Frequency and role of hepatitis-C virus and type II cryoglobulinemia in membranoproliferative glomerulonephritis.

BACKGROUND: Many studies have claimed a major role of chronic hepatitis-C virus (HCV) infection in immune-mediated diseases such as membranoproliferative glomerulonephritis (MPGN). Chronic HCV infection is also known to produce essential mixed cryoglobulinemia (EMC), which in turn may manifest as vasculitis and cryoglobulinemic MPGN. OBJECTIVE: The aim of the study therefore, was to determine frequency of association and pathogenetic role of HCV infection as well as that of EMC in MPGN patients. METHODS: Fifty-three adult patients of MPGN were studied for HCV, HBsAg, EMC, C3, anti-nuclear antibody (ANA), rheumatoid factor serologically. Histopathology, immunofluorescence (IF) were conducted in all patients and electron microscopy (EM) in those who were found HCV positive. Simultaneously 37 follow-up patients of HCV associated chronic hepatitis were investigated for EMC, renal functions and urinalysis done for evidence of glomerulonephritis (GN). RESULTS: Thirteen percent MPGN patients were HCV positive, however, no viral particle could be seen in electron microscopy in glomeruli of these patients. There was no serologic evidence of HCV induced immune complex GN. None of the MPGN patients showed cryoglobulinaemia. Similarly none from HCV associated chronic hepatitis group had EMC nor showed evidences of glumerulonephritis. CONCLUSION: Thirteen percent of adult MPGN patients in north India were seropositive for HCV, indicating significant association. However, clear evidence in favour of its pathogenetic role was lacking in our study. Secondly, this study reveals that MPGN is non-cryoglobulinemic and HCV is not a major cause in our population compared to what is reported from other countries. These observations need confirmation by a larger study.

Pulmonary mucormycosis in a diabetic renal transplant patient.

A 50-year-old male, diabetic, post transplant patient had recurrent pneumonia. The first episode responded well to antibiotics, while on the second occasion he had a necrotising pneumonia, which developed into a thick-walled cavity. Despite antibiotics, his condition rapidly deteriorated precluding bronchoscopy or percutaneous biopsy. Post-mortem lung biopsy revealed typical hyphae of mucormycosis.

Pneumocystis carinii pneumonia: role of high resolution computed tomography.

Pneumocystis carinii (PC) is a common opportunistic infection in renal transplant recipients and requires an early diagnosis for its successful treatment. For its definitive diagnosis PC needs to be demonstrated in bronchoalveolar lavage (BAL) fluid. At times BAL may not be possible or get delayed. In such conditions typical appearances seen on high resolution CT of the chest help in early diagnosis of PC pneumonia (PCP). This easily performed procedure helped in early diagnosis of PCP in two patients.

Results of renal transplantation on conventional immunosuppression in second decade in India: a single centre experience.

BACKGROUND: In-spite of many renal transplant (RT) centres in the country, there is paucity of data on the survival results in India. Furthermore, there is hardly any data of results in second decade. In this study we present the results of RT in second decade at our centre. METHODS: RT at our hospital is being done since 1972. First eight years saw occasional RT and complete data is not available in these patients. So, we have excluded these patients from the study. We have included rest all 144 patients who had RT between Jan. 1981 to Dec. 1989, so as to have at least 10 years of follow-up or more. All these patients were on conventional immunosuppression. RESULTS: Of the 144 patients, 126 (87.5%) were males and the mean age was 29.5 +/- 8.5 years (range 14-54). Basic disease was presumed chronic glomenulonephritis (CGN) in 79.9%, vesicouretenic reflux (VUR) in 8% and diabetic nephropathy in 1.4% patients. Mean number of haemodialysis (HD) and blood transfusion before RT were 44 +/- 24.7 and 8.9 +/- 4.7 (range 0-25), respectively. Mean donor age was 40.9 +/- 10.1 year (range 18-62). HLA matching was haploidentical in 74.5% cases, HLA identical in 3% cases and 11.5% were less than two-antigen match. Of the 63% patients, who had at least one acute rejection (AR) during their follow-up, 78.8% cases had this AR within first three months after the renal transplant. During 10 years of follow up, 65 patients died (23 with normal graft function and 42 with chronic rejection) and 17 lost to follow-up. Eight patients lost their graft but were surviving at 10 years and 54 had functioning graft till the time of analysis. With mean follow-up of 83.9 +/- 61.2 (range 1-216) months, 10-year actuarial patients and graft survival was 53% and 47%, respectively. Graft half-life in these patients is 92 months. In multivariate analysis of the donor age, number of blood transfusion (BT), degree of HLA matching and AR, only AR was found to be statistically correlated with the graft outcome (p=0.004). CONCLUSION: Our study concludes that in our set-up during eighties, on conventional immunosuppression, actuarial patient and graft survival at 10 year is 53% and 47%, respectively with graft half-life being 92 months. Only acute rejection has been found to affect the graft outcome in these patients.

