Relative hypoparathyroidism and calcitriol up-regulation in hypercalciuric calcium renal stone formers--impact of nutrition

Abstract

The issue of secondary hyperparathyroidism in idiopathic hypercalciuria (IH) was addressed in 61 male idiopathic calcium stone formers (SF) who underwent metabolic evaluation on a free-choice diet as well as bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry. They were divided into hypercalciurics (HCSF, n = 30, UCa X V > 7.5 mmol/day) and normocalciurics (NCSF, n = 31, UCa X V < 7.5 mmol/day). At identical blood Ca2+ levels, parathyroid hormone (PTH) was lower in HCSF (25.3 +/- 1.8 pg/ml) than in NCSF (31.4 +/- 1.8 pg/ml, p = 0.017). Since neither fasting urinary hydroxyproline nor pyridinoline/deoxypirdinoline excretions nor BMD values were different between HCSF and NCSF, chronic bone dissolution as the cause of relative hypoparathyroidism in HCSF could be excluded. Despite lower PTH in the face of similar phosphate, Ca2+ and IGF-1 blood levels, however, serum 1,25-dihydroxyvitamin D3 (calcitriol) concentrations were slightly (though not significantly) higher in HCSF than in NCSF (52.8 +/- 3.2 vs. 47.3 +/- 2.9 pg/ml, p = NS), and calcitriol/PTH ratio was elevated in HCSF (2.52 +/- 0.29) vs. NCSF (1.66 +/- 0.15, p = 0.001). Creatinine clearance, significantly higher in HCSF than in NCSF (113 +/- 4 vs. 92 +/- 3 ml/min/1.73 m2, p = 0.0001), was positively correlated with excretion rates of urinary markers of both protein and NaCl intake. Since serum calcitriol levels were positively correlated with creatinine clearance (r = 0.350, slope = 0.288, p = 0.006), up-regulation of calcitriol synthesis with subsequent relative hypoparathyroidism in HCSF is-at least partly-explained by exaggerated protein and sodium consumption.