Observations of a Large Dent Disease Cohort

Kidney Int. 2016 Aug;90(2):430-439. doi: 10.1016/j.kint.2016.04.022. Epub 2016 Jun 22.

Abstract

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.

Keywords: Dent disease; hypercalciuria-hypokalemia; proteinuria; renal failure.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Child, Preschool
  • Chloride Channels / genetics*
  • Genetic Association Studies
  • Genetic Diseases, X-Linked / blood
  • Genetic Diseases, X-Linked / complications
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / urine
  • Genotype
  • Glomerular Filtration Rate
  • Humans
  • Hypercalciuria / genetics
  • Hypercalciuria / urine
  • Hypophosphatemia / blood
  • Hypophosphatemia / genetics
  • Kidney Failure, Chronic / epidemiology*
  • Kidney Failure, Chronic / etiology
  • Male
  • Middle Aged
  • Mutation
  • Nephrolithiasis / blood
  • Nephrolithiasis / complications
  • Nephrolithiasis / genetics*
  • Nephrolithiasis / urine
  • Phenotype
  • Phosphoric Monoester Hydrolases / genetics*
  • Proteinuria / genetics
  • Proteinuria / urine
  • Retrospective Studies
  • Young Adult

Substances

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

Supplementary concepts

  • Dent Disease 2
  • Dent disease 1