Influence of HLA compatibility on renal graft survival using live unrelated & cadaver donors in India.

BACKGROUND & OBJECTIVES: Living unrelated donor (LURD) renal transplantation has shown a rising trend over the last 5 yr at our center following the passing of The Transplantation of Human Organs Act by the Government of India in 1994. In this paper, the results of LURD and cadaver (CAD) donor renal transplantation are compared. We have also looked into factors that have a bearing on graft survival such as the extent of HLA mismatch (MM), infections, acute rejections (AR), donor age and sex. METHODS: A total of 42 LURD and 25 CAD renal transplants performed between March 1994 and February 1999 has been included in the study. HLA typing, panel reactive antibody (PRA) screening and T and B cell cross match assay were performed by the complement dependent cytotoxicity (CDC) method for all patients. RESULTS: The graft survival rates were generally higher in the LURD category as compared to the CAD group and were significant at 6 month period (90 vs 56%, P = 0.002). A follow up of the patients up to 60 months revealed a matching effect since the 3, 4 allele MM group had better survival rates as compared to the 5, 6 MM group. Twenty six of the 67 recipients (39%) experienced episodes of acute rejection (AR). Patients with 3, 4 MM had fewer such episodes than those with 5, 6 allele MM (P < 0.05). Of the 32 deaths, 20 were those with a functional kidney, of which 15 were caused by severe infections. INTERPRETATION & CONCLUSION: Better HLA matching ensures fewer episodes of rejection and better long term graft survival in comparison to the poorly matched grafts. The graft survival for LURD recipients was appreciably higher than that of CAD recipients.

Hepatitis C virus related cryoglobulinemic glomerulonephritis.

A 46 years male presented with skin rash and acute nephritic syndrome. He had history of jaundice four months back. Rheumatoid factor and cryoglobulins were present in the serum. Although anti-HCV antibodies were negative, HCV RNA was detected by polymerase chain reaction. Kidney biopsy showed membranoproliferative glomerulonephritis and thrombi in the lumen of the glomerular capillary loops. His renal functions improved with steroids.

Successful pregnancy outcome in advanced chronic renal failure.

A 24 years female of advanced chronic renal failure due to lupus nephritis presented with pregnancy of eight weeks duration she continued the pregnancy against medical advice. At 29 weeks gestation further deterioration of renal function prompted weekly dialysis and hospitalisation for intensive maternal and fetal monitoring. At 35 weeks she was safely delivered by elective caesarian section. This is the first case of dialysis during pregnancy to be reported from India.

Impact of hepatitis C virus infection on renal transplant outcome in India--a single centre study.

