Hypertension: Yamamoto H

Yaginuma T, Yamamoto H. · Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine. · Clin Calcium. · Pubmed #19329829 No free full text.

Abstract: The peritoneal dialysate calcium concentration is an important factor in chronic kidney disease-mineral and bone disorder (CKD-MBD), because dialysate calcium concentrations strongly influence the serum calcium, phosphate, and parathyroid hormone (PTH) levels and the dosage of phosphate binders/vitamin D analogs. High-calcium dialysate has been used to correct hypocalcemia in end-stage renal disease (ESRD). Subsequently, a low-calcium dialysate was produced to increase the dosage of calcium-containing phosphate binders and vitamin D analogs without causing hypercalcemia. However, not enough is known about the effect of low-calcium dialysate in peritoneal dialysis. When we choose low-calcium dialysate, we should keep the risks of deteriorating secondary hyperparathyroidism in mind.

Taketani Y, Shuto E, Arai H, Nishida Y, Tanaka R, Uebanso T, Yamamoto H, Yamanaka-Okumura H, Takeda E. · Department of Clinical Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. · J Med Invest. · Pubmed #17878688 links to  free full text

Abstract: Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Japan and other Westernized countries. Over 50% of the ESRD patients die from cardiovascular events. Cardiovascular disease (CVD) in ESRD patients with diabetes mellitus (DM) are implicated in the endothelial dysfunction caused by hyperglycemia, hyperlipidemia, and hypertension, and in the vascular calcification of intimal and medial arterial blood vessels caused by hyperphosphatemia. Therefore, dietary control of hyperglycemia and hyperphosphatemia should play an important role in the management of ESRD patients with DM. Furthermore, recent findings suggest that high concentrations of serum phosphate, even if within the normal range, may be a risk factor for CVD and mortality. An in vivo study using klotho knockout mice and fibroblast growth factor 23 (FGF-23) knockout mice has revealed that correction of hyperphosphatemia and hypervitaminosis D could ameliorate the premature aging-like phenotype. A low glycemic index and low phosphate diet may provide an advantage in the prevention of aging-related diseases in healthy individuals as well as in those with chronic kidney disease.

Mitome J, Yamamoto H. · Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #15197947 No free full text.

This publication has no abstract.

Horie T, Akashiba T, Muto T, Otsuka K, Yoshizawa T, Saito O, Sasaki G, Kurashina K, Ito D, Suzuki R, Minemura H, Yamamoto H, Kosaka N, Akahoshi T, Kawahara S. · No affiliation provided · Masui. · Pubmed #11871103 No free full text.

This publication has no abstract.

Katayama S, Yagi S, Yamamoto H, Yamaguchi M, Izumida T, Noguchi Y, Inaba M, Inukai K. · Division of Endocrinology and Diabetes, Department of Medicine, School of Medicine, Saitama Medical University, Saitama, Japan. · Hypertens Res. · Pubmed #17664856 No free full text.

Abstract: To explore the effects of various antihypertensive regimes on microalbuminuria, an angiotensin II receptor blocker (ARB), valsartan, was substituted for or added to treatment with a calcium channel blocker (CCB). After a 6-month CCB baseline period, 28 Japanese hypertensive patients with incipient diabetic nephropathy (defined as a urinary albumin excretion [UAE] of 30-300 mg/g creatinine), were assigned to two groups according to their blood pressure (BP) levels: in patients with a BP of more than 130/85 mmHg (n=17), valsartan was added to the CCB (Group A), while in patients with a BP <130/85 mmHg, valsartan alone was given (Group B: n=11) for 12 months. UAE was determined before and at 3, 6 and 12 months after the initiation of ARB. Although the initial BP was significantly higher in Group A (150/83 mmHg) than Group B (127/77 mmHg), BP was decreased to 141/78 mmHg in Group A and slightly, but not significantly, increased to 130/82 mmHg in Group B. In both groups, UAE was significantly decreased after ARB treatment (to 89% of the basal value in Group A and to 40.5% of the basal value in Group B) and did not differ each other and the amount of decrease did not differ significantly between the two groups. These results suggest that combination therapy with an ARB and CCB is very effective in lowering BP and UAE in cases in which BP is not well controlled, while, even in patients with a sufficient BP control of <130/85 mmHg, the use of ARB singly resulted in a significant decrease in UAE without a further decrease in BP, implying that the ARB had a renoprotective action independent of changes in BP.

Maruyama Y, Nakayama M, Yoshimura K, Nakano H, Yamamoto H, Yokoyama K, Lindholm B. · Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-19-18 Nishi-shinbashi, Minato-ku, Tokyo, 105-8471, Japan. · Nephrol Dial Transplant. · Pubmed #17264097 links to  free full text

Abstract: BACKGROUND: Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients. METHODS: Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks. RESULTS: At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner. CONCLUSIONS: Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.

