Vinay Sakhuja

A Randomized, Controlled Trial of Steroids and Cyclophosphamide in Adults with Nephrotic Syndrome Caused by Idiopathic Membranous Nephropathy

Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size, quality, and duration. This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine, development of ESRD, and quality of life in a randomized, controlled trial. Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat basis. A total of 93 patients completed the study. Of the 47 patients who received the experimental protocol, 34 achieved remission (15 complete and 19 partial), compared with 16 (five complete, 11 partial) of 46 in the control group (P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and the likelihood of survival without death, dialysis, and doubling of serum creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia, hyperlipidemia that required therapy, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, and better quality of life on follow-up. The incidence of infections was similar in the two groups. In conclusion, untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function. A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion, arrests progression of renal insufficiency, and improves quality of life.

The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus

Zygomycosis is an emerging infection worldwide. A study was conducted to understand its spectrum in the Indian scenario. All patients diagnosed for invasive zygomycosis at a tertiary care center in north India from 2000-2004, were retrospectively analyzed. A total of 178 cases (mean average of 35.6 cases/year) of zygomycosis were diagnosed. Rhino-orbito-cerebral type (54.5%) was the commonest presentation followed by cutaneous (14.6%), disseminated (9.0%), and gastrointestinal (8.4%) zygomycosis. Renal and pulmonary zygomycosis were seen in 6.7% patients each. Uncontrolled diabetes mellitus (in 73.6% of cases) was the significant risk factor in all types (Odds Ratio 1.5-8.0) except renal zygomycosis. Breach of skin was the risk factor in 46.2% patients with cutaneous zygomycosis. However, no risk factor could be detected in 11.8% patients. Antemortem diagnosis was possible in 83.7% cases. The commonest (61.5%) isolate was Rhizopus oryzae followed by Apophysomyces elegans in 27% patients. Combination of debridement surgery and amphotericin B therapy was significantly better in survival of the patients (P<0.005) than amphotericin B alone (79.6% vs. 51.7% survival). Thus, a rising trend of invasive zygomycosis was observed in patients with uncontrolled diabetes mellitus in India. Consistent diagnosis of renal zygomycosis in apparently healthy hosts and the emergence of A. elegans in India demand further study.

What do we know about chronic kidney disease in India: first report of the Indian CKD registry

BackgroundThere are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics.MethodsData was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively.ResultsThe mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology.ConclusionsThis report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.

Acute Renal Cortical Necrosis—A Study of 113 Patients

Over a 28-year period, 113 out of 2986 (3.8%) patients dialysed for acute renal failure at a referral center in North India were diagnosed to have acute renal cortical necrosis (ACN). Obstetric causes were responsible for ACN in 56.6% patients and nonobstetric causes in 43.4%. Within the obstetric group, ACN developed in association with complications of late pregnancy in 37.1% and following septic abortion in 19.5%. The various nonobstetric causes included viperine snake bite in 14.2%, hemolytic uremic syndrome in 11.5%, renal allograft rejection in 5.3%, acute gastroenteritis in 4.4%, acute pancreatitis in 3.5%, septicemia in 2.7%, and trauma and drug-induced IV hemolysis in 0.9% patients. Total anuria was the commonest presenting feature and was noted in 78.8% of patients. Renal histology showed diffuse cortical necrosis in 62.8% and patchy lesions in 37.2% patients. Computerized tomography (CT scan) of the kidneys revealed characteristic diagnostic findings in all the 5 patients in whom it was done. Dialytic support could be withdrawn as a result of improvement in renal function in 19 patients with patchy cortical necrosis. Dialysis-free survival of as long as 12 years has been recorded. The present study shows that, in contrast to the Western world, ACN continues to be a common cause of acute renal failure in developing countries. CT scan of the kidneys is helpful in establishing an early diagnosis.

