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Background: Repeat renal biopsy is usually done for lupus nephritis (LN) flare or resistant disease. We analyzed the changes between first and repeat biopsy and the contribution of repeat biopsy on renal outcome in LN patients. Methods: This was a retrospective study carried out at a tertiary care center in India. Sixty-two LN patients who underwent repeat biopsy for clinical indications, between January 2012 to December 2016, were included. Clinical and histological parameters at first and second biopsies were compared. Logistic regression analysis was done to determine parameters on repeat biopsy predicting response at last visit. Results: Repeat biopsy was done for relapse in 56% and for resistant disease in 44% patients. Seven (13.7%) out of 51 patients with baseline proliferative histology converted to non-proliferative lesion on second biopsy, while 2 (18.2%) out of 11 with baseline non-proliferative lesion converted to proliferative lesion on second biopsy. On repeat biopsy, the presence of endocapillary proliferation decreased, whereas glomerulosclerosis, interstitial fibrosis/tubular atrophy (IFTA), and glomerular basement membrane thickening increased. At the last visit (median follow-up of 38.6 months after first biopsy and 13.8 months after second biopsy), 79% of patients were in remission and 6.5% needed renal replacement therapy. The presence of IFTA >30% and thrombotic microangiopathy (TMA) on second biopsy independently predicted response at last visit. Conclusion: In Indian patients with LN, chronicity markers and superimposed membranous pattern increased on repeat biopsy done for clinical indications. The presence of IFTA and TMA on second biopsy predicted response at last visit. [ABSTRACT FROM AUTHOR]

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. SUMMARY AT A GLANCE: A novel mutation in the COL4A3 gene in an Indian family with autosomal recessive Alport syndrome is described. The index case underwent a successful renal transplantation with his mother (who possessed the associated missense mutation) as the donor. [ABSTRACT FROM AUTHOR]

The effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. Newly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4+CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. Fifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC (p = 0.002) while PWV (p = 0.007), E-selectin (p < 0.001) and CD4+CD28null T cells (p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% (p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s (p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml (p = 0.002) while the CD4+CD28null T cell population reduced from 5.20 to 3.70% (p = 0.032) of total CD4+ cells. In the PMN cohort, despite significant reduction, E-selectin and CD4+CD28null T cells at follow-up remained higher than in healthy controls. Immunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN. Image 1 • As compared to healthy controls, patients with nephrotic syndrome have endothelial dysfunction at presentation. • Immunosuppressive drugs contribute substantially to improvement in endothelial dysfunction. • Despite treatment, subtle endothelial dysfunction persists in primary membranous nephropathy. [ABSTRACT FROM AUTHOR]

The effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. Newly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4+CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. Fifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC (p = 0.002) while PWV (p = 0.007), E-selectin (p < 0.001) and CD4+CD28null T cells (p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% (p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s (p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml (p = 0.002) while the CD4+CD28null T cell population reduced from 5.20 to 3.70% (p = 0.032) of total CD4+ cells. In the PMN cohort, despite significant reduction, E-selectin and CD4+CD28null T cells at follow-up remained higher than in healthy controls. Immunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN. Image 1 • As compared to healthy controls, patients with nephrotic syndrome have endothelial dysfunction at presentation. • Immunosuppressive drugs contribute substantially to improvement in endothelial dysfunction. • Despite treatment, subtle endothelial dysfunction persists in primary membranous nephropathy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate sexual functioning and its association with disease activity, damage, marital satisfaction, fatigue and psychiatric comorbidity in married women with systemic lupus erythematosus (SLE). Methods: One hundred and twelve premenopausal married women with SLE were included in the study. Disease activity and damage were assessed using Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA‐SLEDAI) and Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) respectively. Female sexual function index (FSFI) and couple satisfaction index (CSI) were used to evaluate sexual function and marital satisfaction respectively. Depression, anxiety and fatigue were assessed using Patient Health Questionnaire 9 (PHQ9), Generalized Anxiety Disorder 7 (GAD7) and fatigue severity scale (FSS) respectively. Results: The mean age of the study group was 34.0 (SD 6.8) years. Mean SELENA‐SLEDAI was 3.67 (SD 4.2) and mean SDI was 0.25 (SD 0.62). Median steroid dose at the time of evaluation was 7.5 mg/d of prednisolone. Based on FSFI total score, impaired sexual functioning was found in 60.7%. However, when the cut‐off of different domains was considered, more than 90% of the participants reported problems in desire, arousal and lubrication. The mean CSI score was 130.39 ± 26.17. Eighteen patients (16.1%) had CSI lower than the cut‐off score (104.5) suggestive of marital distress. On univariate analysis sexual function showed a correlation with marital satisfaction (r = .34, P < .001), dose of steroids(r = −.26, P = .008), disease activity (r = −.21, P = .027), depression (r = −.19, P = .039) and anxiety (r = −.201, P = .034). Conclusion: Sexual dysfunction is highly prevalent in premenopausal married females with SLE. Higher dose of steroids, disease activity, depression,anxiety and marital satisfaction were associated with poor sexual functioning in one or more domains. [ABSTRACT FROM AUTHOR]

