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.

The effect on patient management of temporary non-availability of immunofluorescence for renal biopsy reporting.

Delay in reporting the immunofluorescence findings on renal biopsies, owing to an interruption in supply of reagents, made possible a retrospective analysis of the effect of the lack of this information on patient management. Hospital case records of the 39 patients so affected were reviewed to determine what changes in their management took place after the immunofluorescence findings became available. The clinical, laboratory, and light microscopic findings in all except a case of pauci-immune crescentic glomerulonephritis allowed management decisions to be made that were not influenced by immunofluorescence findings. This was owing to correct prediction of the immunofluorescence findings, as in cases of IgA nephropathy presenting with recurrent haematuria; the adequacy of light microscopy in the interpretation of graft biopsies, in classifying lupus nephritis and in most cases of nephrotic syndrome; and the absence of entities identifiable only by immunofluorescence among these patients.

Captopril-induced changes in effective renal plasma flow in hypertensive renal transplant recipients.

The role of converting enzyme inhibitor enhanced radionuclide investigations in post-transplant hypertension is not clearly defined. Presence of renal failure, chronic rejection and use of cyclosporin A complicates the results. Captopril-induced changes in effective renal plasma flow (ERPF) were studied in 10 patients with severe post-transplant hypertension and no evidence of rejection. Angiographic correlation was available in all. Six patients had a significant increase in ERPF after captopril, and all had a negative angiogram. One patient on CsA with a negative angiogram had no change in ERPF. Three patients had a fall in ERPF, and all 3 had transplant renal artery stenosis. Captopril-induced changes in ERPF can differentiate patients with native-kidney-induced hypertension from those with hypertension secondary to transplant renal artery stenosis in patients without evidence of rejection.

Gastric aspiration for diagnosis of pulmonary tubercolosis in adult renal allograft recipients.

Of 213 renal allgraft recipients suspected to have had pulmonary tuberculosis, 132 had sputum examinations and 14 showed acid-fast bacilli. Of the remaining 118 patients, 25 had gastric aspirations, 18 had bronchoalveolar lavage, and 75 did not require further investigation because of spontaneous improvement or confirmation of an alternative diagnosis. While 9 of the 25 patients' gastric aspirate examination was positive, all the 18 who had bronchoalveolar lavage were negative for acid-fast bacilli. Eighty-one patients without expectoration had gastric aspiration directly and 14 showed acid-fast bacilli. Of the remaining 67 patients only 17 had bronchoalveolar lavage, of which three were positive for AFB and the rest did not require further testing for tuberculosis. A total of 106 patients had gastric aspiration. Acid-fast bacillus positivity was significantly more (P<.01) in patients with abnormal chest radiographs as compared with patients with normal chest radiographs as compared with patients with normal chest radiograph results. We suggest gastric aspiration for AFB in all renal transplant recipients who have fever, scanty expectoration, and abnormal chest radiograph with clinical suspicion of pulmonary tuberculosis.

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.

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.

Active immunization against hepatitis B infection of a haemodialysis population.

BACKGROUND: Patients undergoing haemodialysis run a high risk of developing hepatitis B virus infection. We noted high prevalence rates of this infection in our patients despite a policy of using active hepatitis B vaccination. We, therefore, examined the reasons why haemodialysis-associated hepatitis B virus infection was difficult to control. METHODS: We analysed retrospectively 131 patients who had undergone haemodialysis for end-stage renal disease at our centre between June 1991 and May 1992. Patients given hepatitis B vaccine prior to starting haemodialysis were included in group A while those vaccinated after starting haemodialysis were placed in group B. The vaccination schedule consisted of 3 doses of recombinant hepatitis B vaccine given at monthly intervals. RESULTS: Fifteen patients had hepatitis B infection at entry, of whom 12 had had prior blood transfusions. Active immunization with recombinant hepatitis B vaccine was attempted in the remaining 116 patients. There were 16 patients in group A and 100 in group B. Of the 7 patients in group A and 46 in group B who completed the vaccination schedule, protective antibodies and markers of hepatitis B viral infection were noted in 3 and 2 patients respectively in group A and 7 and 14 patients respectively in group B. Vaccination was not completed in 63 patients as 25 discontinued haemodialysis, 22 developed markers of hepatitis B infection and 16 underwent renal transplantation. CONCLUSIONS: Poor seroprotection rates with the standard vaccination schedule, unscreened blood transfusions and an inability to complete the vaccination schedule were the major reasons why active immunization against hepatitis B viral infection in our patients on haemodialysis has been largely unsuccessful.

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.

Use of levamisole in maintaining remission in steroid-sensitive nephrotic syndrome in children.

A randomized, controlled trial was conducted in a pediatric unit in a teaching hospital in India to assess the efficacy of levamisole in maintaining remission in children with steroid-sensitive nephrotic syndrome. Sixty-one children with steroid-sensitive nephrotic syndrome, who had achieved remission with corticosteroids, were allocated to a treatment group (33 patients) receiving levamisole (2-3 mg/kg/day) twice a week for 12 months or to a control group (28 patients) receiving no treatment. The main outcome measure was duration of remission. Thirty months later, in the levamisole group, 21 of 33 patients were in remission as against 12 of 28 patients in the control group (chi 2 = 2.54, p = 0.11, NS). The median duration of remission maintenance was 12 months in the levamisole group as compared with 10.5 months in the control group. On survival analysis, the difference in duration of remission maintenance between the two groups was not significant (p = 0.10), though there was a trend in favor of the treatment group. On stratified survival analysis, multiple relapsers in the levamisole group had longer remission maintenance than the control group though this did not reach statistical significance (p = 0.08). The clinically significant trend towards increased duration of remission maintenance in steroid-sensitive nephrotic syndrome observed with levamisole therapy, especially in patients with multiple relapses, may require a larger study with a longer follow-up for definitive confirmation.