BACKGROUND: Hepatitis C virus (HCV) infection is currently the main cause of hepatotropic viral infection in renal transplant (RT) recipient throughout the world. Contrary reports are available as regard graft and patient survival and liver disease outcome in these patients. From India, outcome of HCV positive patients following RT has not been documented. Herewith, we present results of RT in HCV positive patients at our centre. METHODS: Study design was prospective case control with primary end point being graft and patient survival and the exposure being HCV infection. Between June 1995 till February 1998, 128 patients had RT at our hospital, of which, 37 (28.9%) were anti-HCV positive at the time of RT. All the patients were on triple immunosuppressive therapy. As a policy of unit, none of the donor had HBV and/or HCV infection. Anti-HCV positive patients formed the subjects (Gr. I), while anti-HCV negative patients severed as control (Gr. II). Anti HCV was done using 3rd generation ELISA tests kit. HCV-RNA could not be done due to non-availability. None of the positive patient was treated with anti-viral therapy. Acute rejection, serious infections, patient and graft survival and outcome of liver disease was compared in these patients. RESULTS: Mean age of the patients, number of males, number of pre-RT haemodialysis and blood transfusion, donor age and HLA-mismatch were comparable in both the groups. Mean follow-up in Gr. I was 28 +/- 9.4 months and in Gr. II 31.4 +/- 7.6 months. At the end of this follow-up, acute rejection was seen in 43% and 33.3% patient in Gr. I and II respectively. In Gr. I, serious infections were seen in 30% while the same in Gr. II was 11.8% (p < 0.01). There was no difference in graft survival in Gr. I and II (72% and 66%) and the patient survival were also similar (72% and 66%). Of the deaths in Gr. I, 80% died of sepsis and 20% died of liver cell failure related to one each of hepatitis B and hepatitis E. Of the deaths in Gr. II, 65% died of sepsis and 17% died of hepatic cell failure. But, there was no difference in causes of deaths in these two groups. In both the groups, none of liver related death was due to isolated HCV infection. There was no effect of donor age, HLA mismatch, number of haemodialysis and pre-RT blood transfusion on the survival of graft as well as patient. CONCLUSION: In conclusion, HCV infection is major problem in RT with us. In a short follow-up of nearly 30 months, graft and patient survival is same in HCV positive and negative patients. However, serious infections are significantly more common in HCV positive patients.

Role of supravital staining of urine sediment and bright field microscopy in diagnosis of acute renal failure in bedside medicine.

BACKGROUND: An early accurate etiological categorization of acute renal failure (ARF) into acute glomerulonephritis (AGN), acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) is very important in clinical medicine. METHODS: To evaluate the efficacy of a simple, cheap supravital staining method developed in our laboratory, we examined urine of 32 cases of ARF at their initial presentation in oliguric phase, which were later biopsied. The stain consisted of 1% crystal violet and 0.5% safranin in normal saline. The coverslip preparations of coded and stained urine sediments were examined under ordinary bright field microscope (BFM) by two independent observers. RESULTS: The renal biopsy showed 12 cases of AGN, 12 ATN and 8 AIN. The diagnosis could be predicted by supravital staining method in 75% cases with 95% uniformity among two observers with a sensitivity of 85.7% for AGN followed by AIN (80%) and ATN (75%). CONCLUSION: Thus this simple supravital staining technique can be used with ordinary BFM for accurate urine sediment analysis in cases of ARF in bedside medicine.

Spectrum of renal diseases in Indian adults.