Mori H, Ukai H, Yamamoto H, Saitou S, Hirao K, Yamauchi M, Umemura S. · Japanese Medical and Dental Practitioners for the Improvement of Medical Care, Tokyo, Japan. · Hypertens Res. · Pubmed #16755149 No free full text.

Abstract: The importance of tight blood pressure (BP) control has been established. We performed cross-sectional studies on the current status of BP control and the prescription and efficacy of antihypertensive drugs in hypertensive patients in Japan. The data were also evaluated in subgroups with or without diabetes mellitus (DM) and in winter and summer. Analyses were performed on the collected data of 12,437 treated hypertensive patients in winter and 5,972 in summer 2002. In winter, 50.3% of patients received calcium channel blockers (CCBs), 15.3% received angiotensin converting enzyme inhibitors (ACEIs) and 11.0% received angiotensin receptor blockers (ARBs). In the patients receiving monotherapy, 69% of patients received a CCB, 13% an ACEI and 11.0% an ARB. A total of 2,918 patients received combination therapy, and CCBs were the most frequently (89.6%) prescribed component of such therapy. Prescriptions of beta-blockers (BBs) decreased and those of CCBs and diuretics (D) increased with age (p<0.001). The rate of patients with adequately controlled BP less than 140/90 mmHg was 40.3% in the CCB group, 37.6% in the D group, and 36.9% in the BB group (p<0.001). In patients receiving combination therapy, those with CCB+D had the best rate of BP control (40.7%). The rate of patients with adequately controlled BP was lower in winter than in summer at both a target BP of 140/90 mmHg (36.2% vs. 43.8%, p<0.001) and a target BP of 130/85 mmHg in patients younger than 60 years old (15.5% vs. 18.6%, p<0.02). In diabetic patients, the target BP (130/80 mmHg) was achieved in only 11.3%, which was lower (p<0.05) than the rate in non-diabetic patients (13.1%). In conclusion, the present cross-sectional study showed that CCBs were the most frequently prescribed agent for the treatment of hypertension in Japan. The rate of adequate BP control was less than 50% and was even worse in patients with DM and in winter. Our results indicate that physicians should treat hypertension more intensively to achieve the target BP.

Mitome J, Yamamoto H, Kato N, Hayakawa H, Ikeda M, Yokoyama K, Nakayama M, Kawaguchi Y, Hosoya T. · Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. · Nippon Jinzo Gakkai Shi. · Pubmed #16296411 No free full text.

Abstract: BACKGROUND: Kidney transplantation is the most ideal treatment in renal replacement therapy for patients with end-stage renal disease. However, the prevalence of transplantation is extremely low and most patients with ESRD should continue dialysis for their whole life. Recently, high transposition rate of renal transplantation from peritoneal dialysis (PD) was reported, however, it was unclear whether a difference in dialytic modality can influence the outcome. Therefore, we evaluated the influence of dialytic modality on the rate of kidney transplantation and outcome in our single center. METHODS: Forty-two kidney transplants were carried among 1,573 dialysis patients from the years 1986 to 2004 in our center. Transposition rates from two modalities (HD and PD) and graft survival were compared. The incidence of acute rejection episode, complications after receiving transplantations, and coexisting diseases were also evaluated between the two modalities prior to transplantation. RESULT: The number of patients who received HD was larger than PD (HD 77.1%, PD 22.9%, respectively). Forty-two patients undergoing dialytic therapy received a living-donor kidney transplantation. Overall graft survival was 92% at 5 years and 75% at 10 years. Among these cases, dialytic modality prior to transplantation was 57.1% in HD, and 42.9% in PD. The transfer rate from PD to transplantation was significantly (p = 0.0036) higher (4.7%) than that of HD (1.9%). The reason for the high transfer rate of PD patients might be cooperation with their family and the provision of relevant information by nephrologists during PD. There were no differences between the two modalities prior to transplantation in the graft survival rate, incidence of acute rejection, and complications before and after transplantation. CONCLUSION: Difference in pretransplant dialysis modality did not affect the outcomes, however, the transfer rate from PD was significantly higher than from HD. Accordingly, PD is useful compared to HD as bridge therapy for kidney transplantation from the high feasibility of living-donor kidney transplantation.

Nakayama M, Tanno Y, Otsuka Y, Takahashi H, Ikeda M, Katoh N, Yokoyama K, Yamamoto H, Tokutome G, Hosoya T. · Department of Kidney and Hypertension, Jikei University School of Medicine, Tokyo, Japan. · Nippon Jinzo Gakkai Shi. · Pubmed #12476589 No free full text.

