Dent disease in Poland: what we have learned so far?

Int Urol Nephrol. 2017 Nov;49(11):2005-2017. doi: 10.1007/s11255-017-1676-x. Epub 2017 Aug 16.

Abstract

Purpose: Dent disease (DD) is a rare tubulopathy characterized by proximal tubular dysfunction leading to chronic kidney disease (CKD). The aim of the study was to characterize patients with DD in Poland.

Methods: A retrospective analysis of a national cohort with genetically confirmed diagnosis.

Results: Of 24 males, all patients except one carried mutations in the CLCN5 gene; in one patient a mutation in the OCRL gene was disclosed. Molecular diagnosis was delayed 1 year on average (range 0-21 years). The most common features were tubular proteinuria (100%), hypercalciuria (87%), and nephrocalcinosis (56%). CKD (≤stage II) and growth deficiency were found in 45 and 22% of patients, respectively. Over time, a progression of CKD and persistence of growth impairment was noted. Subnephrotic and nephrotic proteinuria (20%) was found in most patients, but tubular proteinuria was assessed in only 67% of patients. In one family steroid-resistant nephrotic syndrome prompted a genetic testing, and reverse phenotyping. Five children (20%) underwent kidney biopsy, and two of them were treated with immunosuppressants. Hydrochlorothiazide and angiotensin-converting enzyme inhibitors were prescribed for a significant proportion of patients (42 and 37.5%, respectively), while supplemental therapy with phosphate, potassium, vitamin D (12.5% each), and alkali (4.2%) was insufficient, when compared to the percentages of patients requiring repletion.

Conclusions: We found CLCN5 mutations in the vast majority of Polish patients with DD. Proteinuria was the most constant finding; however, tubular proteins were not assessed commonly, likely leading to delayed molecular diagnosis and misdiagnosis in some patients. More consideration should be given to optimize the therapy.

Keywords: CLCN5; Dent disease; Low molecular weight proteinuria; Nephrotic syndrome; Proteinuria.

MeSH terms

  • Adolescent
  • Adult
  • Calcifediol / blood
  • Child
  • Child, Preschool
  • Chloride Channels / genetics*
  • Delayed Diagnosis
  • Dent Disease / complications*
  • Dent Disease / diagnosis
  • Dent Disease / drug therapy
  • Dent Disease / genetics*
  • Disease Progression
  • Glomerular Filtration Rate
  • Humans
  • Hypercalciuria / etiology
  • Infant
  • Male
  • Mutation
  • Nephrocalcinosis / etiology
  • Phosphoric Monoester Hydrolases / genetics
  • Poland
  • Proteinuria / etiology*
  • Proteinuria / urine
  • Renal Insufficiency, Chronic / etiology*
  • Renal Insufficiency, Chronic / physiopathology
  • Retrospective Studies
  • Vitamin D Deficiency / etiology
  • Young Adult

Substances

  • CLC-5 chloride channel
  • Chloride Channels
  • Phosphoric Monoester Hydrolases
  • OCRL protein, human
  • Calcifediol