Hantavirus species in India : A retrospective study.

Hantaviruses cause hemorrhagic fever with renal syndrome in Europe and Asia. There are about 20 documented hantavirus species and newer species are being described worldwide, especially in non-rodent reservoirs, i.e shrews. Focus reduction neutralization test is the classical serotyping technique for hantavirus. However, this study employs a previously established serotyping ELISA, to retrospectively analyze known hantavirus IgG reactive samples for infecting serotypes. The result suggests presence of Thailand virus- like and Hantaan virus -like strains in India.

Pre-tertiary hospital care of patients with chronic kidney disease in India.

BACKGROUND & OBJECTIVES: There is paucity of data available on how chronic kidney disease (CKD) is treated before referral to a tertiary hospital. This study was conducted to assess pre-tertiary hospital care of patients with CKD 5 at their presentation to nephrology services at a tertiary care hospital. METHODS: Over a period of 8 months, consecutive patients with CKD 5 presenting at the Nephrology services at Christian Medical College, Vellore, Tamil Nadu, and their relatives were interviewed to assess the pre-tertiary hospital care and knowledge about CKD 5 and its treatment. RESULTS: A total of 561 patients with CKD 5 were enrolled. The mean duration (months) of known CKD was 12.4 +/- 23.1 and known CKD 5 was 3.2 +/- 3.5. Of these, 369 patients (65.8%) had been under the care of a nephrologist; 305 patients had CKD 5 as the initial presentation of renal illness. Vaccination against hepatitis B had been initiated in only 133 patients (23.7%). Only 172 patients(38%) had an adequately controlled blood pressure. Care under a nephrologist was more likely to result in appropriate investigation, treatment and patient education though blood pressure control did not differ. INTERPRETATION & CONCLUSION: Paucity of symptoms in the initial stages of certain forms of CKD probably led to 50 per cent of patients presenting with CKD 5 as the initial presentation of renal disease. Inadequate vaccination against hepatitis B infection highlights the need for appropriate vaccination. Prevention of CKD and its progression are important targets which requires physician awareness at all levels. Early referral to a nephrologist's care is more likely to result in appropriate investigations and treatment.

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. The present therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this sampling period? AIM: To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. SETTINGS AND DESIGN: Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paired data. MATERIALS AND METHODS: Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept were evaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the time after transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the 12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factor applied. These two AUCs were then compared. STATISTICAL ANALYSIS: Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were applied to the data. RESULTS: Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. No bias was seen with a Bland Altman plot or by calculation. CONCLUSION: For patients on Cellcept with prednisolone +/- cyclosporine the 6-hour corrected is an accurate measure of the full 12-hour AUC.

Spectrum of severe chronic kidney disease in India: a clinicopathological study.

BACKGROUND: The healthcare burden due to chronic kidney disease has increased worldwide in the past decade. Elucidating the aetiology of chronic kidney disease may help in identifying strategies for prevention, both in the population and the Individual patient. Only a clinicopathological study can define the exact spectrum of chronic kidney disease since epidemiological studies have not shown a consistent aetiological profile. The histological evidence used to support the diagnosis varies with the degree to which renal biopsy is done. Renal biopsy is the gold standard in making an aetiological diagnosis in renal failure, but as a diagnostic tool in chronic kidney disease it is underutilized. METHODS: This prospective study done at Christian Medical College, Vellore in southern India from 1998 to 2003 aimed to determine the aetiological profile of severe chronic kidney disease by analysing renal biopsies. The value of pre-renal biopsy clinical Judgement in predicting the histological diagnosis was also assessed. Patients with diabetic nephropathy were excluded from the study. RESULTS: Four hundred and fifty-seven patients had evidence of chronic kidney disease as evidenced on biopsy as well as on clinical parameters. Three hundred and twenty-two of these patients (70.5%) had glomerulonephritis as the histological diagnosis. Fifty-five (12%) had Interstitial nephritis, 30 (6.6%) had hypertensive arteriosclerosis and 28 (6.1%) had metabolic nephropathies. The positive predictive value of a pre-biopsy clinical diagnosis in predicting interstitial nephritis was very low (33%). A large number of patients clinically diagnosed to have chronic interstitial nephritis had other aetiologies of chronic kidney disease. CONCLUSION: Glomerulonephritis was the most common cause of chronic kidney disease, not including diabetic nephropathy, followed by interstitial disease and benign arterionephrosclerosis. In patients with unidentified severe chronic kidney disease, renal biopsy provided an aetiological diagnosis.

Pre-transplant risk factors for renal allograft dysfunction at one year in Indian patients.