Abstract: The administration of angiotensin II receptor antagonist(AIIA) to patients with advanced chronic renal failure(CRF) is not actively recommended. This study was performed to verify the appropriateness of this situation and to determine if there are any substantial differences between patients with a serum creatinine(SCr) level higher than 3 mg/dl and those with a lower SCr level in terms of the clinical effects such as renal function, serum potassium level and systemic blood pressure(BP) after the administration of AIIA. Sixteen patients with advanced CRF who were admitted to the out-patient clinic in Jikei University Hospital(1998/1-1999/12) were enrolled(average age: 65 years, underlying renal disease: diabetic nephropathy 6, CGN 5, and other 1). They had never been administered AIIA before. The patients were classified into two groups in accordance with their level of SCr: group A(SCr lower than 3.0 mg/dl; n = 11), and Group B(SCr higher than 3.0 mg/dl; n = 5). Losartan(50 mg/day) administration was started in order to examine parameters such as the SCr, potassium, BP at the out-patient clinic, and urinary protein excretion at the 0, 1, 3, 6, 9, and 12 month time points. Although the 1/SCr values provided negative slopes with time in both groups, no significant difference was found between the two slopes. There were no changes in the serum potassium levels or urinary protein excretion during the study period in either group, and no statistical difference was found between the two groups. Although the serum potassium level exceeded 5.5 mEq/l in two patients each in both groups, the level was controlled by diet therapy with restricted potassium. BP was reduced significantly in both groups during the study period, and no statistical difference in BP reduction was observed between the two groups. In conclusion, the results indicate there were no differences in the effect on renal function, serum potassium levels or systemic BP between the patients with a SCr level higher than 3.0 mg/dl and those with a lower level. The results also support the notion that patients with advanced renal dysfunction are not precluded from AIIA administration.

Matsuo N, Yamamoto H, Kobayashi A, Yamamoto I, Mitome J, Maruyama Y, Hayakawa H, Miyazaki Y, Utsunomiya Y, Hosoya T, Yamaguchi Y. · Division of Kidney and Hypertension, Department of Internal Medicine, Kashiwa Hospital, The Jikei University School of Medicine, Chiba, Japan. · Clin Transplant. · Pubmed #19594591 No free full text.

Abstract: A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis underwent kidney transplantation from a living unrelated spousal donor. The blood type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6 locus mismatch. She had become pregnant twice by her donor and had never received blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She initially underwent one week of immunosuppression with mycophenolate mofetil (MMF) and double filtration plasmapheresis (DFPP) immediately before transplantation to reduce the risk of antibody-mediated rejection. Induction therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and basiliximab. The allograft function was excellent immediately after the operation. However, the urine output and platelet count declined rapidly on post-operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase levels rose gradually. Subsequently, we could not detect the diastolic arterial flow on Doppler sonography. We diagnosed accelerated acute rejection and treated her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The first episode biopsy on POD 7 revealed acute vascular rejection and acute antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased beginning on POD 13, while the sCr level decreased gradually and reached 0.9 mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor-specific antibody (DSA). This case suggested that, for successful kidney transplantation in highly sensitized recipients, such as husband-to-wife spousal kidney transplantation with a history of pregnancy, we should keep the risk of AMR in mind, even if the sensitive antibody detection tests are negative.

Matsuo N, Maruyama Y, Terawaki H, Ikeda M, Yamamoto H, Yokoyama K, Ogura M, Kimura Y, Nakayama M, Hosoya T. · Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. · Nippon Jinzo Gakkai Shi. · Pubmed #19238907 No free full text.

Abstract: Peritoneal dialysis (PD) is recommended as the first line of treatment for end-stage renal disease patients in terms of integrated renal replacement therapy (RRT), since PD can preserve residual renal function and fluid homeostasis. However, few analyses have been studied regarding the risk factors for death among patients, including cases transferred from PD. This study retrospectively examined 98 patients (63-years-old, male/female ratio: 59/39, non-DM/DM: 57/41) who started PD for their first RRT between Jan. 1999 and Dec. 2003 in a single center. The risk factors for patient death were evaluated During the average observational period of 28 months, 35 cases (35.7%) were withdrawn from PD, and among these, 24 patients (24.5%) died (including 7 cases after transferal to HD). The leading causes of death were cardiovascular disease (CVD) and infectious disease in 8, respectively (33.3% each) and no cases were found who developed encapsulating peritoneal sclerosis. As compared to living patients, the group of patients who died was significantly older and had a high frequency of CVD history. Their serum albumin (Alb) level was significantly lower, whereas the D/P (dialysate/plasma) creatinine (Creat) ratio as well as diastolic blood pressure was higher. In the Cox Hazard model, D/P Creat ratio >0.65 (category high/high average), DM nephropathy and history of CVD were independent predictors of death (hazard ratio (HR): 1.78, 95% CI: 1.10-2.94, HR: 1.81, 95% CI: 1.11-3.11, HR: 2.23, 95% CI: 1.37-3.73). These results suggest that DM nephropathy, history of CVD and higher peritoneal permeability at PD initiation are independent risk factors of death in patients starting PD for their first RRT. Hence, a strict follow-up is needed in these patients.

