gastrins and Kidney-Calculi

The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH (30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration (1 g calcium gluconate) and, on a separate occasion, after peptone loading test (protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration (P < 0.01) and peptone loading (P < 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule (where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.

Topics: Administration, Oral; Aged; Calcitonin; Calcium Gluconate; Calcium Metabolism Disorders; Female; Gastrin-Secreting Cells; Gastrins; Humans; Kidney Calculi; Middle Aged; Parathyroid Hormone; Peptones; Receptors, Calcium-Sensing; Thyroid Gland

We evaluated serum gastrin, acid-base status, variables of mineral metabolism in fasting blood, as well as pH, relative supersaturation of stone forming constituents, and crystalluria in the associated fasting urine, of control subjects (n = 12), and in age- and weight-matched male normocalciuric (n = 12) and hypercalciuric (n = 12) patients with idiopathic recurrent calcium urolithiasis (RCU). In RCU, mineral metabolism and acid-base data are unchanged, whereas mean serum gastrin is only insignificantly higher as compared to controls. Subclassification of all participants into categories with either high-normal or low-normal gastrin reveals that in RCU with low-normal gastrin there is a higher-than-normal urinary pH and significantly elevated supersaturation of urine with hydroxyapatite. Crystalluria and stone analysis support the assumption that the physico-chemical environment accompanied by low gastrin levels predisposes to urinary precipitation of calcium phosphate with subsequent formation of a stone nidus. pH in fasting urine and integrated fasting serum gastrin correlate significantly, suggesting that low fasting serum gastrin in RCU patients may be considered a risk factor for calcium phosphate stone formation.

Topics: Acid-Base Equilibrium; Adolescent; Adult; Calcium Oxalate; Calcium Phosphates; Chemical Precipitation; Crystallization; Durapatite; Fasting; Gastrins; Humans; Hydroxyapatites; Kidney Calculi; Male; Risk

Topics: Adolescent; Adult; Aged; Animals; Blood Group Antigens; Child; Coronary Disease; Disease Models, Animal; Disease Susceptibility; Diseases in Twins; Ethnicity; Female; Gastric Emptying; Gastrins; Genetic Markers; Humans; Kidney Calculi; Lung Diseases; Male; Mice; Mice, Inbred NZB; Middle Aged; Models, Genetic; Multiple Endocrine Neoplasia; Pepsinogens; Peptic Ulcer; Urticaria Pigmentosa; Zollinger-Ellison Syndrome