = 10) and recurrent GN (n = 4) as the cause of graft loss. AMR was due to noncompliance to drug (n = 7) and remaining (n = 3) refused treatment of AMR with ultimate graft loss. Recurrent GN was IgA nephropathy (n = 3) and necrotizing GN (n = 1).

Among patients SWGF, chronic renal allograft injury was due to recurrent IgA nephropathy (n = 2), focal segmental glomerulosclerosis (n = 1), chronic transplant glomerulopathy (n = 1), interstitial fibrosis/tubular atrophy (n = 1), BK virus nephropathy (n = 1), steroid nonresponsive ACR (n = 1), and unknown etiology as biopsy was not done (n = 2).

Patient and graft survival rate

Survival analysis has shown patient survival rate at 1, 3 years and end of study of 97.9%, 95.8%, and 95.8%, respectively [Figure 1]a with no significant difference between different induction agents daclizumab, basiliximab, and ATG (100% vs. 94.1% vs. 100% at 1 year and 97.4% vs. 94.1% vs. 95.5% at end of the study), respectively [Figure 1]b.
Figure 1: (a) Patient survival rate. (b) Patient survival rate among different induction agent.

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The 1–4 years and end of the study noncensored graft survival of patient was 97.9%, 88.4%, 86.2%, 80.7%, and 77.5%, respectively and 1 year and end of the study noncensored graft survival in daclizumab induction group was 100% and 73.5%, in basiliximab induction group was 94.1% and 84.6% and in ATG induction group was 100% and 86.4%, respectively [Figure 2]a and [Figure 2]b.
Figure 2: (a) Death noncensored graft survival rate. (b) Death noncensored graft survival rate among different induction agent.

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The 1–4 years and end of the study death censored graft survival of patient was 100%, 92.3%, 90%, 84.3%, and 80.9%, respectively and 1 year and end of the study noncensored graft survival in daclizumab induction group was 100% and 75.4%, in basiliximab induction group was 100% and 89.8% and in ATG induction group was 100% and 90.5%, respectively [Figure 3]a and [Figure 3]b.
Figure 3: (a) Death censored graft survival rate. (b) Death censored graft survival rate among different induction agent.

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  Discussion Top


KT resumes complete kidney function with increased risk of life threatening infection and cardiovascular morbidity compared to general population and the possibility of graft loss at any time.[11],[12],[13] Multiple factors related to patient and health facility for early detection and treatment of complications have a direct impact on the outcome. Moreover, poverty and ignorance with increased noncompliance to drugs and low hygienic status have shown the direct negative impact on transplant outcome in developing countries.[14]

The present study has analyzed the early and intermediate-term patient, and graft outcomes in a resource limited low-income country with no facility for HLA typing, HLA crossmatch, and calcineurin drug level monitoring until 2011. All these tests were done by sending the blood sample to India with reports to reach us in another 5–6 days.

Although excellent EGF is the goal, poor EGF described as DGF needing posttransplant dialysis and slow graft function (SGF) taking a longer time to normalize the allograft function is observed more in deceased donor transplant compared to live donor transplant [15] and predicts acute rejection and poor long-term graft outcome.[16],[17] In the present study, the incidence of poor EGF was found in 20% (DGF in 10.5% and SGF in 9.5%) patients. It is slightly higher than the reported incidence of poor EGF after live donor KT from centers in the USA with 15.4% of transplantation from 1997 to 2001[18] and 16.3% of transplantation from 1996 to 2005[16] and a center in the Netherlands with 13.7% of transplantation from 1996 to 2010.[17] In all these reports, poor EGF was shown to be associated with worse acute rejection-free survival and worse graft survival directly or indirectly due to acute rejection. Fortunately, in our cohort, all patients with poor EGF except two had recovered complete renal function before discharge from hospital showing posttransplant normal allograft function in a total 97.9% of recipients and poor EGF was not related to donor factors except one patient with Alport's syndrome with mother being donor and biopsy revealed scarred kidney.