Background C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. An immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly in studies from the west. We report the clinical outcome of 17 Indian C3G patients treated with MMF with or without steroids. Methods The clinical and histology details of the C3G patients treated with MMF for at least 6 months with a follow-up of at least 12 months were retrieved from the medical records of our center. Results The median serum creatinine and proteinuria at presentation were 0.8 mg/dL and 3.7 g/day, respectively, with the majority (88.2%) presenting as nephrotic syndrome. The mean dose of MMF was 1.65 (±0.56) g/day, and the median duration of MMF therapy was 18 months. Two-thirds (64%) of the patients responded to the treatment, with complete remission in 4 (23%) and partial remission in 7 (41%) (median time: 9 months). Three patients progressed to end-stage renal disease (ESRD) on follow-up. Of the three patients, one (33%) had an initial response in proteinuria to MMF but did not respond after a relapse and subsequently progressed to ESRD and two (67%) other patients were nonresponsive to MMF from the start of the therapy. Conclusion Despite a small sample size and lack of a control arm, this study describes the effectiveness of MMF in treating C3G patients from Asia and forms a basis for future randomized trials. [ABSTRACT FROM AUTHOR]

Background: Neurological manifestations are an important cause of morbidity in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It is not clear whether or not they are indicative of a severe disease course with multiple organ involvement and shortened survival.Aims and Objectives: To characterize the neurological manifestations of AAV and analyze their relationship with other organ system and cumulative survival.Methods: This was a retrospective single-center cohort study of AAV patients at a tertiary care hospital in North India. Data was collected from medical records regarding clinical history, neurological examination, Birmingham Vasculitis Activity Score (BVAS), serology, electrophysiology, imaging, and histopathological examination findings of patients.Results: Ninety-two patients of systemic vasculitis were identified, 67 with granulomatosis with polyangiitis (GPA), 14 with microscopic polyangiitis, 8 with Churg-Strauss syndrome (CSS), and 3 with undifferentiated AAV. The median BVAS at presentation was 18.0 (interquartile range (IQR): 12.0). The median duration of follow-up was 31.3 months (IQR: 40.5). A total of 45.7% patients had neurological manifestations among which 23.8% presented with neurological complaints. Peripheral neuropathy was the most common manifestation noted in 23.9% of the patients. Among patients with GPA, 40.3% had neurological involvement (seen in 33.3% patients at presentation). Patients with nervous system disease were more likely to have associated musculoskeletal manifestations (P = 0.046) and less likely to have renal involvement (P = 0.017). The estimated cumulative survival of the subgroup with neurological involvement was 95.1 months from the time of diagnosis, which was not significantly different from the cohort without neurological involvement (113.8 months, P = 0.631).Conclusion: Neurological morbidity commonly accompanies systemic vasculitis. Nervous system disease does not affect the survival significantly in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The incidence and clinical features of antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) have been shown to vary according to geographical areas, with granulomatosis with polyangiitis (GPA) being more common in northern Europe and microscopic polyangiitis (MPA) being more common in Asian countries. The annual incidence of GPA among Asians varies between 0.37/million to 2.1/million population. The prevalence of GPA has been estimated to be 1.94/100 000 in a Chinese population. Polymorphisms in class II major histocompatibility genes and ETS1 proto‐oncogene has been shown in Asian patients with GPA. There is a difference in mean age at onset and proteinase 3 (PR3) or myeloperoxidase (MPO) positivity in GPA patients from different Asian countries. Those from India had mean age of 40 years and those from Japan had mean age of 65 years. Sixty percent of GPA patients from China and Japan were MPO ANCA positive while the majority of patients from India and Korea were PR3 positive. Geographical variation with lower frequency of renal involvement in Indian studies and higher frequency in Chinese patients has also been noted. Treatment outcomes have been similar to those reported from other parts of the world. Remission was achieved in about two‐thirds of patients while relapses were noted in one‐third to half of the patients. Apart from minor differences in the organ systems involved, MPO‐ANCA GPA and PR3‐ANCA GPA had similar rates of remission and relapses. [ABSTRACT FROM AUTHOR]

