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.

Infections with atypical mycobacteria in renal transplant recipients.

Infections due to atypical mycobacteria are infrequent in renal transplant recipients but they cause serious morbidity. These pathogens are common in patients with acquired immune deficiency syndrome (AIDS). We report four proven cases of infections caused with atypical mycobacteriae from 1997 to 2003, by different organisms namely, M. chelonei, M.fortuitum, M. abcessus and M. terrae in renal transplant recipients. Infection with M. terrae documented here is the first occurrence in a renal transplant patient. Histopathological examination of aspirates or biopsy specimens from involved areas and staining and culture for mycobacteriae are essential for diagnosis. Treatment involves antimycobacterial therapy, reduction in immunosuppression and surgery, if indicated. Atypical mycobacterial infections, though currently uncommon, are significant and could prove to be an emerging pathogen in renal transplant recipients in the context of the AIDS epidemic in India.

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.

Severe hyponatraemia: current concepts on pathogenesis and treatment.

Severe hyponatraemia (serum sodium <120 mEq/L) is a serious electrolyte disorder associated with life-threatening neurological complications. It develops most often when the ability of the kidney to excrete free water is impaired. The initial adaptation of the brain to hyponatraemia includes loss of water, sodium, potassium and chloride into the cerebrospinal fluid and the late adaptation consists of the loss of organic osmolytes. Adaptation of the brain to hyponatraemia causes potential problems during therapy, as re-adaptation requires a considerably longer time. Rapid correction of hyponatraemia may lead to the development of the osmotic demyelination syndrome. Though the ideal treatment for severe hyponatraemia remains controversial, a consensus regarding therapeutic guidelines has emerged. The rate of correction and the type of infusate depend on the duration and cause of the hyponatraemia, clinical presentation, volume status, renal function and the serum potassium level. The prognosis of the osmotic demyelination syndrome is rather dismal although several therapeutic modalities have been tried.

Plasmcapheresis--principles and practice.

The concept of removal of blood "blood letting" was practised in ancient times. In the last four decades plasmapheresis, plasma exchange, or apheresis as the modality of treatment of certain specific disorders has become available. This article is a review of the principles of plasmapheresis. The equipment needed, the technique of plasmapheresis and guidelines for its use are discussed.

Characterization of antibody response to human cytomegalovirus in Indian renal transplant patients.

BACKGROUND & OBJECTIVES: Cytomegalovirus (CMV) disease in seroendemic transplant populations is due to reactivation of the virus, or reinfection. In this context, the antibody response is likely to influence presentation, clinical severity and outcome of the disease, and may provide a diagnostic and prognostic marker. This study was carried out in Indian renal transplant patients and healthy adults to characterize the antibody response to cytomegalovirus. METHODS: Thirty three transplant recipients with CMV illness (symptomatology with IgM and/or nPCR positive status), 20 recipients who were asymptomatic in the 6 months of follow up after transplantation and 62 healthy controls were investigated for markers of CMV infection. These individuals were tested for IgG avidity and neutralizing antibody by ELISA techniques. RESULTS: All 53 transplant recipients were found to have an IgG avidity index of > 50 per cent. Antibody to a CMV envelope glycoprotein gB/AD-1 (putative neutralizing antibody) was expressed as S/N ratio and was > or = 5 in asymptomatic (65%) and symptomatic (27%) immunosuppressed renal transplant recipients. However, none of the 53 CMV IgG positive healthy controls were positive for neutralizing antibodies S/N ratio > or = 5 (S/N ratio = sample mean OD/mean OD of 3 negative controls in each run). We observed the simultaneous presence of CMV PCR signal in leukocytes and neutralizing antibody (S/N ratio > or = 5) in the plasma in 22 (41.5%) of the 53 renal transplant recipients. INTERPRETATION & CONCLUSIONS: In this study among the immunosuppressed transplant patients we observed an association between symptomatic disease and the relative absence of neutralizing antibodies. The neutralizing antibodies are less frequently demonstrable among controls; while appearance in a higher proportion of asymptomatic recipients especially in association with high IgG avidity (> 90%) is suggestive of its role in control of CMV disease despite reactivation as evidenced by DNAemia while on immunosuppressive therapy.

Immunosuppression in live-related donor renal transplantation.

