Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts
Pediatric Nephrology(2019)
摘要
Background Dent disease type 1 (DD1) is a rare X-linked disorder caused mainly by CLCN5 mutations. Patients may present with nephrotic-range proteinuria leading to erroneous diagnosis of focal segmental glomerulosclerosis (FSGS) and unnecessary immunosuppressive treatments. Methods The following cohorts were screened for CLCN5 mutations: Chronic Kidney Disease in Children (CKiD; n = 112); Multicenter FSGS-Clinical Trial (FSGS-CT) ( n = 96), and Novel Therapies for Resistant FSGS Trial (FONT) ( n = 30). Urinary α 1 -microglobulin (α 1 M), albumin (A), total protein (TP), and creatinine (Cr) were assessed from CKiD subjects ( n = 104); DD1 patients ( n = 14); and DD1 carriers (DC; n = 8). TP/Cr, α 1 M/Cr, α 1 M/TP, and A/TP from the CKiD cohort were compared with DD1 and DC. Results No CLCN5 mutations were detected. TP/Cr was lower in DC and CKiD with tubulointerstitial disease than in DD1 and CKiD with glomerular disease ( p < 0.002). α 1 M/Cr was higher in DD1 than in CKiD and DC ( p < 0.001). A/TP was lower in DD1, DC, and CKiD with tubulointerstitial disease and higher in CKiD with glomerular disease ( p < 0.001). Thresholds for A/TP of ≤ 0.21 and α 1 M/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease. Conclusions CLCN5 mutations were not seen in screened CKiD/FSGS cohorts. In our study, a cutoff of TP/Cr > 600 mg/g (> 68 mg/mmol) and A/TP of < 0.3 had a high sensitivity and specificity to distinguish DD1 from both CKiD glomerular and tubulointerstitial cohorts. α 1 M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.
更多查看译文
关键词
Dent disease,FSGS,CLCN5,Proteinuria,Low molecular weight proteinuria,α1-Microglobulin
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络