Indian Transplant Recipients Research Articles

Infections in Hematopoietic Stem Cell Transplant Recipients in India – Think Global, Act Local

Infections in Hematopoietic Stem Cell Transplant Recipients in India – Think Global, Act Local

A Single Centre Case-Series of Covid-19 Infection in Kidney Transplant Recipients

INTRODUCTION: Severe acute respiratory syndrome coronavirus (SARS-CoV) has mutated over time, affecting its virulence, pathogenicity and disease severity. In December 2019, a new coronavirus (SARS-CoV-2) has emerged causing a disease known as coronavirus disease (COVID-19). The COVID-19 has a broad spectrum of severity ranging from an asymptomatic to a severe acute respiratory syndrome requiring mechanical ventilation. COVID-19 is often more severe in people aged 60 years or more, or those with health conditions like lung or heart disease, diabetes, or conditions that affect the immune system including kidney transplant recipients. In this case series, we presented our experience with 17 kidney transplant recipients who had COVID-19 infection. In India, COVID-19 peaked twice: once between August and November 2020, and again between March and June 2021. Thus, there was paucity of COVID-19 data in kidney transplant recipients in India during these times. MATERIAL AND METHODS: Our case series constituted a retrospective observational study involving 17 kidney transplant recipients who experienced COVID-19 infection from November 2020 to September 2021 at a solitary tertiary care center in Pune. Within our institution, the nephrology team assessed kidney transplant recipients with COVID-19 for appropriate immunosuppression dosing, renal drug clearance when deemed necessary, and overall well-being. Treatment for COVID-19 adhered to institutional protocols. RESULTS: In our case series, majority of the patients (n=13) had COVID-19 in March 2021 to July 2021 and the commonest presenting symptoms were fever and cough. Out of 17 kidney transplant recipients included in this case series, 13 patients survived while 4 patients succumbed to infection. CONCLUSION: An individualized, case-based approach to managing transplant recipients with COVID-19 is crucial for achieving favorable clinical outcomes.

#6888 COMPARISON OF COMBINATION OF RITUXIMAB WITH LOW DOSE THYMOGLOBULIN VERSUS LOW DOSE THYMOGLOBULIN ALONE AS INDUCTION AGENT IN RENAL TRANSPLANTATION

Abstract Background and Aims Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. However full dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity. There is not much data available on the use of single dose low dose rATG and rituximab, a Anti CD 20 chimeric antibody in low sensitized Indian transplant recipients. To compare the efficacy of low dose single dose rATG(1–1.2mg/kg) versus combination of rituximab with low dose single dose rATG in ABO compatible low sensitization renal transplant recipients. Method Retrospective analysis of all renal transplant recipients between 2010 and 2022 in our center who received low dose rATG(1-1.2mg/kg) or a combination of single dose rituximab(375mg/m2) and low dose thymoglobulin were studied. Demographic data, donor characterstics, HLA matches, infections,rejections was collected Graft function at 3,6 and 12 months post transplant if available was collected. Data was analysed using SPSS 16. Results Of 86 patients studied, 58(67.4%) received single dose of low dose rATG(1-1.2 mg/kg/day) (Grp1) and 28 received a combination of single low dose rATG & Rituximab(375mg/m2)(Grp 2)(32.5%). There was no significant difference between the Grp 1 and Grp 2 in terms of age,gender,vintage of dialysis, PRA status prior to transplant, no of HLA Matches, donor age and Donor GFR. There were 9(15%) of Acute cellular rejections (ACR) in Group1 when compared to 8 (28%) in-group 2(p = 0.263). The number of steroid resistant ACR were 2 (3%)in Grp 1 when compared to 3 (10%)in grp 2(p = 0.365) The number of ABMR were 5(8.6%) in group 1 when compared to 1(3.5%)in grp 2(p = 0.658) 15.5% had graft loss by 1 year in group 1 compared to none in grp 2(p = 0.322)CMV and BKV infections were seen in 1 and no pts and 1 patient in each group respectively.Overall infection rate was 24% when compared to 46.4% in grp 2(p = 0.03). The mean egfr(ml/min/1.73m2) at the end of 3 months, 6 months and 1 year was &95.6,93,95 respectively in grp 1 when compared to 92, 89.4 & 84.3 in grp 2. Conclusion The % of steroid resistant ACR and the number of infections were higher in the 1 year in the Single low dose rATG+Rituximab induction when compared to low single dose rATG alone. However ABMR was lower in the combination grp. Further prospective RCT s are required to establish the role of Rituximab in ABO Compatible transplants.

