Laura Soldati

Influence of Calcium-Sensing Receptor Gene on Urinary Calcium Excretion in Stone-Forming Patients

Calcium-sensing receptor (CaSR) is a plasma membrane protein that regulates tubular reabsorption of Ca. To establish its role in idiopathic hypercalciuria, the association of urinary Ca excretion with the polymorphisms of CASR gene has been studied in healthy subjects and in hypercalciuric and normocalciuric Ca stone formers. CASR exon 7 single nucleotide polymorphisms (SNP), G/T at codon 986, G/A at codon 990, and C/G at codon 1011, were evaluated by PCR amplification and direct sequencing in 97 normocalciuric stone formers, 134 hypercalciuric stone formers, and 101 normocalciuric healthy controls. Four haplotypes were defined on the basis of CASR gene SNP: haplotype 1 was characterized by the most frequent sequence; haplotypes 2, 3, or 4 by the presence of a single polymorphic variant at codon 986, 990, or 1011, respectively. The relative risk of hypercalciuria was calculated with multinomial logistic regression and was significantly increased only in individuals carrying haplotype 3 (Odds ratio, 13.0 [95% confidence interval, 1.7 to 99.4]). Accordingly, Ca excretion was higher in subjects bearing haplotype 3, whereas those bearing haplotype 2 showed a slight increase of plasma Ca concentration. Multiple regression analysis showed that haplotype 3 explained 4.1% of the total variance of Ca excretion and 12.6% of the variance explained by the variables considered in the study. In conclusion, CASR gene could be a component of the complex genetic background regulating Ca excretion. Arg990Gly polymorphism could facilitate activation of CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria.

Calcium-Sensing Receptor Polymorphisms and Human Disease

Abstract The calcium-sensing receptor (CaSR) is a plasma membrane protein that senses calcium in the extracellular fluid. Cloned from bovine parathyroid cells in 1993, CaSR is mainly expressed in the parathyroid glands and renal distal tubules, and it enables these tissues to regulate parathyroid hormone secretion and calcium excretion, respectively, in response to changes in serum calcium. CaSR is also crucial for normal growth plate development and bone remodeling. Therefore CaSR is a key regulator of calcium homeostasis. Moreover, CaSR polymorphisms have been associated with serum calcium concentration and urine calcium excretion in humans. Polymorphisms decreasing CaSR expression in renal tubular cells may increase risk for developing calcium oxalate kidney stones. CaSR gene polymorphisms may modify the phenotype of healthy subjects and patients with primary and secondary hyperparathyroidism, and it may allow identification of individuals prone to developing kidney stones.

Nephrolithiasis and nutrition in obesity

Background Obesity is a risk factor for nephrolithiasis (NL). According to an American study of a large cohort with a BMI >30, males increased the risk of NL of 30% and females of 200%. Moreover, diet plays an important role as NL risk factor, mainly in those western countries characterized by a large meet consume. This epidemiology study investigated the NL frequency in an obese Italian population, also considering the relation with metabolic syndrome and interaction with diet.