Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts
Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts
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DOI：
10.1007/s00467-019-04210-0
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发表时间：
2020-04-01
影响因子：
3
通讯作者：
Lieske, John C.
中科院分区：
文献类型：
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作者：
Beara-Lasic, Lada;Cogal, Andrea;Lieske, John C.
背景1型齿状神经病(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，导致误诊为局灶性节段性肾小球硬化(FSGS)和不必要的免疫抑制治疗。方法对儿童慢性肾脏病(CKiD；n=112)、多中心FSGS临床试验(FSGS-CT)(n=96)和FSGS耐药新疗法试验(FONT)(n=30)进行CLCN5突变筛查。测定104例CKiD患者、14例DD1患者和8例DD1携带者的尿α(1)-微球蛋白(αM-1)、白蛋白(A)、总蛋白(TP)和肌酐(Cr)。将CKiD队列中的TP/Cr、αM-1/Cr、αM-1/TP和A/TP与DD1和DC进行比较。结果未检测到CLCN5突变。肾小管间质病变组和慢性肾小球病变组TP/Cr均低于肾小球病变组(P<；0.002)。αM~(-1)/Cr在慢性阻塞性肺疾病组明显高于慢性阻塞性肺疾病组和直肠癌组(P<0.001)。A/TP在肾小管间质病变组、慢性肾小球病变组和慢性肾小球病变组较低，而在慢性肾小球病变组较高(p<；0.001)。A/TP=120 mg/g(>；13.6 mg/mmor)是诊断Dent病的良好指标。结论在筛查的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对区分DD1与CKiD肾小球和肾小管间质有很高的敏感性和特异性。Alpha M-1/Crgt；=120 mg/g(>；13.6 mg/mmo1)在区分DD1和研究CKiD群体时具有最高的敏感性和特异性。
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 alpha(1)-microglobulin (alpha M-1), 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, alpha M-1/Cr, alpha M-1/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). alpha M-1/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 = 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. alpha M-1/Cr >= 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.