Department of Pediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Int J Mol Sci. 2024 Nov 15;25(22):12275. doi: 10.3390/ijms252212275.
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, < 0.001, I = 92.0%). The pooled proportion of NPHS2 mutations was slightly lower, at 0.11 (95% CI 0.08; 0.14, < 0.001, I = 73.8%). Among the 18 studies that reported ESRF, the pooled proportion was 0.47 (95% CI 0.34; 0.61, < 0.001, I = 75.4%). Our study showed that the NPHS1 (β = 1.16, = 0.35) and NPHS2 (β = 5.49, = 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 ( < 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.
NPHS1 和 NPHS2 是肾脏基因成分，分别编码足细胞裂孔隔膜蛋白 Nephrin 和 Podocin。它们在先天性肾病综合征 (CNS) 和激素耐药性肾病综合征 (SRNS) 的进展中发挥作用。因此，本研究旨在确定 CNS 和 SRNS 儿科患者中 NPHS 突变的患病率和肾脏结局。我们还旨在确定该患者队列中 NPHS 突变的潜在预测因素。总体而言，这项研究包括 33 项研究，共纳入 2123 例患者筛查 NPHS1 突变，而 40 项研究中有 2889 例患者筛查 NPHS2 突变。患者的平均年龄为 4.9 ± 1 岁（出生至 18 岁），56%的患者为男性（n = 1281）。使用随机效应模型，CNS 和 SRNS 儿科患者中 NPHS1 突变的合并比例为 0.15（95%CI 0.09；0.24， < 0.001，I = 92.0%）。NPHS2 突变的合并比例略低，为 0.11（95%CI 0.08；0.14， < 0.001，I = 73.8%）。在报告 ESRF 的 18 项研究中，合并比例为 0.47（95%CI 0.34；0.61， < 0.001，I = 75.4%）。我们的研究表明，NPHS1（β=1.16， = 0.35）和 NPHS2（β=5.49， = 0.08）突变并不能预测 CNS 和 SRNS 儿科患者的 ESRF。然而，来自欧洲大陆的 NPHS2 突变患者发生 ESRF 的风险显著增加（<0.05，β=1.3，OR=7.97，95%CI 0.30；2.30），而 NPHS1 突变患者则无此风险。我们建议进行 NPHS 突变筛查，以便更早地诊断并避免不必要的类固醇治疗。需要更多的数据来更好地了解 CNS 和 SRNS 儿科患者中 NPHS 突变的影响。
