NPHS Mutations in Pediatric Patients with Congenital and Steroid-Resistant Nephrotic Syndrome

Abstract

NPHS1 and NPHS2 are kidney gene components that encode for nephrin and podocin, respectively. They play a role in the progression of congenital (CNS) and steroid-resistant (SRNS) nephrotic syndrome. Hence, this study aimed to determine the prevalence and renal outcomes of NPHS mutations among pediatric patients with CNS and SRNS. We also aimed to identify potential predictors of NPHS mutations in this patient cohort. Overall, this study included 33 studies involving 2123 patients screened for NPHS1, whereas 2889 patients from 40 studies were screened for NPHS2 mutations. The patients' mean age was 4.9 ± 1 years (ranging from birth to 18 years), and 56% of patients were male (n = 1281). Using the random-effects model, the pooled proportion of NPHS1 mutations among pediatric patients with CNS and SRNS was 0.15 (95% CI 0.09; 0.24, p < 0.001, I² = 92.0%). The pooled proportion of NPHS2 mutations was slightly lower, at 0.11 (95% CI 0.08; 0.14, p < 0.001, I² = 73.8%). Among the 18 studies that reported ESRF, the pooled proportion was 0.47 (95% CI 0.34; 0.61, p < 0.001, I² = 75.4%). Our study showed that the NPHS1 (β = 1.16, p = 0.35) and NPHS2 (β = 5.49, p = 0.08) mutations did not predict ESRF in CNS and SRNS pediatric patients. Nevertheless, patients from the European continent who had the NPHS2 mutation had a significantly higher risk of developing ESRF (p < 0.05, β = 1.3, OR = 7.97, 95% CI 0.30; 2.30) compared to those who had the NPHS1 mutation. We recommend NPHS mutation screening for earlier diagnosis and to avoid unnecessary steroid treatments. More data are needed to better understand the impact of NPHS mutations among pediatric patients with CNS and SRNS.

Keywords: NPHS1; NPHS2; congenital nephrotic syndrome; end-stage renal failure; pediatric; steroid-resistant nephrotic syndrome.

Figure 1

Flow chart of the study selection process (flow chart adapted from PRISMA).

Figure 2

Forest plot showing NPHS1 mutation in CNS and SRNS pediatric patients [8,9,18,21,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52].

Figure 3

Forest plot showing NPHS2 mutation in CNS and SRNS pediatric patients [8,9,18,20,21,24,25,26,27,28,29,31,33,34,35,37,38,39,40,44,45,46,47,48,49,50,51,53,54,55,56,57,58,59,60,61,62,63,64,65].

Figure 4

Forest plot showing ESRF in CNS and SRNS pediatric patients with NPHS mutations [8,9,21,24,25,26,28,29,32,33,34,42,44,49,50,51,58,59].

Figure 5

Meta-regression bubble plot of ESRF in CNS and SRNS pediatric patients with NPHS mutations against country continents.

Figure 6

(a) Role of NPHS1 and NPHS2 in glomerular filtration in normal kidney and (b) impact of NPHS1 and NPHS2 mutations in SRNS/CNS pediatric patients.