Paulose P. Thomas

Epidemiology of systemic mycoses among renal-transplant recipients in India

Background. Systemic mycoses have a high impact on tropical renal-transplant recipients. Methods. Data from 1,476 primary renal-transplant recipients was prospectively recorded from 1986 to 2000 at a single center. Cumulative incidence of systemic mycoses, its time of occurrence, risk factors, outcome, and postmortem findings in 30 patients with systemic mycoses were analyzed. Results. A total of 110 episodes of systemic mycoses occurred in 98 patients. The fungal genera Aspergillus, Cryptococcus, and Candida constituted 61% of pathogens, 45% localizing to the lungs. Cytomegalovirus (CMV) disease caused a 5-fold and chronic liver disease a 2-fold increase in systemic mycoses. Tuberculosis (TB) with or without nocardiosis was a significant coinfection. Cyclosporine (CsA) was associated with nearly a 4-fold risk of systemic mycoses less than 6 months from the time of transplantation as compared with prednisolone+azathioprine (PRED+AZA) therapy. Overall, the probability of survival with systemic mycoses was 73.4%, 60.8%, 39.5%, and 25.6% and was 92.5%, 87.5%, 80.0%, and 75.5% without systemic mycoses at 1, 2, 5, and 10 years, respectively (P <0.0001). An extended Cox model with time-independent and dependent covariates showed greater than 15 times the risk of death among those who develop systemic mycoses. Similarly, Posttransplantation (postTX) TB±Nocardiosis, preTX TB, CMV disease, diabetes mellitus, PTDM, chronic liver disease (>40 months), and Pred+AZA immunosuppression (>2 years) had 3.5, 1.5, 2.9, 1.9, 1.4, 1.6, 2.3 times the risk for death, respectively, as compared with those who did not have those risk factors. Conclusions. There is a recent predominance of Aspergillus among the transplant recipients. The risk factors for systemic mycoses are CMV disease, chronic liver disease, and hyperglycemia, and TB is an important coinfection. Systemic mycoses increased in the early postTX period with CsA. The risk factors for death are systemic mycoses, CMV disease, chronic liver disease (>40 months), diabetes mellitus, and Pred+AZA immunosuppression (>2 years). Overall, the probability of survival with systemic mycoses was poor; however, survival has recently improved.

Management and outcome of brain abscess in renal transplant recipients

Although infection is the commonest central nervous system complication following renal transplantation, brain abscess is uncommon. Over the last 11 years, five renal transplant recipients who had brain abscesses were treated by computed tomography (CT)-guided stereotactic aspiration. Three patients had a fungal abscess, one a tuberculous abscess and the other had a methicillin-resistantStaphylococcus aureus abscess. One patient required a craniotomy for the excision of a fungal abscess which was persistent after two CT-guided stereotactic aspirations. The survivors in this group are the patient with a tuberculous abscess who is alive and well 5 years after diagnosis, and another with a dematiaceous fungal abscess (phaeohyphomycosis). CT-guided stereotactic surgery is minimally invasive, and can safely be performed in these patients. It often leads to an aetiological diagnosis in renal transplant recipients with brain abscesses. Specific antibiotic management directed towards the causative organism rather than empirical treatment can be instituted following the procedure. Although the ultimate prognosis in these patients is bleak even with specific antibiotic therapy, an occasional patient might have a good outcome with prompt and appropriate therapy.

Sirolimus and ketoconazole co-prescription in renal transplant recipients.

Ketoconazole inhibits cytochrome P 3A4, leading to a 10-fold increase in sirolimus blood levels. Although it has not been reported in the clinical setting so far, sirolimus and ketoconazole co-prescription can lead to cost saving by reducing the dose of sirolimus administered. After informed consent was obtained, sirolimus and ketoconazole co-prescription was studied in six patients who could not afford the current recommended doses. Patients received one-eighth to one-fourth of the recommended dose of sirolimus (0.25-0.5 mg) with 100 to 200 mg of ketoconazole. Sirolimus levels were monitored, and the dose of ketoconazole was increased to achieve target levels of sirolimus. The loading dose was 3 mg of sirolimus with 100 mg of ketoconazole. After sirolimus rescue therapy was started, serum creatinine decreased in five patients. The mean serum creatinine for the group decreased from 2.6 +/- 0.3 mg/dL at the initiation of rescue therapy to 2.2 +/- 0.5 mg/dL on the last follow-up. Sirolimus ketoconazole co-prescription with monitoring of sirolimus levels is possible and safe and needs to be explored further.

Nocardiosis in tropical renal transplant recipients

Background: The epidemiology of nocardiosis in the tropics among renal transplant recipients has not been reported.

Leprosy and renal transplantation

Nine cases of leprosy in patients treated at a large renal transplant centre in South Asia are described. Three had leprosy diagnosed before transplantation and had either completed or were continuing chemotherapy at the time of transplantation. One showed exacerbation of undisclosed leprosy after transplantation. Five patients developed the disease for the first time 22 months to 12 years after transplantation. Immunosuppression did not adversely affect the treatment of leprosy in any of the patients though concurrent liver disease required cessation of rifampicin in one patient.

Pre- and postrenal transplantation pharmacokinetics of cyclosporine microemulsion.

UNLABELLED The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit. METHODS We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC. RESULTS The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations. CONCLUSIONS CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.

Low prevalence of hepatitis D (delta) virus infection in a nephrology unit in South India

Fifty-five consecutive patients with end-stage renal disease entering haemodialysis programmes over a two-month period and 48 consecutive recipients of renal allografts during a period of 6 months were investigated for hepatitis B virus (HBV) and hepatitis D virus (delta) infection. HBV markers were present in 25 of the former and 40 of the latter. Of the 65 patients with HBV infection, 12 were not available for delta antibody screening. HBV infection was present for a mean of 2.5 months and 45.3% of those infected had clinical hepatitis; none had fulminant hepatitis. All the patients tested were negative for antidelta antibody. An additional patient on dialysis with delta superinfection and hepatic encephalopathy is also reported.