|Year : 2021 | Volume
| Issue : 2 | Page : 55-61
Kidney transplant and its outcomes: Five-year single-center experience from Central India
Riteshkumar Krishnanarayan Banode, Piyush D Kimmatkar, Charulata P Bawankule, Vandana P Adamane
Department of Nephrology, Government Medical College and Superspeciality Hospital, Nagpur, Maharashtra, India
|Date of Submission||12-Aug-2021|
|Date of Decision||19-Sep-2021|
|Date of Acceptance||05-Oct-2021|
|Date of Web Publication||30-Dec-2021|
Riteshkumar Krishnanarayan Banode
Department of Nephrology, Government Medical College and Super Speciality Hospital, Beside Rashtra Sant Tukdoji Cancer Hospital, Hanuman Nagar, Manewada Road, Nagpur - 440 024, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Kidney transplantation has become the treatment of choice for most patients with end-stage kidney disease (ESKD). However, there is a remarkable disparity in the access and outcome of kidney transplant across the world. We present the clinical and survival data from the nephrology and kidney transplantation center for a period of 5 years in a cost-limited setting from Central India.
Materials and Methods: This is a retrospective study of 66 kidney transplants performed in a single transplant center over a period of 5 years from 2016 to 2020. All data of recipients and donors were obtained from hospital records. Kaplan–Meier method was used for survival analysis.
Results: Of 66 included patients, 86% were living donor and 14% were cadaveric kidney transplant. The mean age of the recipient was 30.64 ± 10.66 years. Fifty-five (83%) were male recipients and 11 (17%) were female recipients. The most common cause of ESKD in recipients was chronic glomerulonephritis (55%). The mean hemodialysis vintage was 11.04 ± 10.12 months. Seventy-four percent of donors were female and 24% of donors were male. Induction therapy with rabbit antithymocyte globulin was used in 20 (30%) and basiliximab in 21 (32%) recipients. Thirty (45%) recipients underwent graft kidney biopsy in view graft dysfunction. Acute cellular rejection was the most common cause of graft dysfunction seen in 8 (28%) of graft kidney biopsy. Graft survival and patient survival at 1, 3, and 5 years after transplant were 89%, 81%, and 77% and 90%, 84%, and 81%, respectively.
Conclusions: Our observation showed that graft survival and patient survival after transplant were lower compared to other studies due to higher rejection rate and mortality due to infections. Hence, attention to immunological risk factors with proper immunologic testing pretransplant and early detection and adequate treatment of rejection episode even in cost-limited settings are suggested. Also after kidney transplant, prevention and prompt treatment of infection would offer the greatest potential to improve the chance of living longer with functioning graft.
Keywords: Graft function, graft survival, kidney transplant, outcome, rejection
|How to cite this article:|
Banode RK, Kimmatkar PD, Bawankule CP, Adamane VP. Kidney transplant and its outcomes: Five-year single-center experience from Central India. J Curr Res Sci Med 2021;7:55-61
|How to cite this URL:|
Banode RK, Kimmatkar PD, Bawankule CP, Adamane VP. Kidney transplant and its outcomes: Five-year single-center experience from Central India. J Curr Res Sci Med [serial online] 2021 [cited 2022 May 24];7:55-61. Available from: https://www.jcrsmed.org/text.asp?2021/7/2/55/334463
| Introduction|| |
Kidney transplantation remains the best therapy for patients with end-stage kidney disease (ESKD). Over the period of time, marked improvements in early graft survival and long-term graft function have made kidney transplantation a more cost-effective alternative to dialysis., However, there is a remarkable disparity in the access and outcome of kidney transplant across the world. This is due to modest expenditure on health care by governments and economic deprivation leading to relatively poor transplantation activity in developing countries. There are no current regional data on the magnitude and pattern of chronic kidney disease (CKD) in Vidharbha region of Central India. Farming is the main occupation of population staying at this region, with majority of CKD patients from poor socioeconomic background. High incidence of CKD of unknown origin has been reported at many parts from this region linked to extreme heat during summer causing dehydration and contamination of drinking water with lead, copper, and cadmium from clay soil and pesticides.
