Importance:Glomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain. Objectives:To evaluate the efficacy and safety of finerenone in patients with glomerular diseases. Design, Setting, and Participants:Prespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g. Intervention:Finerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457). Main Outcomes and Measures:Annualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes). Results:Of 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97). Conclusions and Relevance:In this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population. Trial Registration:ClinicalTrials.gov Identifier: NCT05047263.

Rationale & Objective:Primary glomerular diseases frequently affect women of childbearing age, creating challenges during pregnancy. There is limited data from low and middle-income countries where health care disparities and differing disease patterns may alter outcomes. This study assessed pregnancy and kidney outcomes in women with primary glomerular diseases at a tertiary center in India. Study Design:We conducted a retrospective review of medical records from 2012 to 2022. Setting & Participants:This study was conducted at a single-center and included women aged 18-45 years with biopsy-confirmed primary glomerular disease. In total, 32 women with 44 pregnancies were included. Exposures or Predictors:The exposure of interest was pregnancy following diagnosis of primary glomerular disease, comparing women who achieved live births with a control group who did not conceive after diagnosis of kidney disease. Outcomes:Pregnancy outcomes included preterm delivery, intrauterine growth restriction (IUGR), pre-eclampsia, mode of delivery, and elective and spontaneous abortions. Kidney outcomes included relapse (proteinuria ≥ 3.5 g/day, or ≥ 1 g/day for IgA nephropathy) and kidney disease progression (>40% sustained estimated glomerular filtration rate decline or progression to kidney failure). Analytical Approach:Descriptive analyses were performed, and kidney survival in women with live births was compared to non-pregnant controls using Kaplan-Meier analysis and log-rank testing. Cox regression analysis was used to examine association with kidney disease progression. Results:Of 44 pregnancies, 15 (34.1%) underwent elective and 4 (9.1%) had spontaneous abortions, and (25) 56.8% resulted in live births. The median age at conception was 27.5 years. 10 (40%) live births were preterm and 16 (64%) had IUGR. Pre-eclampsia occurred in 6 (24%) pregnancies. Kidney disease relapsed with 8 (32%) pregnancies. Kidney disease progression occurred in 4 (20%) women with live births, and pregnancy was not associated with disease progression (adjusted hazard ratio: 1.4; 95% CI, 0.2-9.0; P = 0.71). Limitations:Retrospective design, small sample size, and single-center data limit interpretation and generalizability. Conclusions:Pregnancy was associated with adverse maternal and fetal outcomes in women with primary glomerular diseases, with significant risk of IUGR, but did not affect the long-term kidney outcome in our patients.

QuestionWhat is the effect of finerenone in patients with chronic kidney disease due to glomerular diseases?FindingsIn this prespecified exploratory analysis of a randomized clinical trial that enrolled 903 participants with glomerular diseases, finerenone, compared with placebo, slowed kidney function decline (difference in eGFR slope decline, 073 mL/min/1.73 m2 per year), reduced albuminuria, and lowered the risk of kidney failure or sustained loss of kidney function, with consistent effects across glomerular disease subtypes.MeaningFinerenone may have an important role in preserving kidney function in patients with glomerular diseases. ImportanceGlomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain.ObjectivesTo evaluate the efficacy and safety of finerenone in patients with glomerular diseases.Design, Setting, and ParticipantsPrespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g.InterventionFinerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457).Main Outcomes and MeasuresAnnualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes).ResultsOf 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97).Conclusions and RelevanceIn this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population.Trial RegistrationClinicalTrials.gov Identifier: NCT05047263 This exploratory analysis of a randomized clinical trial evaluates the efficacy and safety of finerenone in reducing chronic kidney disease of participants with glomerular diseases, including disease subtype.

Anemia is common in patients with CKD and ESKD, with a 50% prevalence in the USA and higher in India. The overall prevalence of anemia in CKD is twice the general population, increasing with CKD progression. The last guidelines for anemia in India were published in 2013 by the Indian Society of Nephrology (ISN). There is a need for revised guidelines/consensus statements incorporating the significant developments in patient monitoring and treatment, which have occurred in the last decade to guide evidence-based clinical practice, especially for the Indian population. We searched PubMed/Medline, Embase, Web of Science Core Collection, and CINAHL databases to perform a systematic review of the literature examining anemia prevention and treatment in adult CKD/ESKD patients, with 29 studies identified out of 1668 records screened. We then performed data extraction to write consensus guidelines and rationale, with supplemental literature evidence discussing the diagnosis and management of CKD and ESKD anemia patients in an Indian context.

