Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Oct;40(10):3111-3120.
doi: 10.1007/s00467-025-06842-x. Epub 2025 Jun 5.

Relationship between clinical and pathologic findings and the presence of genetic variants in patients with steroid-resistant nephrotic syndrome

Koichi Kamei  1 , Kandai Nozu  2 , Tomoko Horinouchi  2 , Nana Sakakibara  2 , Kentaro Nishi  3 , Naoya Fujita  4 , Shuichiro Fujinaga  5 , Hiroshi Kaito  6 , Aya Inaba  7 , Riku Hamada  8 , Yuko Shima  9 , Takayuki Okamoto  10 , Junya Hashimoto  11 , Masaki Yamamoto  12 , Yoshimitsu Gotoh  13 , Yusuke Okuda  14 , Hirotsugu Kitayama  15 , Junya Fujimura  16 , Shingo Ishimori  2 , Naohiro Kamiyoshi  17 , Norishige Yoshikawa  18
Affiliations
Multicenter Study

Relationship between clinical and pathologic findings and the presence of genetic variants in patients with steroid-resistant nephrotic syndrome

Koichi Kamei et al. Pediatr Nephrol. 2025 Oct.

Abstract

Background: Genetic analysis, crucial in determining treatment strategies for steroid-resistant nephrotic syndrome (SRNS), can be performed in limited facilities and requires a long time. Predicting the presence or absence of genetic variants by clinical and pathologic features is preferable.

Methods: In this multicenter, retrospective study, we compared the clinical or pathologic features between the patients with and without genetic variants in children with SRNS and evaluated the efficacy of immunosuppressive treatment and long-term kidney outcomes.

Results: Fifty-three patients in 17 institutes were included, and 11 patients (21%) showed genetic variants. Two patients with a family history of nephrotic syndrome harbored genetic variants. Serum albumin level at onset was significantly lower in patients without genetic variants (p = 0.001). The receiver operating characteristic curve analysis showed that a cutoff value of serum albumin level of 2.3 g/dL at onset had a sensitivity and specificity of 82% and 90%, respectively, in predicting genetic variants. Patients with asymptomatic proteinuria at onset were more likely to harbor genetic variants (p = 0.05). None of the pathologic features was significantly different between the two groups. Mesangial proliferation and diffuse foot process effacement were observed more in patients without genetic variants, although statistically insignificant. Immunosuppressive treatment was less effective, and the 5-year kidney survival was poorer (31% and 78%, p = 0.03) in patients with genetic variants than in those without genetic variants.

Conclusions: Higher serum albumin levels at onset can predict the presence of genetic variants. Pathologic features might have limited utility in predicting them.

Keywords: Acute kidney injury; Columbia classification; Foot process effacement; Genetic variant; Serum albumin; Steroid-resistant nephrotic syndrome (SRNS).

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval: This study was conducted in accordance with the principles of the Declaration of Helsinki and the Ethical Guidelines for Medical and Biological Research Involving Human Subjects of the Ministry of Health, Labor, and Welfare, Japan. This study was approved by the Ethics Committee of the National Center for Child Health and Development (approval no. 2020–328). In addition, this study was approved by the ethics committees of the study institutions other than the National Center for Child Health and Development. Consent to participate: Informed consent was obtained in the form of opt-out from the patients or family members. Consent for publication: Not applicable. Competing interests: Koichi Kamei received research funding from the Public Foundation of Vaccination Research Center and the Taiju Life Social Welfare Foundation; donations from Chugai Pharmaceutical, Teijin Pharma, Kyowa Kirin, Taiho Pharmaceutical, Shionogi, Daiichi Sankyo, and Mitsubishi Tanabe Pharma; and lecture fees from Terumo. Kandai Nozu is a member of the advisory groups for Kyowa Kirin Co. Ltd., Toa Eiyo LTD., Zenyaku Kogyo Co. Ltd., and Taisho Pharmaceutical Co. Ltd.; has a patent for developing exon skipping therapy for patients with Alport syndrome; received lecture fees from Ono Pharma, Astellas Pharma, Novo Nordisk Pharma, Alexion Pharma, Sumitomo Pharma, Sanofi, Otsuka Pharma, Daiichi Sankyo, and Miyarisan; and received grants from Zenyaku Kogyo and Torii Co. Ltd.

References

    1. Kikunaga K, Ishikura K, Terano C, Sato M, Komaki F, Hamasaki Y, Sasaki S, Iijima K, Yoshikawa N, Nakanishi K, Nakazato H, Matsuyama T, Ando T, Ito S, Honda M, Japanese Pediatric Survey Holding Information of Nephrotic syndrome (JP-SHINE) study of the Japanese Study Group of Renal Disease in Children (2017) High incidence of idiopathic nephrotic syndrome in East Asian children: a nationwide survey in Japan (JP-SHINE study). Clin Exp Nephrol 21:651–657. https://doi.org/10.1007/s10157-016-1319-z - DOI
    1. Trautmann A, Bodria M, Ozaltin F, Gheisari A, Melk A, Azocar M, Anarat A, Caliskan S, Emma F, Gellermann J, Oh J, Baskin E, Ksiazek J, Remuzzi G, Erdogan O, Akman S, Dusek J, Davitaia T, Özkaya O, Papachristou F, Firszt-Adamczyk A, Urasinski T, Testa S, Krmar RT, Hyla-Klekot L, Pasini A, Özcakar ZB, Sallay P, Cakar N, Galanti M, Terzic J, Aoun B, Caldas Afonso A, Szymanik-Grzelak H, Lipska BS, Schnaidt S, Schaefer F; PodoNet Consortium (2015) Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin J Am Soc Nephrol 10:592–600. https://doi.org/10.2215/CJN.06260614 - DOI
    1. Mason AE, Sen ES, Bierzynska A, Colby E, Afzal M, Dorval G, Koziell AB, Williams M, Boyer O, Welsh GI, Saleem MA; UK RaDaR/NephroS Study (2020) Response to first course of intensified immunosuppression in genetically stratified steroid resistant nephrotic syndrome. Clin J Am Soc Nephrol 15:983–994. https://doi.org/10.2215/CJN.13371019 - DOI
    1. Jiao J, Wang L, Ni F, Wang M, Feng S, Gao X, Chan H, Yang X, Lee H, Chi H, Chen X, Wu D, Zhang G, Yang B, Wang A, Yang Q, Wan J, Yu S, Li X, Wang M, Chen X, Mai X, Ruan X, Yang H, Li Q (2022) Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome. Genes Dis 9:1662–1673. https://doi.org/10.1016/j.gendis.2022.03.023 - DOI - PubMed - PMC
    1. Nagano C, Yamamura T, Horinouchi T, Aoto Y, Ishiko S, Sakakibara N, Shima Y, Nakanishi K, Nagase H, Iijima K, Nozu K (2020) Comprehensive genetic diagnosis of Japanese patients with severe Proteinuria. Sci Rep 10:270. https://doi.org/10.1038/s41598-019-57149-5 - DOI - PubMed - PMC

Publication types

Supplementary concepts

LinkOut - more resources