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Originals

Calcium-sensing receptor gene polymorphism affects the parathyroid response to moderate hypercalcemic suppression in patients with end-stage renal disease

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

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Volume 57 (2002) p. 131 - 135

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.

Originals

Serum β₂ microglobulin (β₂MG) level is a potential predictor for encapsulating peritoneal sclerosis (EPS) in peritoneal dialysis patients

K. Yokoyama, H. Yoshida, N. Matsuo, Y. Maruyama, Y. Kawamura, R. Yamamoto, K. Hanaoka, M. Ikeda, H. Yamamoto, M. Nakayama, Y. Kawaguchi and T. Hosoya

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Volume 69 (2008) p. 121 - 126

Abstract

K. Yokoyama, H. Yoshida, N. Matsuo, Y. Maruyama, Y. Kawamura, R. Yamamoto, K. Hanaoka, M. Ikeda, H. Yamamoto, M. Nakayama, Y. Kawaguchi and T. Hosoya

¹Division of Kidney and Hypertension, Department of Internal Medicine,
Jikei University School of Medicine, Tokyo and ²Research Division of Dialysis and Chronic Kidney Disease, Tohoku University Graduate School of Medicine, Sendai Miyagi, Japan
Background: Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). The aim of this study was to find a predictor for EPS. Methods: Patients with EPS who were detected by a historical cohort study using clinical data of 219 CAPD patients at our hospital. We recruited 25 patients with EPS who were compared with the patients without EPS who were matched for age and dialysis period as controls. Differences between the two groups (non-EPS group and EPS group) with respect to age, gender, primary disease, dialysis period, serum urea nitrogen, serum creatinine, β₂MG, CRP and PET (peritoneal equilibration test) category (determined by the peritoneal function testing) were analyzed. Results: According to multiple regression analysis, a high β₂MG level was an independent risk factor for EPS (odds ratio 1.162, 95% confidence interval 1.026 – 1.317, p = 0.018). Other clinical markers did not show positive significance. A ROC (receiver operating characteristic) curve was prepared to evaluate the suitability of β₂MG measurement as a screening test. The sensitivity was 64% and the specificity was 80% when a β₂MG level of 37.0 mg/dl was taken as the cut-off value. The odds ratio for occurrence of EPS was 8.8 when β₂MG level was in the range of 35 – 40 mg/dl, 13.5 when β₂MG level was > 40 mg/dl and 1 when β₂MG level was < 30 mg/dl. Conclusion: These findings suggest that β₂MG is useful as a screening test for the onset of EPS, and that β₂MG and accumulation of middle-molecular uremic substances may be related to the pathophysiology of EPS.Correspondence to:
K. Yokoyama, MD, Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
Email: [email protected]

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