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2014 ; 42
(4
): 301-7
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Determination of urinary lithogenic parameters in murine models orthologous to
autosomal dominant polycystic kidney disease
#MMPMID24817661
Ferraz RR
; Fonseca JM
; Germino GG
; Onuchic LF
; Heilberg IP
Urolithiasis
2014[Aug]; 42
(4
): 301-7
PMID24817661
show ga
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.