The clinical characteristics of patients with congenital nephrotic syndrome secondary to NPHS1 mutation: Is nephrectomy still a therapeutic option for selected cases?

Abstract

Background: Managing congenital nephrotic syndrome (CNS) remains a clinical challenge. While albumin infusions and nephrectomy have been long-standing treatments, a conservative approach is increasingly favored. This study aimed to compare clinical outcomes between nephrectomy (Nx) and non-Nx in patients with bi-allelic NPHS1 mutations.

Methods: This retrospective cohort study included 29 pediatric CNS patients (15 female, 14 male) with confirmed NPHS1 mutations. Clinical parameters including albumin infusion requirements, infections, hospitalizations, growth, and survival rates were analyzed in the Nx and non-Nx groups.

Results: The median age at the time CNS was diagnosed was 29 days (IQR: 11-62 days). In all, 24 patients (82.8%) had homozygous NPHS1 mutations and 5 (17.2%) had compound heterozygous NPHS1 mutations. None of the patients had Fin-major mutation (i.e., p. Leu41 Aspfs*50). Unilateral/bilateral nephrectomy was performed in 16 patients. At 12 months post-nephrectomy the number of albumin infusions required, infections, and hospitalizations decreased significantly in the Nx group, as compared to the pre-nephrectomy period (p = 0.001, p = 0.027, and p = 0.004, respectively). Among the 13 (44.8%) patients in the non-Nx group, at 12 months after CNS was diagnosed the number of serum albumin infusions required significantly decreased (p = 0.007); however, the number of infections and hospitalization did not differ significantly (p = 0.589 and p = 0.5, respectively). Receiver operating characteristic (ROC) analysis showed that requiring albumin infusions ≥ 14 days/month predicted the decision to perform nephrectomy with 68% accuracy (73% sensitivity and 62% specificity).

Conclusions: Nephrectomy reduces albumin infusions, infections, and hospitalizations, suggesting it may be a beneficial treatment for selected CNS patients with NPHS1 mutations.

Keywords: NPHS1 mutation; Congenital nephrotic syndrome; Nephrectomy; Nephrin.

A higher resolution version of the Graphical abstract is available as Supplementary information

Fig. 1

Genetic analysis and clinical outcome of the patients

Fig. 2

eGFR (A), the serum albumin level (B), and the serum creatinine level (C) before and after nephrectomy (n = 16)

Fig. 3

eGFR (A), the serum albumin level (B), and the serum creatinine level (C) before and after the diagnosis of CNS