Abstract Candida parapsilosis is a rare cause of endocarditis, which is seen to affect the native valves in patients who are known intravenous drug abusers or following contamination during surgery for prosthetic valves. We discuss a unique constellation of autopsy findings in a 35-year-old chronic opium abuser who presented with left-sided weakness followed by low-grade fever. He was diagnosed to have C. parapsilosis native valve endocarditis with septic emboli involving the myocardial vessels, left middle cerebral artery, spleen, and common iliac artery. In addition, autopsy highlighted a right basal ganglia infarct, focal segmental glomerulonephritis, and talc granulomatosis in the lungs and liver. Highlights • This case highlights a rare form of fungal endocarditis due to Candida parapsilosis that is associated with high mortality. • This case also highlights findings of talc granulomas in the lungs of an intravenous drug abuser. [ABSTRACT FROM AUTHOR]

Abstract: The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M‐type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow‐up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow‐up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non‐malignant associated MN with monoclonal deposits on IF. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) commonly affects upper/lower respiratory tract and kidneys. It causes necrotizing vasculitis of small and medium-sized blood vessels. Gastrointestinal (GI) involvement is an uncommon manifestation of GPA, and presentation with predominant GI manifestation is noteworthy. We report a case of 50-year-old male with melena due to GI vasculitis along with other systemic involvement. The patient was treated with pulse methylprednisolone, cyclophosphamide, and plasmapheresis. To manage the refractory GI bleed, the patient underwent surgical resection, and the histology of the surgical specimen confirmed necrotizing vasculitis. [ABSTRACT FROM AUTHOR]

Aim Primary membranous nephropathy (PMN) accounts for only 1-2% of nephrotic syndrome in children. Antibodies to m-type phospholipase A2 receptor (aPLA2R) is seen in 70% of adult PMN cases. The present study was undertaken to study m-type phospholipase A2 receptor (PLA2R) status and clinical behavior in adolescent PMN cases. Methods The present prospective observational study included adolescent (10-19 years) onset biopsy proved PMN. Patients were followed on a monthly basis with urine protein, serum albumin and creatinine. Serum aPLA2R was done at baseline and at 6 and 12 months of starting treatment. Patients were treated as per unit's protocol. Results During the study period a total of 18 patients were enrolled. The mean age of the cases was 16.27 ± 2.39 (11-19) years. Seventeen (94.44%) patients presented with nephrotic syndrome. The mean proteinuria and serum albumin was 4.52 ± 1.93 (2.43-9.20) g/day and 2.1 ± 0.6 (1.1-3.4) g/dL respectively. PMN was PLA2R related in 83%. aPLA2R and enhanced staining for PLA2R in glomeruli was seen in 14 (77.78%) and 13 (72.22%), respectively. Clinical remission at the end of 6 and 12 months of therapy was seen in 11 (61.11%) and 9 (50%) subjects respectively. There was a significant association of aPLA2R to clinical remission/ resistance. Conclusion Primary membranous nephropathy in adolescent population is aPLA2R related in over three-quarters of the cases and the response to therapy is seen in only half of them. aPLA2R monitoring is clinically relevant and should be incorporated in the management of adolescent onset PMN. [ABSTRACT FROM AUTHOR]