Real-world utilization and acceptance of tacrolimus-based immunosuppression in solid organ transplant recipients in India

<p><strong>Background:</strong> The objectives of the study were to describe the demographics and utilization pattern of tacrolimus (TAC)-based immunosuppressive regimens in recipients with solid organ transplant in India.</p><p><strong>Methods:</strong> This real-world, multicenter (134 centers), retrospective analysis included data of solid organ transplant recipients between 2010 and 2022 who had received TAC-based immunosuppressive therapy. The study data was collected between April 2021 and March 2022.</p><p><strong>Results:</strong> Data of a total of 1022 recipients with kidney transplant (KT, n=899) or liver transplant (LT, n=123) who received TAC-based immunosuppression was analyzed. The mean age of recipients among KT and LT was 41.04±10.62 and 42.88±11.32 years, respectively. The most common diseases leading to end stage organ failure were diabetes (24.7%), hypertension (15.8%), concomitant diabetes and hypertension (14.9%), chronic kidney disease (9.2%), nephrotic syndrome (5%), and end stage renal disease (ESRD, 4.4%) in KT recipients, whereas for LT, the common indications were liver cirrhosis (32.5%), hepatitis B viral infection (11.4%), alcoholic liver disease (10.6%), fatty liver disease (12, 9.8%) and non-alcoholic steatohepatitis (NASH, 5.7%). The source of transplant was living donor in majority of both KT (91.2%) and LT (77.2%) recipients. The most common induction regimen in KT was anti-thymocyte globulin (ATG), TAC, mycophenolate mofetil (MMF), and steroid (ATG+TAC+MMF+steroid, 42.3%) whereas in LT, it was TAC+MMF+steroid (67.5%); TAC+MMF+steroid was most common maintenance regimen (KT: 91.1%, LT: 78%).</p><p><strong>Conclusions:</strong> Tacrolimus-based immunosuppression is widely used in the recipients of solid organ transplantation, including KT or LT in real‑world clinical practice in India.</p>

COVID-19 Pandemic Research Opportunities in India: What the Pandemic Is Teaching Us About Transplantation

Coronavirus disease (COVID-19) has engulfed the whole world, and India has been the second worst-hit nation. Organ transplant services were halted in both the public and private care sectors of India, with public care sectors more adversely affected. Deceased donations were disproportionately more affected, with unfavorable rates at the peak of the pandemic. Mortality outcomes of COVID-19 among different organ transplant recipients in India have been lower compared with the Western world, with younger age and less comorbidities among Indian populations partly responsible for the lower mortality. Mortality and graft loss were mostly associated with older age and those with chronic graft dysfunction. During the pandemic, invasive fungal infections, like mucormycosis, have been reported, illustrating the need for multidisciplinary management. The Indian transplant societies have formulated and timely revised guidelines for transplantation in the COVID-19 era. Living donor transplants (both liver and kidney) after recovery from COVID-19 were both first described in India, providing a guiding tool for the world. Follow-up reports of recovered solid-organ transplant recipients have also been reported in Indian studies, showing reassuring long-term outcomes. Data of breakthrough COVID-19 cases after vaccination among both transplant recipients and waitlist candidates and research in vaccine efficacy for solid-organ transplant recipients is still underway. We suggest continuing and intensifying research activities for a better plan and strategy in case of a future pandemic.

POS-812 FACTORS PREDICTING POST RENAL TRANSPLANT TUBERCULOSIS: A TERTIARY CARE CENTRE EXPERIENCE

Tuberculosis (TB) is one of the most common causes of morbidity and mortality in renal transplant recipients in India. We studied factors predicting tuberculosis in post renal transplant period and its impact on graft and patient outcomes.

Risk factors and outcomes of COVID associated mucormycosis in kidney transplant recipients.