Invasive zygomycosis in India: experience in a tertiary care hospital

Aim: To report the natural history and clinical course of zygomycosis from a single tertiary care centre in India where doctors maintain an institutional zygomycosis registry. Methods: The clinical and laboratory data collected prospectively from patients with antemortem diagnosis for invasive zygomycosis, and retrospectively from autopsy diagnosed cases, over an 18 month period (July 2006–December 2007) were combined and analysed. Results: During the period 75 cases (50 cases/year) of zygomycosis were reported. Antemortem diagnosis could be made in 81% of cases and 9% of patients had nosocomial zygomycosis. The spectrum of disease included rhino-orbito-cerebral (48%), pulmonary (17%), gastrointestinal (13%), cutaneous (11%), renal and disseminated zygomycosis (5% each). Uncontrolled type 2 diabetes (58%) and diabetic ketoacidosis (38%) in the rhino-orbito-cerebral type, renal failure (69%) in the pulmonary type, prematurity (70%) in the gastrointestinal type, and breach of skin (88%) in cutaneous zygomycosis, were the significant (p<0.05) underlying illnesses. Rhizopus oryzae (69%) was the most common isolate followed by Apophysomyces elegans (19%). Overall mortality was 45% in patients who could be treated. Outcome was significantly poor when surgical debridement could not be performed or the patients were treated only with amphotericin B deoxycholate. On multivariate analysis, patients with a Glasgow Coma Score (GCS) ⩾9 had a better prognosis. Conclusions: Zygomycosis is a threat in uncontrolled diabetes. New risk factors such as renal failure and chronic liver disease require attention. A elegans is an emerging agent in India. The need for surgical debridement in addition to medical treatment is emphasised. GCS is an independent marker of prognosis in cases of invasive zygomycosis.

Apophysomyces elegans: an Emerging Zygomycete in India

ABSTRACT Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG)5 and (GAC)5] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.

The high incidence of BK polyoma virus infection among renal transplant recipients in India.

BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.

The Utility of 1‐ and 3‐Month Protocol Biopsies on Renal Allograft Function: A Randomized Controlled Study

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1‐ and 3‐month protocol biopsies findings on 1‐year renal allograft function in a prospective randomized study. Out of 102 living‐donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2‐h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short‐term renal allograft function.

Acute Renal Failure Following Poisonous Snakebite

This study describes acute renal failure (ARF) following snakebite in humans and the effects of viperide venoms on the renal structure and function in subhuman primates. ARF developed in 45 of 157 patients with a history of snakebite admitted to the hospitals of the Postgraduate Medical Institute, Chandigarh, India. They were studied clinically, hematologically, and in 35 cases, for renal histopathology. All 45 were treated with antibiotics, and 8 received anti-snake venom. Ten cases had bilateral renal cortical necrosis (BRCN), eight of whom died; less severe acute tubular lesions (ATL) occurred in 23 patients, four of whom died (P less than .001). Sepsis was significantly more common with BRCN than ATL (P less than .05). No statistical difference was found between these groups in bleeding incidence, disseminated intravascular coagulation (DIC), hemolysis, or hypotension. Monkeys given lethal doses of viperide venom developed hypotensive shock, DIC, and hemolysis, with significantly reduced serum complement, and died within 24 hours. However, no renal functional changes or lesions were found. Monkeys given sublethal doses of viperide venom showed a significant increase in serum creatinine levels after 48 hours, and renal lesions were observed in a majority of animals. In conclusion, ARF in snakebite victims appears to be multifactorial in origin. Although hypotension, hemolysis, and DIC are likely to be important pathogenetic factors, a direct cytotoxic effect of the venom on the kidney in producing ARF cannot be excluded.

Renal Mucormycosis: Computerized Tomographic Findings and Their Diagnostic Significance

Isolated renal involvement by mucormycosis has been reported rarely in immunocompromised individuals. We describe four patients with mucormycosis confined to the kidneys, three of whom did not exhibit any predisposing factors. Only one patient had acute viral hepatitis with fulminant hepatic failure as the preceding disease. Two patients presented with oliguric renal failure of undetermined etiology and investigations revealed bilateral extensive involvement of the kidneys. Computerized tomography showed diffuse enlargement of the kidneys and multiple low-density areas. Treatment included systemic amphotericin B therapy in all four patients and nephrectomy in three patients. Two patients recovered completely. Our experience emphasizes the need for a high index of suspicion and recognition of computed tomographic scan appearances for making a prompt diagnosis. Early surgical intervention and systemic antifungal therapy are necessary for survival in this life-threatening condition.