INTRODUCTION: Inspite of nephrology as a specialty since seventies, there is still paucity of data regarding the spectrum of renal diseases in India. Available literature from few hospitals shows data on specific clinical syndrome of renal diseases or specific renal diseases rather than the overall spectrum as a whole. This information will be useful for better resource management. MATERIAL AND METHODS: We studied spectrum of renal diseases among 14,796 patients presenting for the first time to nephrology outpatients between January 1987 to Oct. 1998. Majority of patients in our clinic were adults. Patients 14 years or below who mostly attend pediatric renal unit of the hospital were excluded from the analysis. Till 1991, the study was retrospective but after 1991, patients were followed prospectively. Patients were grouped according to classical renal syndrome. After the initial presentation, patients were followed subsequently till their last follow-up in the clinic or till the time of reporting the present data. RESULTS: Mean age of patients was 38.69 +/- 15.5 years with male predominance in majority of presentations. Chronic renal failure (CRF), nephrotic syndrome (NS), nephritic syndrome and hypertension were the four common presentations seen in 47.8%, 15.03%, 4.6% and 4.9% cases respectively. Other presentations were acute renal failure (1.9%), urinary tract infection (2.9%), stone disease (4.6%), obstructive uropathy (2.1%), isolated haematuria (1.2%) and asymptomatic urinary abnormalities (0.3%). Chronic glomerulonephritis was seen in 49.4% cases of CRF followed by diabetic nephropathy in 28.4% cases. Of the nephrotic syndrome cases, primary glomerulonephritis was seen 58.5% cases, of which minimal change disease was the commonest cause in 38% cases. Of the secondary glomerular diseases, diabetic nephropathy was commonest cause of NS (53%) followed by amyloidosis (16.4%) and lupus (8.3%). Tuberculosis was the commonest cause of renal amyloidosis seen in 50% cases. Of the nephritic syndrome, post-infective glomerulonephritis was commonest cause followed by rapidly progressive glomerulonephritis being the second commonest cause. In the hypertensive group, essential hypertension was the commonest cause followed by renovascular hypertension. CONCLUSION: It is the first large study of its kind presenting the spectrum of renal diseases in the tertiary-care government hospital of the country and we expect the disease pattern to be reasonably similar in other similar government hospital of the country. Chronic renal failure, nephrotic syndrome and diabetes are three major diseases, with which we have to deal maximum. As CRF in young male patients is the largest load, with its wide social and economical implications in the Indian context, we must gear up to organise ourselves for providing the best possible care to these patients with the limited resources.

Hepatitis C virus infection during haemodialysis in India.

BACKGROUND: Hepatitis C viral (HCV) infection is a major cause of hepatitis during haemodialysis after the control of hepatitis B following vaccination and isolation measures. Magnitude of this problem in India has not been studied and there are only few reports of HCV infection during haemodialysis from this country. This study was conducted to find out the incidence of HCV infection in patients of end stage renal disease (ESRD) and haemodialysis (HD), along with its source and to find out the clinical course of HCV positive patients. METHODS: HCV infection was diagnosed by detecting anti-HCV antibodies using the IIIrd generation ELISA kits. RESULTS: Of the 208 consecutive patients of ESRD accepted for the study, HCV prevalence was 4.3% at the time of start of study. Of the all risk factors studied, past history of jaundice and number of blood transfusion (BT) were significantly higher in HCV positive patients as compared to HCV negative patients. Of the 208 patients, 20 (9.6%) died, 119 (57.2%) lost follow-up and 69 (33.2%) got renal transplant (RT). Incidence of HCV in patients who died, lost follow-up and got RT was 10%, 3.4% and 36.2% while prevalence was 15%, 4.2% and 42% respectively. In these groups, duration of HD was 8.4, 5.2 and 22.7 weeks respectively while the mean blood transfusion (BT) was 1.2, 0.8 and 5.4 in number respectively. Mean age of patients in these groups was 37.85, 37.9 and 32.53 years and percentage of males were 65%, 75% and 89.9% respectively. At no stage of follow-up, patients with HCV infection had any symptoms or high serum bilirubin. Major abnormality was fluctuating ALT in these patients. HCV in 512 units of blood transfusions given to these patients and healthy volunteers was 1.17% and 0.66% respectively. Marked increase of HCV infection while patients were on HD is likely to be due to nosocomial spread. Blood transfusion was not found to be important source of HCV infection. Longer the patients remain on HD; more will be chance of HCV infection. CONCLUSION: It is concluded that HCV is a major cause of concern in haemodialysis patients in India and the predominant source of spread of infection is nosocomial. In our set-up, blood transfusion is not an important source of infection. Majority of these patients remains asymptomatic at least for the short terms follow-up.

Comparison of two schedules of hepatitis B vaccination in patients with mild, moderate and severe renal failure.