Tagami T, Yamamoto H, Moriyama K, Sawai K, Usui T, Shimatsu A, Naruse M. · Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Fukakusa, Kyoto, Japan. · Endocrinology. · Pubmed #19147680 No free full text.

Abstract: Angiotensin type 1 receptor blockers are widely used for the treatment of hypertension, and one angiotensin type 1 receptor blocker, telmisartan, specifically activates the peroxisome proliferator-activated receptor (PPAR)-gamma. We studied the impact of PPARgamma mutants on transcriptional control and interaction with cofactors to elucidate differences in the molecular mechanism between telmisartan and other PPARgamma agonists, thiazolidinediones (TZDs). We created several amino acid substitutions in the ligand binding domain of PPARgamma that, based on molecular modeling, may affect the binding of these agents. In transient expression experiments, wild-type PPARgamma-mediated transcription stimulated by telmisartan was more than one third of that stimulated by TZDs. The activation stimulated by TZDs was impaired, whereas activation stimulated by telmisartan was retained, in the H323Y, S342A, and H449A mutants. In the Y473A mutant, the TZD-induced activation was further impaired and lower than that of telmisartan-induced activation. Coexpression of coactivators enhanced the activation by both telmisartan and TZDs, but activation by telmisartan always exceeded that of TZDs in the Y473A mutant. Based on a mammalian two-hybrid assay, the interaction with corepressors was retained in Y473A. Telmisartan and TZDs, but not 9cis retinoic acid, dissociated corepressors from the wild-type PPARgamma. Telmisartan most effectively dissociated corepressors from Y473A. The interaction with coactivators was enhanced by TZD activation of wild-type PPARgamma and both telmisartan and TZD activation of Y473A. Thus, the Y473A mutant is selectively stimulated by telmisartan but not TZDs, suggesting that telmisartan and TZDs have differential effects on the transcriptional control. In conclusion, these PPARgamma mutants could be powerful tools for developing novel therapeutic agents that retain the metabolic efficacy of PPARgamma activation with fewer adverse effects, such as the increase in body weight associated with TZDs.

Imazu M, Ono K, Tadehara F, Kajiwara K, Yamamoto H, Sumii K, Tasaki N, Oiwa J, Shimohara Y, Gomyo Y, Itabe H. · Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Japan. · Int Heart J. · Pubmed #18971563 links to  free full text

Abstract: The role of plasma levels of oxidized low density lipoprotein (OxLDL) in the development of coronary heart disease (CHD) has not been fully elucidated. We examined the relationship among plasma levels of OxLDL, measured by an enzyme immunoassay using an antibody against OxLDL (FOH1a/DLH3) and apolipoprotein B, CHD, and modalities at the onset of acute coronary syndrome (ACS). A total of 115 individuals who underwent coronary angiography were studied. Of these, 21 patients complicated with extracoronary cardiovascular diseases were excluded. Consequently, 94 patients (63 men) (ACS: 23, stable angina pectoris (SAP): 46, and normal coronary artery (NCA):25) were eligible for inclusion in the study. Elevated plasma levels of OxLDL were associated with CHD, especially with ACS. In patients with NCA, hypertension was associated with plasma OxLDL. Plasma levels of OxLDL were significantly higher in patients with new-onset type ACS than in those with worsening type ACS (2.98 versus 1.53 mg/dL, P = 0.002). In conclusion, plasma levels of OxLDL are associated with CHD and significantly higher in patients with new-onset ACS. The findings of the present study suggest that plasma OxLDL can be a marker of the development of CHD and modalities of ACS.

Tatsukawa Y, Hsu WL, Yamada M, Cologne JB, Suzuki G, Yamamoto H, Yamane K, Akahoshi M, Fujiwara S, Kohno N. · Department of Clinical Studies, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan. · Hypertens Res. · Pubmed #18957810 No free full text.

Abstract: Although several studies have shown that high WBC count is a risk factor for hypertension, the relationship between WBC count and the incidence of hypertension in Japanese is poorly understood, as are the effects of WBC components on that relationship. Our objective was to verify in a Japanese population whether WBC or differential WBC count predicts hypertension incidence. A total of 9,383 initially hypertension-free subjects (3,356 men and 6,027 women), whose WBC counts were within the normal range (3,000 to < 10,000 cells/mm3), were followed from 1965 to 2004. During this 40-year follow-up, 4,606 subjects developed hypertension. After adjusting for conventional risk factors, including smoking status, we found that elevated WBC count was associated with hypertension incidence in a Cox regression model with both fixed and time-varying covariates for women. For men, elevated WBC count was a significant risk factor for hypertension only in the time-varying Cox-regression covariate. We also observed a significant association between increased neutrophil count and hypertension incidence among women. In a fully adjusted model, the relative risks of hypertension incidence, from the lowest to the highest quartiles of neutrophil count, were 1.00, 1.18, 1.28, and 1.22 in women (p for trend < 0.001). In conclusion, elevated WBC count predicted an increased incidence of hypertension in Japanese, especially among females. Moreover, neutrophils were the major WBC component contributing to the increased risk.

