Mukut Minz

The Utility of 1‐ and 3‐Month Protocol Biopsies on Renal Allograft Function: A Randomized Controlled Study

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1‐ and 3‐month protocol biopsies findings on 1‐year renal allograft function in a prospective randomized study. Out of 102 living‐donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2‐h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short‐term renal allograft function.

Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: A pilot study

This pilot study assesses the safety and feasibility of autologous mesenchymal stromal cell (MSC) transplantation in four patients that underwent living donor renal transplantation, and the effect on the immunophenotype and functionality of peripheral T lymphocytes following transplantation.

CYP3A5*1/*3 genotype influences the blood concentration of tacrolimus in response to metabolic inhibition by ketoconazole.

Objectives Ketoconazole retards metabolic degradation of tacrolimus through its effect on the cytochrome P-450 enzyme system and allows reduction in treatment costs. Enzyme activity is determined by a single nucleotide polymorphism (*1/*3) in the CYP3A5 gene. Methods We prospectively investigated the impact of this polymorphism on tacrolimus concentration in a cohort of 79 renal transplant recipients on ketoconazole. Genotyping was carried out by using polymerase chain reaction-restriction fragment length polymorphism technique. Dose-adjusted trough level (C0) was calculated at baseline and at 3, 7, 15, 30, and 60 days. Results The baseline C0 was significantly lower in those with at least one *1 allele [44.95±14.12 vs. 63.43±14.72 (ng/ml)/(mg/kg/day), P<0.0001]. After starting ketoconazole in all genotypes, dose-normalized C0 increased and the cost of therapy decreased. Compared with baseline, the magnitude of increase was 112% and 79% in those without and with *1 allele, respectively (P<0.001). The cost savings were 32% and 39% in mycophenolate mofetil-treated and 47% and 61% in azathioprine-treated patients who were with and without one *1 allele, respectively. Conclusion We show that the CYP3A5*1/*3 polymorphism is an important determinant of the response to inhibition of tacrolimus metabolism by ketoconazole, with a 30% greater inhibition in those lacking *1 allele. This finding will allow better dose adjustment and minimize exposure to subtherapeutic or toxic concentrations.

Prospective monitoring of BK virus reactivation in renal transplant recipients in North India.

R. Thakur, S. Arora, R. Nada, M. Minz, K. Joshi. Prospective monitoring of BK virus reactivation in renal transplant recipients in North India.
Transpl Infect Dis 2011: 13: 575–583. All rights reserved

Use of autogenous internal iliac artery for bridging the external iliac artery after excision of Aspergillus mycotic aneurysm in renal transplant recipients

Repair of vascular defects in the presence of infection remains a challenging task in immunocompromised patients. We report two patients with postrenal transplant Aspergillus mycotic aneurysms of the allograft renal artery involving the external iliac artery which were excised along with the allograft. The defect in the external iliac artery was repaired successfully with interposition of autogenous internal iliac artery graft. Use of an internal iliac artery graft in such settings has been rarely reported in English literature. Autogenous internal iliac artery grafts provide a useful method to bridge the vascular defects created by radical debridement in the presence of fungal infections.

Deferred Pre-Emptive Switch from Calcineurin Inhibitor to Sirolimus Leads to Improvement in GFR and Expansion of T Regulatory Cell Population: A Randomized, Controlled Trial

Background Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (Treg) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and Treg frequency. Methods In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. Treg population was estimated by flowcytometry. Results Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94±11.78 vs 80.59±16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in Treg population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event. Conclusions A deferred pre-emptive switch over from CNI to SIR safely improves renal function and Treg population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034)

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.

Laryngeal Tuberculosis In Renal Transplant Recipients

BACKGROUND Tuberculosis is the most common non-pyogenic infection encountered among renal transplant recipients in India. Although the lung is the most common site of involvement, a number of extrapulmonary organs can be involved. There is often a delay in diagnosis and institution of effective chemotherapy when there is an unusual site of involvement. METHODS AND RESULTS We report two renal transplant recipients with laryngeal tuberculosis who presented with prolonged hoarseness of voice and painful dysphagia. Acid-fast bacilli were demonstrated on laryngeal biopsy and smear. Fever and pulmonary involvement were seen in only one patient. This is the first report of laryngeal tuberculosis in renal transplant recipients. CONCLUSIONS Laryngeal tuberculosis should be suspected in renal transplant recipients who develop hoarseness of voice and odynophagia. Demonstration of acid-fast bacilli on biopsy or smear obtained by direct laryngoscopy helps in determining the diagnosis.

Potential of organ donation from deceased donors: study from a public sector hospital in India

Deceased donor organ programme is still in infancy in India. Assessing deceased donation potential and identifying barriers to its utilization are required to meet needs of patients with organ failure. Over a 6‐month period, we identified and followed all presumed brainstem dead patients secondary to brain damage. All patients requiring mechanical ventilation with no signs of respiratory activity and dilated, fixed and nonreacting pupils were presumed to be brainstem dead. All events from suspicion of brainstem death (BSD) to declaration of BSD, approach for organ donation, recovery and transplants were recorded. Subjects were classified as possible, potential and effective donors, and barriers to donation were identified at each step. We identified 80 presumed brainstem dead patients over the study period. The mean age of this population was 35.9 years, and 67.5% were males. When formally asked for consent for organ donation (n = 49), 41 patients’ relatives refused. The conversion rate was only 8.2%. The number of possible, potential and effective donors per million population per year were 127, 115.7 and 9.5, respectively. The poor conversion rate of 8.2% suggests a huge potential for improvement. Family refusal in majority of cases reflects poor knowledge and thus warrants interventions at community level.

Challenges in containing the burden of hepatitis B infection in dialysis and transplant patients in India

Aim:  Whether or not completing the hepatitis B vaccination in patients who have undergone kidney transplantation in the middle of incomplete vaccination schedule leads to development of protective antibody titres is not known. This study was designed to determine whether the strategy of completing hepatitis B virus (HBV) vaccination after transplantation is efficacious.