Tatsuo Hosoya

The Jikei University School of Medicine, Tokyo, Tokyo-to, Japan

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Publications (384)1037.88 Total impact

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    ABSTRACT: Background/Aims: Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. Methods: In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 ± 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. Results: At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 ± 0.11, and 1.8 ± 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. Conclusions: In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=368389 © 2014 S. Karger AG, Basel.
    Blood Purification 11/2014; 38(2):149-153. · 1.92 Impact Factor
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    ABSTRACT: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder caused by mutations in UMOD that encodes uromodulin. Topiroxostat, a novel non-purine analog, selectively inhibits xanthine oxidase and reduces the serum uric acid levels and the urinary albuminuria.
    Clinical and Experimental Nephrology 09/2014; · 1.71 Impact Factor
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    ABSTRACT: Hyperuricemia (HU) is common in patients with chronic kidney disease (CKD), and accumulating evidence suggests it has a pathogenic role in the progression of the disease. However, a major challenge in treating patients with HU is the adverse effects caused by urate-lowering drugs used to treat CKD. Because of these untoward effects, doses need to be reduced, which leads to suboptimal efficacy. Febuxostat has been shown to be highly efficacious in reducing serum uric acid (sUA) and is well tolerated in patients with mild kidney dysfunction. However, its safety and efficacy have not been well studied in more advanced cases of CKD. We studied the safety and efficacy of escalating doses of febuxostat over a 24-week period in 70 patients with CKD stages 3b, 4 and 5, and we also observed the changes in blood pressure, estimated glomerular filtration rate (eGFR) and proteinuria following the reduction of sUA. Drug-related adverse events (AEs) occurred in only 5 out of 70 patients. All but one of the events were mild, and all five patients fully recovered. By 24 weeks, the reduction of sUA levels was >40% in CKD stage 3b and >50% in CKD stages 4 and 5. More than 70% of patients achieved target sUA levels of 6 mg dl(-1) or less. Multivariate analysis showed that a greater reduction in sUA with febuxostat was associated with an increase in eGFR and a tendency toward decreased proteinuria. Febuxostat was safe and efficacious in the treatment of CKD stages 3b-5.Hypertension Research advance online publication, 19 June 2014; doi:10.1038/hr.2014.107.
    Hypertension Research 06/2014; · 2.94 Impact Factor
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    ABSTRACT: Gout/hyperuricemia is a common multifactorial disease having typical environmental risks. Recently, common dysfunctional variants of ABCG2, a urate exporter gene also known as BCRP, are revealed to be a major cause of gout/hyperuricemia. Here, we compared the influence of ABCG2 dysfunction on serum uric acid (SUA) levels with other typical risk factors in a cohort of 5,005 Japanese participants. ABCG2 dysfunction was observed in 53.3% of the population investigated, and its population-attributable risk percent (PAR%) for hyperuricemia was 29.2%, much higher than those of the other typical environmental risks, i.e. overweight/obesity (BMI ≥ 25.0; PAR% = 18.7%), heavy drinking (>196 g/week (male) or >98 g/week (female) of pure alcohol; PAR% = 15.4%), and aging (≥60 years old; PAR% = 5.74%). SUA significantly increased as the ABCG2 function decreased (P = 5.99 × 10(-19)). A regression analysis revealed that ABCG2 dysfunction had a stronger effect than other factors; a 25% decrease in ABCG2 function was equivalent to "an increase of BMI by 1.97-point" or "552.1 g/week alcohol intake as pure ethanol" in terms of ability to increase SUA. Therefore, ABCG2 dysfunction originating from common genetic variants has a much stronger impact on the progression of hyperuricemia than other familiar risks. Our study provides a better understanding of common genetic factors for common diseases.
    Scientific Reports 06/2014; 4:5227. · 5.08 Impact Factor
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    ABSTRACT: Calcium channel blockers are one of the most useful antihypertensive agents because of their definite blood pressure lowering action. Although the antihypertensive effect of calcium channel blockers is attributed predominantly to the blockade of L-type calcium channels, recent studies demonstrate that the blockade of other subtypes of calcium channels, including T-type and N-type calcium channels, offers renal protective action because of their beneficial action on glomerular capillary pressure, renal fibrotic process, sympathetic nerve activity and aldosterone synthesis. It requires more extensive studies to clarify whether the ostensibly beneficial actions of these calcium channel blockers are available in a clinical setting.
