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

Autor(es)

Nogueira Ferraz, Renato Ribeiro ^[1] ; Fonseca, Jonathan Mackowiak ^{[2, 3]} ; Germino, Gregory George ^[4] ; Onuchic, Luiz Fernando ^{[2, 3]} ; Heilberg, Ita Pfeferman ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Nephrol, BR-04023900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Div Nephrol, Sao Paulo - Brazil

^[3] Ctr Cellular & Mol Studies & Therapy NETCEM, Sao Paulo - Brazil

^[4] NIDDK, Bethesda, MD - USA

• Tipo de documento: Artigo Científico
• Fonte: UROLITHIASIS; v. 42, n. 4, p. 301-307, AUG 2014.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 10/17424-0 - Bases da Hipertensão Arterial e de Disfunções Renais Associadas à Doença Renal Policística Autossômica Dominante: Estudo em Modelos Distintos de Deficiência do Gene Pkd1 em Camundongos
• Beneficiário: Luiz Fernando Onuchic
• Modalidade de apoio: Auxílio à Pesquisa - Regular