Objective There has been a significant decrease in the number of published reports of classical polyarteritis nodosa ( PAN) in the post-Chapel Hill consensus conference ( CHCC) nomenclature era with only two series published from Asia. We report a case series of PAN from north India. Patients and Methods A retrospective study of all patients diagnosed to have PAN according to American College of Rheumatology criteria/ CHCC nomenclature. The details of clinical presentation, investigation findings, treatment details and outcomes were noted from the records. These findings between the hepatitis B positive and negative groups were compared. Results Twenty-seven patients (20 male, seven female) were diagnosed as having PAN, out of which seven (25.9%) were hepatitis B surface antigen positive. Nervous system involvement was most common with 24 patients (88.9%) having mononeuritis multiplex. Weight loss was present in 20 (74%), fever in 14 (51.9%), renal involvement in 16 (59.3%), cutaneous in nine (33.3%), peripheral gangrene in eight (29.6%), gastrointestinal (GI) involvement in eight (29.6%), testicular pain in 6/20 (30%) and cardiac involvement in four (14.8%). Twenty-three (85.2%) patients recovered, three died (11.1%) and one was lost to follow-up. Median follow-up duration was 37 (interquartile range 22.00-69.75) months. The cumulative survival was 114.16 months (95% CI: 98.27-129.95). There was no significant difference in five factor score ( FFS) or revised FFS between those patients who died and those who survived ( P = 0.248, 0.894, respectively). Hepatitis B-related PAN had a lower FFS compared to non-hepatitis B-related PAN ( P = 0.039). No other significant differences were noted between the two groups. Conclusion In comparison to classic PAN in other populations, classic PAN in north India is associated with higher neurological involvement and lower GI involvement. [ABSTRACT FROM AUTHOR]

Pancreatic transplantation is currently the only effective cure for Type 1 diabetes mellitus. It allows long-term glycemic control without exogenous insulin and amelioration of secondary diabetic complications. In India, pancreas transplant has not yet established with only a single successful transplant reported so far in the literature. We report a 24-year-old Type 1 diabetic patient with renal failure who underwent a simultaneous pancreas kidney transplant. On postoperative day 15, he had leak from the graft duodenal stump for which a tube duodenostomy and proximal diversion enterostomy was done. He had a high output pancreatic fistula following the procedure which was managed conservatively. The tube duodenostomy was removed at three and half months and enterostomy closure with restoration of bowel continuity was done at 6 months. After a follow up of 7 months, patient is doing well with a serum creatinine of 0.8 mg/dl and normal blood sugars, not requiring any exogenous insulin or oral hypoglycemic drugs. Managing patients with graft duodenal complications after pancreas transplant is challenging. Tube duodenostomy is a safe option in management of duodenal leak, although can lead to a persistent pancreatic fistula. A proximal diversion enterostomy allows early oral feeding and avoids the cost as well as the long term complications associated with parenteral nutrition. [ABSTRACT FROM AUTHOR]

Background. Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. Methods. A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by Taq- Man assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. Results. Of 114 patients, 66.7% showed elevated serum anti- PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti- PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. Conclusion. To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy. [ABSTRACT FROM AUTHOR]

Aims Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4 TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. Methods This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4 TIN followed for a minimum period of 1 year or until end-stage renal disease. Results IgG4 TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. Conclusion IgG4 TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease. [ABSTRACT FROM AUTHOR]

Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar. [ABSTRACT FROM PUBLISHER]