Invasive mucormycosis (IM) is a life-threatening fungal infection occurring mostly in solid organ transplant (SOT) recipients, patients with hematological malignancies, and diabetes. A sudden spurt of mucormycosis has been reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in India; however, there is little data about coronavirusdisease 2019 (COVID-19) associated mucormycosis (CAM) in kidney transplant recipients (KTRs). We describe the clinical presentations, risk factors, treatment and outcomes of 11 mucormycosis cases in KTRs post-COVID-19 infection from February 2020 to June 2021 at a single center in India. Mucormycosis was seen in 11/102 (10.7%) KTRs during the pandemic. Six patients had mild disease and rest five had moderate disease. Seven patients had pre-existing diabetes mellitus and four developed new onset hyperglycemia after receiving steroids for COVID-19 infection. All had poorly controlled sugars at the time of presentation. Most common presentation was rhino-orbital-cerebral mucormycosis (ROCM) in 10/11 (89%) patients and one has pulmonary mucormycosis. All patients received combination of amphotericin B and surgical debridement/excision of affected tissue followed by posaconazole prophylaxis. Nine patients recovered, however two patients succumbed to their illness after median of 14 (7-21) days from diagnosis. One patient developed acute T-cell-mediated rejection during the course of recovery. At last follow up, the mean serum creatinine was 2.05mg/dl as compared to 1.4mg/dl at presentation. IM is a common fungal infection in transplant recipients in India after COVID-19. Early diagnosis and prompt treatment with combination of surgical debridement and liposomal amphotericin B are key to better outcomes in CAM. Judicious use of steroids and control of hyperglycemia is key to avoid flaring up of the fungal infection.

P1613INFLUENCE OF GENETIC POLYMORPHISM IN MMPS AND TIMPS ON ALLOGRAFT OUTCOME IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Renal transplantation (RT) is currently the most effective replacement therapy and believed as a boon for patients with end-stage renal disease (ESRD). Allograft rejection remains to be one of the crucial impediments in successful renal transplantation. Matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMPs) play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The study of MMPs and TIMPs in transplant rejection may also lead to novel approaches in the therapy of rejection processes. To investigate the association of functional polymorphisms in MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G); MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A); TIMP1(+536 C/T) and TIMP3(-1298 C/T gene with risk of allograft rejection in renal transplant recipients of North India. Method A total of two hundred live related renal transplant donors and recipients pairs blood sample was collected and were genotyped for MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G); MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A); TIMP1(+536 C/T) and TIMP3(-1298 C/T) gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) methodology. All two hundred renal transplant recipients were categorized into 162 non-rejecters and 32 rejecters and were analyzed further. All the statistical analysis was done using SPSS software. Results The genotype frequencies of MMP1 (-1607 1G/2G) [2G/2G; odds ratio (OR) = 2.97, 95% confidence intervals (95% CI) = 1.69-5.20, P ≤ 0.05]; MMP9 (Q279R) [RQ; odds ratio (OR) = 0.47, 95% confidence intervals (95% CI) = 0.25-0.99, P = 0.02 & QQ; odds ratio (OR) = 0.49, 95% confidence intervals (95% CI) = 0.25-0.94, P = 0.03]; MMP9 (P574R) [PR; odds ratio (OR) = 2.70, 95% confidence intervals (95% CI) = 1.77-4.13, P ≤ 0.05 & RR; odds ratio (OR) = 2.70, 95% confidence intervals (95% CI) = 1.09-6.71, P = 0.03]; TIMP1(+536 C/T) [CT; odds ratio (OR) = 15.41, 95% confidence intervals (95% CI) = 9.12-26.05, P ≤ 0.05 & TT; odds ratio (OR) = 7.01, 95% confidence intervals (95% CI) = 3.39-14.49, P ≤ 0.05] and TIMP3(-1298 C/T) [CT; odds ratio (OR) = 0.31, 95% confidence intervals (95% CI) = 0.19-0.50, P ≤ 0.05] was significantly associated with allograft rejection. On comparison of genotypic frequencies for MMP-1, MMP-3, MMP-9, TIMP1 and TIMP3 gene polymorphisms between rejecters and non-rejecters no significant difference was found while comparing genotypic frequencies of non-rejecters with donors a significant association was observed in MMP1 (-1607 1G/2G) [P ≤ 0.05]; MMP9 (Q279R) [P = 0.02]; MMP9 (P574R) [P ≤ 0.05]; TIMP1 [P ≤ 0.05] and TIMP 3 [P ≤ 0.05] respectively. Therefore, MMP1 (-1607 1G/2G), MMP9 (Q279R), MMP9 (P574R), TIMP1 and TIMP3 demonstrated significantly reduced risk for allograft rejection. MMP1 (-1607 1G/2G) [P ≤ 0.02]; MMP9 (P574R) [P ≤ 0.05]; TIMP1 [P ≤ 0.05] and TIMP3 [P =0.01] was also found significantly associated on comparison between rejecters and donors. Conclusion Mutant genotypes/ alleles for MMP1 (-1607 1G/2G); MMP9 (Q279R); MMP9 (P574R); TIMP1 (+536 C/T) and TIMP3 (-1298 C/T) are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.

