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      The Negative Ca 2+ Balance Is Involved in the Stimulation of PTH Secretion

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          The low calcium (Ca<sup>2+</sup>) dialysate have been developed to diminish the risk of hypercalcemia with the administration of active vitamin D and Ca<sup>2+</sup> carbonate as phosphate binder. Today, increasing numbers of hemodialysis (HD) patients have been on the low Ca<sup>2+</sup> dialysate (Ca<sup>2+</sup> = 2.5 mEq/l). However, the clinical consequences of a negative calcium net-balance which may be induced by the use of low Ca dialysate are not well evaluated. In the present study, we explored the effects of low Ca<sup>2+</sup> dialysate on the calcium balance and the PTH secretion. Eighty one chronic HD patients (male/female: 47/34; mean age: 60.2 ± 1.5 years; mean HD periods: 11.1 ± 0.8 years) who had been dialyzed with 3.0 mEq/l Ca<sup>2+</sup> dialysate were studied. All patients were transferred to the low Ca dialysate, which actually brought about a negative net-balance in Ca (mean: –94.5 mg) and an increase in serum intact PTH levels (mean: +23.7%: p = 0.03) during a single HD session. However, no changes in serum ionized Ca<sup>2+</sup> were found in spite of negative Ca<sup>2+</sup> balance. One month after change to the low Ca<sup>2+</sup> dialysate (total 12 sessions in each case), serum intact PTH levels increased significantly (186.7 ± 19.5 vs. 216.2 ± 21.9 pg/ml: p = 0.01) in spite of the fact that no changes were found in serum ionized Ca<sup>2+</sup>, Pi and Mg. This result indicates that the negative Ca<sup>2+</sup> balance during low-Ca<sup>2+</sup> hemodialysis-stimulated PTH secretion, which offset the decrease of serum Ca<sup>2+</sup>; a trade-off phenomenon between negative Ca balance and PTH. This suggests that low Ca<sup>2+</sup> dialysate may exaggerate the progression of secondary hyperparathyroidism.

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          Vitamin D Receptor Gene Polymorphism Detected by Digestion with Apa I Influences the Parathyroid Response to Extracellular Calcium in Japanese Chronic Dialysis Patients

          Background: To play its physiological role, 1,25(OH) 2 D 3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca 2+ in the dialysate. Methods: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca 2+ ] e ), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca 2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. Results: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 ± 9.4%) than in group AA+Aa (19.7 ± 7.2%). There were no significant differences between the two groups in [Ca 2+ ] e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. Conclusions: The study results showed that the patients in group aa were more sensitive to changes in [Ca 2+ ] e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca 2+ ] e , which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.

            Author and article information

            S. Karger AG
            September 2002
            14 August 2002
            : 92
            : 1
            : 86-90
            aDivision of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, bDivision of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe, Japan
            64484 Nephron 2002;92:86–90
            © 2002 S. Karger AG, Basel

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