Aim There have been very few studies comparing cyclophosphamide ( CTX) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy ( NIST) resistant idiopathic membranous nephropathy ( IMN). The present study was aimed at comparing the efficacy and safety of tacrolimus ( TAC)/steroids with cyclical CTX/steroids ( Modified Ponticelli regimen ( MPR)) in patients with IMN. Methods Idiopathic membranous nephropathy patients ( n = 70) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally randomized to receive TAC with oral prednisolone ( TAC*) or MPR. Antibodies against m-type phospholipase A2 receptor ( PLA2R Ab) were tested for at baseline and, at 6 and 12 months after the start of therapy. The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups. Results Intention-to-treat analysis showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; P = 0.30) and 12 months (71% with TAC* vs. 77% with MPR; P = 0.78) were comparable. PLA2R Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum albumin (r −0.49/−0.53) at the end of therapy. Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity. Conclusion In NIST refractory IMN, both TAC* and MPR are comparable, but with different adverse effect profile. PLA2R Ab has a very good association with proteinuria, and should be regularly monitored on clinical follow-up. [ABSTRACT FROM AUTHOR]

Aim A significant proportion of pauci-immune glomerulonephritis ( PIGN) patients are reported to have absence of anti-neutrophilic cytoplasmic antibodies ( ANCA). However, studies are controversial regarding their significance and there is limited data after the new prognostic classification of PIGN. Methods Renal biopsy-proven cases of PIGN were included and their clinical details, ANCA status by immunofluorescence ( IIF) and enzyme-linked immunosorbent assay ( ELISA), Birmingham Vasculitis Activity Score ( BVAS) and treatment outcomes at 6 months were noted. The renal biopsies were classified according to the proposed histopathological classification. Scoring was done from 0-3 for interstitial edema, interstitial fibrosis and tubular atrophy ( IFTA), interstitial inflammation and arteriosclerosis. The percentage of glomeruli with sclerosis, cellular and fibrous crescents, and percentage of subjects with glomerulitis, tuft necrosis, interstitial granuloma and vasculitis were noted. Results Out of the 84 subjects included in the study, 33 (39.3%) were negative for ANCA by both IIF and ELISA. These subjects had significantly higher renal involvement, less extra-renal manifestations and lower BVAS. On histology, they had significantly higher proportion of crescentic class (66.7% vs. 41.2%, P = 0.039), higher number of cellular crescents (66.12% vs. 53.3%, P = 0.00008), higher IFTA (1.53 vs. 1.02, P = 0.009) and less interstitial edema (1.44 vs. 1.96, P = 0.003). The treatment outcomes were worse in ANCA-negative PIGN subjects, with significantly less improvement (37.2% vs. 62.8%, P = 0.02), more deterioration (40.7% vs. 14%, P = 0.006), and reduced probability of becoming dialysis free (31.6% vs. 69.6% P = 0.009). Conclusions A negative ANCA in PIGN is associated with crescentic class, more IFTA and poor treatment outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Giant cell arteritis (GCA) is a granulomatous large vessel vasculitis with very scarce data from India. The purpose of this study was to present a comprehensive data of all published Indian cases along with our experience from North India.Materials and Methods: This was a retrospective study of all patients diagnosed to be having GCA according to the American College of Rheumatology criteria at a large tertiary care hospital. The demographic data, clinical, investigations, treatment details, and outcomes were noted. Details of all case series and case reports published from India were pooled along with our experience in order to generate a cumulative data of all cases from India. This was then compared with several large published case series from South America, Europe, and Asia.Results: A total of 72 patients (17 patients in the present series and another 55 patients from other Indian case series and case reports) were identified. The findings of our study are similar to the studies published from other parts of the world, except for the onset of the disease a decade earlier, a male predilection, a lower temporal artery biopsy positivity, and a higher incidence of ophthalmic complications.Conclusions: Indian patients with GCA have an earlier age of onset, male preponderance, and higher ophthalmic complications. [ABSTRACT FROM AUTHOR]