Our hospital is a tertiary care government hospital in Vidharbha region of Central India and only government hospital providing both live donor kidney transplant and deceased donor kidney transplant (DDKT) services. Herewith, we present the clinical and survival data from the nephrology and renal transplantation center for a period of 5 years. Although studies on kidney transplant outcome are available from various institutes from India, there is no data available from Central India till to date. Our study will highlight the challenges of managing patients with kidney transplant including the limitations that the caregivers including nephrologists encounter with these patients.
| Materials and Methods|| |
This is a retrospective study performed in a single transplant center over a period of 5 years from 2016 to 2020. Ours is a both live and deceased donor, blood group compatible kidney transplant program. All patients were transplanted for the first time. Data were collected through a review of patient's medical records, hospital records, and transplantation clinic follow-up data. Detailed evaluation of both donor and recipient was done prior to transplant as per the standard hospital protocol and clearance from authorization committee. All the patients were ascertained to be free from any medical, surgical, or psychosocial factors that could be a contraindication for kidney transplantation. All patients underwent only complement-dependent cytotoxicity (CDC) crossmatch due to financial constraints. Outcome of transplant was assessed and data were collected and analyzed in terms of graft function (measured as serum creatinine, urine analysis, and proteinuria at various intervals of follow-up), incidence of graft dysfunction and rejection, incidence of major infections, new-onset diabetes after transplant (NODAT) in previously nondiabetic patients, graft failure and cause of graft failure, mortality, and cause of death. Delayed graft function (DGF) was defined as the requirement of dialysis during the 1st week after transplantation. Slow graft function (SGF) was defined as a slower decline in serum creatinine compared to immediate graft function but without the need for dialysis. Acute rejection was defined as an acute worsening in allograft function associated with specific pathologic changes in the graft. Patients who had graft dysfunction underwent graft biopsy and were diagnosed as per the modified Banff classification.
Patients received either no induction or basiliximab 20 mg (day 0 and day 4) or rabbit antithymocyte globulin (r-ATG), 1.5 mg/kg single dose, administered intraoperatively depending upon recipients risk profile for rejection. All patients received methylprednisolone 1000 mg day 0 and 250 mg on days 1 and 2. Immunosuppressive agents, i.e., calcineurin inhibitors (CNIs), mycophenolate mofetil (MMF), and steroids, were started 2 days before the transplant. CNIs, MMF, and steroids were given as maintenance immunosuppression. All patients received urinary tract infection (UTI) and cytomegalovirus (CMV) prophylaxis for the first 6 months. Rejection was treated with standard antirejection therapy. Cellular rejections were treated with methylprednisolone ± r-ATG. Antibody-mediated rejections were treated with methylprednisolone + plasmapheresis + intravenous immunoglobulin ± rituximab.
All the analysis were carried out on SPSS statistical software version 16.0 (SPSS Inc., Chicago, IL, USA). The results are presented in frequencies, percentages, and mean ± standard deviation. The Chi-square test was used to compare categorical and the unpaired t-test was used to compare continuous variables. P ≤ 0.05 was considered statistically significant. For analyzing the survival rate, Kaplan–Meier probability estimate was used. Patient survival was calculated from the date of transplant to the date of death or last follow-up whereas graft survival was calculated from the date of transplant to the date of irreversible graft failure signified by the need of maintenance dialysis or date of the last follow-up with functioning graft or date of death.