Kasayama S, Tanemura M, Koga M, Fujita K, Yamamoto H, Miyatake A. · Department of Medicine, Nissay Hospital, 6-3-8 Itachibori, Nishi-ku, Osaka 550-0012, Japan. · Clin Chim Acta. · Pubmed #18838067 No free full text.

Abstract: BACKGROUND: Chronic inflammation of the airways plays a major role in the pathogenesis of asthma. Although C-reactive protein (CRP) is now an established circulating marker for cardiovascular diseases, it remains unclear whether asthma is an independent risk for increased plasma CRP. METHODS: In Study 1, we evaluated CRP levels in 329 asthmatic patients and 1684 non-asthmatic subjects. Inhaled corticosteroids were regularly used by 308 asthmatics. In Study 2, the effects of inhaled corticosteroids on CRP levels were examined in 64 corticosteroid-naive asthmatic patients. RESULTS: In Study 1, plasma CRP levels were associated with body mass index (R=0.349, P<0.0001) and age (R=0.111, P<0.0001) in all study subjects, but were higher in patients with asthma, hypertension, diabetes and/or dyslipidemia than in those without these disorders. Multivariate regression analysis identified body mass index, age and asthma, but not hypertension, diabetes or dyslipidemia, as independently associated with an elevation of CRP levels. In Study 2, treatment of 64 corticosteroid-naive asthmatic patients with inhaled corticosteroids for 3 months significantly reduced plasma CRP levels. CONCLUSIONS: Asthma is a disorder associated with increased plasma CRP levels independent of various other factors. Treatment with inhaled corticosteroids was associated with a significant reduction in plasma CRP levels, which may reflect their clinical effect on the inflammatory process within airways.

Yamamoto H, Kasai K, Hamada C, Hasegawa H, Higuchi C, Hiramatsu M, Hosoya T, Itami N, Kawanishi H, Kubota M, Masakane I, Minakuchi J, Mitarai T, Nakao T, Suzuki H, Tomo T, Kawaguchi Y, Anonymous00049. · Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University, School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo 105-8461, Japan. · Perit Dial Int. · Pubmed #18552242 links to  free full text

Abstract: BACKGROUND: In patients on continuous ambulatory peritoneal dialysis (CAPD), dialysate calcium concentration has a strong influence on correction of serum calcium, phosphorus, and parathyroid hormone (PTH); however, the optimal concentration of Ca in PD solution is still uncertain. The aim of the survey reported here was to evaluate the prevalence of patients treated with standard- [SCD (approximately 3.25 - 4.0 mEq/L)] or low-calcium [LCD (approximately 1.8 - 2.5 mEq/L)] dialysate and differences in the clinical effects for correction of abnormalities in divalent ions and PTH. MATERIALS AND METHODS: We used a questionnaire to survey 333 peritoneal dialysis facilities nationwide in Japan. Then, we analyzed serum Ca, P, and PTH levels and the prescription rates for CaCO(3) as a P binder and for vitamin D (VitD) analogs. RESULTS: The 2384 CAPD patients enrolled in this analysis had a mean age of 60.5 +/- 14.2 years and a mean duration of CAPD of 44.1 +/- 39.2 months. The prevalences of SCD, LCD, and combination of SCD and LCD were, respectively, 49%, 50%, and 1% at initiation, and 40%, 38%, and 22% at the time of the survey. In 735 and 876 patients respectively, LCD and SCD had been prescribed from initiation to the time of the survey. In these two groups, we observed no difference in initiation and current serum levels of Ca and P. But prescription rates for CaCO(3) and VitD analogs were higher in the LCD group than in the SCD group, and PTH levels were higher in the LCD group than in the SCD group. CONCLUSIONS: A beneficial effect of LCD was revealed in the increased doses of CaCO(3) and VitD analogs seen in that group without the occurrence of hypercalcemia; however, PTH levels in that group were not maintained within an acceptable range. The survey suggests that more serious attention should be paid to the Ca concentration in peritoneal dialysate so as to lessen mineral and PTH disorders in CAPD.

Sherif AM, Yoshida H, Maruyama Y, Yamamoto H, Yokoyama K, Hosoya T, Kawakami M, Nakayama M. · Department of Kidney and Hypertension, The Jikei University School of Medicine, Tokyo, Japan. · Ther Apher Dial. · Pubmed #18257810 No free full text.

