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Comparative Study
. 2025 Aug;40(8):2539-2549.
doi: 10.1007/s00467-025-06735-z. Epub 2025 Mar 17.

Differences in kidney prognosis between congenital and infantile nephrotic syndrome

Yuta Inoki  1 , Tomoko Horinouchi  2 , Shuhei Aoyama  1 , Yuka Kimura  1 , Yuta Ichikawa  1 , Yu Tanaka  1 , Chika Ueda  1 , Hideaki Kitakado  1 , Atsushi Kondo  1 , Nana Sakakibara  1 , Koichi Kamei  3 , Riku Hamada  4 , Naoya Fujita  5 , Yoshimitsu Gotoh  6 , Yoshitsugu Kaku  7 , Kei Nishiyama  8 , Takayuki Okamoto  9 , Yukiko Toya  10 , Tomohiko Yamamura  1 , Shingo Ishimori  1 , China Nagano  1 , Kandai Nozu  1
Affiliations
Comparative Study

Differences in kidney prognosis between congenital and infantile nephrotic syndrome

Yuta Inoki et al. Pediatr Nephrol. 2025 Aug.

Abstract

Background: More than half of patients with congenital nephrotic syndrome (CNS) or infantile nephrotic syndrome (infantile NS) have a monogenic aetiology. This study aimed to clarify differences in the clinical course, genetic background, and genotype-phenotype correlation between CNS and infantile NS.

Methods: We enrolled patients who were diagnosed with CNS or infantile NS and referred to our hospital for genetic analysis and investigated the clinical characteristics and genetic background of patients with identified causative genes.

Results: Among 74 patients enrolled, disease-causing genetic variants were detected in 50 patients. The median age for developing kidney failure in the genetic CNS (n = 33) and genetic infantile NS (n = 17) groups with monogenic variants was 13.2 and 19.0 months, respectively (P = 0.13). The age at developing kidney failure was significantly earlier in CNS patients with genes other than NPHS1 than in CNS patients with NPHS1 variants (1.0 vs. 31.0 months; P < 0.001). In patients with pathogenic variants other than NPHS1, there was a significant difference in the age at developing kidney failure between CNS and infantile NS patients (1.0 vs. 15.0 months; P < 0.001). Of patients with NPHS1 variants, no infants with NS had any truncating variants or developed kidney failure during follow-up.

Conclusions: The onset of CNS or infantile NS affects the kidney prognosis in patients with genetic nephrotic syndrome. Among patients with pathogenic variants in the same gene, patients with infantile NS may have a milder genotype and better prognosis than those with CNS.

Keywords: Congenital nephrotic syndrome; Genotype–phenotype correlation; Infantile nephrotic syndrome; Kidney prognosis; Pathogenic variants.

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Conflict of interest statement

Declarations. Ethics approval: This study was approved by the Institutional Review Board of Kobe University School of Medicine (IRB approval number: 301). All procedures in this study were conducted in accordance with the Declaration of Helsinki and the ethical guidelines of the Japanese Ministry of Health, Labour, and Welfare. Consent to participate: Informed consent was obtained from all patients or their family members. Conflict of interest: Kandai Nozu is a member of the advisory groups of Kyowa Kirin Co. Ltd., Toa Eiyo Ltd., and Taisho Pharmaceutical Co. Ltd. Kandai Nozu received speaker grants from Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Kyowa Kirin Co., Ltd. The other authors declare that they have no competing interests.

Figures

None
A higher-resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
Age at diagnosis of nephrotic syndrome with detected pathogenic variants in disease-causing genes
Fig. 2
Fig. 2
Probability of developing kidney failure in patients with pathogenic variants. a Comparison of the age at which kidney failure develops between patients with CNS and those with infantile NS. No significant difference in age was observed between the two groups (13.2 vs. 19.0 months; P = 0.13). b Comparison of the age at which kidney failure develops between patients with CNS with NPHS1 variants and patients with CNS with other variants. A significant age difference was observed between the two groups (1.0 vs. 31.0 months; P < 0.001). c Comparison of the age at which kidney failure develops between patients with CNS with NPHS1 variants and patients with infantile NS with NPHS1 variants. A significant age difference was observed between the two groups (31.0 vs. − months; P = 0.025). d Comparison of the age at developing kidney failure between patients with CNS with pathogenic variants other than NPHS1 and patients with infantile NS with pathogenic variants other than NPHS1. A significant age difference was observed between the two groups (1.0 vs 15.0 months; P < 0.001). CNS, congenital nephrotic syndrome; infantile NS, infantile nephrotic syndrome
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