BACKGROUND:AA amyloidosis is a rare but significant cause of chronic kidney disease (CKD). We aimed to characterize the clinical profile of patients with AA amyloidosis affecting the kidneys in the Indian subcontinent. METHODOLOGY:In this retrospective cohort study, we evaluated patients with kidney biopsy-confirmed AA amyloidosis and compared them with a control group of patients with diabetic kidney disease (DKD). Primary outcome was defined as a composite of ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage kidney disease (ESKD). RESULTS:AA amyloidosis (n = 91) accounted for 1.9% of all kidney biopsies. The median age was 45 years, and 75.8% were male. Chronic infections or inflammatory diseases were reported in 58.2%, tuberculosis being most common (35.2%). Baseline median eGFR was 66.0 mL/min/1.73 m2 and urine protein creatinine ratio was 4.9 g/g. During median follow-up of 5.58 years, 38.6% experienced worsening kidney outcomes. Adjusted analyses showed significantly better kidney survival than DKD (0.29 (95% CI: 0.14-0.66, p = 0.002). CONCLUSION:AA amyloidosis is an uncommon but important cause of CKD. Tuberculosis is the leading predisposing factor in Indian patients. These patients exhibit slower eGFR decline compared to DKD despite progressive proteinuria, suggesting distinct pathophysiology.

BACKGROUND:There is a growing need to understand how glomerular diseases impact patients' ability to lead a healthy and productive life. We examined the Health-Related Quality of Life (HRQoL) in patients with primary glomerular diseases in India. METHOD:In a cross-sectional study, the Patient-Reported Outcomes Measurement Information System (PROMIS) 29v2.1 questionnaire was administered to adults with primary glomerular diseases at the renal clinic. Demographic and clinical data were collected from medical records. Quality of life domain scores were calculated for physical function, pain interference, fatigue, anxiety, sleep disturbance, depression, and ability to participate in social roles and activities. The composite score was derived to reflect the overall HRQoL. Univariable and multivariable linear regression models were run to assess demographic, socio-economic, and clinical predictors of overall and domain-specific quality of life. RESULTS:Three hundred and one patients were included in the final analysis. 67.2% were male. Edema was present in 16.6% of participants, while 37.2% had recently taken steroids. Female sex (β = -5.3, 95% CI: -7.6 to -3.0, p < 0.001), eGFR < 60 mL/min/1.73 m2 (β = -3.3, 95% CI: -5.6 to -0.96, p = 0.006) and obesity (β = -5.6, 95% CI: -9.5 to -1.8, p = 0.004) were independently associated with worse overall HRQoL and negatively affected most individual domains of HRQoL. Edema and steroid use impacted some individual domains but did not affect overall HRQoL. There was no association with education level and per capita income. CONCLUSION:These findings underscore the negative impact of female sex, lower eGFR, body weight, edema, and recent steroid intake on HRQoL in adults with primary glomerular diseases. The implications of these results extend to the optimisation of long-term care for patients by addressing their concerns and priorities.

Fabry disease (FD) is an inherited X-linked lysosomal disorder resulting in the deficiency of the enzyme alpha-galactosidase-A. This leads to the accumulation of glycoproteins and glycolipids in various organs. It classically presents in males in the first decade with neuropathic pain, with or without renal involvement. In the kidney, Fabry nephropathy is characterised by the presence of concentric lamellar osmiophilic lysosomal inclusions, known as zebra bodies or myelin figures in the podocytes. Similar inclusions are also described with drug toxicities, notably hydroxychloroquine (HCQ) toxicity. We report a female in her late 20s with systemic lupus erythematosus (SLE) on HCQ. Renal biopsy showed Class V lupus nephritis with numerous podocytic myelin figures on ultrastructural examination, raising the differential diagnoses of Fabry nephropathy and HCQ toxicity. Enzyme and genetic studies, however, confirmed FD in this patient with SLE. This report highlights a rare dual pathology and discusses possible pathogenetic mechanisms.