| Results|| |
Total 66 kidney transplants have been performed from 2016 to 2020 at our hospital which include 57 (86%) live donor and 9 (14%) deceased donor kidney transplants. The mean age of the recipient was 30.64 ± 10.66 years. The youngest recipient was 15 years old and the eldest was 64 years old. Out of total transplants, 55 (83%) were male recipients and 11 (17%) were female recipients. Eleven (17%) recipients were seropositive for hepatitis C virus (HCV) at the time of transplant. Fifty-two (79%) transplants were done under government-sponsored scheme. The etiology of ESKD in the recipients was varied and was presumptive in most cases, the details of which are given in [Figure 1]. The most common cause of ESKD in the recipients was chronic glomerulonephritis (55%), followed by chronic interstitial nephritis (23%), IgA nephropathy (8%), diabetic kidney disease (6%), and focal segmental glomerulosclerosis (4%). All patients were on maintenance hemodialysis prior to transplant. The mean hemodialysis vintage was 11.04 ± 10.12 months. Seventy-four percent of donors were female and 24% were male donors. The mean age of donors was 48.83 + 11.17 years. All the live donors were either biologically related (parents, siblings, and uncle) or emotionally related (spouses); none was unrelated. HLA typing was done only in live donor transplant. 62% of patients had three or less HLA mismatches. Induction therapy with r-ATG was used in 20 (30%) recipients, basiliximab in 21 (32%), and anti-human T-lymphocyte immunoglobulin in 1 (2%) recipient. Twenty-four (36%) did not receive any induction therapy prior to transplant. Note of any significant medical and surgical complication from transplant surgery till discharge was done [Table 1]. Forty (61%) recipients had uneventful course posttransplant surgery. Seven (11%) had DGF due to ischemic acute tubular injury, 2 (3%) had SGF, 4 (6%) had acute cellular rejection, and 1 (2%) had acute antibody-mediated rejection. Three (5%) developed postsurgery perinephric hematoma requiring surgical re-exploration. Other events observed are shown in [Table 1]. The average serum creatinine level at discharge, 3 months, 6 months, 1 year, and 2 years posttransplant was 1.12 ± 0.75 mg/dl, 1.18 ± 1.10 mg/dl, 1.19 ± 0.55 mg/dl, 1.28 ± 0.96 mg/dl, and 1.26 ± 0.65 mg/dl, respectively. Thirty (45%) recipients underwent graft kidney biopsy in view of graft dysfunction [Table 2]. Acute cellular rejection was the most common cause of graft dysfunction seen in 8 (28%) of graft kidney biopsy, followed by chronic active ABMR in 5 (17%), mixed rejection in 4 (14%), CNI toxicity in 4 (14%), donor age-related changes in 3 (10%), acute ABMR in 1 (3%), chronic active T-cell-mediated rejection in 1 (3%), acute tubular injury in 1 (3%), BK virus nephropathy in 1 (3%), and graft pyelonephritis in 1 (3%) of graft kidney biopsy [Table 3]. Recurrence of posttransplant glomerulonephritis was seen in 4 (6%) patients (IGA nephropathy in 3 and membranous nephropathy in 1). Three patients had coexisting rejection and one patient presented with subnephrotic proteinuria. Noncompliance with immunosuppression causing rejection was noted in only one patient. The most common infection posttransplant was UTI seen in 14 (21%) recipients, followed by sepsis in 2 (3%), CMV reactivation in 1 (1.5%), BK nephropathy in 1 (1.5%), viral encephalitis in 1 (1.5%), diabetic foot in 1 (1.5%), pulmonary tuberculosis in 1 (1.5%), esophageal candidiasis in 1 (1.5%), and bacterial pneumonia in 1 (1.5%) recipient. Nine (14%) recipients were infected with COVID-19 with mild-to-moderate symptoms and all recovered [Table 3]. NODAT was seen in 5 (8%), posttransplant erythrocytosis (PTE) in 5 (8%), and CNI toxicity in 7 (10%). The mean posttransplant follow-up period was 28 ± 15.5 months. Fifty-four (82%) recipients had functioning graft after 28 months of average follow-up, of which 65% had normal graft function. Chronic graft dysfunction was observed in 7 (11%) due to rejection, 3 (4.5%) due to interstitial fibrosis and tubular atrophy, and 1 (1.5%) due to native kidney disease recurrence [Figure 2]. Graft loss due to death occurred in 10 (15%) recipients and 2 (3%) due to rejection. Seven (70%) deaths were due to infections and 3 (30%) due to cardiovascular causes. On comparison at 1 year, the mean serum creatinine in recipients with rejection was 1.79 ± 1.34 mg/dl and those without rejection had a mean serum creatinine of 1.11 ± 0.42 mg/dl, and the difference between the two groups was significant (95% confidence interval: 0.29–1.0, P = 0.0007). Kaplan–Meier survival curve analysis showed that graft survival was 89% at 1 year, 81% at 3 years, and 77% at 5 years posttransplant and recipient survival was 90%, 84%, and 81% at 1, 3, and 5 years after transplant [Figure 3] and [Figure 4].
