Chakko K. Jacob

Leflunomide Therapy For Cytomegalovirus Disease In Renal Allograft Recepients

Leflunomide has excellent antiviral activity against cytomegalovirus (CMV) in animal models and is considerably less expensive than intravenous ganciclovir. We used leflunomide in four consenting renal allograft recipients with symptomatic CMV disease, who were unable to afford ganciclovir and would otherwise remain untreated. This is the first report of efficacy of leflunomide in humans with CMV disease. They received loading dose of 100 mg of leflunomide once daily on days 1–3 and then 20 mg once daily for 3 months. All four patients were followed up three times weekly with physical examination, total leukocyte counts, blood urea and serum creatinine for a minimum period of 6 weeks. None of the patients showed drug related adverse events, alteration in cyclosporine levels, or decreased graft function, except one who developed leucopenia. Preliminary data presented suggests that leflunomide therapy for CMV disease is effective and could be used with careful monitoring in allograft recipients who cannot afford intravenous ganciclovir therapy. The duration of treatment and the role of leflunomide in secondary prophylaxis and in situations of ganciclovir resistance need to be studied further.

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.

Nondiabetic renal disease in noninsulin-dependent diabetics in a South Indian hospital

Eighty patients with non-insulin-dependent diabetes mellitus being treated in a south Indian hospital were biopsied to confirm suspected nondiabetic renal disease (NDRD). The positive predictive value of the standard clinical indicators for NDRD in the presence or absence of diabetic retinopathy was 54 and 87%, respectively. These values are higher than those given by comparable studies in Western populations. This is probably due to a higher prevalence of NDRD in the population of south India, and especially of proliferative glomerulonephritis, which was found in 21.5% of the patients studied. Standard clinical predictors of NDRD in diabetics have a high predictive value in the tropics where there is a high prevalence of proliferative glomerulonephritis.

A dietary survey in Indian hemodialysis patients.

Malnutrition is a common problem in maintenance hemodialysis (MHD) patients, and compromised intake is an important cause. There is no information available about the nutrient intakes of MHD patients in India. The nutrient intakes of 106 MHD patients were studied cross-sectionally and on follow-up. A 24-hour recall was used on 4 consecutive days. After 2 months on dialysis, the mean energy intake was 29 +/- 6.6 kcal/kg ideal body weight (IBW) and the mean protein intake was.93 +/-.39 g/kg IBW (high biological value [HBV] protein 49% +/- 8.5%). Dietary deficiency of both protein and calories was present in 64.9%. Intake was better on nondialysis days compared with dialysis days, and in women and older patients. On follow-up there was no significant increase in food intake up to 6 months. After that, the total calorie intake increased significantly with a disproportionate drop in high biological value protein consumed and appeared to be derived predominantly from carbohydrate food (mean kcal/kg, 37 +/- 6.9; mean protein g/kg, 0.96 +/- 0.19; ratio of HBV protein to total protein consumed,.42 +/-.09). In summary this study showed suboptimal energy and protein intake in an MHD population. Intakes were further compromised on dialysis days, and with increasing time spent on dialysis, the quality of nutrient intake became poorer.

Presentation, prognosis and outcome of IgA nephropathy in Indian adults

Background:  IgA nephropathy (IgAN) is not well characterized in India. This retrospective study of 478 patients with IgAN was performed to clarify the presenting features, prognostic factors and the renal survival rates of the disease.

Prediction of mortality in acute renal failure in the tropics.

Despite significant improvements in medical care, acute renal failure (ARF) remains a high risk for mortality. It is important to be able to predict the outcome in these patients in view of the emotional and ethical needs of the patients and to address questions of efficiency and quality of care. We analyzed the risk factors predicting mortality prospectively in a group of 265 patients using univariate and multiple logistic regression analysis. A prognostic model was evolved that included 10 variables. The model showed good discrimination [(receiver operating characteristic (ROC) area = 0.91) and correctly classified 88.30% of patients. The variables significantly associated with mortality were coma odds ratio (OR) = 9.8], oliguria (OR = 4.9), jaundice (OR = 3.7), hypotension (OR = 3.1), assisted ventilation (OR = 2.3), hospital acquired ARF (OR = 2.3), sepsis (OR = 2.2), and hypoalbuminemia (OR = 1.7). Age and male gender were included in the model as they are clinically important. The score was validated in the same sample by boot strapping. It was also validated in a prospective sample of 194 patients. The model was calibrated by the Hosmer-Lemeshow goodness-of-fit test. It was compared with two generic illness scores and one specific ARF score and was found to be superior to them. The model was verified in different subgroups of ARF like hospital acquired, community acquired, intensive care settings, nonintensive care settings, due to sepsis, due to nonsepsis etiologies, and showed good predictability and discrimination.

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.

Validation of 24-hour dietary recall: A study in hemodialysis patients

The 24-hour dietary recall method is frequently used for dietary assessment. However, it is subject to errors by both respondent and observer bias and is largely influenced by the motivation and recall ability of the respondent. The weighment method is regarded as the gold standard for estimating nutrient intake. This study was undertaken to assess the validity of dietary recall in a group of seven maintenance hemodialysis patients, who also had corresponding weighed food records. Actual food consumed and residue were weighed separately. A dietary recall was taken on the next day. Subjects were not allowed to take any food or beverage other than that served during the study period. A good agreement was obtained between dietary recall and the weighed food record (the difference was within 10% of the results of weighment), although there was a consistent underestimate by dietary recall. The results also suggested a training effect since improved recall was noted during the later weeks of the study, although this difference was not statistically significant. Therefore, dietary recall as a method of dietary assessment may be of special value in chronic hemodialysis patients in India, who are usually a motivated and informed group.

Renal Functional Reserve in Kidney Donors Assessed in Different Settings Using Scintigraphy

Glomerular filtration rate (GFR) was measured in 9 voluntary male kidney donors by scintigraphy. In the basal state, the mean GFR was 96.1 +/- 22 ml/min/1.73 m2. Four weeks after donor nephrectomy, the GFR of the remaining kidney had increased by 22.8 +/- 20.7% (p < 0.05). A protein meal given at this time failed to significantly augment the GFR. The GFR of the grafted kidney increased by 59.7 +/- 24.4% after 6 months (p < 0.01). Renal functional reserve was thus demonstrated in the remaining kidney and the allograft, though a further reserve could not be elicited in the remaining kidney.