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, Uc_a X V > 7.5 mmol/day) and normocalciurics (NCSF, n = 31, Uc_a 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

Risk factors for low urinary citrate in calcium nephrolithiasis: low vegetable fibre intake and low urine volume to be added to the list

“…Given a population of patients with idiopathic calcium nephrolithiasis studied on their free-choice diet [12], the present study aimed to address the following issues: (1) what is the prevalence of 'idiopathic' hypocitraturia? ; (2) among patients who turn out to have low urinary citrate, how often does the disorder have a metabolic origin, and how often a nutritional one?…”

“…Since the risk of calcium stone formation has been demonstrated to increase exponentially with decreasing 24-h urine volumes below 1200 ml [16], 'low volume' was defined as < 1200 ml/day. All RCSF collected two 24-h urine specimens according to our standard protocol [12]; 24-h urine values are expressed as the means of both collections.…”

“…Citrate (Cit) was measured using the citrate lyase method [17]. Oxalate (Ox) was measured after enzymatic oxidation of oxalate by oxalate oxidase [18] as previously described [12]. Urinary sulphate (Sulph) was measured by an HPLC system utilizing an anion column to separate sulphate from other urinary anions, where sulphate is detected by conductivity change as eluent flows through a conductivity cell [19].…”

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

“…exclusion according to the previously published protocol [10] of established causes of calcium stone formation such as primary hyperparathyroidism, medullary sponge kidney, overt distal renal tubular acidosis, sarcoidosis, excessive vitamin D intake, hypercalciuria due to hypercalcaemia (malignancy or immobilisation), and primary or enteric hyperoxaluria; (3) plasma creatinine concentration < 115 umol/1); and (4) absence of urinary tract infection, any renal disease other than nephrolithiasis, or bone disease.…”

“…All RCSF underwent our standard protocol for metabolic evaluation not prior to 2 months after urological intervention and while adhering to their individual free-choice diet, as previously described [10]. Metabolic work-up consisted of sampling fasting venous blood and 2-h urine after 12 h without eating and 8 h without drinking (only tap water allowed after last meal).…”