Living Donor Renal Allograft Recipients Research Articles

Predictors of Short-Term Outcomes in Living Donor Renal Allograft Recipients: A Prospective Study From a Tertiary Care Center in North India.

BackgroundRenal transplantation is the optimal treatment for patients of all ages with end-stage kidney disease. The long-term outcomes of renal transplantation are assessed by graft and patient survival rates. These outcomes are, in turn, influenced by post-transplant events such as delayed graft function, rejections, post-transplant infections, and post-transplant diabetes mellitus (PTDM). Each of these short-term outcomes is, in turn, determined by the interplay of various factors in the pre-, peri-, and post-transplant period. This prospective study was designed to understand the factors affecting short-term outcomes in living donor transplantation and their effect on graft and patient survival.MethodologyA total of 86 patients underwent live donor renal transplantation between January 1, 2015, and March 31, 2016, at a tertiary care hospital in north India. Of these, five were lost to follow-up, and the remaining 81 patients were prospectively followed up to December 31, 2017.ResultsThe majority of the recipients were males (91%) and the donors were females (74%). Spousal and related donors comprised 49% and 51% of donations, respectively. The mean estimated glomerular filtration rate (eGFR) of donors was 98 ± 9.2 mL/minute/1.73m². Induction therapy with basiliximab was given to 21/81 (26%) recipients. The majority of recipients (68/81, 84%) received triple-drug immunosuppression with prednisolone, tacrolimus, and mycophenolate mofetil. Delayed graft function (DGF) occurred in 4/81 (4.9%) cases. Biopsy-proven acute rejections (BPARs) occurred in 15/81 (18.5%) cases, two-thirds of which were acute antibody-mediated rejections (ABMRs). During the follow-up period, 50 episodes of infections occurred in 35/81 (43.2%) recipients, with the most common being urinary tract infection (23/81, 28.5%). PTDM was diagnosed in 22/81 (27.2%) patients beyond six weeks of transplant. On multivariate logistic regression analysis, the most significant predictor of DGF was acute rejections and vice versa. Acute rejections also predicted the occurrence of post-transplant infections. Pre-transplant hepatitis C virus (HCV) infection and cyclosporine-based therapy were significant predictors of PTDM. At the six-month follow-up, 10/81 (12.3%) patients developed graft dysfunction. The predictors of graft dysfunction at six months were recipients of related donors and rural patients. One-year graft survival, death-censored graft survival, and patient survival rates were 85.2%, 92.6%, and 91.3%, respectively. The most common cause of death was post-transplant infections (5/7, 71.4%) of which the majority (4/5, 80%) were fungal infections. On multivariate logistic regression analysis, the most significant predictor of graft loss and patient loss was low pre-transplant donor eGFR and PTDM, respectively.ConclusionsGraft and patient survival in living donor kidney transplantation are influenced by a multitude of interdependent factors during the pre-transplant (donor eGFR, type of donor, socioeconomic status, HCV infection in recipient, type of immunosuppression) and the post-transplant (DGF, rejections, infections, and PTDM) period.

Hidden Granzyme B-Mediated Injury in Chronic Active Antibody-Mediated Rejection.

Antibody-mediated injury in chronic active antibody-mediated rejection, possibly with other effector T cells, may play a role in graft injury. The role of inflammatory cells in the inflammation and fibrosis and tubular atrophy region has been recently advocated in the progression of injury. Cytotoxic T cells play a prominent role in T-cell-mediated rejection; however, the possible role of cytotoxic T cells in circulation and the intragraft compartment in chronic active antibody-mediated rejection, a common immunological cause of long-term graft failure, has not been well-studied. We measured the frequency of circulating cytotoxic T cells with flow cytometry, serum granzyme B level by enzyme-linked immunosorbent assay and intragraft granzyme B+ cell, and mRNA by immunohistochemistry and real-time polymerase chain reaction in biopsy tissue from living donor renal allograft recipients with stable graft function and chronic active antibody-mediated rejection. The frequency of CD3+ and CD3+CD8+ T cells was similar in both stable graft function patients and chronic active antibody-mediated rejection patients. The frequency of CD3+CD8+granzyme B+ cytotoxic T cells was significantly lower in peripheral blood. Serum granzyme B level and intragraft number of granzyme B+ cells (counts/mm²) were also significantly higher in the chronic active antibody-mediated rejection group compared with that of patients with stable graft function. The intragraft granzyme B+ T cell count was positively correlated with serum creatinine and 24-hour urine proteinuria but negatively correlated with estimated glomerular filtration rate. Granzyme B mediates covert graft injury in patients with chronic active antibody-mediated rejection in addition to antibody-mediated injury.

BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India.

BK virus is a polyoma virus which remains in latent phase in the urinary tract, particularly in the renal tubular epithelial cells. In immunosuppressed patients, it is activated and manifests as tubule-interstitial nephritis causing renal allograft dysfunction. A total of 402 patients who underwent renal allograft biopsy from 2013 to 2016 were included in this study; six patients were diagnosed to have BK virus nephropathy. Histopathology showed ground glass intra-nuclear inclusions accompanied by acute tubular injury, interstitial inflammation, and varying degree of interstitial fibrosis and tubular atrophy. Patients were managed with reduction in the overall immunosuppression. Only one patient progressed to graft failure on follow-up. The overall prevalence of polyoma virus at our center is 1.49%.

Long-term outcomes of hepatitis C virus infected renal allograft recipients

Background and Aim: This study aims to study the long-term outcomes of hepatitis C virus (HCV)-infected renal allograft recipients, which is still debatable. Materials and Methods: In this study (study period - January 2003 to December 2013), we studied long-term outcomes of 106 living donor renal allograft recipients - 53 HCV-infected (33 genotype 3 and 20 genotype 1) and 53 age- and gender-matched HCV-noninfected patients. Results: Thirty-nine (73.6%) patients detected HCV positive during dialysis, while 14 (26.4%) before the start of dialysis. Forty (75.5%) patients were positive for both anti-HCV and HCV RNA, while 13 (24.5%) were HCV RNA positive and anti-HCV negative. Twelve and nine patients died among HCV positive and negative groups, respectively. Major cause of death was sepsis in both groups. Hepatic failure contributed to mortality in four HCV-positive patients, two of them also had graft failure. Patient and death noncensored graft survival rates at 1, 5, and 10 years of follow-up in HCV-positive group were 100% and 100%; 79.8% and 70.8%; 58.9% and 37.8%; respectively; and in HCV-negative group were 100% and 100%; 95.9% and 91.8%; 58.9% and 27.4%; respectively. Conclusions: The long-term survival of HCV-positive renal transplant recipients was not inferior to that of HCV-negative recipients.

Urinary Kidney injury molecule-1 can predict delayed graft function in living donor renal allograft recipients.

Delayed graft function is an early complication leading to impaired creatinine clearance, urine formation and determinant of long term graft outcome. The aim of the present study was to determine the earliest predictive cut-off value of uKIM-1 level in patients with delayed graft function and acute tubular necrosis. We have determined the serial urinary KIM-1 normalized to urinary creatinine (uKIM-1, pg/mg) level at 0, 6, 12, 18, 24 and 48 h of post-transplant by ELISA methods. The normalized uKIM-1 and AUC-ROC, of uKIM-1 were progressively increased up to 48 h in both delayed graft function (DGF) and immediate graft function (IGF). The u KIM-1 values were significantly high at 6, 12, 18, 24 and 48 h in patients with DGF as compared to that of IGF except at half an hour post-transplant values. Although, progressive increase in uKIM-1 values were observed in both groups of patients; there was an overlap of values between two groups up to 12 h. The earliest non-overlapping values of uKIM-1 between the groups were observed at 18 h onwards and minimum difference of 923.43 pg/mg. The earliest predictive AUC-ROC of uKIM-1 in patients with DGF without overlap with IGF was also observed at 18 h post-transplant with specificity of 100% and sensitivity of 89.9%. Serial uKIM-1 measurement can be used as non-invasive diagnostic biomarkers to predict the incident of DGF in living donor renal transplant recipients. At 18(th) post-transplant hour uKIM-1 can predict DGF with 100% specificity and 89.9% sensitivity with a cut-off value of normalized KIM-1 of 923.43 pg/mg.

Biointact FGF23 normalizes faster and correlates better with inorganic phosphorus as compared to intact PTH in living donor renal allograft recipients

Biointact FGF23 normalizes faster and correlates better with inorganic phosphorus as compared to intact PTH in living donor renal allograft recipients

Urinary kidney injury molecule-1 can predict acute tubular necrosis in living donor renal allograft recipients

Urinary kidney injury molecule-1 can predict acute tubular necrosis in living donor renal allograft recipients

Anti-HLA Antibodies and Renal Function in Living Donor Renal Allograft Recipients - A Single Centre Cross Section Study in The Balkans.

Anti-HLA Antibodies and Renal Function in Living Donor Renal Allograft Recipients - A Single Centre Cross Section Study in The Balkans.

Is basiliximab induction, a novel risk factor for new onset diabetes after transplantation for living donor renal allograft recipients?

