TY - JOUR
T1 - Determination of urinary lithogenic parameters in murine models orthologous to autosomal dominant polycystic kidney disease
AU - Ferraz, Renato Ribeiro Nogueira
AU - Fonseca, Jonathan Mackowiak
AU - Germino, Gregory George
AU - Onuchic, Luiz Fernando
AU - Heilberg, Ita Pfeferman
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - ADPKD
KW - Nephrolithiasis
KW - Pkd1 haploinsufficiency
KW - Renal cysts
KW - Uric acid
KW - Urinary analytes
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U2 - 10.1007/s00240-014-0664-1
DO - 10.1007/s00240-014-0664-1
M3 - Article
C2 - 24817661
AN - SCOPUS:84927520134
SN - 2194-7228
VL - 42
SP - 301
EP - 307
JO - Urolithiasis
JF - Urolithiasis
IS - 4
ER -