title: Determination of urinary lithogenic parameters in murine models orthologous to autosomal dominant polycystic kidney disease.
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 (Pkd1(cond/cond):Nestin(cre)) 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.
authors.affiliation: Division of Nephrology, Universidade Federal de Sao Paulo, Rua Botucatu, 740-Vila Clementino, São Paulo, SP, 04023-900, Brazil.
authors.forename: Renato Ribeiro Nogueira
authors.initials: RR
authors.lastname: Ferraz
authors.forename: Jonathan Mackowiak
authors.initials: JM
authors.lastname: Fonseca
authors.forename: Gregory George
authors.initials: GG
authors.lastname: Germino
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Onuchic
authors.forename: Ita Pfeferman
authors.initials: IP
authors.lastname: Heilberg
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D057895:Haploinsufficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D053040:Nephrolithiasis / Q000209:etiology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications*; D050396:TRPP Cation Channels / Q000235:genetics
chemical_list: D050396:TRPP Cation Channels