It was found that, by affecting populations of T lymphocytes and regulatory T cells, basiliximab also indirectly affects pancreatic β-cell function and glucose homeostasis. In this prospective observational study, we included all renal transplant recipients from 1 July 2007 to 31 July 2011. The overall incidence of hyperglycaemia (transient hyperglycaemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and new onset diabetes after transplantation (NODAT)) was compared between patients with and without basiliximab induction. Of the 439 eligible study patients, 105 patients received basiliximab induction and 334 patients did not. Overall hyperglycaemia (transient hyperglycaemia, IFG, IGT and NODAT) was detected in 102/334 (30.5%) patients without induction and 44/105 (41.9%) patients with induction (P = 0.03). Of the 102 patients with hyperglycaemia in patients without basiliximab, 46 (45.1%) patients improved, while only 10 (22.7%) of the 44 patients with basiliximab improved (P = 0.016) at the end of 3 months. Finally, NODAT was observed in 56/334 (16.7%) patients without induction and 102/334 (30.5%) patients with induction. Relative risk of NODAT with basiliximab was 2.3 (95% CI 1.4-3.9) compared to that of patients without induction. Basiliximab and hepatitis C virus infection were independent risk factors for NODAT. Risk of NODAT remained high with basiliximab despite adjusting the acute rejections episodes. Basiliximab induction prevents acute rejection; however, it is associated with increased risk of NODAT.

CYCLOSPORINE MONOTHERAPY IN PRIMARY LIVING DONOR RENAL ALLOGRAFT RECIPIENTS

231 We have tried cyclosporine monotherapy in primary living donor renal allograft recipients and monitored them prospectively more than 7 years. A total of 120 primary living donor renal allograft recipients were enrolled through randomization on control(n=62) and study (n=58) groups. Immunosuppression was induced 2 days prior to the transplantation using cyclosporine (12mg/kg) and corticosteroids (1 mg/kg). Corticosteroids were tapered down to 0.2 mg/kg during the first month after the transplantation. For the control group, corticosteroids (0.2 mg/kg) was maintained after then. In the study group, corticosteroids tapering was continued until zero at the end of post-transplant month 4. Baseline characteristics of both groups, which could impact on graft survival, were comparable with no statistical difference. Overall patient and graft survival at post-transplant 7 years were 87.8% and 74.2% in control group and 89.2% and 72.4% in study group, respectively (p>0.05). There also was no statistical differences in the frequencies of acute rejection within 1, 6, 12 months and after 1 year post-transplantation between two groups. There were 13 and 16 graft failures during the study period with no statistical difference in control and study groups, respectively. We defined immunosuppressive regimen failure when we had to modify immunosuppressive protocol from whatever reasons. A total of 35 and 34 failures of immunosuppressive regimen were developed in control and study groups, respectively. Graft kidney function was measured by serum creatinine concentration(SCr), which showed no differences between control and study groups. In conclusion, cyclosporine monotherapy should be considered as a possible option in living donor renal allograft recipients when it is combined with careful corticosteroids tapering protocol after immediate post-transplant period (first 4 months).

CYCLOSPORINE MONOTHERAPY IN PRIMARY LIVING DONOR RENAL ALLOGRAFT RECIPIENTS

231 We have tried cyclosporine monotherapy in primary living donor renal allograft recipients and monitored them prospectively more than 7 years. A total of 120 primary living donor renal allograft recipients were enrolled through randomization on control(n=62) and study(n=58) groups. Immunosuppression was induced 2 days prior to the transplantation using cyclosporine(12mg/kg) and corticosteroids(1mg/kg). Corticosteroids were tapered down to 0.2mg/kg during the first month after the transplantation. For the control group, corticosteroids(0.2mg/kg) was maintained after then. In the study group, corticosteroids tapering was continued until zero at the end of post-transplant month 4. Baseline characteristics of both groups, which could impact on graft survival, were comparable with no statistical difference. Overall patient and graft survival at post-transplant 7 years were 87.8% and 74.2% in control group and 89.2% and 72.4% in study group, respectively(p>0.05). There also was no statistical differences in the frequencies of acute rejection within 1, 6, 12 months and after 1 year post-transplantation between two groups. There were 13 and 16 graft failures during the study period with no statistical difference in control and study groups, respectively. We defined immunosuppressive regimen failure when we had to modify immunosuppressive protocol from whatever reasons. A total of 35 and 34 failures of immunosuppressive regimen were developed in control and study groups, respectively. Graft kidney function was measured by serum creatinine concentration(SCr), which showed no differences between control and study groups. In conclusion, cyclosporine monotherapy should be considered as a possible option in living donor renal allograft recipients when it is combined with careful corticosteroids tapering protocol after immediate post-transplant period(first 4 months).