Determination of urinary lithogenic parameters in murine models orthologous to autosomal dominant polycystic kidney disease

Renato Ribeiro Nogueira Ferraz, Jonathan Mackowiak Fonseca, Gregory George Germino, Luiz Fernando Onuchic, Ita Pfeferman Heilberg

Research output: Contribution to journalArticle

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), a genetic disease caused by mutations in PKD1 or PKD2 genes, is associated with a high prevalence of nephrolithiasis. The underlying mechanisms may encompass structural abnormalities resulting from cyst growth, urinary metabolic abnormalities or both. An increased frequency of hypocitraturia has been described in ADPKD even in the absence of nephrolithiasis, suggesting that metabolic alterations may be associated with ADPKD per se. We aimed to investigate whether non-cystic Pkd1-haploinsufficient (Pkd1+/−) and/or nestin-Cre Pkd1-targeted cystic (Pkd1cond/cond:Nestincre) mouse models develop urinary metabolic abnormalities potentially related to nephrolithiasis in ADPKD. 24-h urine samples were collected during three non-consecutive days from 10–12 and 18–20 week-old animals. At 10–12 weeks of age, urinary oxalate, calcium, magnesium, citrate and uric acid did not differ between test and their respective control groups. At 18– 20 weeks, Pkd1+/− showed slightly but significantly higher urinary uric acid vs. controls while cystic animals did not. The absence of hypocitraturia, hyperoxaluria and hyperuricosuria in the cystic model at both ages and the finding of hyperuricosuria in the 18–20 week-old animals suggest that anatomic cystic distortions per se do not generate the metabolic disturbances described in human ADPKD-related nephrolithiasis, while Pkd1 haploinsufficiency may contribute to this phenotype in this animal model.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
JournalUrolithiasis
Volume42
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • ADPKD
  • Nephrolithiasis
  • Pkd1 haploinsufficiency
  • Renal cysts
  • Uric acid
  • Urinary analytes

ASJC Scopus subject areas

  • Urology
  • Medicine(all)

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