Dent病是由CLCN5(Dent-1)或OCRL(Dent-2)突变引起的罕见X连锁隐性近端肾小管病。作为一项规则,与肾小球疾病相比,肾小管性蛋白尿的总蛋白排泄(TPE)较低。几位作者报道了Dent病中的肾病性蛋白尿(NP)和肾小球硬化。因此,我们旨在通过系统文献综述分析有CLCN5或OCRL突变的患者的蛋白排泄.
对PubMed和Embase进行了搜索,以寻找有记录的CLCN5或OCRL突变的病例以及有关蛋白质排泄的(半)定量数据。最可靠的数据(即,TPE>蛋白-肌酐比值>Albustix)用于NP分类。
从47份报告中获得了148例患者的数据:126例患有CLCN5和22例OCRL突变。两种形式之间的TPE没有显着差异(p=0.11)。126例Dent-1患者中有55例(43.7%)与13/22例(59.1%)Dent-2患者符合NP的定义(p=0.25)。所有报告病例的血清白蛋白均正常(24/148)。在20/32肾活检中发现肾小球硬化,与肾小管间质纤维化密切相关,但不对肾功能或蛋白尿。
超过一半的患有两种形式的Dent疾病的患者患有NP,在没有水肿和低白蛋白血症的NP患者中存在低分子量蛋白尿,应提示进行基因检测。即使肾功能正常,肾小球硬化和肾小管间质纤维化存在于Dent病中。需要在纵向研究中进一步检查蛋白尿在疾病过程中的作用。
Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature
review.
PubMed and Embase were searched for cases with documented CLCN5 or OCRL mutations and (semi-)quantitative data on protein excretion. The most reliable data (i.e., TPE > protein-creatinine ratio > Albustix) was used for NP classification.
Data were available on 148 patients from 47 reports: 126 had a CLCN5 and 22 an OCRLmutation. TPE was not significantly different between both forms (p = 0.11). Fifty-five of 126 (43.7 %) Dent-1 vs 13/22 (59.1 %) Dent-2 patients met the definition of NP (p = 0.25). Serum albumin was normal in all reported cases (24/148). Glomerulosclerosis was noted in 20/32 kidney biopsies and was strongly related to tubulointerstitial fibrosis, but not to kidney function or proteinuria.
More than half of the patients with both forms of Dent disease have NP, and the presence of low molecular weight proteinuria in a patient with NP in the absence of edema and hypoalbuminemia should prompt genetic testing. Even with normal renal function, glomerulosclerosis and tubulointerstitial fibrosis are present in Dent disease. The role of proteinuria in the course of the disease needs to be examined further in longitudinal studies.