SAT-325 ASSOCIATION OF CYP3A5 POLYMORPHISM WITH TACROLIMUS LEVELS AND GRAFT OUTCOMES IN INDIAN KIDNEY TRANSPLANT RECIPIENTS

Tacrolimus which is the sheet anchor of post-transplant immunosuppression has a narrow therapeutic index. It is imperative to achieve therapeutic tacrolimus levels for optimum graft survival as sub-optimal levels can predispose to graft rejections and toxic levels pose a risk of nephrotoxicity. The inter-individual variations in the pharmacokinetics of tacrolimus can be in part attributed to polymorphism in Cytochrome P450 (CYP) enzymes. The expressor [CYP3A5*1/*1] status leads to faster metabolism of tacrolimus than that in non- expressors [CYP3A5*3/*3]. Although it is well known that these differences in genotype affect tacrolimus levels, but their effect on long term graft outcome is equivocal. It is not proven that knowing the genotype pre-transplant and adjusting the induction dose accordingly improves graft outcomes. We aim to evaluate the association of CYP3A5 genotypes on tacrolimus trough levels and graft outcomes in adult and pediatric kidney transplant recipients. In this single-center study, consecutive kidney transplant recipients, both pediatric and adults, on tacrolimus therapy for atleast 3 months were enrolled. Genotyping was done using PCR-RFLP for CYP3A5 *1/*1, [expressors] *1/*3,[intermediate expressors] *3/*3 [non -expressors] polymorphisms., and patients were divided into these 3 groups. These groups were analyzed with retrospectively available data for differences in dose-adjusted tacrolimus levels at 1,3,12 months and graft outcomes - acute biopsy-proven rejection, chronic rejection, chronic allograft dysfunction, new-onset proteinuria, eGFR at 1,3,12 months and at last followup available, and graft loss. All groups received 0.1mg/kg/day dose of tacrolimus on day 0 of transplant and then the levels were modified according to subsequent trough tacrolimus levels. Out of 142 patients, 26% were females. Median age 48yrs, 11/142 had age <18 yrs. 16% were expressors[CYP3A5 *1/*1], 40.6% were intermediate[CYP3A5*1/*3], 43.4% were non-expressors[CYP3A5*3/*3]. Dose adjusted tacrolimus trough levels were significantly higher in non-expressors at 1 month [p=0.001], 3 months [p=0.015], 12 months [p=0.018]. Acute biopsy proven rejections were more in expressors [31.4%vs 22.6% p =0.042]. Also, chronic rejections were more in expressors [21%vs 6.53% p = 0.044] Non-expressors had higher incidence of chronic allograft dysfunction [48.4% vs 25.2% p=0.0004]. After being started with 0.1mg/kg/day of tacrolimus, expressors requied more dose escalations to reach therapeutic targets - median 3[0-6] vs 0[0-3] p =0.04. Non-expressors required more dose reductions to achieve targets - median 7[4-13] vs 2.5[0-16] p=0.02. The prevalence of non-expressors [CYP3A5 *3/*3] was 43.4% in Indian transplant recipients. When started at 0.1mg/kg/day dose, expressors had higher rates of subtherapeutic levels requiring more dose-escalation, while non-expressors required dose reductions due to supratherapeutic levels. Graft rejections both acute and chronic were more common in the expressors while non-expressors were at a higher risk of chronic allograft dysfunction. Our data support the use of pretransplant CYP3A5 genotyping to facilitate the individualization of tacrolimus dosing. Genotype guided dosing from the day of transplantation can improve graft outcomes by reducing nephrotoxicity [due to high doses] and rejections [due to suboptimal doses].