    Current Hypertension Reviews 05/2014; 9(3):187-192.
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    ABSTRACT: ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is identified as a high-capacity urate exporter, and its dysfunction has an association with serum uric acid levels and gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate "overproduction type," "underexcretion type," and "combined type" based on only renal urate excretion, without considering an extra-renal pathway such as gut excretion. In this study, we investigated the effects of ABCG2 dysfunction on human urate handling and the mechanism of hyperuricemia. Clinical parameters for urate handling including urinary urate excretion (UUE) were examined in 644 Japanese male outpatients with hyperuricemia. The severity of their ABCG2 dysfunction was estimated by genotype combination of two common ABCG2 variants, nonfunctional Q126X (rs72552713) and half-functional Q141K (rs2231142). Contrary to the general understanding that ABCG2 dysfunction leads to decreased renal urate excretion, UUE was significantly increased by ABCG2 dysfunction (P = 3.60 × 10(-10)). Mild, moderate, and severe ABCG2 dysfunctions significantly raised the risk of "overproduction" hyperuricemia including overproduction type and combined type, conferring risk ratios of 1.36, 1.66, and 2.35, respectively. The present results suggest that common dysfunctional variants of ABCG2 decrease extra-renal urate excretion including gut excretion and cause hyperuricemia. Thus, "overproduction type" in the current concept of hyperuricemia should be renamed "renal overload type," which is caused by two different mechanisms, "extra-renal urate underexcretion" and genuine "urate overproduction." Our new concept will lead to a more accurate diagnosis and more effective therapeutic strategy for hyperuricemia and gout.
    Nucleosides Nucleotides &amp Nucleic Acids 04/2014; 33(4-6):266-274. · 0.89 Impact Factor
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    ABSTRACT: Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, unlike calcium, phosphate or parathyroid hormone, the relationship between serum ALP and patient outcome receiving hemodialysis (HD) in Japan is unknown. Baseline data of 185 277 HD patients with duration >90 days (66 ± 12 years, males 61.9%, and median HD duration of 5.8 years) were extracted from a nationwide dialysis registry at the end of 2009 in Japan. Outcomes were then evaluated using the registry at the end of 2010 using a multivariate logistic regression analysis. During 1-year follow-up, 14 230 (7.9%) patients died of all causes, including 6396 (3.6%) cardiovascular deaths. In addition, 1586 patients (1.0%) were newly diagnosed as hip fractures. All-cause and cardiovascular mortality and the incidence of hip fracture were higher in line with the increase in baseline serum ALP. On multivariate analysis, patients with the highest ALP quartile had higher all-cause and cardiovascular mortalities and a higher incidence of hip fracture than those with the lowest quartile [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.33-1.60; OR 1.25, 95% CI 1.10-1.42; and OR 1.71, 95% CI 1.33-2.18, respectively]. In this large cohort study, higher serum ALP levels were independently associated not only with mortality but also with the incidence of hip fracture in Japanese HD patients. Further study is needed to test whether serum ALP measurements could improve the patient outcomes.
    Nephrology Dialysis Transplantation 03/2014; · 3.37 Impact Factor
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    ABSTRACT: To elucidate the genotypic and phenotypic characteristics of Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Japanese populations, we performed a comprehensive search for mutations in PKD1 and PKD2 in 180 Japanese ADPKD patients from 161 unrelated families. We identified 112 (89 PKD1 and 23 PKD2) mutations within 135 families. Patients with PKD2 mutations account for 23.6% of all Japanese ADPKD families in this study. Seventy-five out of the 112 mutations have not been reported previously. The estimated glomerular filtration rate (eGFR) decline was significantly faster in patients with PKD1 mutations than in those with PKD2 mutations (−3.25 and −2.08 ml · min−1 · year−1 for PKD1 and PKD2, respectively, p < 0.01). These results indicate that mutations within PKD1 and PKD2 can be linked to most of the cases of Japanese ADPKD, and the renal function decline was faster in patients with PKD1 mutations than in those with PKD2 mutations also in the Japanese ADPKD. We also found that PKD2 mutations were more frequent in Japanese ADPKD than that in European or American ADPKD.
