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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. Graphical abstract, Author(s): Priyanka Khandelwal [sup.1] , Sharan Thangaraju [sup.1] , Sriram Krishnamurthy [sup.2] , Alpana Ohri [sup.3] , Priya Pais [sup.4] , Georgie Mathew [sup.5] , Jyoti Sharma [sup.6] , Aditi [...]

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]

Intestinal pseudo-obstruction (IPO), characterized by obstruction without an identifiable anatomic cause, is a rare and poorly understood entity that may occur as a primary condition or secondary to other autoimmune disorders such as systemic lupus erythematosus (SLE). A12-year-old female child was brought with abdominal distension, vomiting, and fever for 15 days. Examination showed height and weight less than the third centile for age, tachypnea, tachycardia, and hypertension with severe abdominal distension, copious bilious aspirate, and very sluggish bowel sounds. Abdominal X-ray showed multiple air fluid levels. Ultrasound abdomen and unenhanced computed tomography (CT) scan revealed thickened dilated bowel loops, ascites, and pleural effusion. In view of multisystem nature of the disease, Koch's abdomen or autoimmune disease was suspected and emergency laparotomy procedure was deferred. She was evaluated and diagnosed to have SLE with lupus nephritis class V as per the International Society of Nephrology/Royal Pathology Society. She was managed conservatively with nasogastric decompression, immunosuppressive therapy and supportive hemodialysis. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a leading cause of death in children with chronic kidney disease (CKD). A strong correlation exists between disturbed calcium--phosphate metabolism and cardiac dysfunction. Studies with use of cinacalcet in CKD are few and limited to older children and adults and in improving growth and bone deformities. We present three children with CKD on CAPD with cardiac dysfunction with refractory hyperparathyroidism. Patients were initiated on lowest adult weight-adjusted dose of 0.2 mg/kg/day. Dose was titrated every 30 days to achieve decline in iPTH to a goal of 200-300 pg/ml. Serum calcium, phosphorus and iPTH levels were checked monthly. Complications of therapy related to cinacalcet monitored. Monthly echocardiography done to monitor cardiac dysfunction. None of them experienced significant adverse effects of cinacalcet therapy. [ABSTRACT FROM AUTHOR]

Byline: Uma. Ali, Rachana. Gedam, Alpana. Ohri, Ira. Shah Smith-Lemli-Opitz syndrome is an autosomal recessively inherited disorder. A severe defect in cholesterol biosynthesis has been identified leading to abnormally low [...]

Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS. [ABSTRACT FROM AUTHOR]