Association between vitamin D receptor gene polymorphisms and fasting idiopathic hypercalciuria in recurrent stone-forming patients

Rendina, Domenico; Mossetti, Giuseppe; Viceconti, Roberto; Sorrentino, M.; Castaldo, Rosaria; Manno, G.; Guadagno, Vincenzo; Strazzullo, Pasquale; Nunziata, V.

doi:10.1016/j.urology.2004.05.013

Cited by 57 publications

(47 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Overall, it appears that renal mineral conservation must be abnormal in IH, and bone mineral loss somehow facilitated so that despite the absence of diet calcium to balance renal losses, serum calcium can remain normal and serum PTH suppressed. This is further suggested by studies of calcium kinetics using 47 Ca which demonstrate a larger exchangeable calcium pool and higher calcium turnover, together with increased rates of both bone formation and resorption, in 9 subjects with IH compared to 3 normal subjects [11].…”

Section: Intestinal Absorption Of Calcium In Ihmentioning

confidence: 86%

“…The importance of 1,25(OH) 2 D 3 was further demonstrated by a study of 19 hypercalciuric subjects treated with the P450 inhibitor ketoconazole, which suppresses 1,25(OH) 2 D 3 levels by 30-40% [24]. Twelve subjects had significant decreases in intestinal 47 Ca absorption (76 ± 8 vs 62 ± 8%, p < 0.03) and urine calcium excretion (7.6 ± 1.4 vs 5.7 ± 1.1 mmol/day, p < 0.03) during the ketoconazole treatment, suggesting that these abnormalities were at least in part secondary to 1,25(OH) 2 D 3; however, 9 subjects had minimal or no change in gut and renal calcium handling, despite similar drops in 1,25(OH) 2 D 3 levels, suggesting that in their cases, these abnormalities were independent of 1,25(OH) 2 D 3 . In addition, of the 12 subjects who responded to ketoconazole, nine had 1,25(OH) 2 D 3 levels that were not elevated, leading to the possibility that increased sensitivity to 1,25(OH) 2 D 3 rather than frankly elevated vitamin D levels caused the alterations.…”

Section: Altered 125(oh) 2 D 3 Activity In Ihmentioning

confidence: 92%

“…Vitamin D receptor-Polymorphisms of the Vitamin D receptor gene that segregate with hypercalciuria have been detected in some [47], but not all, studies [48]. A study of a cohort of 54 French Canadian sibships found evidence for linkage to nephrolithiasis of a gene in the region of the VDR [49].…”

Section: Genetic Associations Of Ih and Hypercalciuriamentioning

confidence: 99%

See 2 more Smart Citations

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Worcester

Coe

2008

Seminars in Nephrology

141

122

View full text Add to dashboard Cite

Idiopathic hypercalciuria (IH) is the commonest metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is above 250 mg/day in women and 300 mg/day in men. Subjects with IH have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, negative calcium balance is commonly seen in balance studies, especially on a low calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered PTH levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for the manifestations of IH in at least some patients. Definition of HypercalciuriaCalcium, the most abundant cation in human beings, is an important participant in many physiologic processes, including hormonal secretion, cardiac contraction, blood clotting, and neurotransmission. In addition, growth and repair of our skeleton demands an adequate supply of calcium, and careful maintenance of extracellular calcium concentrations. For this reason, prevailing levels of intracellular and extracellular calcium are tightly regulated, by a complex system of control mechanisms. These mechanisms control calcium absorption by gut and renal tubular epithelia, as well as fluxes of calcium on and off bone, during varying dietary calcium intakes. In healthy, non-pregnant adults, whose skeleton is no longer growing, net intestinal calcium absorption is matched by renal excretion, and provides sufficient calcium for skeletal maintenance; however, under pathologic conditions, some urine calcium may derive from bone loss.Abnormalities of calcium homeostasis could result in a number of undesired consequences, including abnormally high or low serum calcium levels, or inadequate maintenance of bone mineral. Hypercalciuria might be defined as any level of urine calcium that exceeds net intestinal absorption, leading to net loss of calcium. However, in practice net intestinal absorption is seldom measured, and under the assumption that urine calcium is primarily derived from intestinal absorption, the working definition of hypercalciuria is urine calcium excretion that exceeds that found in the majority of healthy adults eating their usual diets. In practice, this is usually defined as a daily calcium excretion over 250 mg/day in women or 300Mailing address: Elaine Worcester, M.D., Nephrology Section, Suite 511 / MC 5100, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, Phone: 773-702-7459, Fax: 773-702-5818. Publisher's Disclaimer: This is a PDF file ...

show abstract

Section: Intestinal Absorption Of Calcium In Ihmentioning

confidence: 86%

Section: Altered 125(oh) 2 D 3 Activity In Ihmentioning

confidence: 92%

See 1 more Smart Citation

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Worcester

Coe

2008

Seminars in Nephrology

141

122

View full text Add to dashboard Cite

show abstract

“…It is a multifactorial disorder resulting from the interaction between environmental influences and hormonal and genetic factors. Rendina et al in their study reported; genetic factors to be important determinants for kidney stone (1). A recent report demonstrated MGP gene polymorphism to be associated with kidney stones formation (2).…”

Section: Introductionmentioning

confidence: 92%

Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis

Mittal

Mishra

Srivastava

et al. 2010

Indian J Clin Biochem

View full text Add to dashboard Cite

show abstract

“…Several studies about common allelic variations in VDR in disorders of calcium metabolism, using Bsm I, Apa I, Taq I and Fok I restriction enzymes have been performed, but the results were controversial [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. While some studies disclosed an association between VDR polymorphism and bone mineral density (BMD) [12,13,14,15], others did not [16,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Receptor and Calcium-Sensing Receptor Gene Polymorphisms in Hypercalciuric Stone-Forming Patients

2009

View full text Add to dashboard Cite

Background/Aim: Some studies have identified an association of kidney stone formation with vitamin D receptor (VDR) or calcium-sensing receptor (CaSR) polymorphisms. We aimed to evaluate the association between these polymorphisms with urinary calcium excretion (uCa) in calcium- stone-forming patients. Methods: VDR polymorphism, detected by BsmI digestion, and 3 CaSR polymorphisms (G/T at codon 986, G/A at codon 990 and C/G at codon 1011), detected by direct sequencing, were evaluated in 100 hypercalciuric (HCa) and 101 normocalciuric (NCa) calcium-stone-forming patients. Results: The total allelic frequency of VDR polymorphism was: 16% BB, 49% Bb and 35% bb. The prevalence of bb genotype was significantly higher in the HCa when compared to the NCa group (43 vs. 27%). With respect to CaSR polymorphisms, 986S, 990G and 1011E variant alleles were detected, respectively, in 5, 4 and 3% of the whole sample and 5 CaSR haplotypes were identified: 94% ARQ (wild-type), 3% SRQ, 1.5% AGQ, 1.0% ARE and 0.5% AGE. No statistical differences have been observed between NCa and HCa with respect to these CaSR haplotypes. Conclusions: The present study suggested that bb homozygous for VDR polymorphism was overrepresented in hypercalciuric stone formers. Urinary calcium excretion was not associated with CaSR polymorphism in the present sample.

show abstract

Association between vitamin D receptor gene polymorphisms and fasting idiopathic hypercalciuria in recurrent stone-forming patients

Cited by 57 publications

References 25 publications

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis

Vitamin D Receptor and Calcium-Sensing Receptor Gene Polymorphisms in Hypercalciuric Stone-Forming Patients

Contact Info

Product

Resources

About