|Figure 1: Native kidney disease in recipients. CGN: Chronic glomerulonephritis, CTIN: Chronic tubulointerstitial nephritis, IGAN: IgA nephropathy, DKD: Diabetic kidney disease, FSGS: Focal segmental glomerulosclerosis, PUV: Posterior urethral valve, MN: Membranous nephropathy|
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| Discussion|| |
Kidney transplantation, although the treatment of choice for ESKD, is still infrequently performed in developing countries. The prevalence of ESKD requiring transplantation in India is estimated to be between 151 and 232 per million populations. It is estimated that near about 220,000 people require kidney transplantation in India. However, currently, approximately 7500 kidney transplantations are performed at 250 kidney transplant centers in India. Of these, more than 90% come from living donors and <10% from deceased donors. The mean age of the recipients in our study was 30.64 ± 10.66 years. Krämer et al. in an observational study from Italy reported the average age of recipients to be 43 years. In an Indian study by Gupta et al., the mean age of patients was 35.61 years. The average age of recipients in our study is lower than that observed in the Western population, thus ESKD patients in the subcontinent are younger as compared to their Western counterparts. This may be due to delay in detection and failure to institute strategies that delay progression of renal failure contributes to ESKD at a younger age and younger ESKD patient given priority for kidney transplant. Moreover, majority of our recipients underwent a living donor kidney transplant, with donors being their relatives; they received the kidney transplant at a relatively younger age. Whereas in the Western world, most of the patients undergoing renal transplant are with cadaveric donors, hence their wait time for receiving a transplant may be higher. The gender distribution among recipients in our study group was constituted by 83% of males and 17% of females which suggestive that male patients were preferred for kidney transplant, as represented by the male to female ratio of 5:1. Similarly, 74% of donors were female and 24% were male donors. Mittal et al. also noticed a similar observation in their study in which 72.2% of donors were females. In our study, the mean age of donors was 48.83 + 11.17 years. The median age of donors in a study from the US was 41 years. We observed that 48% of donors were mothers, followed by 15% by fathers and 11% by wives. Muthusethupathi et al. in a study from a government hospital reported that 37% of all donors were mothers, and the kidneys went mostly to their sons (76%); 29% of donors were sisters, and 88% of the beneficiaries of these kidneys were brothers. This could be attributed to the sociocultural peculiarities of Indian populations, where male gender has preferred status. Eighty-six percent of our transplants were from live donors and 14% were from deceased donors. Among countries with active kidney transplant programs, the proportion of kidney transplants from living donors varies from <5% to more than 70%. Living kidney donation represents between one-third and one-half of all kidney transplants in the United States. Deceased donor kidney transplant (DDKT) is still infrequent in India, constituting <10% of the total renal transplants. Seventy-nine percent of transplants were done under government-sponsored scheme in our hospital as majority of patients were from low socioeconomic background. Seventeen percent of recipients in our study were seropositive for HCV at the time of transplant. HCV prevalence varies in ESKD patients on hemodialysis from 4% to as high as 20%. High prevalence of HCV infection in our cohort may be due to higher dialysis vintage pretransplant, and most of our patients were on dialysis at peripheral dialysis units where compliance with the infection transmission prevention measures is poor. All HCV-positive recipients in our study were treated with directly acting antiviral (DAA) postkidney transplant due to nonavailability of DAA which can be used in ESKD patients on hemodialysis at our center. All patients were evaluated pretransplant to know the underlying native kidney disease. Based on the previous medical history, laboratory records, radiological evidences, kidney biopsy (if done), and clinical features, the native kidney disease of the patients was noted. Chronic glomerulonephritis (55%) was the most common cause of ESKD in the recipients; similar observations were seen from other developing countries., This is in contrast to studies in which diabetes was the most common cause of CKD in India. The most probable reason for this may be as the mean age of diabetic patients who reach ESKD is about 60 years and recipients in our study were of younger age. All recipients were on maintenance hemodialysis prior to kidney transplant, none was on peritoneal dialysis, and none was preemptive transplant. The mean duration of pretransplant hemodialysis was 11.04 ± 10.12 months which is much shorter as compared to the Western world as this higher duration of dialysis may be due to higher waiting period as majority of transplants done in Western countries are cadaveric transplant. This is consistent with a report of only 2.5% of incident patients with ESKD undergoing transplantation as their initial modality of treatment. Both peritoneal dialysis and preemptive transplant are underused modality of kidney replacement therapy in India. Sixty-four percent of our recipients received induction therapy before transplant. Basiliximab was used in 32% of recipients and r-ATG in 30% of recipients and anti-human T-lymphocyte immunoglobulin in 2%. No induction was given in 36% of patients. Selection of induction therapy was based on the risk–benefit considerations for each patient. Patients with high immunological risk, multiple blood transfusions, and cadaveric transplant received r-ATG. Patients with low-to-intermediate risk received basiliximab or without induction depending upon patient preferences and financial constraints as cost of induction was not covered under government scheme. There is considerable heterogeneity between centers regarding the use of induction agents specifically; this did not appear to be guided by standardized rules but seemed to depend more on center-specific practices than on evidence-based results. The use of r-ATG between the centers ranged from 41% to 75%. We prefer to give basiliximab induction even in low-to-intermediate risk patients, however, 36% of recipients did not receive induction due to financial constraints. Forty-five percent of recipients underwent graft kidney biopsy at some point of time during follow-up period in view graft dysfunction. The most common cause of graft dysfunction was acute cellular rejection in 28% of graft kidney biopsy followed by chronic ABMR in 17% and mixed rejection in 14%. Of all cases of graft dysfunction, 64% of graft dysfunction was due to graft rejection (44% had acute rejection and 20% had chronic rejection). Although recurrence of glomerulonephritis was seen in 6% of recipients, it was detected coexisting with rejection in majority of patients. In an Indian study, acute rejection was observed in 27.3% of cases. Thus, the incidence of rejection was higher in our study. Guidelines recommend performing CDC crossmatching, flow crossmatching, and donor-specific antibody (DSA) testing in all renal transplant recipients before proceeding to renal transplant. We performed only CDC crossmatching, irrespective of sensitization history, due to financial constraints and nonavailability of other immunologic tests at our center. When we consider our current evidence, flow crossmatching and DSA should be performed in patients with history of sensitization. With the higher rejection rates and poor graft survival due to inadequate immunologic work-up shown here, best efforts should be made for advanced immunologic work prior to transplant, even in resource-limited settings.