IgA nephropathy (IgAN) is a common glomerular disease in adults with a smoldering course and high risk of progression to end-stage kidney disease (ESKD) in South Asians. We investigated serum IgA/C3 ratio as a potential biomarker for IgAN. We measured serum levels of IgA and C3 in 258 patients with IgAN and 90 controls with non-IgAN primary glomerular disease and examined if serum IgA/C3 ratio differentiates IgAN from other glomerular diseases and if it predicts renal survival in IgAN. The primary outcome was lack of renal survival, defined as irreversible decline in eGFR > 50% from baseline or progression to ESKD. Median serum IgA/C3 ratio was higher in IgAN patients compared to controls (2.4, IQR: 1.9-3.0 vs. 1.8, IQR: 1.3–2.5, p < 0.001). The AUC for the receiver operating curve of IgA/C3 ratio was 0.6760 (95% CI: 0.6074–0.7446). The sensitivity and specificity of IgA/C3 ratio > 2.0 were 70.5% and 62.2% respectively, for differentiating IgAN from other non-IgAN glomerular diseases. With a median duration of follow-up of 35.0(IQR 16-56.8) months, 26.7% patients reached the primary outcome. Compared to patients with a low IgA/C3 ratio(≤ 2.0), those with a high ratio(> 2.0) were significantly older [median age 34 vs. 29 years, p = 0.003], more likely to have hypertension (70.6% vs. 50.5%, p = 0.001), had lower median eGFR [47.7 mL/min/1.73 m² vs. 77.7 mL/min/1.73 m², p < 0.001], lower urine protein creatinine ratio [2.0 g/g vs. 2.5 g/g, p = 0.015] and a significantly higher proportion of segmental glomerulosclerosis (S1 lesions) (80.4% vs. 62.1%, p = 0.005). Renal disease progression was comparable (26.3% vs. 27.0%, p = 0.906) between the low and high IgA/C3 ratio groups respectively. High IgA/C3 ratio (> 2.0) was not a significant predictor of primary outcome (HR = 1.32 95% CI: 0.80–2.2, p = 0.278). Serum IgA/C3 ratio is elevated in IgAN compared to other glomerular diseases but has limited diagnostic and prognostic utility in our patients.

Abstract Background and Aims Parvovirus B 19 (PVB-19) virus infection can cause severe, persistent and/or refractory anaemia in kidney transplant recipients (KTR). There is paucity of data on the clinical manifestations, diagnosis and management of this infection and limited to case reports and case series. Method We performed a literature search of kidney transplant recipients infected with PVB-19 in MEDLINE, EMBASE and Cochrane databases and 93 articles were identified as suitable for assessment. The review was conducted in accordance with PRISMA statement. Results A total of two hundred and eighty-two patients were included from the studies assessed in the review. The mean age of the cohort was 37.05 years. The infection was more common in males when compared to females. The median onset of PVB-19 infection post transplantation was at 5 weeks (2, 15 weeks). One fourth of the recipients had at least one episode of rejection prior to PVB-19 infection. Majority of the patients were on Tacrolimus, MMF and corticosteroids maintenance. One third of the patients had co-infections with other organisms (EBV, CMV, etc.). Anemia and fever were the most common manifestations among all the kidney transplant patients infected with PVB-19 while CNS manifestations and rash were least reported. Hemoglobin was low (<10 mg/dl) in ninety eight percent of the patients (n=151). The lowest hemoglobin reported in the due course of illness was 6 mg/dl (5, 7.2 mg/dl) and with corrected reticulocyte count being only 0.2% (0.1%, 0.6%). The most consistent finding on peripheral smear was normocytic, normochromic anemia while a few reported helmet cells too. Pure Erythroid hypoplasia alone (45.3%) combined with giant pronormoblasts and inclusion bodies (49%) were the most common findings on bone marrow aspirate. Majority of PVB-19 diagnosis was made with the help of multiple methods of detection like IgM assay, PCR—qualitative and quantitative (42.2%). The average PCR copies detected were 1.3*107 (4.28*105, 2.53*109). IVIG only (47.2%) and combined IVIG + immunosuppression reduction (41.2%) was the mainstay of the treatment in majority. The median time to recover was 8 weeks (3, 16 weeks). One fourth of the patients had recurrence after recovery. A majority of the patients (96.7%) recovered from reactivation of PVB-19. Conclusion Parvovirus infection is not uncommon in the early post-transplant period. Though data is insufficient, immunosuppression reduction with IVIG remains the treatment of choice for affected patients. Prospective studies to assess the hemoglobin cutoffs and dose of IVIG are needed to frame screening and treatment protocols.