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Genetics of childhood steroid-sensitive nephrotic syndrome

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Abstract

The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last 20 years over 50 genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, and at least two disease loci for two pathologic variants of SRNS (focal segmental glomerulosclerosis and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid-sensitive nephrotic syndrome (SSNS) remain elusive, partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. Here we review what is currently known about the genetics of SSNS and also discuss how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS.

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Acknowledgments

R.A.G. is supported by National Institutes of Health (NIH)/National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) grant DK098135-01A1, and DK094987.

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  1. Department of Pediatrics, Division of Nephrology, Emory University, Atlanta, GA, USA

    Alana M. Karp

  2. Department of Pediatrics, Division of Nephrology, Duke University Medical Center, Durham, NC, USA

    Rasheed A. Gbadegesin

  3. Duke Molecular Physiology Institute, Duke University, 300 North Duke Street, Durham, NC, 27701, USA

    Rasheed A. Gbadegesin

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Karp, A.M., Gbadegesin, R.A. Genetics of childhood steroid-sensitive nephrotic syndrome. Pediatr Nephrol 32, 1481–1488 (2017). https://doi.org/10.1007/s00467-016-3456-8

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