Melding Pharmacogenomic Effect of MDR1 and CYP3A5 Gene Polymorphism on Tacrolimus Dosing in Renal Transplant Recipients in Northern India

IntroductionTacrolimus (TAC) is the mainstay immunosuppressant for renal transplantation. A narrow therapeutic index, multiple drug interactions, and interindividual variability in pharmacokinetics make it obligatory to monitor therapeutic drug levels. The Multidrug resistance gene 1 (MDR1) and CYP3A5 gene polymorphism may blend to achieve the optimal level. The optimal dose as per body weight is difficult to single out in the early posttransplantation period. In this study, we aimed to analyze the melding effect of both gene polymorphisms and to elicit the dose depending on the combination of genetic single nucleotide polymorphisms (SNPs) in northern Indian transplant recipients, for whom data are limited.MethodsThe daily TAC dose, weight-adjusted doses (mg/kg per day), TAC trough blood concentration (average of at least 3 levels), dose normalized with a corresponding dose using TAC concentration/weight-adjusted dose ratio (ng/ml per mg/kg per day) of 248 patients were recorded. All recipients were genotyped for the SNPs of CYP3A5 at intron 3 A6986G (the *3 or *1 allele), MDR1 at exons 12 (C1236T), 21 (G2677A/T), and 26 (C3435T). We analyzed the blending effect of mutant SNPs of the MDR gene and CYP3A5 for optimized TAC levels.ResultsAmong CYP3A5 genotypic variants, the dose-adjusted TAC level was significantly lower, and the TAC dose required to achieve the target level was significantly higher, in CYP3A5*1*1 (expressor) than that of CYP3A5*1*3 and CYP3A5*3*3. Of the MDR1 gene SNPs, only the G2677T/A homozygous mutant was significantly associated with TAC level, and it was strongly correlated with P-gp expression.The daily TAC dose requirement was highest with a combination of CYP3A5*1*1 and homozygous mutant TT+AA genotype of G2677T/A, and was lowest with CYP3A5*3*3 and wild-type GG of the G2677T/A genotype.ConclusionBoth CYP gene and MDR1 gene polymorphism affect TAC dose requirements, and there is a need to look for both in an individual to achieve the target trough concentration.

Immunosuppression with prolonged-release tacrolimus in kidney or liver transplantation in India

Aim: Tacrolimus has proven efficacy as an immunosuppressive therapy to prevent transplant rejection and is widely used as an immediate-release formulation in a twice-daily regimen. Once-daily prolonged-release tacrolimus aims to improve the outcomes by reducing variability in exposure and improving adherence. However, there are limited published data available on prolonged-release tacrolimus in routine clinical practice in India. Methods: This was a Phase IV, multicenter, prospective study of prolonged-release tacrolimus conducted over 12 weeks in adult patients eligible for de novo kidney or liver transplantation in India. Primary efficacy end-point was the event rate of biopsy-confirmed acute rejections (BCARs). Secondary end-points included corticosteroid-resistant rejection incidence, time to first BCAR, graft loss, and death. Safety end-points included renal function, lipid profile, incidence of new-onset diabetes mellitus after transplantation (NODAT), and infection. Results: The study enrolled 92 patients undergoing kidney (81 [88.0%]) or liver transplantation (11 [12.0%]); a total of 76 patients (82.6%) completed the study. Ten kidney transplant patients (overall 10.9%) experienced BCAR. There were seven corticosteroid-sensitive and three corticosteroid-resistant rejections. Median (range) time to kidney transplant rejection was 6.5 (1.0–76.0) days. Renal function was stable or improved. Lipid levels showed a significant increase. Eleven instances of NODAT and seven infections occurred and there were eight deaths (8.7%; six kidney and two liver transplant patients). Conclusions: In de novo kidney and liver transplant recipients in India, prolonged-release tacrolimus was well-tolerated and efficacious with a low incidence of acute rejection. Safety profile was similar to immediate-release tacrolimus from published data.

Lack of persistent hepatitis E virus infection as a cause for unexplained transaminase elevation in renal transplant recipients in India.

