Clinical and Pathological Predictors of Outcomes in Pediatric Steroid-Resistant Nephrotic Syndrome

Genetic steroid-resistant nephrotic syndrome (SRNS), high proteinuria (>8,000 mg/g) at disease onset, low eGFR, and persistent hypoalbuminemia during early follow-up are key predictors of poor outcomes, characterised by lack of remission and reduced kidney survival rates. These findings were published online on March 1, 2025, in Pediatric Nephrology.

This retrospective single-center study analyzed data of 65 pediatric SRNS patients treated at a paediatric outpatient clinic in Berlin between 2000 and 2023 with the objective to identify predictive factors for remission status and kidney survival by comparing genetic and non-genetic forms of the disease. More than half (57%) of the study participants were male. The median age of disease onset was 4.0 years. Clinical, laboratory, and treatment data were systematically recorded at multiple time points during the study. Outcomes were assessed based on remission status, kidney survival (chronic kidney disease [CKD] stages I-IV), and progression to CKD stage V (kidney failure) and death. The genetic group included 19 (29%) patients, whereas non-genetic group (negative screening results) included 33 (51%) patients.

Complete remission was defined as protein–creatinine ratio (PCR) < 0.2 g/g, or negative/trace dipstick in first void urine on three consecutive days. Partial remission was defined as ≥ 50% reduction of proteinuria with PCR ranging between 0.2 and 2 g/g and serum albumin ≥ 30 g/L.

After a median follow-up duration of 5.9 years, 26 (40%) patients achieved complete remission, 12 (18%) had partial remission, and 27 (42%) showed no remission. Fifteen of 19 patients (79%) in the genetic group did not achieve remission.

The kidney survival rates were 71% at 5 years and 56% at 10 years. At the last follow-up, 74% of patients in the genetic group progressed to kidney failure within a median of 7.4 months, while 27% of those in the non-genetic group experienced progression within a median of 27.9 months. High initial nephrotic-range proteinuria (>8000 mg/g), a confirmed genetic diagnosis, reduced eGFR, and hypoalbuminemia at 3-month and 1-year follow-ups were identified as negative predictors of complete or partial remission. These factors were also strongly associated with an increased risk of progression to CKD stage V; hypoalbuminemia at the 1-year follow-up was strongly associated with a nearly 50-fold increased risk for kidney failure with hazard ratio of 48.3.

These findings indicate that early detection of high-risk patients based on genetic screening and clinical variables such as proteinuria, eGFR, and hypoalbuminemia is essential. They also emphasize the need for targeted therapeutic approaches and timely interventions to improve kidney survival in pediatric SRNS.

Reference 

1.    PediatrNephrol. 2025 Mar 1. doi: 10.1007/s00467-025-06705-5.