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Objectives: To study the prevalence, correlates, and outcomes of GI manifestations in a prospectively enrolled nationwide cohort of SLE in India (INSPIRE)., Methods: It is an observational cohort study with analysis of the baseline database of the INSPIRE cohort with early outcomes assessed till April 10, 2023. Cases with GI manifestations as per the BILAG index were selected, pertinent clinical and laboratory data were retrieved for analysis. Patients with GI manifestations were compared with the rest of the cohort and factors associated with death were determined., Results: Of the 2503 patients with SLE enrolled in the INSPIRE cohort, 243(9.7%) had GI manifestations observed early in the disease course(1,0-3 months). Ascites(162,6.5%), followed by enteritis(41,1.6%), pancreatitis(35,1.4%) and hepatitis(24,0.9%) were the most prevalent manifestations.All patients received immunosuppressive therapy, and four patients required surgery. Twenty-nine patients died(11.9%), with uncontrolled disease activity(17,58.6%) and infection(6,20.7%) accounting for the majority of deaths. Low socioeconomic class[lower(Hazard Ratio (95% Confidence intervals- CI) 2.8(1.1-7.9); upper lower 7.5(2-27.7); reference as upper class] and SLEDAI 2K[1.06(1.02-1.11)] were associated with death in the GI group.GI manifestations were significantly associated with age[Odds Ratio & 95% CI 0.97(0.96-0.99)], pleural effusion[4.9(3.6-6.7)], thrombocytopenia[1.7(1.2-2.4)], myositis[1.7(1.1-2.7)], albumin[0.7(0.5-0.8)], alkaline phosphatase(ALP)[1.01(1.0-1.002)], low C3[1.9(1.3-2.5)], total bilirubin[1.2(1.03-1.3)], alopecia[0.62(0.5-0.96], elevated anti-dsDNA[0.5(0.4-0.8)], and anti-U1RNP antibody[0.8(0.5-0.7)] in model one; and age[0.97(0.96-0.99)], creatinine[1.2(1.03-1.4)], total bilirubin[1.2(1.03-1.3)], ALP[1.01(1.0-1.002)], albumin[0.6(0.5-0.7)], andanti-U1RNP antibody[0.6(0.5-0.8)] in model two in multivariate analysis compared with patients without GI features. The mortality was higher in the GI group(11.9% and 6.6%, p= 0.01) as compared with controls., Conclusion: GI manifestations were observed in 9.7% of the cohort and were always associated with systemic disease activity and had higher mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: SLE is associated with significant mortality, and data from South Asia is limited. Thus, we analysed the causes and predictors of mortality and hierarchical cluster-based survival in the Indian SLE Inception cohort for Research (INSPIRE)., Methods: Data for patients with SLE was extracted from the INSPIRE database. Univariate analyses of associations between mortality and a number of disease variables were conducted. Agglomerative unsupervised hierarchical cluster analysis was undertaken using 25 variables defining the SLE phenotype. Survival rates across clusters were assessed using non-adjusted and adjusted Cox proportional-hazards models., Results: Among 2072 patients (with a median follow-up of 18 months), there were 170 deaths (49.2 deaths per 1000 patient-years) of which cause could be determined in 155 patients. 47.1% occurred in the first 6 months. Most of the mortality (n = 87) were due to SLE disease activity followed by coexisting disease activity and infection (n = 24), infections (n = 23), and 21 to other causes. Among the deaths in which infection played a role, 24 had pneumonia. Clustering identified four clusters, and the mean survival estimates were 39.26, 39.78, 37.69 and 35.86 months in clusters 1, 2, 3 and 4, respectively (P < 0.001). The adjusted hazard ratios (HRs) (95% CI) were significant for cluster 4 [2.19 (1.44, 3.31)], low socio-economic-status [1.69 (1.22, 2.35)], number of BILAG-A [1.5 (1.29, 1.73)] and BILAG-B [1.15 (1.01, 1.3)], and need for haemodialysis [4.63 (1.87,11.48)]., Conclusion: SLE in India has high early mortality, and the majority of deaths occur outside the health-care setting. Clustering using the clinically relevant variables at baseline may help identify individuals at high risk of mortality in SLE, even after adjusting for high disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown., Objective: This study explores the effect of thyroid hormone replacement therapy on eGFR and 24-hour urine protein excretion in patients with severe primary hypothyroidism., Design and Participants: This study was a prospective, observational cohort study in adults with severe primary hypothyroidism (serum thyrotropin [TSH] > 50 µIU/mL). Individuals with preexisting or past kidney disease, kidney or urinary tract abnormalities, calculi or surgery, diabetes mellitus, or hypertension were excluded. The participants received thyroid hormone replacement therapy. Thyroid functions, eGFR, 24-hour urine protein excretion, and biochemical parameters were measured at baseline and 3 months., Setting: This study took place at a single center, a tertiary care referral and teaching hospital., Results: Of 44 enrolled participants, 43 completed 3 months of follow-up. At 3 months, serum TSH levels decreased and thyroxine levels increased (P < .001 for both). Significant increases in eGFR (mean difference, 18.25 ± 19.49 mL/min/1.73 m2; 95% CI, 12.25 to 