Several studies have indicated that up to 60% of idiopathic calcium stone formers present hypercalciuria. Many authors have described reduced bone mineral density (BMD) in stoneformers with hypercalciuria, but osteopenia has also been found in normocalciuric patients. Moreover, Jaeger’s group found that bone mass was reduced in all patients with calcium stone disease, independently of hypercalciuria. Many factors may contribute to the pathogenesis of osteopenia in stone formers. A predominant role has been given to the low-calcium diet that is still prescribed in nephrolithiasis. Also slight metabolic acidosis, which is frequently present in stone formers eating a diet rich in animal protein, can contribute to bone loss. Finally, some authors described a pathogenetic role for cytokines, prostaglandins and vitamin D receptor gene polymorphisms.
Citrate is a weak acid that is formed in the tricarboxylic acid cycle or that may be introduced with diet. In the present paper all the mechanisms involved in intestinal absorption, renal handling and modulation of citrate will be reviewed. The evaluation of plasma citric acid is scarcely used in the diagnosis of human diseases. On the contrary urinary citrate excretion is a common tool in the differential diagnosis of kidney stones, renal tubular acidosis and it plays also a role in bone diseases. Therefore the importance of hypocitraturia will be reviewed with regard to bone mass, urine crystallization and urolithiasis. Finally particular attention will be paid to the incidence of hypocitraturia and to the therapy with citrate salts, both in kidney stone disease and in osteopenia.
Several authors have described an association between idiopathic calcium (Ca) stone disease and bone mass reduction. Hypocitraturia is a frequent feature of urolithiasis, and alkaline citrate has been recommended as one of the choice treatments in this disease. Some evidence exists as to the positive effect of potassium (K) citrate therapy on bone mass. The aim of this work was the longitudinal evaluation of bone mineral density (BMD) changes in a group of Ca oxalate stone formers treated with K citrate for two years. Enrolled patients were 120; 109 subjects completed the study (51 males and 58 females). A metabolic study and distal radius BMD measurements were conducted both at baseline (BAS) and at the end of the study (END). BMD (0.451 +/- 0.081 vs 0.490 +/- 0.080 g/cm2), T-score (-1.43 +/- 1.02 vs -0.90 +/- 1.04), net gastrointestinal alkali absorption (40.37 +/- 50.57 vs 61.26 +/- 42.26 mEq/day), urinary citrate (2.53 +/- 1.15 vs 3.10 +/- 1.44 mmol/day) and K (58.93 +/- 22.28 vs 65.45 +/- 23.97 mmol/day) excretion significantly increased from BAS to END. Urinary Ca excretion remained unchanged from BAS to END (5.16 +/- 2.74 vs 5.57 +/- 2.85 mmol/ day). Our results indicate that long-term treatment with K citrate increases forearm BMD in idiopathic Ca stone formers. It seems probable that the alkali load provided by this drug reduces bone resorption by a buffering of the endogenous acid production. K citrate appears to be a further therapeutic opportunity for the management of osteoporosis in Ca stone formers.
1 Pharmacological and experimental studies have shown that ibopamine (SB 7505, di-isobutyric ester of N-methyldopamine) is capable of increasing renal blood flow, diuresis, urinary sodium, potassium and creatinine excretion. 2 SB 7505 was given to twelve volunteer patients, six of whom had normal renal function and six with various degrees of chronic renal impairment. 3 In both groups the drug yielded a prompt increase in urinary excretion of water, sodium and potassium, while creatinine clearance was also seen to increase. 4 Heart rate and arterial pressure were unaffected by SB 7505 in all patients. 5 Results seen encouraging and call for further study on the proper use of the drug in clinical nephrology.
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