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
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
The effect of angiotensin receptor blockade (ARB) on the regression of left ventricular hypertrophy in hemodialysis patients: comparison between patients with D allele and non-D allele (ACE gene polymorphism)
M. Nakayama, H. Nakano, N. Tsuboi, T. Kurosawa, Y. Tsuruta, Y. Iwasaki, K. Yokoyama, T. Hosoya and M. Fukagawa
Volume 64 (2005) p. 358 - 363
Abstract
M. Nakayama1, H. Nakano2,3, N. Tsuboi3, T. Kurosawa4, Y. Tsuruta5, Y. Iwasaki6, K. Yokoyama3, T. Hosoya3 and M. Fukagawa7
1Research Division of Dialysis and Chronic Kidney Disease, Tohoku University Graduate School of Medicine, Sendai, 2Dialysis Center, Kashima Hospital, Iwaki, 3Department of Kidney and Hypertension, The Jikei University School of Medicine, Tokyo, 4Dialysis Division, Sumiyoshi Clinic Hospital, Mito, 5Dialysis Division, Meiyo Clinic, Toyohashi, Aichi, 6Nursing and Health Science, Oita University of Nursing and Health Sciences, Oita, 7Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe, Japan
Objective: It is revealed that LVH is one of risk factors for the development of cardiac complications in long-term HD patients. Therefore, maneuvers to reduce hypertrophy of cardium are very important for improving life prognosis. Angiotensin II receptor blockade (ARB) could reduce LVH in general populations without renal failure. However, no conclusive data has been available regarding the clinical consequences of ARB administration on the regression of LVH in HD patients. Furthermore, it has not clearly determined if ACE gene polymorphism has a possible influential effect on it. This study is conducted to clarify these issues. Subjects and method: 32 hypertensive patients on regular HD (male/female: 21/11, mean age: 60.5 years, mean duration of HD: 52.8 months) were studied. Patients were classified into two groups according to the different type of ACE gene polymorphism: cases with D allele (DD/ID; D group: n = 13) and those without (II; non-D group: n = 19). All patients were administered ARB (losartan 50 – 100 mg/day) and echocardiography (UCG) was performed at 6-month-interval regularly until the end of observation (24 months). Results: Before the commencement of ARB, no differences were found between the two groups, neither in mean blood pressure (MBP: D group/non-D group: 120 ± 13 vs. 115 ± 14 mmHg) nor in left ventricular mass index (LVMI: D/non-D: 172 ± 41 vs. 165 ± 41 g/m2). During the 24-month follow-up, there were significant and similar reductions in MBP in both groups. In respect to LVMI, a significant reduction of LVMI was found in the D group after six months (p < 0.01 vs. basal) with a final reduction rate (FRR) –26 ± 13%, whereas in the non-D group it was found at 24 months (p < 0.01 vs. basal) with FRR –11 ± 16% (p < 0.01 vs. D group). There were significant differences between the two groups at all points (p < 0.05 at 6, 18 and 24 months, p < 0.005 at 12 months, respectively). Conclusion: It is indicated that ARB could insert a regression effect on LVH predominantly in patients with D allele ACE polymorphism, due partly to factor (s) independent of its anti-hypertensive effect.Correspondence to:
M. Nakayama, MD
Research Division of Dialysis and Chronic Kidney Disease
Tohoku University Graduate School of Medicine
Seiryo machi 1-1 Aoba-ku
Sendai, 980-8574, Japan
Email: [email protected]
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
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]
Original
Osteoprotegerin affects the responsiveness of fibroblast growth factor-23 to high oral phosphate intake
S. Kagami, I. Ohkido, K. Yokoyama, T. Shigematsu and T. Hosoya
Volume 70 (2008) p. 306 - 311
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]
Clinical impact of a combined therapy of peritoneal dialysis and hemodialysis
N. Matsuo, K. Yokoyama, Y. Maruyama, Y. Ueda, H. Yoshida, Y. Tanno, R. Yamamoto, H. Terawaki, M. Ikeda, K. Hanaoka, H. Yamamoto, M. Ogura, S. Watanabe, Y. Kimura and T. Hosoya
Volume 74 (2010) p. 209 - 216
Abstract
Clinical Nephrology, Vol. 74 – No. 3/2010 (209-216)
Clinical impact of a combined therapy of peritoneal dialysis and hemodialysis
N. Matsuo1, K. Yokoyama1, Y. Maruyama1, Y. Ueda1, H. Yoshida1, Y. Tanno1, R. Yamamoto1, H. Terawaki1, M. Ikeda1, K. Hanaoka1, H. Yamamoto1, M. Ogura1, S. Watanabe2, Y. Kimura1 and T. Hosoya1
1Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, and 2Department of Internal Medicine, Kobari General Hospital, Chiba, Japan