Abstract: Reports analyzing the histopathological differences between encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis (non-EPS) and those comparing the pathology of early and late EPS are limited. We present pathological comparisons between EPS and non-EPS, also between the early and late EPS stages. We compared peritoneal membrane (PM) samples (Group B) of 12 EPS patients (Group A) and 23 non-EPS cases regarding; mesothelial loss, submesothelial compact zone degenerated layer and compact zone thicknesses, densities of total and diseased vessels, fibrin stain, new membrane formation and degenerative changes. Group A was subdivided into 7 early (group A1) and 8 late (group A2) EPS cases; we compared both subgroups in the same manner and finally compared groups A1, A2, and B. No differences were found between groups A and B in the incidences of mesothelial detachment, new membrane formation and compact zone degenerative changes between the two groups. Furthermore, there were no differences in compact zone thickness, and vascular densities in the compact zone of respective vascular grade. Whereas, fibrin deposition and thickness of the submesothelial degenerated layer were significantly higher in group A than group B (P = 0.01 and 0.05, respectively), and the thickness of the compact zone was less in group A1 than in group A2 (P = 0.03). Positive fibrin stains and thick degenerative compact zone layers are important pathological findings in EPS. Angiogenesis, vasculopathy, new membrane formation, fibrosis and degenerative changes of the compact zone are not unique characteristics for EPS. Larger size studies are recommended to verify this issue.

Inatani M, Iwao K, Kawaji T, Hirano Y, Ogura Y, Hirooka K, Shiraga F, Nakanishi Y, Yamamoto H, Negi A, Shimonagano Y, Sakamoto T, Shima C, Matsumura M, Tanihara H. · Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. · Am J Ophthalmol. · Pubmed #18243153 No free full text.

Abstract: PURPOSE: To determine the risk factors for intraocular pressure (IOP) elevation after the injection of triamcinolone acetonide (TA). DESIGN: Retrospective interventional case-control study. METHODS: SETTING: Multicenter. PATIENT POPULATION: Four hundred and twenty-seven patients. OBSERVATION PROCEDURES: Intraocular pressure levels after TA treatment by the sub-Tenon capsule injection (STI; 12 mg, 20 mg, or 40 mg), intravitreal injection (IVI; 4 mg or 8 mg), or the combination of STI (20 mg) and IVI (4 mg), and IOP levels after two TA treatments. MAIN OUTCOME MEASURE: Risk factors for IOP levels of 24 mm Hg or higher. RESULTS: Younger age (hazards ratio [HR], 0.96/year; P < .0001), IVI (HR, 1.89/year; P < .0001), and higher baseline IOP (HR, 1.15/mm Hg; P = .003) were identified as risk factors. Dose dependency was shown in STI-treated eyes (HR, 1.07/mg; P = .0006), as well as after IVI (HR, 1.64/mg; P = .013). The combination of STI and IVI was a significant risk factor (HR, 2.27; P = .003) compared with STI alone. In eyes receiving two TA treatments, IVI (HR, 2.60; P = .010), higher IOP elevation after the first injection (HR, 1.18/mm Hg; P = .011), and increased dosage of STI (HR, 1.07/mm Hg; P = .033) were risk factors. CONCLUSIONS: Younger age, higher baseline IOP, IVI, and increased TA dosage were associated with TA-induced IOP elevation. IOP elevation after repeated TA injection was frequently associated with eyes treated with IVI, high IOP elevation after the first injection, and high doses of STI.

Yokoyama K, Yoshida H, Matsuo N, Maruyama Y, Kawamura Y, Yamamoto R, Hanaoka K, Ikeda M, Yamamoto H, Nakayama M, Kawaguchi Y, Hosoya T. · Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. · Clin Nephrol. · Pubmed #18218305 No free full text.

Abstract: 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, beta2MG, CRP and PET (peritoneal equilibration test) category (determined by the peritoneal function testing) were analyzed. RESULTS: According to multiple regression analysis, a high beta2MG 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 I(2)2MG measurement as a screening test. The sensitivity was 64% and the specificity was 80% when a beta2MG level of 37.0 mg/dl was taken as the cut-off value. The odds ratio for occurrence of EPS was 8.8 when beta2MG level was in the range of 35 - 40 mg/dl, 13.5 when I(2)2MG level was > 40 mg/dl and 1 when beta2MG level was < 30 mg/dl. CONCLUSION: These findings suggest that beta2MG is useful as a screening test for the onset of EPS, and that beta2MG and accumulation of middle-molecular uremic substances may be related to the pathophysiology of EPS.

