Kenichiro Shigemoto

Osteoprotegerin and bone mineral density in hemodialysis patients.

IntroductionOsteoprotegerin is a soluble glycoprotein that belongs to the tumor-necrosis-factor receptor superfamily. In vitro, osteoprotegerin blocks osteoclastogenesis in a dose-dependent manner. The serum osteoprotegerin level shows a positive correlation with bone metabolism markers and a negative correlation with bone mineral density in healthy persons, but these relationships are unclear in hemodialysis patients. We investigated the role of osteoprotegerin in bone loss in hemodialysis patients.MethodsWe measured baseline serum osteoprotegerin, bone metabolism markers, and bone mineral density in hemodialysis patients. A total of 201 patients (114 men and 87 women) were followed for 12 months, and bone mineral density was measured again to calculate the annual percent change in bone mineral density. Serum osteoprotegerin was also measured in 20 healthy persons.ResultsThe osteoprotegerin levels of the hemodialysis patients were about three times higher than those of the healthy controls. The osteoprotegerin level showed a negative correlation with various bone metabolism markers. In multiple regression analysis, the annual percent change in bone mineral density showed a positive correlation with osteoprotegerin level, while there was a negative correlation with duration of hemodialysis and intact parathyroid hormone level. The osteoprotegerin levels of the hemodialysis patients were about three times higher than those of the healthy controls. The osteoprotegerin level showed a negative correlation with various bone metabolism markers. In multiple regression analysis, the annual percent change in bone mineral density showed a positive correlation with osteoprotegerin level, while there was a negative correlation with duration of hemodialysis and intact parathyroid hormone level.ConclusionsThese correlations of osteoprotegerin are opposite to those found in healthy persons. However, osteoprotegerin might act to prevent bone loss even in hemodialysis patients.

Bone mineral density may be related to atherosclerosis in hemodialysis patients

Biological interactions between the bone and the blood vessels are gradually being clarified. To investigate the relationship between bone mineral density and atherosclerosis in hemodialysis patients, we examined the bone mineral density and the intima-media thickness of the carotid artery in 83 dialysis patients with non-diabetic nephropathy (44 men and 39 women) aged from 23 to 83 years. The duration of hemodialysis ranged from 2 to 344 months. The bone mineral density of the radius was measured by dual-energy X-ray adsorptiometry, and the ratio of this value to the standard value for the same age and gender was calculated (Z-score). As an index of atherosclerosis, the intima-media thickness of the carotid artery was measured by high resolution B-mode ultrasonography. Then the relationship between the Z-score and various factors was examined using Spearmans rank correlation analysis and multiple regression analysis. The Z-score showed a negative correlation with the duration of hemodialysis, the carotid intima-media thickness, and the levels of alkaline phosphatase, intact parathyroid hormone, and low-density lipoprotein cholesterol by Spearmans rank correlation analysis. In addition, the Z-score showed a positive correlation with the lipoprotein (a) level and a negative correlation with the duration of hemodialysis, intima-media thickness, intact parathyroid hormone, and low-density lipoprotein cholesterol by multiple regression analysis. These findings suggest that the decrease of bone mineral density in hemodialysis patients is correlated with secondary hyperparathyroidism and hyperlipidemia, which are factors known to promote atherosclerosis, and thus bone density changes might be related to the progression of atherosclerosis, or vice versa.

Increased Serum Osteoprotegerin Level in Older and Diabetic Hemodialysis Patients

Abstract:  Osteoprotegerin is a circulating osteoclastogenesis inhibitory factor and serum osteoprotegerin levels are elevated in hemodialysis patients. This study investigated whether osteoprotegerin levels correlated with various clinical parameters in hemodialysis patients. The subjects were 45 men and 37 women aged from 27 to 94 years (mean = 60.4 ± 13.9 years), and the duration of dialysis was 9–277 months (mean = 89.5 ± 64.7 months). Serum osteoprotegerin levels were measured by enzyme‐linked immunosorbent assay. Data were analyzed by stepwise multiple regression analysis. The mean osteoprotegerin level of the hemodialysis patients was 303 ± 210 pg/mL, which was higher than in age‐matched healthy controls. Osteoprotegerin levels increased with age, a longer duration of dialysis, and the presence of diabetes. Skeletal resistance to parathyroid hormone might be increased by aging, a long dialysis period, and diabetes, perhaps explaining why adynamic bone disease is more common in older or diabetic patients.

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage N. Noriaki Yorioka H. Hiroaki Oda T. Takahiko Ogawa Y. Yoshihiko Taniguchi S. Shigeyuki Kushihata A. Atsuo Takemasa K. Koji Usui K. Kenichiro Shigemoto S. Satoru Harada M. Michio Yamakido 2nd Department of Internal Medicine, Hiroshima University School of Medicine, and Ichiyokai Harada Hospital, Hiroshima, Japan

Multicenter Study of Pegylated Interferon α-2a Monotherapy for Hepatitis C Virus-Infected Patients on Hemodialysis: REACH Study

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)‐infected dialysis patients. The rate of HCV‐infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α‐2a (PEG‐IFNα‐2a) monotherapy in HCV‐infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 μg PEG‐IFNα‐2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 μg PEG‐IFNα‐2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG‐IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.