    Clinical Genetics 03/2014; · 3.65 Impact Factor
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    ABSTRACT: Bioelectrical impedance analysis (BIA) is a non-invasive method to estimate total body water (TBW) and extracellular water (ECW) volume. Crit-Line(®) (CL), on the other hand, assesses intravascular water (IVW) volume. We evaluate continuous changes in body water composition during hemodialysis (HD) with concurrent use of BIA and CL. BIA at the start and the end of the HD session was measured using a BIA device. To investigate the shifting pattern of body water composition, patients were subjected to simultaneous monitoring of BIA with CL. Both TBW resistance (Rt) and ECW resistance (Re) increased in response to changes in the ultrafiltration (UF) ratio. There was a positive correlation between ΔRe/Rt and the UF ratio, and the ratio of Re/Rt at the end of HD was significantly higher than that at the start of HD. Simultaneous monitoring of BIA with CL showed a parallel shift of the change in the Re (ΔRe) and the change in hematocrit (ΔHt). In one patient with increasing inflammatory response, change in ΔHt was dissociated from change in ΔRe. One hyponatremic patient showed a different pattern of changing ΔRe between the first half and the latter half of the HD session. Our study suggests that the concurrent use of BIA and CL may be a useful technique to simulate water shift patterns across the different compartments in HD.
    Clinical and Experimental Nephrology 02/2014; · 1.71 Impact Factor
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    ABSTRACT: NFE2-related factor 2 (Nrf2) is a master regulatory transcription factor for antioxidant genes. Inhibition of its adaptor protein, Kelch-like ECH-associated protein 1 (Keap1), activates Nrf2. Podocyte injury triggers the progressive deterioration of glomerular damage toward glomerulosclerosis. We examined whether modulation of the Keap1-Nrf2 system has an impact on this process. Nrf2 null-mutant (KO) and Keap1 hypomorphic knockdown (KD) mice were crossed with NEP25 mice, in which podocyte-specific injury can be induced by an immunotoxin. Thiobarbituric acid reactive substances, 8-hydroxydeoxyguanosine and phosphorylated JNK were increased in the injured NEP25 kidney. Real-time PCR revealed that Keap1 KD upregulated Nrf2 target genes, including Gclc, Gclm, Gstp1, Gstp2 and Nqo1 in the glomerulus. However, podocyte injury did not upregulate these genes in Keap1 wild-type mice, nor did it further increase the expression of those genes in Keap1 KD mice. Three weeks after the induction of podocyte injury, glomerulosclerosis was considerably more attenuated in Keap1 KD mice than in control mice (median sclerosis index, 0.27 versus 3.03, on a 0-4 scale). Keap1 KD mice also showed considerably preserved nephrin staining (median index, 6.76 versus 0.91, on a 0-8 scale) and decreased glomeruli containing desmin-positive injured podocytes (median percentage, 24.5% versus 85.8%), along with a decrease in mRNAs for Fn1, Tgfb1, Col4a4 and Col1a2. Thus, podocyte injury cannot effectively activate Nrf2, but Nrf2 activation by Keap1 knockdown attenuates glomerulosclerosis. These results indicate that the Nrf2-Keap1 system is a promising drug target for the treatment of chronic kidney diseases.
    Nephrology Dialysis Transplantation 02/2014; · 3.37 Impact Factor
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    ABSTRACT: Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long-term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long-term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non-EPS. To evaluate the impact of PD-associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non-EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non-EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long-term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD-associated peritonitis could be critical in preventing EPS.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 02/2014; 18(1):68-73. · 1.53 Impact Factor
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    ABSTRACT: Topiroxostat, a selective xanthine oxidase inhibitor, shows effective reduction in the serum urate level in hyperuricemic patients with or without gout. The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout. The study design was a 22-week, randomized, multicenter, double-blind study. The enrolled patients were randomly assigned to treatment with topiroxostat 160 mg/day (n = 62) or to the placebo (n = 61). The endpoints were the percent change in the serum urate level, change in the estimated glomerular filtration rate, the urinary albumin-to-creatinine ratio, the proportion of patients with serum urate levels of 356.88 μmol/L or less, blood pressure, and serum adiponectin. After 22 weeks, although the changes in the estimated glomerular filtration rate and blood pressure were not significant, the percent change in the serum urate level (-45.38 vs. -0.08 %, P < 0.0001) and the percent change in urinary albumin-to-creatinine ratio (-33.0 vs. -6.0 %, P = 0.0092) were found to have decreased in the topiroxostat as compared with the placebo. Although the incidence of 'alanine aminotransferase increased' was higher in the topiroxostat, serious adverse event rates were similar in the two groups. Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout.