24.25, P < .001) and declines in 24-hour urine protein excretion (mean difference, -68.39 ± 125.89 mg/day; 95% CI, -107.14 to -29.65, P = .001) were observed. Serum cholesterol and low-density lipoprotein levels also significantly decreased (P < .001)., Conclusions: Thyroid hormone replacement therapy in patients with severe primary hypothyroidism improves eGFR and decreases 24-hour urine protein excretion, thereby suggesting reversible alterations., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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 TaqMan 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., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: Management of adults with steroid-resistant (SR) nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is a challenging task. Is tacrolimus (TAC) effective in this situation without serious adverse effects? This prospective study was done to answer this question., Materials and Methods: In patients with SR nephrotic syndrome due to FSGS, oral TAC (0.1 mg/kg/day) was started targeting a trough level of 5-10 ng/mL along with oral prednisolone (0.15 mg/kg/day) for 48 weeks. In patients with complete remission (CR), TAC dose was reduced to a target of 3-6 ng/mL whereas in partial responders, TAC trough levels were kept at 5-10 ng/mL. TAC was discontinued in those with no remission at 24 weeks and was deemed TAC resistant. Outcome, namely CR and partial remission (PR), was assessed at the end of 24 and 48 weeks. All patients were prospectively followed for 60 weeks. Relapses after CR or PR were recorded; adverse effects, namely nephrotoxicity (>25% rise in creatinine), cosmetic effects, infections and hyperglycemia, were recorded every month., Results: A total of 44 SR-FSGS [not otherwise specified 33 (75%), tip lesion 03 (6.8%) and cellular variant 8 (18.1%)] were analyzed. Mean age was 25.16 ± 8.26 (18-51) years. Of 44 patients, CR and PR were achieved in 17 (38.6%) and 06 (13.6%) patients, respectively. TAC resistance was seen in 21 (47.7%) patients. Time taken to achieve remission was 15.2 ± 6 weeks. Five (21.7%) patients with CR had relapse on tapering the dose and seven (30.4%) after stopping TAC. Reversible nephrotoxicity was seen in seven (15.9%) and irreversible in four patients (9%). TAC-related diarrhea was the problem in 10 (22.7%), and infections were seen in 19 patients (43.1%). Impaired fasting glucose and diabetes mellitus were seen in 10 patients (22.7%)., Conclusion: TAC is an effective agent in the management of SR-FSGS. However, strict renal function and blood sugar monitoring is required due to its potential nephrotoxicity and diabetogenic potential., (© The Author 2014. Published by Oxford University Press on behalf of ERAEDTA. All rights reserved.)

Given an unknown multicomponent alloy, and a set of standard compounds or alloys of known composition, can one improve upon popular standards-based methods for energy dispersive X-ray (EDX) spectrometry to quantify the elemental composition of the unknown specimen? A method is presented here for determining elemental composition of alloys using transmission electron microscopy-based EDX with appropriate standards. The method begins with a discrete set of related reference standards of known composition, applies multivariate statistical analysis to those spectra, and evaluates the compositions with a linear matrix algebra method to relate the spectra to elemental composition. By using associated standards, only limited assumptions about the physical origins of the EDX spectra are needed. Spectral absorption corrections can be performed by providing an estimate of the foil thickness of one or more reference standards. The technique was applied to III-V multicomponent alloy thin films: composition and foil thickness were determined for various III-V alloys. The results were then validated by comparing with X-ray diffraction and photoluminescence analysis, demonstrating accuracy of approximately 1% in atomic fraction.

Background: The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on the effect of mycophenolate mofetil (MMF) for these conditions are scarce and confounding., Methods: We compared the efficacy of an MMF-based therapy with standard therapies in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot study. MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2-3 months. Conventional therapy was prednisolone 1 mg/kg/day for 3-6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN. The primary end point was change in urinary protein/creatinine ratio., Results: A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were randomized to receive MMF (group A) and 26 were on conventional treatment (group B). There was no difference in the proportion of patients achieving remission in two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses and incidence of infections was also similar. FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose., Conclusions: A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term. It induces remission faster and reduces steroid exposure in FSGS patients. Studies with more cases and longer follow-up are required to evaluate its impact on preservation of kidney function.