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 α1-microglobulin (α1M), 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, α1M/Cr, α1M/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). α1M/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 α1M/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. α1M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.

中文翻译：

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低分子量蛋白尿的患病率和蛋白尿人群中的Dent疾病1 CLCN5突变。

背景技术1型Dent疾病（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蛋白尿，导致误诊为局灶性节段性肾小球硬化症（FSGS），并进行了不必要的免疫抑制治疗。方法筛选以下人群的CLCN5突变：儿童慢性肾脏病（CKiD； n = 112）；儿童慢性肾病（CKiD； n = 112）。多中心FSGS临床试验（FSGS-CT）（n = 96），以及抗性FSGS试验的新型疗法（FONT）（n = 30）。从CKiD受试者（n = 104）评估尿α1-微球蛋白（α1M），白蛋白（A），总蛋白（TP）和肌酐（Cr）。DD1位患者（n = 14）；和DD1载波（DC； n = 8）。将来自CKiD队列的TP / Cr，α1M/ Cr，α1M/ TP和A / TP与DD1和DC进行比较。结果未检测到CLCN5突变。肾小管间质疾病的DC和CKiD的TP / Cr低于肾小球疾病的DD1和CKiD的TP / Cr（p <0.002）。DD1中的α1M/ Cr高于CKiD和DC（p <0.001）。在肾小管间质疾病中，DD1，DC和CKiD的A / TP较低，而在肾小球疾病中的CKiD的A / TP较高（p <0.001）。A / TP阈值≤0.21和α1M/ Cr≥120 mg / g（> 13.6 mg / mmol）肌酐阈值是Dent疾病的良好筛查方法。结论在筛选的CKiD / FSGS队列中未观察到CLCN5突变。在我们的研究中，TP / Cr> 600 mg / g（> 68 mg / mmol）的临界值和A / TP <0.3具有很高的敏感性和特异性，可将DD1与CKiD肾小球和肾小管间质群区分。当区分DD1和研究CKiD群体时，α1M/ Cr≥120 mg / g（> 13.6 mg / mmol）具有最高的灵敏度和特异性。