    Clinical and Experimental Nephrology 01/2014; · 1.71 Impact Factor
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    ABSTRACT: Gout is a common disease which results from hyperuricemia. We have reported that the dysfunction of urate exporter ABCG2 is the major cause of renal overload (ROL) hyperuricemia, but its involvement in renal underexcretion (RUE) hyperuricemia, the most prevalent subtype, is not clearly explained so far. In this study, the association analysis with 644 hyperuricemia patients and 1,623 controls in male Japanese revealed that ABCG2 dysfunction significantly increased the risk of RUE hyperuricemia as well as overall and ROL hyperuricemia, according to the severity of impairment. ABCG2 dysfunction caused renal urate underexcretion and induced hyperuricemia even if the renal urate overload was not remarkable. These results show that ABCG2 plays physiologically important roles in both renal and extra-renal urate excretion mechanisms. Our findings indicate the importance of ABCG2 as a promising therapeutic and screening target of hyperuricemia and gout.
    Scientific Reports 01/2014; 4:3755. · 5.08 Impact Factor
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    ABSTRACT: Hyperuricemia is a risk factor for the onset of chronic kidney disease (CKD) and is significantly associated with the progression of CKD. However, there is no sufficient evidence by interventional research supporting a cause-effect relationship. Hyperuricemic patients without gouty arthritis, whose serum urate (SUA) concentration is >=8.0 mg/dL and who have a complication, are treated by pharmacotherapy in addition to lifestyle guidance. Nevertheless, there is no evidence that rationalizes pharmacotherapy for patients with hyperuricemia who have no complication and whose SUA concentration is below 9.0 mg/dL. The FEATHER (FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3) study is a prospective, multicenter, double-blind, randomized, placebo-controlled trial of febuxostat--a novel, nonpurine, selective, xanthine oxidase inhibitor. The present study will enroll, at 67 medical institutions in Japan, 400 Japanese patients aged 20 years or older who have hyperuricemia without gouty arthritis, who present CKD stage 3, and whose SUA concentration is 7.1-10.0 mg/dL. Patients are randomly assigned to either the febuxostat or the control group, in which febuxostat tablets and placebo are administered orally, respectively. The dosage of the study drugs should be one 10-mg tablet/day at weeks 1 to 4 after study initiation, increased to one 20-mg tablet/day at weeks 5 to 8, and elevated to one 40-mg tablet/day at week 9 and then maintained until week 108. The primary endpoint is estimated glomerular filtration rate (eGFR) slope. The secondary endpoints include the amount and percent rate of change in eGFR from baseline to week 108, the amount and percent rate of change in SUA concentration from baseline to week 108, the proportion of patients who achieved an SUA concentration <=6.0 mg/dL, and the incidence of renal function deterioration. The present study aims to examine whether febuxostat prevents a further reduction in renal function as assessed with eGFR in subjects and will (1) provide evidence to indicate the inverse association between a reduction in SUA concentration and an improvement in renal function and (2) rationalize pharmacotherapy for subjects and clarify its clinical relevance.Trial registration: UMIN Identifier: UMIN000008343.
    Trials 01/2014; 15(1):26. · 2.12 Impact Factor
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    ABSTRACT: Recently, the number of patients with gout and hyperuricemia has increased in Japan; therefore, we expected to find an increase in the number of uric acid stones in our study. We examined the frequency of uric acid stones and its relationship with the number of patients with gout and hyperuricemia or their nutritional state. We reviewed the records of 5477 patients with urolithiasis who visited our hospital between 1975 and 1993. During this period, the incidence of calcium-containing stones remained at 86%. The percentage incidence of uric acid and urate stones during the same period showed a steady increase to 7.2%. This increase was computed to be 3-fold that of 1975. The male gender dominates among the patients with uric acid and urate stones. We believe that the increases in the incidence of gout and hyperuricemia and alcohol consumption are responsible for this trend.