CAPD catheter malfunction is a common problem. Obstruction due to wrapping by appendices epiploicae of sigmoid colon has been rarely reported in literature. We report a case of CAPD catheter malfunction caused by catheter tip migration and obstruction by appendices epiploicae that was successfully managed by laparoscopic hanging loop technique. This case report highlights the ease with which epiplopexy can be performed and catheter tip migration can be prevented by this innovative laparoscopic procedure. [ABSTRACT FROM AUTHOR]

Rapidly progressive renal failure is a common but severe feature of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A histopathological classification for ANCA-associated pauci-immune glomerulonephritis was developed for prognostication of these patients. The present study aims to classify patients of pauci-immune glomerulonephritis according to this classification and its impact on outcome. Eighty-six subjects with pauci-immune glomerulonephritis between July 2006 and October 2012 were included in the study. Their renal biopsies were reviewed and classified into focal, crescentic, sclerotic and mixed class as per the new classification. The outcomes were analyzed after 6 months of treatment. Of the 86 subjects, 34 (39.53 %) were granulomatosis with polyangiitis, 36 (41.86 %) microscopic polyangiitis, 1 eosinophilic granulomatosis with polyangiitis, while the rest (17.44 %) were unclassifiable. Thirteen (15.5 %), 43 (51.2 %), 12 (14.3 %) and 16 (19 %) patients were classified as focal, crescentic, sclerotic and mixed class, respectively. The mean serum creatinine at baseline was 280.23, 659.46, 573.72 and 542.78 µmol/L in focal, crescentic, sclerotic and mixed class, respectively. The probability of improvement in renal functions at 6 months decreased from focal to crescentic to mixed to sclerotic class, while the probability of death was highest in the sclerotic class followed by the mixed class. This difference in outcome was maintained irrespective of the clinical diagnosis or the Birmingham Vasculitis Activity Score. Our study has shown that the histopathological classification can be used to predict the severity of renal dysfunction as well as the treatment outcomes in pauci-immune glomerulonephritis. [ABSTRACT FROM AUTHOR]

Recent studies have identified sprue-like illness associated with the use of the antihypertensive agent olmesartan medoxomil. However, whether this condition is specific to the use of olmesartan or is associated with the use of drugs belonging to the class of "sartans" remains to be clarified. A 45-year-old woman with chronic kidney disease along with hypothyroidism and hypertension presented with chronic diarrhea and significant weight loss. Endoscopy of the upper gastrointestinal tract showed scalloping and grooving of the duodenum, and histopathological examination showed subtotal villous atrophy. She was on telmisartan for hypertension, which was discontinued. Subsequently, diarrhea ameliorated dramatically, and she regained weight. To our knowledge, this is the first study to report telmisartan-associated sprue-like enteropathy. Further, we have reviewed the cases of patients with sprue-like enteropathy caused by valsartan, irbesartan, and eprosartan. [ABSTRACT FROM AUTHOR]

Aim Many patients with systemic necrotizing vasculitis ( SNV) satisfy classification criteria of different disease entities when different classification systems are used. A new classification algorithm has been proposed recently by using the American College of Rheumatology criteria, Chapel Hill Consensus Criteria ( CHCC) and Sorensen surrogate markers for a more uniform classification of patients suffering from these rare disorders. Methods We applied this algorithm to patients diagnosed as having systemic vasculitis between 2007 and 2011. We also analyzed the data using this algorithm by incorporating the recently proposed revised CHCC nomenclature of vasculitis in place of the older criteria. Results Seventy-nine patients with SNV were studied. One patient diagnosed as microscopic polyangiitis ( MPA) had to be excluded from analysis as she had previously been diagnosed as having Behcet's disease. All patients of eosinophilic granulomatosis with polyangiitis ( EGPA), granulomatosis with polyangiitis ( GPA) and MPA were reclassified to the same diagnostic subcategory after application of the algorithm. Three (16.7%) of 18 polyarteritis nodosa patients were unclassifiable after application of the consensus algorithm while two (11.1%) were reclassified as MPA. All previously unclassifiable patients could be classified either as MPA or GPA after application of the new algorithm. There was no difference in the results when the CHCC 2012 nomenclature was used instead of the older CHCC in the consensus algorithm. Conclusion The new classification algorithm is a reliable method for classification of SNV for epidemiological purposes in our population. [ABSTRACT FROM AUTHOR]

