Hypercalciuria is one of the risk factors for Ca-oxalate/apatite kidney stone. Serum levels of 1,25-(OH)2-vitamin D are often elevated among hypercalciuric stone-formers, independent of parathyroid hormones. 1,25-(OH)2-D is a critical determinant of both daily and fasting urinary Ca excretion because of the effects of this hormone to augment intestinal Ca absorption and to stimulate net bone resorption. All of the factors regulating renal 1,25-(OH)2-D synthesis and thus serum 1,25-(OH)2-D concentrations have not been defined but previous studies have suggested that PO4, in addition to Ca and PTH, as well as caloric intake or some other feature of diet composition, are important. We propose to continue studies in Ca-stone formers and in healthy adults to 1) determine whether Ca-stone formers exhibit increased rates of net intestinal Ca absorption independent of prevailing serum 1,25-(OH)2-D concentrations, 2) the roles of dietary intake of calories, animal as opposed to vegetable-cereal protein and sugar as opposed to complex carbohydrate as determinants of serum 1,25-(OH)2-D levels and whether such factors are mediated by PO4, insulin, growth hormone or somatomedin-C 3) whether Ca-stone formers with absolutely elevated serum 1,25-(OH)2-D levels exhibit elevated serum insulin, GH and somatomedin-C levels when fasting, on an integrated basis over 24-hours and after acute nutrient loading. In addition, we will continue studies of the in vitro regulation of 1,25-(OH)2-D3 production by primary cultures of mouse kidney cortical cells in serum-free medium. This system requires further characterization, especially with respect to the production of 19-nor-10-keto-25-OH-D3, a cross-reacting 25-OH-D3-metabolite. The effects on 1,25-(OH)2-D3 production of gastronintestinal hormones, endogenous opioids and the interaction of these hormones with PTH, as well as the effects of the original sex of the cells and of added sex steroids will be evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK015089-21
Application #
3483087
Study Section
General Medicine B Study Section (GMB)
Project Start
1978-02-01
Project End
1991-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
21
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Lemann Jr, Jacob; Bushinsky, David A; Hamm, L Lee (2003) Bone buffering of acid and base in humans. Am J Physiol Renal Physiol 285:F811-32
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Lemann Jr, J (1999) Relationship between urinary calcium and net acid excretion as determined by dietary protein and potassium: a review. Nephron 81 Suppl 1:18-25
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Lemann Jr, J; Pleuss, J A; Hornick, L et al. (1995) Dietary NaCl-restriction prevents the calciuria of KCl-deprivation and blunts the calciuria of KHCO3-deprivation in healthy adults. Kidney Int 47:899-906
Balaghi, M; Horne, D W; Wagner, C (1993) Hepatic one-carbon metabolism in early folate deficiency in rats. Biochem J 291 ( Pt 1):145-9
Balaghi, M; Wagner, C (1993) DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun 193:1184-90
Lemann Jr, J; Pleuss, J A; Gray, R W (1993) Potassium causes calcium retention in healthy adults. J Nutr 123:1623-6
Kennedy, D G; Blanchflower, W J; Scott, J M et al. (1992) Cobalt-vitamin B-12 deficiency decreases methionine synthase activity and phospholipid methylation in sheep. J Nutr 122:1384-90

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