Hepatitis E virus (HEV) infection is highly endemic in India, being the most common cause of acute hepatitis; however, no case of chronic infection has been reported. All the human isolates of HEV from India till date have belonged to genotype 1. In contrast, in non-endemic areas, genotype 3 is the most prevalent, and persistent HEV infection has been reported among solid-organ transplant recipients. Whether persistent infection occurs with genotype 1 HEV is unclear. We therefore looked for evidence of HEV infection among renal transplant recipients with elevated alanine transaminase (ALT). Renal transplant recipients receiving immunosuppressive therapy were screened for ALT levels, irrespective of time duration since renal transplant. For those with ALT levels equal to or exceeding 50IU/mL on at least two occasions ≥3weeks apart, serum was tested for HEV RNA using a sensitive real-time reverse transcription polymerase chain reaction assay. For those testing positive, HEV genotyping and follow up for duration of viral persistence were planned. Of the 275 patients studied, 49 (17.8%, 44 male, median age = 39.5years) had elevated ALT levels (median = 62 [range = 50-477] IU/L). None of these 49 patients had detectable HEV RNA in the serum using an assay with detection sensitivity of 300 copies of RNA/mL of specimen. Our data indicate that persistent HEV infection is an infrequent cause of ALT elevation in Indian renal transplant recipients who are receiving immunosuppressive drugs. This suggests that infection with genotype 1 HEV may have either no or low potential to cause persistent infection.

Human cytomegalovirus glycoprotein N polymorphisms among renal transplant recipients in India

Background Human Cytomegalovirus (HCMV) is one of the most common infectious complications in renal transplant recipients. Extensive genetic polymorphisms in envelope glycoproteins of HCMV have been demonstrated among clinical HCMV isolates. Some previous studies have proposed the potential linkage between HCMV gN genotype to the frequency of symptomatic infection and clinical outcome in renal transplant recipients. No data available on circulating HCMV strains among renal transplant recipients in India.

A Comparative Study of Renal Function and Vitamin D Levels Between African and Indian Transplant Recipients

Introduction: There is a paucity of information on graft function in native African patients compared to Indian patients. As the Africans have higher BMI and muscle mass, they may have higher BUN and serum creatinine pre-transplantation. This study was undertaken to compare the outcome of transplantation with regard to renal function between the two groups. Materials and methods: Our retrospective study comprises 388 patients of Indian and African origin. Details such as age, gender, diabetic status, renal parameters pre and post-transplant, HLA typing, induction therapy, immunosuppressive medication and rejection rates were collected. Analysis was done using PASW Statistics 18 with chi-square test and one way Anova with post-hoc Tukey. All African patients received grafts from their own close relatives or spouses. Results: Of the 388 patients, 291 were Indian and 97 were of African origin. Details of the analysis are shown in Tables 1 and 2. It can be observed that the pre-transplant and immediate post-transplant renal function shown by blood urea and serum creatinine of the African patients were higher compared to their Indian counterparts (p< .001) However, the 1 month and 1 year post transplant renal functions were insignificantly different reflecting a similar overall outcome. While 38% of patients were diabetic, diabetic status was not significantly different. (p=0.153) A significant number of Indian patients had 1 or less HLA mismatches (44.5%) as compared to the African patients (15.9%) (p< .001). 27 patients died overall (6.9%) and mortality was not significantly different between the two ethnic groups. (p=0.106) Africans have higher levels of 25,OH Vitamin D3 levels (p=0.038)Table: [Demographic and Laboratory Parameters]Table: [Renal parameters]Conclusion: Our study shows that while the African population tended to have higher blood urea and creatinine pre and immediate post-operatively, this becomes insignificant at 1 month and 12 months and, thus, their overall outcome was similar to that of the Indian population despite a higher incidence of HLA mismatch. This may be attributed to achievement of adequate immunosuppression and overall higher Vitamin D levels.