BACKGROUND: Only a few patients with end-stage renal disease in the Indian subcontinent receive optimal treatment. Of these only a minority can afford a second renal transplant. Awareness of modifiable pre-transplant risk factors that influence allograft function is crucial before embarking on the first transplant. There are no reports from the Asian subcontinent describing the pre-transplant risk factors. METHODS: We studied the effect of donor age, gender, and relation with the recipient, patient age, gender, HLA matching, native kidney disease and immunosuppression on one-year allograft function using data from 1177 consecutive primary living related donor renal transplants at the Christian Medical College Hospital, Vellore. We performed a univariate followed by a multivariate analysis using a logistic regression model to calculate the odds ratio for the effect of the above factors on two levels of graft function (serum creatinine > 1.4 mg/dl and > 2 mg/dl) at one year. RESULTS: On univariate analysis, older donors, women donors, mother being the donor, men recipients, < 1 HLA antigen match, cyclosporine-based immunosuppression and patient age between 16 and 40 years were associated with serum creatinine levels > 1.4 mg/dl at one year. Multivariate analysis showed that donor-related factors, namely mother as donor, older donors, and a < or = 1 HLA antigen match, were risk factors for graft dysfunction (serum creatinine level > 1.4 mg/dl) at one year. Recipient-related risk factors were male patients and those between the age of 16 and 40 years. CONCLUSION: In patients undergoing living related donor renal transplants from large extended families, a younger haplomatched donor, for instance, a brother, is a better choice than an older haplomatched donor, for instance, the mother, particularly in young male recipients at a higher risk of renal dysfunction.

Role of molecular techniques in the detection of HBV DNA & HCV RNA among renal transplant recipients in India.

In this study we have investigated the occurrence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among 68 renal transplant recipients. Replicative HBV and replicative HCV infections were seen in 12 (17.6%) and 38 (55.9%) patients respectively, the difference was statistically significant (P < 0.001). Among the 38 HCV RNA+ individuals, anti-HCV was present only in 23. Anti-HCV in the absence of HCV RNA was detected in one patient. Anti-HDV antibody was seen in 2 (15.4%) of the 13 HBV infected individuals. Nine (13.2%) of the 68 individuals had replicative dual infection with HBV and HCV. Triple infection (HBV DNA+, HCV RNA+, anti-HDV+) was seen in 2 transplant recipients. There was significantly higher demonstration of replicative HCV (P < 0.001) in transplant recipients having elevated liver enzymes (n = 34) as compared to transplant recipients having normal liver enzyme levels (n = 34). Though not significant, a higher detection rate was also seen with replicative HBV infection and replicative dual infection among transplant recipients with elevated liver enzymes. The higher detection of HCV in renal transplant recipients by molecular techniques, emphasizes the need for HCV RNA testing. Further deliberate attempts to change practices to reduce this problem may also improve graft and patient survival in recipients.

Prognostic factors in diffuse proliferative lupus nephritis.

BACKGROUND: Patients with diffuse proliferative lupus nephritis (DPLN) can have variable clinical course. Identification of the predictors of outcome would help to improve the management. We have studied the prognostic significance of clinical, laboratory and histological parameters in patients with DPLN. METHODS: Twenty nine patients diagnosed to be having DPLN seen between 1987 and 1991 were followed up for over 57 months. Parameters assessed for prognostic significance included serum creatinine, urine protein at the time of biopsy, blood pressure, type of immunosuppression, composite scores and individual components of activity index (AI) and chronicity index (CI). Kaplan-Meier survival curves were plotted and the results were compared using log rank test. Fishers' exact test was used to study the risk factors. RESULTS: End stage renal failure developed in 7/29 (24.1%) patients; 7/19 (36.8%) who had hypertension and 7/16 (43.8%) who had nephrotic proteinuria developed renal failure, while none who had normal blood pressure or nonnephrotic proteinuria, developed renal failure (p < 0.01). Three patients had high activity index (> 12) and all three developed renal failure. Other parameters such as age, gender, serum creatinine, type of immunosuppression, CI and individual components of AI failed to predict the outcome (p > 0.05). CONCLUSION: Hypertension, nephrotic proteinuria and high AI were predictive of progression to end stage renal failure in patients with diffuse proliferative lupus nephritis.

The effect of cyclosporin A on plasma lipids during the first year after renal transplantation.

BACKGROUND: The serum lipid profile of renal transplant recipients from the Indian subcontinent is not available. Cyclosporin A causes dyslipidaemia, a major risk factor for coronary artery disease which is a significant cause of mortality in these patients. We compared the effect of two dosage schedules of cyclosporin A on the lipid profile of transplant recipients. METHODS: Two hundred and eight renal allograft recipients were randomized to receive either a high or a low dose of cyclosporin A for 12 months. Their cholesterol and triglyceride levels were measured at monthly intervals for the first six months and at the ninth and twelfth months. The area under the curve was measured and multiple linear regression analysis was done. ANOVA for repeated measures was carried out. RESULT: Patients receiving a higher dose of cyclosporin A had higher cholesterol and triglyceride levels compared to those receiving the lower dose schedule. The multivariate analysis showed that a low dose of cyclosporin A was significantly associated with reduced cholesterol (p < 0.07) and triglyceride levels (p < 0.04) after controlling the effect of other covariates. ANOVA for repeated measures showed that cholesterol levels were significantly lower in the low-dose cyclosporin A group (p < 0.05). CONCLUSION: Low dose cyclosporin A reduces the risk of dyslipidaemia in Indian renal transplant recipients.

