INTRODUCTION:Primary membranous nephropathy (PMN) is an autoimmune disease. Both T-regulatory cells (TREGs) and B-regulatory cells (BREGs) are decreased in patients with autoimmune disease. We evaluated the TREG and BREG population in patients of PMN treated with cyclical cyclophosphamide and steroid therapy (cCYC/GC). METHODS:Twenty-four patients with PMN resistant to a restrictive strategy and treated with cCYC/GC therapy and 10 healthy controls were enrolled. The proteinuria, serum creatinine, and serum albumin were tested at monthly intervals and blood samples were collected before starting cCYC/GC and at 6 and 8 (2 months wash out) months of therapy. The peripheral blood mononuclear cells (PBMCs) after staining with fluorochrome-conjugated antibodies were then subjected to flow cytometric analysis for detection of TREGs (CD3+CD4+CD25hiCD127loFoxP3+) and BREGs (CD19+CD5+CD1dhiIL10+). TREGs and BREGs are presented as the percentage of T and B cells, respectively. Cases with remission at month 18 were classified as responders, and those without any remission as nonresponders. RESULTS:Patients with PMN had a lower percentage of TREGs (P = 0.07) and BREGs compared with healthy controls (P = 0.0007). As compared with baseline, there was a significant increase in both BREGs (P = 0.001) and TREGs (P = 0.02) with the treatment (8 months). Patients who responded to therapy by 18 months had an increase in TREG (P = 0.05) and BREG (P = 0.0001) at month 8 compared with baseline. CONCLUSION:As compared with healthy controls, patients with PMN displayed a lower percentage of BREGs. Both TREGs and BREGs significantly improved with disease-specific therapy. BREGs had an association with clinical activity.

Patients with community-acquired acute kidney injury (CA-AKI) requiring dialysis have an excess risk of mortality and development of end-stage renal disease. Convective forces enhance clearance of heavy molecular weight cytokines when added with diffusion and improve outcomes in sepsis-related AKI patients. The current study is aimed to assess the differential impact of post-dilution online hemodiafiltration on renal recovery, as compared to conventional high flux hemodialysis in non-critically ill CA-AKI patients with systemic inflammatory response syndrome (SIRS).

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above-mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early-onset end-stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.

Acute Kidney Injury (AKI) causes a significant burden on healthcare. Impaired endothelial function plays an essential role in the pathogenesis of AKI, the progression of AKI to Chronic kidney disease (CKD) and future atherosclerotic events. Patients with AKI have demonstrable endothelial dysfunction. However, what happens to the endothelial dysfunction with the recovery of renal functions is not known. Hence, we undertook the study to evaluate functional and immunological markers of endothelial dysfunction in dialysis (<3 weeks) requiring AKI patients with the recovery of renal functions.

Cytomegalovirus(CMV) is the most common viral infection in renal allograft recipients. Retrospective and few randomised control studies have shown oral valganciclovir in the recommended dose of 900mg once daily for prophylaxis can result in an increased risk of cytopenias and temporary discontinuation of anti-proliferative agents risking acute rejection. The above mentioned may predispose to increased risk of rejection and also add to the economic burden of the patient in resource-limited countries.

Oral iron supplementation, given as divided daily doses, is commonly prescribed in pre-dialysis CKD as iron deficiency and anemia are common. In healthy individuals, the amount of iron absorbed with once daily (OD) dosing has been shown to be as good as with twice daily (BD) dosing despite double cumulative dose with BD dosing. Recently, it has been shown in non-anemic iron deficient young females that elevation in serum hepcidin due to multiple daily doses of oral iron impairs oral iron absorption and that alternate day single dose of oral iron might be preferable.

C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. Immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly from the west. We report the clinical outcome of South-Asian (Indian) patients of C3G treated with MMF with or without steroids.

OBJECTIVE:End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long-term kidney survival. This study was undertaken to identify short-term end points that predict long-term kidney outcomes for use in clinical trials. METHODS:A database of 944 patients with LN was assembled from 3 clinical trials and 12 longitudinal cohorts. Variables from the first 12 months of treatment after diagnosis of active LN (prediction period) were assessed as potential predictors of long-term outcomes in a 36-month follow-up period. The long-term outcomes examined were new or progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the need for permanent renal replacement therapy (RRT). To predict the risk for each outcome, hazard index tools (HITs) were derived using multivariable analysis with Cox proportional hazards regression. RESULTS:Among 550 eligible subjects, 54 CKD, 55 SKI, and 22 RRT events occurred. Variables in the final CKD HIT were prediction-period CKD status, 12-month proteinuria, and 12-month serum creatinine level. The SKI HIT variables included prediction-period CKD status, International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class, 12-month proteinuria, 12-month serum creatinine level, race, and an interaction between ISN/RPS class and 12-month proteinuria. The RRT HIT included age at diagnosis, 12-month proteinuria, and 12-month serum creatinine level. Each HIT validated well internally (c-indices 0.84-0.92) and in an independent LN cohort (c-indices 0.89-0.92). CONCLUSION:HITs, derived from short-term kidney responses to treatment, correlate with long-term kidney outcomes, and now must be validated as surrogate end points for LN clinical trials.