Matrix metalloproteinase (MMP-9 and MMP-2) gene polymorphisms influence allograft survival in renal transplant recipients

Matrix metalloproteinases (MMPs), especially basement membrane-degrading MMP-9 and MMP-2, play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in MMP-9 (836A>G, 1721G>C and 2003G>A) and MMP-2 (-735C>T) genes with risk of allograft rejection in renal transplant recipients of North India. Three hundred and six renal transplant recipients categorized into 228 non-rejecters and 78 rejecters were genotyped for MMP-9 and MMP-2 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methodology. A significant difference in genotype/allele frequencies was observed between healthy individuals in comparison to non-rejecters/rejecters for MMP-9 836A>G, MMP-9 2003G>A and MMP-2 -735C>T. Mutant allele carriers for MMP-9 2003G>A [GA+AA-; odds ratio (OR) = 0.45, 95% confidence intervals (95% CI) = 0.24-0.85, P = 0.014] and MMP-2 -735C>T (CT+TT-; OR = 0.40, 95% CI = 0.18-0.91, P = 0.029) demonstrated significantly reduced risk for allograft rejection. The mean time to first rejection episode was significantly higher in GA/AA and CT/TT genotype recipients for MMP-9 2003G>A (log P = 0.026) and MMP-2 -735C>T (log P = 0.003), respectively. Haplotypes with mutant alleles for MMP-9 1721C>G-2003G>A and mutant allele genotype combinations for both MMP-9 2003G>A and MMP-2 -735C>T conferred significantly reduced risk for allograft rejection. Mutant alleles for MMP-9 2003G>A and MMP-2 -735C>T are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.

Impact of Chemokine Receptor CCR2 and CCR5 Gene Polymorphism on Allograft Outcome in North Indian Renal Transplant Recipients

The CC chemokine receptors, CCR2 and CCR5, contribute to the trafficking of leucocytes into the sites of the immune response in transplanted kidney. Therefore, the inter-individual differences in CCR2 and CCR5 gene expression, due to single-nucleotide polymorphism, have the potential to influence various immune responses within the graft, eventually deciding the allograft outcome. In this study, we genotyped 296 North Indian renal transplant recipients and 277 healthy controls for CCR2V64I and CCR5-Delta32 polymorphisms by sequence-specific primers and restriction fragment length polymorphism and examined their association with allograft outcome. The frequency of CCR2+/64I (heterozygous) and CCR2-64I/64I (homozygous mutant) genotype were comparatively higher in non-rejecters when compared with transplant recipients experiencing one or more than one rejection episode (20.4% versus 8.2%), thereby resulting in a significantly reduced risk of allograft rejection (OR = 0.331, P = 0.026). The Kaplan-Meier curve also suggested higher mean time for the first rejection episode in CCR2-64I allele carriers (32.83 +/- 1.36 months) when compared with CCR2+/+ recipients (28.09 +/- 0.93 months, log P = 0.027). The CCR5-Delta32 variant had no profound effect on allograft outcome. In conclusion, our study confirmed CCR2-64I allele to be associated with reduced risk for allograft rejection in North Indian transplant recipients influencing allograft outcome.

Incidence of Glucose Metabolic Abnormalities in Indian Living Renal Allograft Recipients on Tacrolimus-Based Triple Drug Immunosuppression

Objective The prevalence of glucose metabolic abnormalities (GMA) and overt diabetes in the Indian population is higher than the Western population. Tacrolimus (generic form), which is known to cause GMA, was recently introduced in India and data on its use in India are scarce. Herein we have presented our experience of the use of tacrolimus in renal transplantation. Patients and Methods We performed a retrospective analysis of 122 consecutive patients receiving tacrolimus-based triple drug immunosuppression at a single center. Target levels were 10 to 15 ng/mL in the first month, 8 to 10 ng/mL in the second to third months, and 5 to 8 ng/mL thereafter. GMA was defined as fasting blood sugar >110 mg% or postprandial blood sugar >140 on more than one occasion. All episodes of graft dysfunction were evaluated by graft biopsy. In addition, all consenting patients underwent protocol biopsy at 1, 3, and 6 months. Overall mean age of recipients was 34.5 ± 10.1 years; male to female ratio 108:14; mean donor age 40.1 ± 10.1 years; and mean follow-up 16.8 ± 5.9 months. Results The patient and graft survivals at 18 months were 96.7% and 94.8%, respectively. Incidence of clinical biopsy-proven acute rejection was 5.7%. In addition, 8.13% patients had subclinical rejection. The mean serum creatinine at last follow-up was 1.3 ± 0.6 mg%. Of the nondiabetic recipients, 54.5% developed GMA and 32.7% required drug therapy for glycemic control, of which only 5.5% were insulin dependent. The prevalence of hepatitis C virus (HCV) infection was 20.0% in the cohort. Conclusion Use of tacrolimus results in a low incidence of clinical acute rejection but a high incidence of GMA in Indian transplant recipients.

