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Abstract

K. Yokoyama, T. Shigematsu, T. Tsukada, S. Hara, A. Yamada, Y. Kawaguchi and T. Hosoya

¹The Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, ²Nephrology and Dialysis Unit, Department of Internal Medicine, Sakura National Hospital, Chiba, ³Department of Clinical Physiology, Toranomon Hospital, Tokyo, ⁴Kidney Center, Toranomon Hospital, Tokyo, Japan
Aim: The basic mechanism of secondary hyperparathyroidism is still unclear, but a change in Ca2+ sensing by parathyroid cells is possibly involved in this uremic complication. A rightward shift of the calcium set-point and an increase of the minimum secretion rate have been found in secondary hyperparathyroidism, indicating abnormal calcium sensing. Methods: We evaluated the effect of calcium sensing receptor (CaR) gene polymorphism (codon G990R) on the response of the parathyroid gland to moderate hypercalcemic suppression in 77 ESRD patients on regular hemodialysis (HD using 2.5 mEq/l Ca2+ dialysate). All patients underwent an HD session with 3.0 mEq/l Ca2+ dialysate to suppress parathyroid hormone (PTH). Then we investigated the effect of CaR gene polymorphism on the parathyroid response to hypercalcemic stimulation. Results: Patients were divided into 3 groups on the basis of genotype (GG = 33 patients (42.9%), GR = 39 patients (50.6%), RR = 5 patients (6.5%)). Baseline intact PTH levels in patients without the R allele were not significantly different from those in patients with the R allele (GG group, 181.4 ± 31.1 pg/ml vs. GR and RR groups, 230 ± 51.2 pg/ml: mean ± SEM). The significant effect of moderate hypercalcemic suppression on the intact PTH level was observed in the GG group (p < 0.01) but not in the GR and RR groups, despite the identical increase in Ca2+. Conclusion: Our results suggest that CaR gene polymorphism (codon G990R) influences the responsiveness of the parathyroid gland to changes of extracellular Ca2+ in ESRD patients. The glands of patients with the GG genotype of the CaR gene may be more sensitive to extracellular Ca2+ changes.

Abstract

S. Kagami¹, I. Ohkido¹, K. Yokoyama¹, T. Shigematsu² and T. Hosoya¹

¹Department of Internal Medicine, Division of Nephrology and Hypertension, The Jikei University School of Medicine, Tokyo, ²Department of Internal Medicine, Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama, Japan
Background: Both fibroblast growth factor-23 (FGF-23) and osteoprotegerin (OPG) are associated with phosphate metabolism, and are produced by bone tissue. Methods: In order to clarify the influence of bone turnover on phosphate metabolism, we examined the response of FGF-23 to an oral phosphate load in 4 groups of mice (2 OPG knockout (KO) and 2 wild-type (WT) groups) given either a high-phosphate diet or a normal diet by performing serum and urinary biochemical assays. Results: Although there was no significant difference in serum phosphate/ calcium levels between the groups, the decrease in tubular reabsorption rate of phosphate (%TRP) by oral phosphate load was smaller in the OPG KO mice than in the WT mice. FGF-23 level was significantly increased by a high-phosphate diet in WT mice, but not in OPG KO mice. However, there was no significant difference of intact PTH and calcitriol levels between the OPG KO and WT mice. Conclusion: Therefore, OPG may play a key role in mediating the response of FGF-23 to an oral phosphate load in bone cells.Correspondence to:
S. Kagami, MD; Division of Nephrology and Hypertension, Department of Internal Medicine,
The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
Email: [email protected]

Abstract

T. Shigematsu¹ and the Lanthanum Carbonate Group

¹Division of Nephrology and Blood Purification Medicine, Department of Medicine, Wakayama Medical University, School of Medicine, Wakayama City, Japan
Background: The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study. Methods: The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders. Results: In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium × phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group. Conclusion: Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.Correspondence to:
T. Shigematsu, MD, PhD; Nephrology and Blood Purification Medicine, Wakayama Medical University, 881-1, Kimiidera Wakayama-City, Wakayama Prefecture, 641-8509, Japan
Email: [email protected]

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