BACKGROUND: Triple immunosuppression with cyclosporine, azathioprine and prednisolone is the most common regimen employed following renal transplantation. No information is available regarding its impact on the results of renal transplantation in India. The present study is an audit of a fixed-dose cyclosporine-based immunosuppressive regimen in an exclusively live-related donor transplant programme, with specific regard to graft and patient outcomes. METHODS: Patients transplanted over a 3-year period and receiving cyclosporine-based immunosuppression were studied. The relationship between immunosuppression and graft outcomes [rejection episodes (RE), graft function, graft survival], and patient outcomes (patient survival) was analysed in those receiving triple immunosuppression. Dosage schedules were audited. Cyclosporine trough level monitoring was employed at graft dysfunction episodes, or at dose reduction points. RESULTS: The median follow up was 14 months. Triple drug immunosuppression was used in 191 patients and double drug therapy in 26. The overall one-year patient survival rate was 91% and the corresponding graft survival rate was 90%. An audit of dosing schedules showed that over the first 6 months post-transplant, cumulatively, 20%-50% of patients received azathioprine, and 55%-60% received cyclosporine in doses below the protocol. The immunosuppressive doses (both of cyclosporine and azathioprine) in the first month were significantly related to the RE (p < 0.01) in the first month and the total number of RE in the first 6 months (p < 0.01). The other predictors were younger recipient age and older donor age. The sixth-month serum creatinine level was predicted by the donor age, the level of serum creatinine in the first month and the total number of RE in the first 6 months post-transplant. While no specific predictors of graft loss were identified in this cohort, diabetic nephropathy (p = 0.000) as the native renal disease, and the total number of RE were strongly related to patient mortality. The occurrence of > or = 2 RE in the first 6 months was an independent predictor, increasing the risk of death in the first 2 years post-transplant by 2.3 (p = 0.0001, 95% CI: 1.5-3.4). CONCLUSIONS: Sub-therapeutic baseline immunosuppression in the early post-transplant period predisposes to acute RE. This has an impact not only on graft function but also forms an important proximate marker of mortality, as seen in this cohort. Thus, immunosuppressive drug dosage should be optimized and therapeutic drug level monitoring strategies should be preemptive rather than event related, especially in the early post-transplant period. While fixed-dose immunosuppressive drug schedules are widely followed, it is possible to fall short of the target unless a specific effort is made to meet and sustain schedules.

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.

A randomised controlled trial of intradermal hepatitis B vaccination and augmentation of response with erythropoietin.

AIM: Intradermal administration of Hepatitis B vaccine (HBV) achieves better seroconversion in patients on dialysis compared to intramuscular administration. The aim of the study was to determine whether twice weekly intradermal injections of the vaccine can further augment the vaccine response as compared to once weekly injections. Patients with end stage renal failure on haemodialysis were randomly allocated over a period of 22 months to receive 20 mu gms of recombinant HBV by intradermal injections once a week (group 1) or twice a week (group 2) for 6 weeks. The patients recruited during the first 12 months of the study did not receive recombinant human erythropoietin (Epo) as it was not available (phase 1). During the last 10 months of study all patients received Epo (phase 2) in addition to HBV. RESULTS: A total of 85 patients were enrolled of whom 77 completed the study. There were 41 patients in group 1 and 36 patients in group 2. Seroprotection (anti HBs > 10 mIU/ml in the absence of HBs Ag and anti HBc) was achieved in 56.1% patients of group I compared to 77.8% of group 2 (p < 0.05). The seroprotection rate was 78.1% among patients receiving Epo (phase 2) compared to 60% among 45 who did not receive Epo (phase 1). Anti HBs titre in responders was 308.5 +/- 148.7 mIU/ml in patients of phase 2 compared to 198 +/- 112.8 mIU/ml in patients of phase 1 (p < 0.05). The subgroup receiving both Epo and twice weekly vaccine (group 2 of phase 2) had the highest seroprotection rate of 86.7%. CONCLUSION: Twice weekly intradermal vaccination is more effective than once weekly regime in achieving rapid seroconversion. The vaccine response may be augmented by use of Epo probably due to reduction in transfusion requirement and concomitant immunosuppression.

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.

Transplant associated Kaposis sarcoma.

This case reports the first transplant associated Kaposis sarcoma reported from India.

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.