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

Urolithiasis - Tập 42 - Trang 301-307 - 2014
Renato Ribeiro Nogueira Ferraz1, Jonathan Mackowiak Fonseca2,3, Gregory George Germino4, Luiz Fernando Onuchic2,3, Ita Pfeferman Heilberg1
1Division of Nephrology, Universidade Federal de Sao Paulo, São Paulo, Brazil
2Division of Nephrology, University of Sao Paulo School of Medicine, São Paulo, Brazil
3Center for Cellular and Molecular Studies and Therapy (NETCEM), São Paulo, Brazil
4National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, USA

Tóm tắt

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: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.

Tài liệu tham khảo

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Urolithiasis

Tập 42

301-307

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