Sawada H, Mitani Y, Maruyama J, Jiang BH, Ikeyama Y, Dida FA, Yamamoto H, Imanaka-Yoshida K, Shimpo H, Mizoguchi A, Maruyama K, Komada Y. · Department of Pediatric and Developmental Science, Mie University Graduate School of Medicine, Tsu City, Japan. · Chest. · Pubmed #17934115 links to  free full text

Abstract: BACKGROUND: Pulmonary hypertension (PH) is a fatal disorder that is associated with structural changes and inflammatory responses in the pulmonary vasculature. Nuclear factor (NF)-kappaB is a key transcription factor that is involved in the tissue remodeling mediated by inflammatory and fibroproliferative responses. However, the contribution of NF-kappaB-mediated inflammatory pathways to the development of PH is unknown. METHODS: We therefore investigated whether NF-kappaB activation and the expression of a downstream product vascular cell adhesion molecule (VCAM)-1 is associated with pulmonary vascular diseases in rats that have been injected with the toxin monocrotaline (MCT), and whether a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), ameliorates such diseases in rats. RESULTS: VCAM-1 expression and the nuclear localization of the p65 subunit of NF-kappaB, as analyzed immunohistochemically, was significantly up-regulated in the endothelium of diseased vessels on the days 8 to 22 (p < 0.05). Next, 39 rats were divided into three groups (rats injected with MCT and treated with saline solution or PDTC, and controls similarly treated with saline solution). Compared to controls, MCT treatment increased the mean (+/- SE) pulmonary artery pressure (31.2 +/- 1.4 mm Hg [p < 0.05] vs 22.8 +/- 0.9 mm Hg, respectively), which was reduced by PDTC treatment (24.3 +/- 1.2 mm Hg; p < 0.05). Indexes of right ventricular hypertrophy and pulmonary vascular diseases induced by MCT were similarly inhibited (p < 0.05), which was associated with the suppression of VCAM-1 expression and macrophage infiltration. CONCLUSIONS: We concluded that the NF-kappaB nuclear localization and VCAM-1 expression is temporally and spatially associated with the development of MCT-induced PH in rats, which was ameliorated by administering a NF-kappaB inhibitor, PDTC.

Tsujikawa K, Yayama K, Hayashi T, Matsushita H, Yamaguchi T, Shigeno T, Ogitani Y, Hirayama M, Kato T, Fukada S, Takatori S, Kawasaki H, Okamoto H, Ikawa M, Okabe M, Yamamoto H. · Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. · Proc Natl Acad Sci U S A. · Pubmed #17923674 links to  free full text

Abstract: Calcitonin gene-related peptide (CGRP) is thought to be a prominent neuropeptide in cardiovascular regulation and neuroimmune modulation. There are two isoforms of CGRP (alphaCGRP and betaCGRP), and the main CGRP receptors are probably composed of a calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP)1. However, the physiological functions of CGRP that are mediated through the CLR/RAMP1 receptors remain to be clarified. For an improved understanding of the functions, we generated mice deficient in RAMP1, a specific subunit of CGRP receptors, by a conditional gene-targeting technique. The RAMP1-deficient mice (RAMP1(-/-)) exhibited high blood pressure, with no changes in heart rate. alphaCGRP was found to have a potent vascular relaxant activity compared with betaCGRP in the artery of the WT (RAMP1(+/+)) mice. The activities of both CGRP isoforms were remarkably suppressed in the arteries of the RAMP1(-/-) mice. The LPS-induced inflammatory responses of the RAMP1(-/-) mice revealed a transient and significant increase in the serum CGRP levels and high serum levels of proinflammatory cytokines compared with the RAMP1(+/+) mice. alphaCGRP and betaCGRP equally suppressed the production of TNF-alpha and IL-12 in bone marrow-derived dendritic cells stimulated with lipopolysaccharide. Their inhibitory effects were not observed in the bone marrow-derived dendritic cells of the RAMP1(-/-) mice. These results indicate that CGRP signaling through CLR/RAMP1 receptors plays a crucial role in the regulation of both blood pressure by vascular relaxation and proinflammatory cytokine production from dendritic cells.

Yamamoto H, Teramoto S, Yamaguchi Y, Hanaoka Y, Ishii M, Hibi S, Ouchi Y. · Department of Geriatric Medicine, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · Sleep Med. · Pubmed #17512795 No free full text.

Abstract: BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients compared to an age-matched control group. We further hypothesized that oxygen administration treatment may decrease OSAS-induced hypoxic stress and ADM levels. METHODS: We examined short-term and long-term oxygen administration effects on circulating ADM in 48 OSAS patients. RESULTS: The circulating levels of ADM in untreated OSAS patients were significantly greater than those in the controls. We did not observe a significant effect in 2 weeks of oxygen administration on the circulating ADM in the patients, but we observed a significant effect in long-term oxygen administration for more than 3 months on plasma ADM levels. Long-term oxygen therapy decreased both the magnitude of arterial oxygen desaturation and plasma ADM levels in patients but did not decrease blood pressure. CONCLUSIONS: These observations suggest that long-term oxygen therapy could reduce OSAS-induced nocturnal hypoxemia and plasma ADM levels in patients with OSAS.