UTI was the most common infection encountered as seen in most other studies, and our figure of 21% is comparable to their observation., Nine (14%) of our transplant patients were infected with COVID-19 infection with mild-to-moderate symptoms, all treated in inpatient department with remdesivir and dose reduction of MMF. All recovered, but three recipients developed graft rejection (two – mixed rejection and one – CABMR) post-COVID-19 in subsequent month. Studies have shown high mortality in transplant recipients, but luckily, our recipients recovered without any serious complication. However, whether rejection in three out of nine recipients is related to direct COVID-19 viral effect or consequence of immunosuppression reduction during COVID illness is unexplained. More experience and research in coming time may improve our understanding. Post transplant erythrocytosis (PTE) was seen in 8% of recipients and reported prevalence in literature ranges from 8% to 15% of kidney transplant recipients and usually affects patients with well-preserved graft function. In our study, the mean posttransplant follow-up period was 28 ± 15.5 months. Fifty-four (82%) recipients had functioning graft after 28 months of average follow-up. The kidney allograft survival at 1, 3, and 5 years after transplant was 89%, 81%, and 77%, respectively, and patient survival 90%, 84%, and 81% at 1, 3, and 5 years after transplant, respectively. A study from Chandigarh, India, reported that the renal allograft survival at 1, 3, and 5 years after transplant was 94%, 90%, and 79%, respectively, and patient survival at 1, 3, and 5 years after transplant of 92%, 87%, and 83%, respectively. In a study from neighboring country, 1- and 5-year graft survival rates were 92% and 85% and patient survival rates were 96% and 90%, respectively. The overall 1- and 5-year graft and patient survival in our study was lower than these studies. This lower graft survival was due to higher rejection rate. Furthermore, many of our recipients had delayed and inadequate treatment of rejection episodes due to financial constraints. Majority of our patients were from lower socioeconomic status and financially drained out by pretransplant hemodialysis expenses and do not have resources for antirejection therapy as r ATG, IVIG, rituximab, plasma filters were not available under government scheme. Although noncompliance with immunosuppression was uncommon in our cohort, but delay in reporting may be one of the factors for poor outcome in our study as majority of our patients were from a rural area with inadequate health infrastructure. The mortality rate was 10 (15%) in our study and 70% of deaths are due to infections and 30% were from cardiovascular diseases. Most common cause of mortality in our patient is due to infections which is in contrast to the observation from Western world where cardiovascular events were major cause of death post transplant. A study from BHU, India, also reported 25.51% mortality among their cohort over a mean follow-up of 79.91 ± 60.05 months, with infections as a leading cause of death. Although transplant recipients are susceptible to invasive fungal infection but we did not report invasive fungal infection in our cohort, this may be due to small sample size. These higher rates of mortality are related to higher prevalence of infectious diseases in our country similar to other developing countries.
Our study has certain limitations; first, the retrospective design restricts the amount of data that can be collected from the medical records of the patients. This study was done at low-volume transplant center, so learning curve of transplant team could have affected the outcome. Furthermore, because of small sample size, no comparative analysis was done which could be more informative. With each year, a number of kidney transplants done at our center are rising. Furthermore, many new transplant centers are coming up in near future in this region. Hence, a larger prospective multicentric study in future might help us in predicting the long-term outcomes of the graft.
| Conclusions|| |
Ours was a single-center observational study in resource-limited government setting, with majority of patients from lower socioeconomic status. Our recipients were relatively younger with majority recipients were male and donors were female indicating male gender bias in Indian society where males are preferred as kidney recipients and females are preferred as kidney donors. Our observation showed that graft survival and patient survival at 1, 3, and 5 years after transplant were lower compared to other studies due to higher rejection rate and higher mortality due to infections. Hence, attention to immunological risk factors with proper immunologic testing pretransplant, early detection, and adequate treatment of rejection even in cost-limited settings is suggested. Also after kidney transplant, prevention and prompt treatment of infection would offer the greatest potential to improve the long term graft and patient survival. Enhancement of the capacity of the public health-care system providing transplantation services, coverage of immunosuppression medication, and antirejection therapy under government schemes will not only improve transplant numbers but overall patient and graft survival.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]