In steroid-resistant nephrotic syndrome that meets the strict definition, monogenic variants are less common than expected

• Published in: Pediatric nephrology (Berlin, West) Vol. 39; no. 12; pp. 3497 - 3503
• Main Authors: Ichikawa, Yuta, Sakakibara, Nana, Nagano, China, Inoki, Yuta, Tanaka, Yu, Ueda, Chika, Kitakado, Hideaki, Kondo, Atsushi, Ishimori, Shingo, Horinouchi, Tomoko, Iijima, Kazumoto, Nozu, Kandai
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2024; Springer Nature B.V
• Subjects: Adolescent; Child; Child, Preschool; Drug Resistance - genetics; Edema; Female; Genetic analysis; Genetic Testing - methods; Humans; Infant; Kidney diseases; Male; Medicine; Medicine & Public Health; Mutation; Nephrology; Nephrotic syndrome; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - genetics; Original; Original Article; Patients; Pediatrics; Proteinuria; Proteinuria - genetics; Remission; Retrospective Studies; Steroids; Steroids - therapeutic use; Urology; Edema; Steroid-resistant nephrotic syndrome; Acute kidney injury associated with nephrotic syndrome; Complete remission; Monogenic variants
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-024-06468-5

Background
In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics.
Methods
We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1–18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy.
Results
The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (
p
 < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)).
Conclusions
Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes.
Graphical abstract
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Supplementary information