Yamamoto I, Yamaguchi Y, Yamamoto H, Hosoya T, Horita S, Tanabe K, Fuchinoue S, Teraoka S, Toma H. · Division of Kidney and Hypertension, The Jikei University School of Medicine, Tokyo, Japan. · Transplant Proc. · Pubmed #17175254 No free full text.

Abstract: Lymphatic vessels are an essential part of the immunological response. Nevertheless, little is known about the pathology of renal transplant rejection. In part the reason may be not distinguishing peritubular capillaries from lymphatic vessels by periodic acid-Schiff (PAS) staining. This study examined the morphology of lymphatic vessels in early renal allografts using double staining with PAS and podoplanin. The 41 cases were divided into four categories: (I) acute antibody-mediated rejection, (II) acute cellular rejection, (III) peritubular capillaritis only, and (IV) controls. I through III had the evidence of peritubular capillaritis exceeding grade 1 on a biopsy obtained an average of 17.3 +/- 5.5 days after kidney transplantation. In addition, each lymphatic vessel density (LVD) and nodular lesion of lymphocytes (NL) were quantified as the number of each podoplanin-positive vascular profiles and NL per unit area of cortex measured Lumina Vision (Mitani). The average of the LVD was 73.0, 35.1, 37.1, and 8.1 per 10 mm2 for groups I to IV and the average of NL was 2.8, 5.5, 1.3, 0.9, respectively. There was a significant correlation between LVD and NL. NL showed a strong relation to the accumulation of lymphocytes in lymphatic vessels (AL); 22% of the AL scores were greater than the peritubular capillaritis grade. We found lymphatic vessels to be strongly associated with any kind of inflammatory process that occurred unexpectedly soon after kidney transplantation. In addition, to avoid misdiagnosis of peritubular capillaritis, NL in early renal allograft must especially be excluded.

Yamamoto M, Nojima M, Ohara M, Suzuki C, Naishiro Y, Itoh Y, Yamamoto H, Takahashi H, Kitajima Y, Endo T, Imai K. · First Department of Internal Medicine, Sapporo Medical University, School of Medicine, South 1-West 16, Chuo-ku, Sapporo 060-8543, Japan. · Mod Rheumatol. · Pubmed #17143701 No free full text.

Abstract: In August 1994, a 19-year-old woman presented to her dermatologist with a slight fever, arthralgia, and a butterfly rash. Discoid lupus erythematosus was suspected, and serological testing yielded positive results for antinuclear antibody. She was diagnosed with systemic lupus erythematosus without organ failure and was treated with only nonsteroidal antiinflammatory drugs. She became pregnant in June 2001, at age 26. In November her obstetrician noted that she had severe hypertension, edema of the low limbs, and proteinuria. On admission, she was diagnosed with severe preeclampsia, and cesarean section was performed. On hospital day 3 the patient developed sudden epigastric pain and vomiting. Laboratory tests revealed thrombocytopenia, liver dysfunction, and microangiopathic hemolytic anemia, leading to a diagnosis of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Plasma exchange was performed for 5 days. The thrombocytopenia, liver dysfunction, and proteinuria diminished quickly. Later testing revealed a high titer of plasma phosphatidylserine-dependent anti-prothrombin antibody. This case is useful for exploring the relations between SLE, HELLP syndrome, and anti-prothrombin antibody.

Koyama H, Shoji T, Fukumoto S, Shinohara K, Shoji T, Emoto M, Mori K, Tahara H, Ishimura E, Kakiya R, Tabata T, Yamamoto H, Nishizawa Y. · Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. · Arterioscler Thromb Vasc Biol. · Pubmed #17082489 links to  free full text

Abstract: OBJECTIVE: Receptor for advanced glycation end-products (RAGE) is involved in diabetic vascular complications. We have recently shown that plasma endogenously secretory RAGE (esRAGE), an alternatively spliced form of RAGE, is closely associated with metabolic syndrome and atherosclerosis. Here, we evaluated if plasma esRAGE is a predictor of cardiovascular mortality in a cohort of 206 (171 nondiabetic) patients with end-stage renal diseases (ESRD). METHODS AND RESULTS: The cohort was followed for a median of 111 months, and 74 deaths including 34 cardiovascular deaths were recorded. Plasma esRAGE was measured at baseline. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly higher in subjects in the lowest tertile of plasma esRAGE than those in the middle or the highest tertile both in all and nondiabetic subjects alone. In all subjects, as compared with the lowest tertile of plasma esRAGE, the hazards ratios for the highest and middle tertile were 0.40 (95% CI, 0.18 to 0.89) and 0.26 (0.10 to 0.66), respectively. The higher risk for lower esRAGE was still significant even after adjusted either with body mass index, hypertension, dyslipidemia and vascular complications, but was confounded by age and diabetes. CONCLUSIONS: Low circulating esRAGE is a predictor for cardiovascular mortality in ESRD patients.