Seroconversion rate following hepatitis B vaccination in patients of chronic renal failure (CRF) has been in the range of 10%-82% in various studies. Different approaches have been tried to improve seroconversion rate. We studied two schedule of hepatitis B vaccination, 0,1,2 (Group A) and 0,1,2,6 (Group B) in mild (creatinine 1.5 to 3.0 mg%), moderate (creatinine 3.0 to 6.0 mg%) and severe CRF (creatinine > 6.0 mg%). Between Oct. 93 to Oct. 95, 117 patients with CRF who were negative for HBsAg and anti-HBs were included in the study. Forty micrograms of recombinant vaccine "ENGIREX" (20 micrograms in each deltoid region) was given in both the groups. Number of cases of mild, moderate and severe CRF were 18, 15 and 42 in group A and 12, 13 and 17 in group B, respectively. One month after the last dose of vaccination, anti-HBs was measured using ELISA kit (Abbot Laboratories, India). Anti-HBs titres of > 10 IU/L were taken as criteria of positive seroconversion. In group A seroconversion rate was 87.5%, 66.6% and 35.7% in mild, moderate and severe CRF respectively while same results in group B were 100%, 77% and 36.36%, respectively. We conclude that patients of chronic renal failure should be vaccinated at very early stage of the disease using 40 micrograms of vaccine. Four doses schedule of 0,1,2,6 give better results than three doses schedule in early CRF.

Post transplant diabetes mellitus in live related renal allograft recipients: a single centre experience.

The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250 patients who underwent live-related renal transplantation at our hospital between 1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine in addition (triple-therapy). Three patients (25%) developed PTDM during or immediately following anti-rejection therapy with intravenous methylprednisolone. Eight patients (66.6%) developed PTDM within six months of transplantation. Majority of our patients (66.6%) could be managed successfully with oral hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were symptomatic for their hyperglycemia with two patients presenting as 'pseudorejection' and one with diabetic ketoacidosis. Females were more predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were the commonest phenotypes in our PTDM patients. No other known predisposing or triggering factors associated with PTDM were found in our patients. The current study suggests, that addition of cyclosporine to the conventional immunosuppression in live-related renal allograft recipients has contributed to an increased incidence of post-transplant diabetes mellitus. Close and regular blood sugar monitoring is thus recommended in post-transplant patients especially those on triple drug immunosuppression.

The quality of life in successful live-related renal allograft recipients in India.

BACKGROUND. The high cost of maintenance of haemodialysis makes most patients in India and elsewhere opt for a renal transplant. The degree of rehabilitation can best be assessed by evaluating the quality of life in successful recipients. METHODS. We studied vocational rehabilitation, social relations, sexual and married life, psychological status and life satisfaction in 51 successful live-related renal allograft recipients using Schwab's depressive scale, Bigot's life satisfaction index and the Kamofsky physical scale. RESULTS. Eight-four per cent of our patients had returned to their original jobs. Ninety-eight per cent of patients had a Kamofsky scale of 90-100 and 81% were leading a normal married life. Ninety-four per cent of them led an active social life. CONCLUSION. Successful live-related renal transplantation is associated with a good quality of life and should be the treatment of choice for patients with end-stage renal disease.

Blood pressure profile, urinary sodium and body weight in the 'Oraon' rural and urban tribal community.

Blood pressure and nutritional profiles in the 'Oraon' tribal community of India living in rural and urban areas were studied between 1981-85 after a house to house survey of 4523 rural tribal people (RT) and 935 of their urban tribal counterparts (UT). Prevalence of hypertension was found to be 4.8/1000 males and 4.3/1000 females in rural tribal group giving an overall rate of 4.6/1000. In contrast the same were 27.1/1000 males and 21.4/1000 females in UT group, overall rate being 25.6/1000. Average calorie consumption were 1750 and 2280 and mean 24 hour-urinary sodium excretions 58 and 118 milliequivalents in RT and UT groups respectively. Of the total of 21 subjects in RT and 24 in UT detected to be hypertensive, 7 had common family inheritance. Increased mean arterial pressure correlated with increased sodium consumption and body weight. Hypertensives from both the groups showed higher urinary sodium excretion (P < 0.05). This epidemiologic study proves the role of a genetic factor/defect complicated by higher salt consumption in causation of increased blood pressure.