Hemoglobin Maintenance and Dosing Strategies Using Intravenous Continuous Erythropoietin Receptor Activator in Japanese Hemodialysis Patients

Methoxy polyethylene glycol‐epoetin beta, a continuous erythropoietin receptor activator (CERA), is reported to be effective in managing renal anemia but there is little data about CERA in Japan. This study aimed to ascertain the effects of CERA in Japanese hemodialysis patients and the appropriate starting dose of CERA when switching from other erythropoiesis‐stimulating agents. We switched 61 stable hemodialysis patients to 4‐weekly intravenous CERA, from either epoetin beta (rHuEPO) or darbepoetin alpha (DA). When determining the initial dose of CERA, we used guidelines recommended by the Japanese supplier for switching from rHuEPO, but for DA we based the CERA dose on European reports, because no Japanese guidelines exist. Fifty‐two patients completed the 28‐week study. Hemoglobin was maintained within the target range (10.0–12.0 g/dL). The required CERA dose decreased over the 28 weeks. The hemoglobin level and CERA dose stabilized faster when switching from DA. CERA showed similar efficacy in diabetic and non‐diabetic patients. The effect of CERA is similar regardless of whether patients switch from low‐ or high‐dose erythropoiesis‐stimulating agents. In conclusion, CERA is effective for Japanese hemodialysis patients at a lower dose than expected.

Vitamin K_2 Alters Bone Metabolism Markers in Hemodialysis Patients with a Low Serum Parathyroid Hormone Level

Background: A low level of intact parathyroid hormone (PTH) is an indicator of adynamic bone disease in hemodialysis patients, and is associated with a significant increase of all-cause mortality. Thus, effective treatment for adynamic bone disease is required. We previously investigated the effect of vitamin K2 on adynamic bone disease. In this study, we assessed the efficacy of oral vitamin K2 in a controlled trial. Methods: Forty hemodialysis patients with low intact PTH levels (<100 pg/ml) were randomly divided into two groups, which were a vitamin K2 group receiving oral menatetrenone (45 mg/day) for 1 year and a control group without vitamin K2. Venous blood samples were collected at baseline and during the study for measurement of bone metabolism parameters. Results: Thirty-three patients completed follow-up. There was a significant increase of the serum intact osteocalcin level after 1 month of vitamin K2 administration. Serum levels of intact PTH, bone alkaline phosphatase, and cross-linked N-terminal telopeptide of type I collagen increased significantly after 12 months in the vitamin K2 group. The serum osteoprotegerin level was decreased after 12 months in the vitamin K2 group, but the change was not significant. Conclusion: Vitamin K2 therapy improves bone remodeling in hemodialysis patients with a low intact PTH level.

Calcium channel antagonists reduce restenosis after percutaneous transluminal angioplasty of an arteriovenous fistula in hemodialysis patients.

Abstract:  Percutaneous transluminal angioplasty (PTA) for stenosis of hemodialysis fistulas is associated with a high incidence of restenosis, and improvement of the patency rate after PTA is greatly needed. In addition, angiotensin II receptor blockers (ARB), calcium channel antagonists (CCA) and antiplatelet agents (APA) are commonly administered to most hemodialysis patients. This study retrospectively examined the effect of these medications on the incidence of restenosis after angioplasty for hemodialysis fistulae. The subjects were 92 patients—54 with anastomotic stenosis of an arteriovenous fistula (AVF) and 38 with stenosis of the draining veins of an arteriovenous graft (AVG)—who underwent angioplasty between January 2001 and December 2003. The patency period was defined as the interval from the first to the second angioplasty or surgical reconstruction. We excluded patients who received angioplasty two or more times. The effect of each drug on the patency of the AVF or AVG was assessed by the Kaplan‐Meier method with the log‐rank test and multiple logistic regression analysis. The group receiving CCA therapy showed a higher patency rate for both an AVF and an AVG. Although multiple logistic regression analysis also showed that a CCA reduces restenosis independently in an AVF, there was no significant correlation between a CCA and patency in an AVG. Treatment with an ARB and an APA was not associated with significantly higher patency rates for either an AVF or AVG. A CCA may reduce the incidence of restenosis after percutaneous intervention for stenosis of an AVF.

Hepatocyte growth factor in nephronophthisis-medullary cystic disease complex

Abstract. A 13-year-old Japanese girl presented with severe anemia and renal dysfunction. The nephronophthisis-medullary cystic disease complex was diagnosed from the results of renal biopsy and a family study. Immunohistochemical detection of hepatocyte growth factor in the epithelial cells of dilated renal tubules suggested that it may have a role in the development of the tubular cystic changes which are characteristic of this disease.

Lower serum fibroblast growth factor-23 levels may suggest malnutrition in maintenance haemodialysis patients

It is reported that high serum fibroblast growth factor‐23 (FGF‐23) levels are associated with increased mortality in haemodialysis patients, and can be caused by hyperphosphataemia and loss of residual renal function. However, hypophosphataemia is also associated with increased mortality in maintenance haemodialysis (MHD) patients. We studied the determinants of the serum FGF‐23 levels in MHD patients, focusing on nutritional status and residual renal function.