Treatment of diffuse proliferative lupus nephritis: an Indian experience.

BACKGROUND: Immunosuppressive therapy has improved the prognosis in lupus nephritis. However, infectious complications may contribute to morbidity. There is also debate on the best form of therapy. We, therefore, compared the results of two different forms of therapy. METHOD: Twenty-nine patients diagnosed to have diffuse proliferative lupus nephritis were followed up over 54 months. The treatment consisted of azathioprine (1.5 mg/kg/day) or pulse intravenous cyclophosphamide (500 mg/m2 body surface area monthly) along with prednisolone (2 mg/kg on alternate days). RESULTS: Seventeen patients received azathioprine (group A) and 12 received cyclophosphamide (group B). The mean (SD) follow up in groups A and B were 54.35 (33.6) and 52 (35.8) months, respectively. Apart from the higher number of males in group B, both groups were comparable for age, presence of hypertension, renal function, 24-hour urinary protein excretion and composite scores for histological activity and chronicity indices (p > 0.05). The renal survival estimated by the Kaplan-Meier method was similar in both groups (p > 0.05). Four patients had renal failure requiring replacement therapy in group A and 3 in group B. Major infective episodes were more common in group B than in group A (p = 0.03). CONCLUSION: Azathioprine was as effective as pulse intravenous cyclophosphamide in preserving renal functions up to 54 months. Major infective episodes were more common with pulse intravenous cyclophosphamide.

Aetiology of hyperkalaemia in hospital inpatients.

BACKGROUND: Hyperkalaemia is a common metabolic disorder; if left untreated it can lead to life-threatening consequences. We conducted this study to determine the common aetiological factors for hyperkalaemia in hospital inpatients. METHODS: This prospective cross-sectional study was conducted in a referral teaching hospital in south India. One hundred and forty-three patients with hyperkalaemia (> 5 mEq/L) were selected on 20 random week days over a 3-month period. All the patients were clinically and biochemically evaluated for the aetiology of hyperkalaemia. RESULTS: Hyperkalaemia was twice as common amongst males. Potassium supplementation and drugs were the leading causes for hyperkalaemia, with renal failure being a distant second. Hyperkalaemia developed after admission to hospital in more than 75% of the patients. Severe hyperkalaemia (> 6 mEq/L) was seen in one-third of the patients. CONCLUSION: Potassium supplementation and other iatrogenic conditions lead to hyperkalaemia in inpatients. Males are at increased risk for hyperkalaemia.

Primary drug resistance to Mycobacterium tuberculosis in renal transplant recipients.

BACKGROUND. After renal transplantation, patients have an up to 5% chance of being infected with Mycobacterium tuberculosis and there are reports from western countries of a 24% mortality if the infection is drug resistant. We investigated primary drug resistance in renal transplant recipients in Vellore, Tamil Nadu. METHODS. Between January 1987 and December 1993 we studied 695 patients (who had received 717 renal allografts) for evidence of tuberculosis, and performed drug sensitivity tests. RESULTS. Forty-three patients had culture-proven infection with Mycobacterium tuberculosis of whom 40 had drug sensitivity tests done. Initial drug resistance was seen from 1991. Rifampicin resistance was seen in 2, 1 and 4 patients and isoniazid resistance in 1, 2 and 2 patients in 1991, 1992 and 1993, respectively of the 23 isolates tested for drug susceptibility. Multi-drug resistance was seen in 1 and 2 patients in 1992 and 1993. CONCLUSIONS. This is probably the first report in India of primary drug resistance of Mycobacterium tuberculosis in renal allograft recipients. It is a cause for concern as it may indicate a large reservoir of drug-resistant patients in the community.

Free radical injury in human renal allograft rejection.

Plasma and renal tissue levels of lipid peroxide and plasma vitamin E were estimated as measures of free radical injury in five renal allograft recipients with untreated and four with unsuccessfully treated acute cellular rejection and compared with 11 control patients with minimal change disease. Plasma lipid peroxide was significantly higher in patients studied before antirejection therapy (13.2 +/- 3.5 nmol/ml; P < 0.01) as well as in those after unsuccessful antirejection treatment (11.7 +/- 0.7 nmol/ml; P < 0.01), compared to controls (5.7 +/- 2.8 nmol/ml). Levels of plasma vitamin E and renal tissue lipid peroxide were similar in both groups, however the latter was significantly raised in patients evaluated prior to antirejection therapy than in those after unsuccessful antirejection therapy (5.1 +/- 1.7 and 3.0 +/- 0.8 nmol/mg protein; P < 0.05). These findings suggest possible free radical mediated injury during renal allograft rejection.