    Modern Rheumatology 01/2014; 7(2):135-144. · 2.21 Impact Factor
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    ABSTRACT: Serum uric acid (UA) concentration is regulated by its production in the liver and/or intestine and its rate of excretion from the kidneys. However, little is known about skeletal muscle involvement in determining the physiological UA level. The present trial explores whether muscle strength and/or muscle volume is associated with UA levels. Muscle strength was evaluated in terms of grasping power calculated as an average of right and left hand measurements in relation to other parameters in 14,333 subjects (median age; 41.2 years), who were recruited to the study. Skeletal muscle volume was calculated based on the bioimpedance method by subtracting estimated fat volume plus estimated bone weight from the total body weight. 1) Multiple regression analyses to explain the association with UA levels (dependent variable) revealed that BMI, BUN, triglyceride, muscle strength, AST, age and sex are independent variables. 2) Higher UA levels (assessed as 4 UA quartiles) are associated with higher muscle volume, muscle strength, BMI, DBP, and serum creatinine (Cr) concentration. 3) Greater DBP (assessed as 2 UA categories) was associated with higher BMI, muscle strength, muscle volume, UA levels and serum Cr concentration. 4) Regression coefficient "t" for muscle strength was the largest among the other parameters including serum Cr concentration in the UA level ranging from 5.5 to 6.5 mg/dL. There was an association between muscle strength/volume and UA levels in the near physiological UA range, suggesting that the circulating UA levels can be, at least in part, controlled by its production in the skeletal muscles.
    Nihon Jinzo Gakkai shi. 01/2014; 56(8):1260-9.
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    ABSTRACT: The detector system of SENJU—a single-crystal time-of-flight neutron diffractometer—is described. SENJU is the first diffractometer employing a large-area two-dimensional wavelength-shifting fiber-based scintillator detector at the Materials and Life Science Experimental Facility at the Japan Proton Accelerator Research Complex. Thirty-seven detectors were installed in the instrument to cover a scattering angle of 30%. The detector modules exhibited a detector efficiency of 37–47±1% (mean±standard deviation) for thermal neutrons, a 60Co gamma-ray sensitivity of 1.4–5.1±0.1×10‑6, a background count rate of 2.1–3.8±1.0×10‑4 cps/cm2 and a tolerance to stray magnetic fields up to 120 G. The detector exhibited stable performance under the operating conditions used, such as stable count rates over 400 days and a count temperature coefficient of ‑0.01±0.02%/°C at around 20 °C. The detector system and its performance metrics are presented together with the specific detector design.
    Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment 01/2014; · 1.32 Impact Factor
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    ABSTRACT: Recent studies have reported that podocytes are postnatally generated from progenitor cells localized in Bowman's capsule or in the bone marrow. In the present study, we investigated whether or not podocyte regeneration is important in the repair of injured glomeruli after mild podocyte injury in mice. Mild podocyte injury was induced in NEP25 mice (n = 8) by injecting an immunotoxin, LMB2 (0.625 ng/g body weight). Control mice, not injured by LMB2 injection (n = 7) was used as a comparison. Proliferating cells were labeled by continuous infusion of bromodeoxyuridine (BrdU). Podocytes, identified by nephrin, WT1 or podocin staining, that had incorporated BrdU were enumerated 4 weeks later. A total of 742 corpuscles were inspected in serial sections stained for BrdU and nephrin; 19% showed sclerosis. BrdU(+) cells were observed in both the glomeruli and Bowman's capsules, averaging 2.5 ± 3.1 in non-sclerotic corpuscles and 7.0 ± 5.8 in sclerotic corpuscles. Only one BrdU(+) cell was also positive for nephrin. Another cell, localized at a position consistent with its potential identification as a podocyte, was nephrin negative but had incorporated BrdU. WT1 staining similarly revealed that only two nuclei were doubly positive for BrdU and WT1. Additional 1676 corpuscles were inspected by double staining for BrdU and podocin; none were doubly positive. Podocytes are not replenished by proliferation of endogenous progenitor cells in mice with glomerular injury.
