Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have established a colony of genetic hypercalciuric (IH) rats as a model of idiopathic hypercalciuria in humans. To test the hypothesis that hypercalciuria can cause crystallization in kidneys through increased supersaturation, in the absence of confounding effects of diet and whatever complex inhibitor disorders underlay stone disease, we fed males and females of the 21st generation of IH rats 13 g per day of a low calcium (LCD, 0.02% Ca), followed by a normal calcium (NCD, 0.6% Ca) and then a high calcium (HCD, 1.2% Ca) diet, each for seven days. During the last 24 hours of each period complete urine collections were obtained and analyzed for all substances known to affect urinary calcium oxalate (CaOx) and brushite (CaHPO4) supersaturation. Relative supersaturation with respect to the solid phases of CaOx and CaHPO4 were then calculated. Compared to same gender controls (Ctl) urine calcium excretion was higher in the female IH rats on all diets and in the male IH rats on NCD and HCD. The female and male IH rats on NCD and HCD were supersaturated with respect to CaOx; however, the male and female Ctl were supersaturated with respect CaOx only on HCD. The female IH rats on NCD and HCD and the male IH rats on NCD were supersaturated with respect to CaHPO4; however, neither the male nor female Ctl rats were supersaturated with respect to CaHPO4 on any diet. On NCD and HCD urine supersaturation with respect to CaHPO4 by females exceeded that of males.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased urinary saturation and kidney calcium content in genetic hypercalciuric rats. 812 22

A fundamental mechanism for hypercalciuria in genetic hypercalciuric rats appears due to a primary increase in intestinal calcium absorption. However previous studies could not exclude additional mechanisms to account for the hypercalciuria. To determine if enhanced bone mineral dissolution either as a primary abnormality or secondary to a defect in renal tubule calcium reabsorption is responsible for a component of the augmented calcium excretion we studied rats continually inbred for hypercalciuria. Nineteenth generation adult female idiopathic hypercalciuric (IH) and non-inbred control (Ctl) rats were fed 13 g/day of a normal calcium diet (0.6% calcium, NCD) for 10 days. Urine calcium excretion over the last seven days was greater in IH (34 +/- 2 mg/7 day) than in Ctl (2.9 +/- 0.3, P < 0.01) rats. Some rats in each group were continued on the same diet while others were fed a low calcium diet (0.02% calcium, LCD) for an additional 10 days; balance measurements were made over the final seven days. With LCD, urine calcium excretion was approximately 8-fold higher in IH compared to Ctl (13 +/- 2 mg/7 day vs. 1.6 +/- 0.1, IH vs. Ctl, respectively, P < 0.01). In IH rats percent calcium absorption was greater (59 +/- 3% vs. 45 +/- 3, IH vs. Ctl, P < 0.01), however calcium retention was negative (-1.9 +/- 2.0 mg/7 day vs. 6.5 +/- 0.5, IH vs. Ctl, P < 0.01) compared to Ctl rats. The fall in urine calcium excretion when IH rats are fed LCD indicates that enhanced intestinal calcium absorption is a primary mechanism of the hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of genetic hypercalciuric rats to a low calcium diet. 843 58

The pathogenesis of idiopathic hypercalciuria (IH) has not been elucidated yet, but a correlation between IH and altered bone metabolism has been proposed. Since nitric oxide (NO) regulates osteoclasts' bone resorption, a possible role for NO can be suggested. In this study we evaluated iNOS gene expression by reverse transcription of mRNA from monocytes, followed by polymerase chain reaction in patients with IH subdivided into fasting (FH) and absorptive (AH) hypercalciuria. Since superoxide (O2-), which metabolizes NO, is overproduced by osteoclasts during bone resorption, peroxynitrite plasma level was evaluated as index of O2-. Vertebral BMD in IH as a whole group was lower vs controls (C) (Z score=-1.78+/-0.2 vs 0.51+/-0.25, p<0.001), but only FH patients showed a reduced bone density (2.13+/-0.18 vs 0.51+/-0.25, p<0.0001). PTH and calcitriol were not different. FH showed an increase in b-ALP vs AH and C (41.1+/-2.6 vs 30.1+/-3.9 vs 26.6+/-3.6 U/l p<0.02), and higher uHP, either on NCD (17.7+/-1.6 vs 11.4+/-1.3 mg/g uCr, p<0.04) or after LCD (26.7+/-2.5 vs 16.7+/-1.9, p<0.01). Cells from FH patients, but not from both AH patients and C, expressed iNOS. Peroxynitrite plasma level was elevated in FH (0.30+/-0.07) pmol/l while not detectable in AH and C. This study confirms an altered bone metabolism only in FH which shows an abnormal NO system. The increased iNOS gene expression in FH, in fact, points toward an altered NO system's activity downstream the generation of NO. A possible interaction of NO with O2-, which breaks down NO, and the role of this interaction in the pathophysiology of IH is discussed.
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PMID:Idiopathic hypercalciuria: O2(-)NO relationship and altered bone metabolism. 1080 Jul 59