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Urinary sediment mRNA level of CREBBP and CYBA in children with steroid-resistant nephrotic syndrome

ABSTRACT: This study aimed to evaluate gene expression patterns in urinary sediment samples of children with steroid-resistant nephrotic syndrome (SRNS).

ORGANISM(S): Homo sapiens

PROVIDER: GSE189734 | GEO | 2022/02/23

REPOSITORIES: GEO

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Urinary sediment mRNA level of CREBBP and CYBA in children with steroid-resistant nephrotic syndrome

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Transcriptome profile of leukocyte RNA from children with steroid sensitive and resistant nephrotic syndrome

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The effect of serum from children with nephrotic syndrome on transcriptome of human immortalized podocytes cultured in vitro

Project description:Nephrotic syndrome (NS) is an unfavorable disease with heterogeneous causes and variable prognosis. One of the clinically crucial prognostic feature is the response to initial glucocorticoid treatment. Whereas in some children with steroid-sensitive nephrotic syndrome (SSNS) the treatment may induce long-term remission of the disease, steroid-resistant cases (SRNS) are at risk of renal failure requiring renal replacement therapy. The aim of this project was to explore whether sera from children with the two main clinically defined types of NS induce changes in transcriptome of in-vitro cultures of immortalized human podocytes. After 3 days of culture, total RNA was isolated and then library from polyadenylated RNA was prepared and RNA sequencing was performed. Log2 (fold-changes) were calculated to describe differential gene expression. Within the Reactome online tool, Camera methodology was implemented to identify functionally linked gene groups (pathways) that could distinguish the two patient groups. Significant transcriptome differences were found between samples from children with SSNS and SRNS. This may help to reveal the molecular mechanisms of the disease and open up for an effective individualized treatment.

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DNA Copy Number Variations in Children with Vesicoureteral Reflux and Urinary Tract Infections

Project description:RIVUR Trial participants had Agilent 1M probe and or Nimblegen 2.1M probe aCGH performed on genomic DNA. The study was designed to discover DNA copy number variations in genes critical in kidney/urinary tract development and urinary tract infection susceptibility. Reference DNA used is a single male sample

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Prediction of steroid resistance and steroid dependence in nephrotic syndrome children.

Project description:BackgroundSteroid resistant (SR) nephrotic syndrome (NS) affects up to 30% of children and is responsible for fast progression to end stage renal disease. Currently there is no early prognostic marker of SR and studied candidate variants and parameters differ highly between distinct ethnic cohorts.MethodsHere, we analyzed 11polymorphic variants, 6 mutations, SOCS3 promoter methylation and biochemical parameters as prognostic markers in a group of 124 Polish NS children (53 steroid resistant, 71 steroid sensitive including 31 steroid dependent) and 55 controls. We used single marker and multiple logistic regression analysis, accompanied by prediction modeling using neural network approach.ResultsWe achieved 92% (AUC = 0.778) SR prediction for binomial and 63% for multinomial calculations, with the strongest predictors ABCB1 rs1922240, rs1045642 and rs2235048, CD73 rs9444348 and rs4431401, serum creatinine and unmethylated SOCS3 promoter region. Next, we achieved 80% (AUC = 0.720) in binomial and 63% in multinomial prediction of SD, with the strongest predictors ABCB1 rs1045642 and rs2235048. Haplotype analysis revealed CD73_AG to be associated with SR while ABCB1_AGT was associated with SR, SD and membranoproliferative pattern of kidney injury regardless the steroid response.ConclusionsWe achieved prediction of steroid resistance and, as a novelty, steroid dependence, based on early markers in NS children. Such predictions, prior to drug administration, could facilitate decision on a proper treatment and avoid diverse effects of high steroid doses.

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