    Nephrology Dialysis Transplantation 12/2013; · 3.37 Impact Factor
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    ABSTRACT: Pigment epithelium-derived factor (PEDF) plays a protective role against atherosclerosis. Although serum PEDF level is increased in patients undergoing regular hemodialysis (HD), the pathophysiological role of PEDF in HD patients is unknown. We measured serum PEDF levels in 74 HD patients, and the association between serum PEDF and adverse events such as all-cause death and cardiovascular accident was evaluated prospectively. During the follow up of 45.4 ± 25.1 months, 24 patients (32.4%) experienced cardiovascular accident and 18 (24.3%) died. Significantly higher incidences of all-cause mortality and cardiovascular accident were observed in the lower PEDF group than in the higher PEDF group. After adjusting for propensity score calculated from multiple confounding factors (age, gender, systolic blood pressure, history of previous cardiovascular disease, level of carbonyl content, albumin, hemoglobin, total cholesterol, creatinine, C-reactive protein, dialysis vintage, Kt/V-urea and history of diabetes), lower predialytic PEDF was a significant risk factor for all-cause mortality (relative hazard = 6.060, standard error = 0.68467, P = 0.0085). Lower levels of predialytic PEDF was associated with an increased risk of mortality.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 12/2013; 17(6):625-630. · 1.53 Impact Factor
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    ABSTRACT: Applying a direct renin inhibitor (DRI) to advanced stage chronic kidney disease (CKD) patients is a matter of controversy. The purpose of this study was to evaluate the effect of the DRI, aliskiren, in patients with therapy-resistant hypertension undergoing hemodialysis (HD). The study was a prospective, randomized multicenter trial exploring the antihypertensive effect of aliskiren in comparison with amlodipine, a calcium channel blocker, in patients undergoing HD. A total of 83 participants whose blood pressure (BP) had previously been treated with more than one antihypertensive agent and not having achieved the BP goal of <140/90 mmHg were randomly assigned to either aliskiren 150 mg or amlodipine 5 mg as an add-on therapy. A significant decrease in pre-dialysis clinic BP and home BP was found only in the amlodipine group and not in the aliskiren group. In contrast, there was a significant decrease in atrial natriuretic peptide (ANP) in the aliskiren group but not in the amlodipine group. N-terminal pro-B-type natriuretic hormone remained unchanged in both groups. Aliskiren significantly reduced angiotensin I and II, plasma renin activity, and increased plasma renin content. However, such changes were not observed in the amlodipine group. Amlodipine, not aliskiren, effectively reduces BP in CKD patients with refractory hypertension undergoing HD. Aliskiren suppresses the renin-angiotensin system and reduces ANP. Whether the DRI is beneficial in improving cardiovascular events in patients undergoing HD remains to be elucidated in future studies.
    Clinical and Experimental Nephrology 11/2013; · 1.71 Impact Factor

Publication Stats

4k Citations
1,037.88 Total Impact Points


  • 1990–2014
    • The Jikei University School of Medicine
      • • Department of Internal Medicine H
      • • Division of Kidney and Hypertension
      Tokyo, Tokyo-to, Japan
  • 2013
    • Fukushima Medical University
      Hukusima, Fukushima, Japan
    • RIKEN
      • Laboratory for Endocrinology, Metabolism and Kidney Diseases
      Wako, Saitama-ken, Japan
  • 2009–2013
    • National Defense Medical College
      Tokorozawa, Saitama, Japan
  • 2012
    • Ibaraki University
      • College of Engineering
      Mito-shi, Ibaraki-ken, Japan
  • 1998–2009
    • Tokyo Saiseikai Central Hospital
      Edo, Tōkyō, Japan
    • Toranomon Hospital
      Edo, Tōkyō, Japan
    • Hirosaki University
      Khirosaki, Aomori Prefecture, Japan
  • 2008
    • Kanagawa Children's Medical Center
      Yokohama, Kanagawa, Japan
    • Tokyo Women's Medical University
      Edo, Tōkyō, Japan
    • Tokyo University of Pharmacy and Life Science
      • Department of Pathophysiology
      Tokyo, Tokyo-to, Japan
    • Numazu City Hospital
      Sizuoka, Shizuoka, Japan
  • 2004
    • Teijin
      Edo, Tōkyō, Japan
    • Tottori University
      TTJ, Tottori, Japan
  • 2002–2004
    • Kyorin University
      Edo, Tōkyō, Japan