Background Recent studies have documented high variation in epidemiologic transition levels among Indian states with noncommunicable disease epidemic rising swiftly. However, the estimates suffer from non-availability of reliable data for NCDs from sub populations. In order to fill the knowledge gap, the distribution and determinants of NCD risk factors were studied along with awareness, treatment and control of NCDs among the adult population in Haryana, India. Methods NCD risk factors survey was conducted among 5078 residents, aged 18-69 years during 2016-17. Behavioural risk factors were assessed using STEPS instrument, administered through an android software (mSTEPS). This was followed by physical measurements using standard protocols. Finally, biological risk factors were determined through the analysis of serum and urine samples. Results Males were found to be consuming tobacco and alcohol at higher rates of 38.9% (95% CI: 35.3-42.4) and 18.8% (95% CI: 15.8-21.8). One-tenth (11%) (95% CI: 8.6-13.4) of the respondents did not meet the specified WHO recommendations for physical activity for health. Around 35.2% (95%CI: 32.6-37.7) were overweight or obese. Hypertension and diabetes were prevalent at 26.2% (95% CI: 24.6-27.8) and 15.5% (95% CI: 11.0-20.0). 91.3% (95% CI: 89.3-93.3) of the population had higher salt intake than recommended 5gms per day. Conclusion The documentation of strikingly high and uniform distribution of different NCDs and their risk factors in state warrants urgent need for evidence based interventions and advocacy of policy measures.

Cryptococcosis particularly if disseminated or extrapulmonary, in an otherwise immune-competent individual, especially if young, requires thorough evaluation for underlying primary immunodeficiency including Mendelian susceptibility to mycobacterial disease (MSMD).In this context, we describe an adolescent diagnosed with disseminated cryptococcosis involving skin, lymph nodes, spleen and hepato-biliary involvement with reduced IL-12β1 receptor expression suggesting underlying MSMD.Following initial management with conventional amphotericin and flucytosine, along with antibiotics for cholangitis and later suppressive prophylaxis with fluconazole our patient showed good response with resolution of jaundice, normalization of liver function tests by second month of follow-up and had significant regression of lymph nodes as well as skin lesions by six months.

Although rare, both Cladophialophora bantiana (C. bantiana) and Toxoplasma gondii have been known to be associated with brain abscess in renal transplant recipients (RTRs), however co-infection has never been reported till date. In the present case, 40 years old renal transplant recipient on curtailed immunosuppressive therapy presented with progressive headache and altered sensorium. The computed tomography of head showed multiple ring-enhancing discrete lesions in the left frontal lobe, with moderate perilesional oedema. Left frontal craniotomy and aspiration revealed thick yellowish brown pus, which on culture showed the growth of dematiaceous fungal hyphae “C. bantiana” and co-infection with “Toxoplasma” was confirmed by PCR as well as serology (both IgM and IgG – Toxoplasma) positivity. Stereotactic aspiration/open craniotomy and drainage is imperative to arrive at microbiological diagnosis and provide timely therapy to the patient.

Steroid-resistant nephrotic syndrome (SRNS) is difficult to treat and carries a high risk of progression to chronic kidney disease (CKD). Calcineurin inhibitors (CNIs) are preferentially used in the treatment of SRNS. Variable response to treatment, the risk of nephrotoxicity and high rates of relapse on stopping treatment are major concerns with CNIs. Urokinase-type Plasminogen Activator Receptor (uPAR) – β3 integrin signaling is involved in the calcineurin-nuclear factor of activated T cells (NFAT) induced podocyte injury and hence the antiproteinuric effect of CNIs may be partially attributed to its inhibition of uPAR-β3 integrin signaling axis in podocytes.

A 63-year-old diabetic gentleman with microvascular complications presented with advanced azotemia and anemia. He was stabilized with blood transfusion and hemodialysis. With the probable diagnosis of diabetic nephropathy-related end-stage renal disease, he underwent kidney transplantation. He had delayed graft function. Graft biopsy done on the 2nd postoperative day showed acute tubular necrosis. Graft biopsy repeated after 2 weeks for persistent graft dysfunction showed myeloma cast nephropathy (MCN) and light chain proximal tubulopathy. Work-up for multiple myeloma was positive. He was started on plasmapheresis and chemotherapy. However, he suffered sudden cardiac death during dialysis after 1 week. The presence of MCN in the early graft biopsy implies that it must have been the cause for his native kidney failure. Thus, renal failure in a diabetic should not always be presumed to be due to diabetic nephropathy, and kidney biopsy should be done in diabetics with atypical features.

Massive rectal bleeding is an uncommon presentation of ileal tuberculosis (TB). We report an uncommon cause of anemia in a post-renal transplant patient due to massive lower gastrointestinal (LGI) bleed. The index case had a normal upper and LGI endoscopy, but the (99)technetium labeled red blood cell scan showed active bleeding from terminal ileum and caecum. Microscopic examination of the resected specimen revealed tubercular granuloma with acid-fast bacilli. Intestinal TB should be a differential diagnosis for massive LGI bleed in immunosuppressed patients in developing country.

KDIGO recommends Cyclical cyclophosphamide/steroids (cCTX/GC) and calcineurin inhibitors (tacrolimus or cyclosporine)/steroids as the 1st line agent in the management of antiproteinuric resistant primary membranous nephropathy (PMN). Long-term outcome of cCTX/GC is available. However, the long-term outcome of patients treated with tacrolimus/steroids (TAC/GC) is not known. We report the 5-year outcome of patients who were randomised to receive cCTX/GC or TAC/GC.