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.

Toxic megacolon in a renal allograft recipient with cytomegalovirus colitis.

We report a 35-year-old man, a renal allograft recipient, who presented with toxic megacolon. Segmental biopsies from the colon were consistent with cytomegalovirus colitis. Serum polymerase chain reaction for cytomegalovirus DNA confirmed the diagnosis. He was treated with ganciclovir but, though his abdominal condition improved initially, he worsened later and succumbed to his illness.

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.

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.

Primary IgA nephropathy in adults.

IgA nephropathy was found in 9.6% of 649 adults with primary glomerulonephritis. Hypertension was detected in 51.6% and renal failure in 32.3%. A nephrotic presentation was seen in 22.6% and recurrent macroscopic hematuria in 17.7%. On light microscopy, mesangial hypercellularity and an increase in mesangial matrix were frequently seen (74.2%). Immunofluorescence studies demonstrated IgA in all patients along with C3 in 61.3%, IgM in 27.4% and IgG in 11.3%. Followup was possible in 61.3% for mean period of 17.3 months. No clinical or biochemical abnormalities were detected on followup in 26.3%. Progression to end stage renal disease was noted in 7.9%.

Continuous renal replacement therapy in critically ill patients with renal failure.

Continuous arterio-venous and veno-venous haemodiafiltration (CAVHD, CVVHD), combine convection and diffusing solute clearance. We performed CVVHD on critically ill patients with renal failure, of whom 15 were on inotropic support and 10 on ventilators. Satisfactory diafiltration could be performed in all the patients with adequate solute and fluid removal. The main complication was clotting of the filter. The procedure was simple, safe and could be done by staff with no special training in dialysis technology.

Iron stores in patients on haemodialysis after renal transplantation.

BACKGROUND. Patients with chronic renal failure receive iron orally and parenterally which can lead to iron overload. However, iron deficiency is common among Indians and it is not known whether the Indian dialysis and transplant patient runs a similar risk of iron overload. The iron status is best quantified by measuring serum ferritin levels when there is no intercurrent inflammatory process. We used this method to assess the iron stores in a random sample of the Indian population on our dialysis and transplantation programme. METHODS. Serum ferritin assay was done using ELISA on samples obtained from 24 patients at entry to dialysis, before renal transplant surgery and 3 to 6 months following the surgery. All patients received 120 mg of elemental iron orally and third party transfusions according to a fixed protocol. RESULTS. None of the patients had iron deficiency despite low haemoglobin values. Fifteen patients at entry, 12 out of 16 pre-transplant and 10 out of 17 post-transplant patients had evidence of iron overload. Three patients developed iron overload during the period of observation and 6 of the 10 who entered the programme with evidence of iron overload continued to have iron overload. CONCLUSION. Indian patients with chronic renal failure have evidence of iron overload similar to those in developed countries. Oral iron supplements in Indian patients are therefore unnecessary.

Live related renal transplantation for end stage diabetic nephropathy.

We report our results with live related renal transplantation in 43 diabetics, most of whom were non-insulin dependent, with end stage renal disease. The overall one year patient survival was 72.1% and graft survival was 65.1%. The use of Cyclosporine was associated with a significant improvement in the one year patient and graft survival (92.3% and 84.6% respectively). The most important cause of mortality was infection. Live related renal transplantation with Cyclosporine as immunosuppression is advisable for the uremic diabetic.