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.

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

BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Changing profile of causes of chronic renal failure.

The incidence and prevalence of end-stage renal disease (ESRD) is increasing. Diabetic nephropathy has increased in absolute numbers and as a proportion of patients with ESRD. This is almost totally accounted for by the explosive outbreak of Type 2 diabetes mellitus (DM). The world is in the midst of an epidemic of Type 2 DM and hence this trend is likely to continue for some more time. The contribution of glomerulonephritis as a proportion of patients with chronic renal failure (CRF) has declined due to increase in other causes such as diabetes. The annual incidence of IgA nephropathy, which is also a very common cause of renal insufficiency, has not changed. The incidence of focal segmental glomerulosclerosis is increasing while that of membranoproliferative glomerulonephritis is decreasing. Peak incidence of ESRD due to hypertension has shifted to a higher age-group. The proportion of renovascular disease as a cause of ESRD is also increasing. Human immunodeficiency virus associated nephropathy is the third leading cause of ESRD in African-Americans aged 20-64 years. Other diseases such as analgesic nephropathy and lead nephropathy are slowly disappearing. The significance of elevated body lead in patients with varying degrees of renal insufficiency requires further evaluation. The incidence of CRF is significantly higher in the elderly and hence there is a "graying" of CRF population. Census projections show that this trend will continue into the foreseeable future. The incidence and prevalence of ESRD vary between different populations, countries and within countries. The reason for the variations requires further study.

Nocardiosis in tropical renal transplant recipients.

BACKGROUND: The epidemiology of nocardiosis in the tropics among renal transplant recipients has not been reported. METHODS: An evaluation of nocardiosis for 30 yr in one of the large transplant centres in South Asian region. RESULTS: Of the 1968 patients who received primary renal allografts at Christian Medical College & Hospital, 27 patients developed nocardiosis over 30 yr. Early nocardiosis (2 yr). Seventeen patients (63%) had two or more associated post-transplant infections, of whom 10 had tuberculosis. Mortality in these patients was associated with chronic liver disease. CONCLUSIONS: Nocardiosis manifests earlier (<2 yr) in CsA treated patients who have chronic liver disease. Among renal transplant recipients of the tropics nocardiosis is a marker of a high susceptibility to tuberculosis and other infections, the association with tuberculosis is stronger in those developing early nocardiosis (<2 yr). Chronic liver disease is a risk factor for death in patients with nocardiosis especially when associated with tuberculosis. This report constitutes the largest single centre experience among renal transplant recipients.