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Background: Thrombotic microangiopathy (TMA) is usually caused due to dysregulation of the alternative complement pathway. Rarely, thrombotic microangiopathy is caused by non-complement mediated mutations in diacylglycerol kinase epsilon (DGKE); information about therapy and outcome of these patients is limited. Methods: Medical records of patients, younger than 18 years, diagnosed with TMA and variants in DGKE were reviewed to include 12 patients from seven centers. Genetic studies included targeted exome sequencing and multiplex-ligation dependent probe amplification of CFH-CFHR5. Results: Patients presented at a median age of 11 (7.5, 12.3) months; all were younger than 2 years. All patients had an infectious prodrome; enteroinvasive, enteropathogenic, and enterotoxigenic Escherichia coli were detected in two patients with diarrhea. Chief features included those of microangiopathic hemolysis (n = 11), microscopic hematuria (n = 10), nephrotic range proteinuria (n = 10), hypoalbuminemia (n = 6), elevated total cholesterol (n = 6), and hypocomplementemia (n = 4). Histopathology showed thrombotic microangiopathy (n = 4), overlapping with membranoproliferative pattern of injury (n = 1). At median 3.3 years of follow-up, significant hypertension and/or proteinuria (40%), relapses (66.7%), and death or progression to CKD (60%) were common. Genetic sequencing showed 13 homozygous and compound heterozygous variants (7 pathogenic, 3 likely pathogenic) located throughout DGKE; 11 variants were novel. Conclusions: This case series highlights the need to suspect DGKE nephropathy in young patients with TMA, especially those with severe proteinuria. Medium-term outcomes are unsatisfactory with risk of relapses, progressive kidney failure, and death. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aims to evaluate the clinical and histopathological profile in children with crescentic glomerulonephritis (CGN) and determine the predictors of renal outcome. Methods: In this retrospective study, we reviewed all native kidney biopsies performed in patients <18 years over 9 years (2011-2019). Individuals with ≥20% crescents with follow-up for at least 1 year were enrolled. Results: This study included 34 patients. The most common variety was immune-complex glomerulonephritis (GN) (type II CGN) (n=21; 62%), including patients with Henoch- Schonlein purpura (n=6), lupus nephritis (n=6), post-infectious GN (n=3), C3GN (n=3), and dense deposit disease (n=3). The second most common was pauci-immune GN (type III CGN; n=12; 35%) followed by anti-glomerular basement membrane disease (type I CGN; n=1; 3%). Hypertension (88%), hematuria (84.2%), and oliguria (64%) were the most common presenting features. The outcome predictors for poor renal survival were the presence of oliguria (HR-5.11, P=0.035), severe hypertension (HR-11.51, P=0.019), estimated glomerular filtration rate <15 mL/min/1.73 m2 at presentation (HR-5.05, P=0.007), percentage of crescents (HR-10.66, P=0.001), presence of fibrous crescents (HR-6.34, P=0.001), and interstitial fibrosis and tubular atrophy (HR-8.88, P=0.0046). The overall outcome of the study revealed complete recovery (n=12), partial recovery (n=6), chronic kidney disease (n=3), and end-stage renal disease (n=13). The renal survival in patients with ≥50% crescents was poor (P=0.037) as compared to subjects with <50% crescents. Conclusion: Renal survival can be predicted by the severity of presenting features and histopathological markers. Two-thirds of patients had type II CGN with renal survival outcomes similar to type III CGN. The percentage of crescents is the most important predictor of renal survival. [ABSTRACT FROM AUTHOR]

Introduction: There is paucity of data of C3 glomerulopathy in Indian children. Methods: First Indian pediatric case series where consecutive renal biopsies done over a period of ten years were reviewed to identify those patients who had isolated or predominant C3 deposits on immunofluorescent microscopy, fulfilling the criteria for C-3 glomerulopathy. The clinical, biochemical, serological, histopathological profile, eGFR and the need for renal replacement therapy was analyzed. Results: Eighteen patients, comprising 5.3% (18/298) of all renal biopsies, had C3 glomerulopathy, four with Dense Deposit Disease (DDD) and fourteen with C3 Glomerulonephritis (C3GN) with a median follow-up of 38.2 months. Median age of presentation was 7.45±3.03 years (2.5yrs- 13.5yrs) with nine boys and nine girls. Presentation was nephrotic syndrome in seven (39%), acute nephritic syndrome in three (16.7%), hematuria in five (27.7%) and acute kidney injury in three (16.7%). Median eGFR was 69 ml/min/1.73m2 (8.2-107 ml/min/1.73m²). Hematuria was seen in 16 (88%), proteinuria in 18 (100%) and low C3 in 16 (88%) at the time of presentation. Mesangioproliferative glomerulonephritis was the predominant pattern in DDD while C3GN showed a mix of mesangioproliferative, membranoproliferative, endocapillary and crescentic GN (p = 0.43). Complete or partial remission was seen in seven patients who received long term alternate day steroids alone or with added mycophenolate mofetil. The cumulative patient survival was 70.8%. Kaplan Meir analyses for renal survival without progression to ESRD was 60.2% at one year and 48.1% at five and ten years. Conclusion: Interstitial fibrosis and tubular atrophy on renal biopsy was an independent predictor of adverse renal outcome in the cohort (p = 0.013, HR8.1;95% CI -1.6-42). [ABSTRACT FROM AUTHOR]