Aims: Although peritoneal dialysis (PD) is recommended as the first-line treatment for end-stage renal disease, limitations exist to achieving good clinical status when the residual renal function (RRF) has declined. Combined therapy with PD and hemodialysis (HD) is the treatment of choice for patients who cannot control body fluid status and/or cannot obtain adequate solute removal by PD alone. The aim of this study was to evaluate the clinical efficacy of this combined therapy. Methods: In this retrospective study, 53 patients on PD and diagnosed with underdialysis and/or overhydration with declining RRF were recruited. Parameters of volume control, uremic solute removal, anemia, and predictors for encapsulating peritoneal sclerosis (EPS) were compared before and 1 year after combined therapy. Results: The patients’ hydration status improved significantly with reductions in atrial natriuretic peptide and blood pressure. Serum creatinine and beta2 microglobulin also decreased significantly. The hemoglobin level increased remarkably from 8.2 ± 1.6 to 10.7 ± 1.2 g/dl (p < 0.01) and the reticulocyte count also increased significantly, even though at the same time the dose of recombinant human erythropoietin decreased significantly. The dialysate to plasma creatinine ratio obtained from the fast peritoneal equilibration test (PET) decreased significantly from 0.65 ± 0.11 to 0.59 ± 0.13, and the level of interleukin 6 in PET drainage also significantly decreased. Furthermore, serum C-reactive protein and fibrinogen decreased significantly. Conclusions: Combined therapy with PD and HD is an effective way to control fluid status and to correct inadequate solute removal, leading to improvement in inflammation, peritoneal function and anemia.Correspondence to:
Dr. N. Matsuo
Division of Kidney 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]
Lead Article
Difference in coronary artery intima and media calcification in autopsied patients with chronic kidney disease
H. Yoshida, K. Yokoyama, T. Yaginuma, I. Ohkido, H. Yamamoto, Y. Utsunomiya, M. Kawakami and T. Hosoya
Volume 75 (2011) p. 1 - 7
Abstract
Clinical Nephrology, Vol. 75 – No. 1/2011 (1-7)
Difference in coronary artery intima and media calcification in autopsied patients with chronic kidney disease
H. Yoshida1, K. Yokoyama1, T. Yaginuma1, I. Ohkido1, H. Yamamoto1, Y. Utsunomiya1, M. Kawakami2 and T. Hosoya1
1Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, and 2Department of Pathology, Seirei Sakura Citizen Hospital, Sakura, Japan
Background: In patients with chronic kidney disease (CKD), coronary artery calcification occurs at two distinct sites in the vessel wall: the intima and the media. Arterial media calcification (AMC), a nonocclusive condition, affects hemodynamics differently compared to arterial intima calcification (AIC), which occurs in atherosclerotic plaques. Arterial calcification is considered a cell-regulated process resembling intramembranous bone formation. The purpose of this retrospective observational study was to clarify the morphological differences between AIC and AMC and to evaluate the role of vascular smooth muscle cells (VSMCs) and macrophages in AIC and AMC formation. Methods: We histologically analyzed 14 tissue specimens from 14 autopsies of patients with CKD Stage 5D who underwent hemodialysis and 5 specimens from 5 patients with CKD Stage 2 – 3 (90 ml/min/1.73 m2 > estimated GFR >= 30 ml/min/1.73 m2). We performed immunohistochemical staining of osteopontin (OPN) as a marker for bone matrix protein, alpha-smooth muscle actin (alphaSMA) for VSMCs, Cbfa1/Runx2 as a marker for osteoblastic differentiation of VSMCs, and CD68 for macrophages. Results: In the CKD 2/3 group, we also found AIC and AMC. OPN and CD68 expression in the CKD 2/3 group was similar to that in the CKD 5D group. Although we did not find Cbfa1/Runx2 positive cell expression in the CKD 2/3 group, we did find it in the CKD 5D group. We found CD68-positive cells predominantly in AIC and absent in AMC in both groups. Conclusions: These findings suggest that the influence of Cbfa1/Runx2 pathway in coronary artery calcification depends on the CKD Stage. Expression of CD68-positive cells depends on the location of the coronary artery calcification.Correspondence to:
H. Yoshida, MD
Division of Kidney and Hypertension
Department of Internal Medicine
The Jikei University School of Medicine
3-25-8, Nishi-Shinbashi, Minato-ku
Tokyo, 105-8471, Japan
Email: [email protected]
