title: Proteinuria in Dent disease: a review of the literature.
abstract: 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.
authors.affiliation: Department of Pediatric Nephrology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Youri
authors.initials: Y
authors.lastname: van Berkel
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: Department of Pediatric Nephrology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Joanna A E
authors.initials: JAE
authors.lastname: van Wijk
authors.affiliation: Department of Pediatric Nephrology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. a.bokenkamp@vumc.nl.
authors.forename: Arend
authors.initials: A
authors.lastname: Bökenkamp
mesh_terms: D001706:Biopsy; D018118:Chloride Channels / Q000235:genetics; D057973:Dent Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000652:urine*; D005820:Genetic Testing; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009395:Nephritis, Interstitial / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000652:urine*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011507:Proteinuria / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D065667:Renal Elimination / Q000235:genetics*; D012709:Serum Albumin / Q000032:analysis
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D012709:Serum Albumin; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human
keywords: CLCN5; Dent disease; Low-molecular weight proteinuria; Nephrotic syndrome; OCRL; Proteinuria; Systematic review