Kidney function and mortality in childhood nephrotic syndrome

Nephrotic syndrome is a common childhood kidney disease. Frequent relapses, acute kidney injuries and immunosuppressive medications may lead to chronic kidney disease (CKD). Our objective was to determine incidence of kidney failure, CKD, cancer and mortality.

A systematic literature search was performed on five databases (MEDLINE, EMBASE, CENTRAL, Web of Science, ClinicalTrials.gov) for English abstracts and full-text articles from 1970 to 2024. Studies that enrolled children with idiopathic nephrotic syndrome (steroid-sensitive and -resistant) and reported kidney failure, CKD, cancer or mortality incidence were included. Data abstraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Meta-analyses calculated incidence rate (IR) of outcomes.

Of 2785 studies screened, 229 were included (32 712 children). Median follow-up was 5.1 (range 0.3-29) years. Among children with steroid-sensitive nephrotic syndrome, incidence of kidney failure was IR 2.65 [95% confidence interval (CI) 1.55-4.54)], CKD was IR 3.80 (95% CI 2.38-6.07) and mortality was IR 2.30 (95% CI 1.14-4.63) per 1000 person-years. Among children with steroid-resistant nephrotic syndrome, incidence of kidney failure was IR 33.34 (95% CI 27.05-41.11), CKD was IR 46.90 (95% CI 39.31-55.96) and mortality was IR 12.52 (95% CI 8.21-19.09) per 1000 person-years. The most common causes of death were kidney failure and infections. The incidence of CKD and death decreased over time among children with steroid-resistant nephrotic syndrome. Cancer occurred in only 16 children in 13 studies (899 children). Many studies were at moderate-to-high risk of bias and used variable surveillance strategies and outcome definitions.

Incidence of kidney failure, CKD and death are <4 per 1000 person-years among children with steroid-sensitive nephrotic syndrome. Children diagnosed with steroid-resistance had significantly higher incidence of CKD and death, although rates are decreasing over time. PROSPERO Registration: CRD42024578001 (19 August 2024).