ESPN 53rd Annual Meeting

ESPN 2021


 
Evaluation of The Genetical Features Affecting Renal Outcome in Children With Steroid Resistant Nephrotic Syndrome
ELIF COMAK 1 ASLI TOYLU 2 UGUR BILGE 3 GULSAH KAYA AKSOY 1 MUSTAFA KOYUN 1 SEMA AKMAN 1

1- AKDENIZ UNIVERSITY MEDICAL FACULTY, PEDIATRIC NEPHROLOGY, ANTALYA, TURKEY
2- AKDENIZ UNIVERSITY MEDICAL FACULTY, MEDICAL GENETICS, ANTALYA, TURKEY
3- AKDENIZ UNIVERSITY MEDICAL FACULTY, BIOSTATISTICS AND MEDICAL INFORMATICS, ANTALYA, TURKEY
 
Introduction:

Although several studies in children with steroid-resistant nephrotic syndrome (SRNS) have shown that mutations in genes encoding proteins in the podocyte skeleton may be responsible for the etiology in only one-third of cases, the genetic features related with renal prognosis and responde to immunosuppressive are not fully recognized. The aim of this study was to investigate the genetic alterations associate with renal prognosis and resistance to immunosuppression in children with SRNS.

Material and methods:

 The children with SRNS were enrolled in this study. Custom genetic panel was designed for next-generation sequencing analysis of 205 SNPs in 33 target genes.

Results:

A total of 25 children, 16 boys (64%), median age at last visit of 17.5 years (13-18 years), median age at diagnosis of 7.5 years (2-15), median follow-up of 9.58±4.54 years, were included in the study. All patients was diagnosed focal segmental glomerulosclerosis on renal biopsy. 13 patients had normal renal function, while the remaning 12 had end stage renal disease (ESRD) after a median of 4.5 years (2-11 years)  follow up period with a median age at ESRD diagnosis of 13.5 years (6-17 years). In study group, patients were treated five different immunosuppressive medications. All patients received steroids and cyclosporin A; 10 patients mycophenolate mofetil, 10 patients tacrolimus, 1 patient cyclophosphamide, 4 patients rituximab. The genetic analysis revealed significant differences in SNP genotype frequencies between groups of ESRD and normal renal function. Genetic alterations in several genes involved in the drug metabolism (CYP3A5, CYP2C19, GSTP1, MPDH2, SLCO1B1), immune response regulation (FCGR3A, FKBP5, CXCL12), glucocorticoid receptor gene (NR3C1)and uromodulin (UMOD) were significantly associated with the lack of response to immunosuppressive treatments and renal function (p<0.05).

Conclusions:

 Our results suggest that heterogeneous genetic alterations in children with SRNS associate with resistance to different immunosuppressive treatments and renal function.