Patient's death with graft function (DWGF) is the biggest setback of the transplant program and infections due to immune-compromised state, particularly in the early period and cardiovascular events in the later period are major causes of mortality.[11],[12] Incidences of DWGF among live donor transplant till 2002 were reported to be 6.3% to 9.7% from Japan and Egypt with infection and cardiovascular disease as the main culprits.[19],[20] The median time to DWGF was found to increase from about 1 year in 1969 to 10 years in 2005 due to better management of cardiovascular risk factors, superior immunosuppressive protocol, and better prophylaxis and treatment of infectious disease in a center in the US.[21] A report from a center in India has shown DWGF in 22.4% of live donor transplant (n = 98) from 1998 to 2010, and the cause of death were an infection in 40.9% and cardiovascular disease in 36.4%. All infection-related mortality occurred within 5 years, and cardiovascular mortality occurred both within and after 5-year posttransplant.[22] In the present study, out of total 95 patients, DWGF occurred in 4.2% patients, two deaths within 1st year and two deaths in 2nd year of transplant with infection being the cause of death in all with no cardiovascular mortality that could be related to young age of recipients, fewer diabetic recipients and shorter duration of dialysis.[12],[13] Renal allografts are always at risk of acute and chronic immunological and nonimmunological injury leading to acute and chronic graft dysfunction and ultimately graft loss.[23],[24] Until, the last day of follow-up, 81.1% of our patients were surviving with functioning graft and chronic allograft renal injury with mean SCr of 2.3 mg/dl was found in 9.5%. Surveillance renal biopsy with clinical and histological evaluation of allograft recipients in Mayo clinic had revealed the death censored graft loss in 11.6% and the etiology were glomerular disease (36.6%), fibrosis/atrophy (30.7%), medical/surgical condition (16.3%), acute rejection (11.8%), and unclassified (4.6%) and the etiology of acute rejection was noncompliance to immunosuppressive medication in one-third patients.[25] Noncompliance is a nonimmunological factor causing increased immunological injury (acute rejection) and thereby graft loss and related to multiple factors including low socioeconomic condition, low level of education and young age.[26] In the present study, death censored graft loss occurred in 14.7% and the cause of graft loss was biopsy proven AMR in 71.4% and glomerular disease in 28.6%. Unfortunately, AMR was related to noncompliance to drugs (not affording drugs) in 70% of patients, and the remaining 30% refused AMR treatment due to the high costs of the therapy.

Kaplan–Meier survival analysis with patient survival rate of 97.9%, 95.8%, and 95.8% at 1, 2, and 6.5 years in the present study is very encouraging and superior to published reports from India and Iran with patient survival rate of 90.8% and 80.2% (at 1 and 5 years)[22] and 95.6% and 93.9% (at 1 and 3 years),[4] respectively. Moreover, death censored graft survival rate at 1 year (100%) is exemplary. However, the graft survival rate at 3 years (90%) is inferior to reports (96.2%–96.4%) from different centers of Iran.[4],[27] Multiple recipient and donor related factors such as cause of ESRD, duration of dialysis, preallosensitization status, type of immunosuppressive drugs used, donor age and sex, SCr at 1 year posttransplant, EGF status and acute rejection episodes were shown to affect graft survival rate.[5],[6],[28],[29] In the present study, PRA ranged from 0% to 32.5% among patients with AMR, and none had anti-HLA Class II donor specific antibody by Luminex crossmatch (Lysate). All patients received similar maintenance immunosuppressive regimens and comparison of patient and graft survival among patients with daclizumab, basiliximab, and ATG induction showed no difference. Moreover, regression analysis has shown no influence of all other factors mentioned above in graft survival. If noncompliance could have been avoided, probably the graft survival rate at 3 years and >5 years would have been better.

The major limitation of the study is the retrospective nature of the data analyzed. The present study could not incorporate CNI drug concentrations at the time of graft dysfunction, evaluation for new-onset diabetes after transplantation, use of CYP inhibitors for drug augmentation.


  Conclusion Top


The early and intermediate-term patient and graft outcomes are satisfactory and comparable to other centers. Low socioeconomic status-related noncompliance is the major cause of graft loss.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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