Beara-Lasic Lada, Cogal Andrea, Mara Kristin, Enders Felicity, Mehta Ramila A, Haskic Zejfa, Furth Susan L, Trachtman Howard, Scheinman Steven J, Milliner Dawn S, Goldfarb David S, Harris Peter C, Lieske John C
Nephrology Division, Department of Medicine and Pediatrics, New York University Langone Health and New York University School of Medicine, New York, NY, USA.
Rare Kidney Stone Consortium, Rochester, USA.
Pediatr Nephrol. 2020 Apr;35(4):633-640. doi: 10.1007/s00467-019-04210-0. Epub 2019 Mar 10.
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.
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-microglobulin (αM), 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, αM/Cr, αM/TP, and A/TP from the CKiD cohort were compared with DD1 and DC.
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). αM/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 αM/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease.
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. αM/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.
1型丹特病（DD1）是一种罕见的X连锁疾病，主要由CLCN5突变引起。患者可能出现肾病范围的蛋白尿，导致局灶节段性肾小球硬化（FSGS）的错误诊断和不必要的免疫抑制治疗。
对以下队列进行CLCN5突变筛查：儿童慢性肾脏病（CKiD；n = 112）；多中心FSGS临床试验（FSGS-CT）（n = 96），以及难治性FSGS试验新疗法（FONT）（n = 30）。对CKiD受试者（n = 104）、DD1患者（n = 14）和DD1携带者（DC；n = 8）评估尿α-微球蛋白（αM）、白蛋白（A）、总蛋白（TP）和肌酐（Cr）。将CKiD队列中的TP/Cr、αM/Cr、αM/TP和A/TP与DD1和DC进行比较。
未检测到CLCN5突变。与患有肾小球疾病的DD1和CKiD相比，患有肾小管间质疾病的DC和CKiD的TP/Cr较低（p < 0.002）。DD1中的αM/Cr高于CKiD和DC（p < 0.001）。患有肾小管间质疾病的DD1、DC和CKiD的A/TP较低，而患有肾小球疾病的CKiD的A/TP较高（p < 0.001）。A/TP≤0.21和αM/Cr≥120 mg/g（>13.6 mg/mmol）肌酐的阈值是丹特病的良好筛查指标。
在筛查的CKiD/FSGS队列中未发现CLCN5突变。在我们的研究中，TP/Cr>600 mg/g（>68 mg/mmol）和A/TP<0.3的临界值在区分DD1与CKiD肾小球和肾小管间质队列方面具有高敏感性和特异性。在区分DD1和所研究的CKiD人群时，αM/Cr≥120 mg/g（>13.6 mg/mmol）具有最高的敏感性和特异性。
