Genetics of congenital and infantile nephrotic syndrome

Background Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations.This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution.We also discussed our different approach secondary to culture and resources.Methods A retrospective single-center study of all children diagnosed as NS before the age of l year over a duration of over one decade.Results Twenty-nine children (12 boys) were included in the study.Their median age (range) was 2.4 (0.1-12) months (20 CNS and 9 INS).Consanguinity was present in 90% of children.The genetic analysis' results were only available for 20 children.An underlying causative homozygous mutation was detected in 18 children (90%):NPHS1 (9),NPHS2(2),LAMB2(3),PLCE1(1),WT1(1),and ITSN1 novel mutation (2).One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease.All CNS cases were all managed with intermittent intravenous albumin infusion,ACEi,diuretics,and indomethacin.None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources.Only one child achieved partial remission,while 15 children died at a median (range) age of 5.8 (1.25-29) months.The remaining 14 children were followed up for an average of 36 (3.9-120) months.Three children progressed to end-stage kidney disease and PD was performed in only two children.Conclusions NPHS1 is the main underlying cause of CNS and INS in our study population.CNS and INS were associated with high morbidity and mortality.

Urinary neutrophil gelatinase-associated lipocalin(NGAL)and serum cystatin C measurements for early diagnosis of acute kidney injury in children admitted to PICU

Background Acute kidney injury(AKI)is common in critically ill children with significant mortality and morbidity.Serum creatinine is an insensitive and late biomarker compared to newly proposed AKI biomarkers.Methods Prospective study in pediatric intensive care unit(PICU)over three months to compare between serum cystatin-C(s-Cys-C)and urinary neutrophil gelatinase-associated lipocalin(uNGAL)as AKI biomarkers at multiple time points with pediatric risk,injury,failure,loss,end-stage renal disease(pRIFLE)classification in diagnosing AKI.Results Forty children were recruited.Of these 40 children,22 developed AKI according to pRIFLE criteria.There was no significant difference between AKI and non-AKI in age(P=0.29).Post cardiac surgery,renal insult was the main cause of AKI(27.3%).There was a twofold increased risk of incident AKI in those patients with high baseline uNGAL at PICU admission and almost a fourfold increased risk in patients with high baseline s-Cys-C at PICU admission.uNGAL levels were highly predictive of AKI during the follow-up period[area under the curve(AUC)=0.76,95%confidence interval(CI)0.61-0.92].The cutoff point with the highest correctly classified proportion was 223 ng/mL(≥12 centiles)which correctly predict 80.0%patients with AKI,with a corresponding sensitivity of 72.7%and a specificity of 89.9%.AUC for s-Cys-C was 0.86(95%CI 0.75-0.97),and the highest correctly classified proportion was 1009μg/L(≥13 centiles);75%of patients with AKI,with a corresponding sensitivity of 63.6%and a specificity of 88.9%.Conclusion uNGAL and s-Cys-C predicts AKI early in critically ill children.