The high incidence of BK polyoma virus infection among renal transplant recipients in India.

BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.

Infections among allogeneic bone marrow transplant recipients in India.

Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and allogeneic bone marrow transplantation (BMT) despite prophylaxis, use of growth factors and newer antimicrobial drugs. We report the clinical profile of infections among 297 patients who underwent 304 allogeneic transplants between 1986 and December 2001. All patients developed febrile neutropenia. There were 415 documented infections among 304 transplants. This included bacterial (34.9%), viral (42.9%), fungal (15.9%) and other infections (6.3%) including tuberculosis. Bacterial pathogens were mainly Gram-negative bacteria (80%) as compared to Gram-positive (20%) bacteria. The common Gram-negative bacteria were nonfermenting Gram-negative bacteria (NFGNB) (24.9%), Pseudomonas (17.9%), Escherichia coli (17.9%) and Klebsiella (9.7%). The major source of positive cultures was blood (53.7%) followed by urine (25.5%) and sputum (8.9%). In all, 133/304 (43.7%) transplants had 178 documented viral infections. The common viral infections were due to cytomegalovirus, herpes group of viruses and transfusion-related hepatitis; and 60/304 (19.7%) transplants had 66 documented fungal infections. Common fungi included Aspergillus species (69.7%), Candida (22.2%) and Zygomycetes (8.1%). Tuberculosis was documented in 2.3% of the transplants. Catheter infections were suspected or documented in 7.8% of the transplants (24/304). The incidence of infections in this series from developing countries is not significantly different from reports from the West. Bone Marrow Transplantation (2004) 33, 311-315. doi:10.1038/sj.bmt.1704347 Published online 1 December 2003

GB virus C/hepatitis G virus and TT virus infections among high risk renal transplant recipients in India.

GB virus C/hepatitis G virus (GBV-C/HGV) and TT virus (TTV) have been widely reported in patients with high parenteral risk such as haemodialysis and renal transplant recipients. The occurrence of these agents in association with hepatitis B virus (HBV) and hepatitis C virus (HCV), in Indian renal transplant recipients, is yet unreported. Molecular and serological markers of GBV-C/HGV and TTV were examined in addition to those for HBV, HCV and hepatitis D virus (HDV) in a selected group of seventy renal transplant recipients. HGV RNA detection was achieved using primers specific for the 5'NCR and NS5a regions of the genome. Anti-GBV-C/HGV antibody was detected using the mu plate anti-HG env kit (Roche, Germany). TTV DNA PCR was performed using primers specific for the coding region (method A) of the genome. In 50% of patients, TTV DNA was also tested for using primers specific for the non-coding region (method B). Host related factors such as age, alanine aminotransferase (ALT) levels, number of transfusions, haemodialysis sessions, and months following transplantation were also studied. Exposure rates to GBV-C/HGV, TTV (method A), HBV, HCV and HDV were 58.6, 32.9, 52.9, 54.3 and 2.9%, respectively. 'Active' infection as measured by viraemia and/or virus-specific antigenaemia for GBV-C/HGV, TTV, HBV and HCV was 52.9, 32.9, 15.7 and 52.9%, respectively. The majority of GBV-C/HGV and TTV infections were seen as co-infections with other hepatitis viruses. Single infection with GBV-C/HGV and TTV was seen in ten (14.2%) and eight (11.4%) patients, and was not associated with ALT elevation when compared to uninfected blood donors. Using univariate analysis, GBV-C/HGV RNA was significantly associated with > or =20 haemodialysis sessions. TTV DNA occurrence was not associated with any risk factors. There is a high occurrence of GBV-C/HGV and TTV in this select group of renal transplant recipients in India. These viruses mostly occurred in the context of co-infections with other hepatitis viruses. Long term effects of multiple hepatotropic viral infections need to be carefully documented in such transplant populations.