Two male patients with end-stage renal disease (ESRD) developed a spontaneous hemorrhage of one of their native kidneys and were referred to our institution. Symptoms included sudden onset abdominal pain, hematuria and shock. Symptoms were associated with a hemoglobin decrease. Computerized tomography (CT) was done and nephrectomy undertaken in both the cases. Histologic findings confirmed bleeding and there was no abnormality other than those related to renal insufficiency (cysts and atrophy). In chronic hemodialysis (HD) patients with hematuria, if other common causes are not identified spontaneous subcapsular or renal cyst rupture should be kept in mind. Surgery is our preferred treatment because of the diagnostic dilemma of tumors and the potential mortality of massive hematomas in morbid patients. [ABSTRACT FROM AUTHOR]

Whether or not completing the hepatitis B vaccination in patients who have undergone kidney transplantation in the middle of incomplete vaccination schedule leads to development of protective antibody titres is not known. This study was designed to determine whether the strategy of completing hepatitis B virus (HBV) vaccination after transplantation is efficacious. Sixty-four end-stage renal disease (ESRD) patients were screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs), hepatitis B e-antigen (HBeAg) and HBV DNA. HBsAg negative patients received four doses of 40 µg recombinant HBV vaccine. Schedule was continued in after transplantation period if it was incomplete before transplant. Anti-Hbs titres were evaluated at 1, 3, 6, 9 and 12 months. Past HBV infection was noted in 12 patients: 10 by serology plus viraemia and two by viraemia alone. Of the 46 patients without current or past HBV infection who had received at least two doses of the vaccine before transplant, 17 each had received two and three doses and 12 had completed the schedule. Seventeen (37%) exhibited protective titres. Patients who had completed vaccination were more likely to have protective titres than those incompletely vaccinated ( P = 0.02). Five patients responded to post-transplant vaccination. Partially vaccinated patients do not mount an adequate antibody response despite continued vaccination in the post-transplant period, whereas complete vaccination provides protection in 60%. The present study data highlights the need of administration of a full schedule of HBV vaccination before kidney transplantation. Nucleic acid-based tests can identify occult HBV infection. Patients partially vaccinated against HBV do not mount an adequate antibody response despite continued vaccination in the post-transplant period. The data presented here highlights the need for administration of a full schedule of vaccination before kidney transplantation for maximal protection against HBV infection. [ABSTRACT FROM AUTHOR]

