Proteinuria in Dent disease: a review of the literature

• Published in: Pediatric nephrology (Berlin, West) Vol. 32; no. 10; pp. 1851 - 1859
• Main Authors: van Berkel, Youri, Ludwig, Michael, van Wijk, Joanna A. E., Bökenkamp, Arend
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2017; Springer; Springer Nature B.V
• Subjects: Albumin; Care and treatment; Creatinine; Dent's disease; Diagnosis; Edema; Excretion; Fibrosis; Genetic screening; Kidney diseases; Literature reviews; Medicine; Medicine & Public Health; Molecular weight; Mutation; Nephrology; Pediatrics; Proteins; Proteinuria; Renal function; Review; Risk factors; Urology; CLCN5; Dent disease; Systematic review; OCRL; Nephrotic syndrome; Low-molecular weight proteinuria; Proteinuria
• DOI: 10.1007/s00467-016-3499-x
• ISSN: 0931-041X

Background 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. Design 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. Results Data were available on 148 patients from 47 reports: 126 had a CLCN5 and 22 an OCRL mutation. 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. Conclusion 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.