Studies of hereditary steroid resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) have generated data to improve our understanding of the pathogenesis of nephrotic syndrome (NS); however, little progress has been made in identifying genetic factors associated with the predominant form of NS, childhood onset steroid sensitive nephrotic syndrome (SSNS). SSNS is responsible for more than 80% of cases seen by Pediatric Nephrologists, yet the biologic basis for disparity in incidence and severity of SSNS between different ethnicities is unknown, neither is the biologic basis for variable therapy response. As a first step towards understanding the more common SSNS, in the last ten years we have created a robust biorepository for childhood onset NS. We now have phenotype and biosamples from over 1000 children with NS. We recently used a novel study design to identify, for the first time, an unbiased exome wide risk locus for childhood SSNS in a subset of our cohort. The locus provided an unbiased genetic evidence that adaptive immunity is important in the pathogenesis of NS. We have continued to build network to study this disease and we have extended our reach to multiple Investigators in the US, UK, Japan, sub-Saharan African countries, South Asian countries, and the Middle East. These collaborations have resulted in the identification of other genetic risk factors for childhood onset nephrotic syndrome. The body of work from these International collaborations have reinforced our initial findings that childhood nephrotic syndrome is largely due to perturbation of adaptive immunity, and these findings has now set the stage for discovery of novel and specific therapeutics for nephrotic syndrome.
- HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.
Gbadegesin RA, Adeyemo A, Webb NJ, Greenbaum LA, Abeyagunawardena A, Thalgahagoda S, Kale A, Gipson D, Srivastava T, Lin JJ, Chand D, Hunley TE, Brophy PD, Bagga A, Sinha A, Rheault MN, Ghali J, Nicholls K, Abraham E, Janjua HS, Omoloja A, Barletta GM, Cai Y, Milford DD, O'Brien C, Awan A, Belostotsky V, Smoyer WE, Homstad A, Hall G, Wu G, Nagaraj S, Wigfall D, Foreman J, Winn MP; Mid-West Pediatric Nephrology Consortium.
J Am Soc Nephrol. 2015 Jul;26(7):1701-10. Epub 2014 Oct 27. PMID: 25349203; PMCID: PMC4483579.
- HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome.
Adeyemo A, Esezobor C, Solarin A, Abeyagunawardena A, Kari JA, El Desoky S, Greenbaum LA, Kamel M, Kallash M, Silva C, Young A, Hunley TE, de Jesus-Gonzalez N, Srivastava T, Gbadegesin R.
Am J Kidney Dis. 2018 Mar;71(3):399-406. Epub 2017 Dec 23. PMID: 29277510; PMCID: PMC5828864.
- Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.
Dufek S, Cheshire C, Levine AP, Trompeter RS, Issler N, Stubbs M, Mozere M, Gupta S, Klootwijk E, Patel V, Hothi D, Waters A, Webb H, Tullus K, Jenkins L, Godinho L, Levtchenko E, Wetzels J, Knoers N, Teeninga N, Nauta J, Shalaby M, Eldesoky S, Kari JA, Thalgahagoda S, Ranawaka R, Abeyagunawardena A, Adeyemo A, Kristiansen M, Gbadegesin R, Webb NJ, Gale DP, Stanescu HC, Kleta R, Bockenhauer D.
J Am Soc Nephrol. 2019 Aug;30(8):1375-1384. Epub 2019 Jul 1. PMID: 31263063; PMCID: PMC6683715.
- Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.
Jia X, Yamamura T, Gbadegesin R, McNulty MT, Song K, Nagano C, Hitomi Y, Lee D, Aiba Y, Khor SS, Ueno K, Kawai Y, Nagasaki M, Noiri E, Horinouchi T, Kaito H, Hamada R, Okamoto T, Kamei K, Kaku Y, Fujimaru R, Tanaka R, Shima Y; Research Consortium on Genetics of Childhood Idiopathic Nephrotic Syndrome in Japan, Baek J, Kang HG, Ha IS, Han KH, Yang EM; Korean Consortium of Hereditary Renal Diseases in Children, Abeyagunawardena A, Lane B, Chryst-Stangl M, Esezobor C, Solarin A; Midwest Pediatric Nephrology Consortium (Genetics of Nephrotic Syndrome Study Group), Dossier C, Deschênes G; NEPHROVIR, Vivarelli M, Debiec H, Ishikura K, Matsuo M, Nozu K, Ronco P, Cheong HI, Sampson MG, Tokunaga K, Iijima K.
Kidney Int. 2020 Nov;98(5):1308-1322. Epub 2020 Jun 14. PMID: 32554042.