Background: Until now, a normal reference range for glomerular filtration rate (GFR) in adult Indian potential kidney donors has not been determined and values from a western population are being used as reference. Aim: To determine the reference range of GFR in healthy adult Indian potential kidney donors. Basic Procedures: GFR was measured in 610 (250 male, 360 female, average age 35.16 years) healthy potential kidney donors using the 99mTc-DTPA (diethylenetriamine pentaacetic acid) two-plasma sample method of Russell. Results: The mean body surface area (BSA)-normalized GFR value of a young healthy Indian adult potential kidney donor was calculated as 81.4 ± 19.4 ml/min/1.73 m2 BSA – for males it was 82.3 ± 21.3 ml/min/1.73 m2 BSA and for females 80.8 ± 18.1 ml/min/1.73 m2 BSA. There was no significant difference between derived mean GFR values in males and females with a p value of 0.37. Conclusions: The normal GFR value for the healthy Indian adult potential kidney donor appears to be much lower than the accepted value for a western population. The mean GFR value of a young healthy Indian adult potential kidney donor is 81.4 ± 19.4 ml/min/1.73 m2 BSA, which is significantly different from the normal value of 109–125 ml/min derived from a western population. These findings might be useful in deciding on a suitable kidney donor in an Indian context. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by circulating autoantibodies and immune complexes involving virtually every organ of the body. However, with respect to central nervous system (CNS), the mechanism of injury is still debated as complement mediated or thrombo-ischemic in nature. We studied the spectrum of neuropathological changes in twelve autopsy cases of SLE and evaluated the role of immune-complexes and complement activation in contributing to the thrombo-ischemic injury and correlated these features with clinical profile. Autopsy records of all cases of SLE over a period of 20 years (2000–2019) were reviewed. Clinical history including neuropsychiatric symptoms and detailed histopathological analysis was performed. Direct immunofluorescence for IgM, IgG, IgA, C1q, C3, C4d, Kappa, Lambda and immunohistochemistry for C5b-9 was performed on lesional areas in paraffin embedded brain sections. Control tissue from brain was taken from two patients who died of sudden cardiac event. Our cohort comprised of 12 cases with age range from 12 to 40 years and all were female patients. Microinfarction and vasculopathy seen in eight cases were the commonest findings. Four cases with microinfarcts had non-bacterial thrombotic endocarditis in heart. Microthrombi adjacent to microinfarcts were seen in 4 cases. Variable deposition of immunoglobulins (predominantly IgG) and complements (C1q, C3, C4d) was evident in cortical arterioles (2 cases) and small capillaries (1 case). Neurological symptoms were seen in four cases, of which, three had associated invasive fungal infection with secondary vasculitis. Active lupus vasculitis was identified in a single case. C5b-9 immunoexpression was not detected in any of the cases. Our study adds observational data to the existing literature that the predominant neuropathological features of SLE are related to thrombo-ischemic injury and small vasculopathic changes. Only in a minor subset (25%), it is mediated by immune-complexes and complements. Immune-complex deposition on immunofluorescence in cortical vessels (cerebral lupus vasculopathy) is a novel finding which has not been reported earlier. [Display omitted] • Microvascular injury is the major underlying pathomechanism in neurolupus manifesting as microinfarction and microthrombosis • Immune-complexes and complement activation contribute to thrombo-ischemic injury in a minor proportion of cases (25%) • Immune-complex deposition on DIF in the cortical arterioles (cerebral lupus vasculopathy) is a novel undescribed finding [ABSTRACT FROM AUTHOR]

Shigellemia is a complication of shigellosis that occurs generally in malnourished children. In adults, shigellemia is usually seen in immunocompromised individuals. Here we report the first case of shigellemia in a renal transplant patient from India. The patient had history of diarrhea, which was treated symptomatically. Subsequently, the patient developed high-grade fever and blood culture was positive for Shigellaflexneri. Recovery was uneventful after the initiation of antimicrobial therapy. In a country like India with high prevalence of shigellosis, screening for Shigella in the pre-transplant period may minimize the morbidity and prolonged hospital stay associated with the complication of septicemia. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) can develop after multiple wasp or bee stings. The etiology is the acute tubular necrosis secondary to shock, pigment toxicity, interstitial nephritis, or direct nephrotoxicity of venom. We report a 40-year-old female who presented with oliguric AKI after a single wasp sting on her hand. Her history, examination, and investigations did not support any of the established causes of AKI in such settings. She did not improve with supportive management and dialysis, and kidney biopsy showed acute cortical necrosis (ACN). This is the first report of ACN after a single wasp sting. [ABSTRACT FROM AUTHOR]

Impaired cell‐mediated, as well as antibody‐mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re‐transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re‐transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re‐consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 63-year old man with granulomatosis with polyangiitis (GPA) who had been diagnosed with GPA 3.5 years ago when he suffered from sinusitis, nasal crusting, microscopic hematuria and renal dysfunction. He was put on prednisolone and azathioprine. The article discusses Pyomyositis, a purulent disease and its various risk factors.

The article presents a case study of a 21-year-old male who was admitted to hospital after regular vomiting and decreased urine output. As mentioned, the patient had a history of redness, pain and swelling of left ankle. According to the results of the physical examination, blood pressure of the patient was increased and a tender swelling on the left ankle with a black discoloration.