Department of Pediatrics, Division of Nephrology, Duke University Medical Center, Durham, NC, 27710, USA.
Department of Pediatrics, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.
Pediatr Nephrol. 2023 Jul;38(7):2003-2012. doi: 10.1007/s00467-022-05831-8. Epub 2022 Dec 2.
Steroid-resistant nephrotic syndrome (SRNS) is the most severe form of childhood nephrotic syndrome with an increased risk of progression to chronic kidney disease stage 5. Research endeavors to date have identified more than 80 genes that are associated with SRNS. Most of these genes regulate the structure and function of the podocyte, the visceral epithelial cells of the glomerulus. Although individuals of African ancestry have the highest prevalence of SRNS, especially those from Sub-Saharan Africa (SSA), with rates as high as 30-40% of all cases of nephrotic syndrome, studies focusing on the characterization and understanding of the genetic basis of SRNS in the region are negligible compared with Europe and North America. Therefore, it remains unclear if some of the variants in SRNS genes that are deemed pathogenic for SRNS are truly disease causing, and if the leading causes of monogenic nephrotic syndrome in other populations are the same for children in SSA with SRNS. Other implications of this lack of genetic data for SRNS in the region include the exclusion of children from the region from clinical trials aimed at identifying potential novel therapeutic agents for this severe form of nephrotic syndrome. This review underlines a need for concerted efforts to advance the genetic basis of SRNS in children in SSA. Such endeavors will complement global efforts at understanding the genetic basis of nephrotic syndrome.
激素耐药性肾病综合征 (SRNS) 是儿童肾病综合征中最严重的一种形式，进展为慢性肾脏病 5 期的风险增加。迄今为止的研究已经确定了 80 多个与 SRNS 相关的基因。这些基因大多数调节足细胞（肾小球的内脏上皮细胞）的结构和功能。尽管非洲裔个体的 SRNS 患病率最高，尤其是来自撒哈拉以南非洲（SSA）的个体，其肾病综合征的患病率高达 30-40%，但与欧洲和北美相比，该地区针对 SRNS 遗传基础的特征和理解的研究几乎可以忽略不计。因此，尚不清楚一些被认为与 SRNS 相关的 SRNS 基因变异是否真的是致病的，以及其他人群中单基因肾病综合征的主要病因是否与 SSA 中患有 SRNS 的儿童相同。该地区缺乏遗传数据对 SRNS 的其他影响包括将该地区的儿童排除在旨在确定这种严重形式的肾病综合征潜在新型治疗药物的临床试验之外。这篇综述强调了需要共同努力推进 SSA 儿童中 SRNS 的遗传基础。这些努力将补充全球对肾病综合征遗传基础的理解。
