Novel insights in the genetics of steroid-sensitive nephrotic syndrome in childhood
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REVIEW
Novel insights in the genetics of steroid-sensitive nephrotic syndrome in childhood Stephanie Dufek-Kamperis 1,2
&
Robert Kleta 2,3 & Detlef Bockenhauer 2,3 & Daniel Gale 2 & Mallory L. Downie 2,3
Received: 15 July 2020 / Revised: 10 August 2020 / Accepted: 14 September 2020 # IPNA 2020
Abstract Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood and there is growing evidence that genetics play a role in the susceptibility for the disease. Familial clustering has been observed and has led to several studies on familial SSNS trying to identify a monogenic cause of the disease. Until now, however, none of these have provided convincing evidence for Mendelian inheritance. This and the phenotypic variability within SSNS suggest a complex inheritance pattern, where multiple variants and interactions between those and the environment play roles in disease development. Genomewide association studies (GWASs) have been used to investigate this complex disease. We herein highlight new insights in the genetics of the disease provided by GWAS and identify how these insights fit into our understanding of the pathogenesis of SSNS. Keywords Steroid-sensitive nephrotic syndrome . SSNS . Genetics . Paediatrics . HLA . GWAS . CALHM6
Introduction Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children worldwide and is characterised by the leakage of protein from the blood into the urine through damaged glomeruli. INS affects approximately 5 in 100,000 children worldwide aged below 16 years and has a 2:1 male predominance. Incidence varies by geographical region and ethnicity, with children of South Asian, African American and Arabic ethnicity having the highest incidence of disease [1]. Children with INS clinically present with heavy proteinuria, oedema and low albumin, and can be classified according to their response to first-line treatment of corticosteroids. The majority of children (80–90%) respond to a course of corticosteroids within 4 weeks and are labelled as having steroid-sensitive nephrotic syndrome (SSNS). The remaining * Stephanie Dufek-Kamperis [email protected] 1
Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
2
Department of Renal Medicine, University College London, London, UK
3
Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
10–20% are non-responsive and are classified as having steroid-resistant nephrotic syndrome (SRNS), leading to less favourable prognosis and often progression to stage 5 chronic kidney disease. In children with SSNS, the majority will experience at least one episode of relapse, and up to 50% of children will develop a frequently relapsing or steroiddependent course [1]. Though disease prognosis is guided by response to corticosteroids, the underlying pathophysiology of INS remains unclear. Kidney biopsies in children with INS are not performed routinely but typically show foot process effaceme
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