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Kōtō-ku, Japan

Doi K.,Japan Science and Technology Agency | Noiri E.,Japan Science and Technology Agency | Maeda-Mamiya R.,Japan Science and Technology Agency | Ishii T.,Japan Science and Technology Agency | And 7 more authors.
Critical Care Medicine | Year: 2010

Objective: This study is aimed to examine whether urinary L-type fatty acid-binding protein can detect the severity of sepsis with animal sepsis models and septic shock patients complicated with established acute kidney injury. Design: Experimental animal models and a clinical, prospective observational study. Setting: University laboratory and tertiary hospital. Subjects and Patients: One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury. Interventions: Animals were challenged by abdominal (cecal ligation and puncture) and pulmonary (intratracheal lipopolysaccharide injection) sepsis models with different severities that were confirmed by survival analysis (n = 24) and bronchoalveolar lavage fluid analysis (n = 38). Measurements and main results: In animal experiments, significant increases of urinary L-type fatty acid-binding protein levels were induced by sepsis (severe cecal ligation and puncture 399.0 ± 226.8 μg/g creatinine [n = 12], less-severe cecal ligation and puncture 89.1 ± 25.3 [n = 11], sham 13.4 ± 3.4 [n = 10] at 6 hrs, p <.05 vs. sham; 200 μg of lipopolysaccharide 190.6 ± 77.4 μg/g creatinine [n = 6], 50 μg of lipopolysaccharide 145.4 ± 32.6 [n = 8], and saline 29.9 ± 14.9 [n = 5] at 6 hrs, p <.05 vs. saline). Urinary L-type fatty acid-binding protein predicted severity more accurately than blood urea nitrogen, serum creatinine, and urinary N-acetyl-d-glucosaminidase levels. In clinical evaluation, urinary L-type fatty acid-binding protein measured at admission was significantly higher in the nonsurvivors of septic shock with established acute kidney injury than in the survivors (4366 ± 192 μg/g creatinine [n = 68] vs. 483 ± 71 [n = 77], p <.05). Urinary L-type fatty acid-binding protein showed the higher value of area under the receiver operating characteristic curve for mortality compared with Acute Physiology and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) scores (L-type fatty acid-binding protein 0.994 [0.956-0.999], APACHE II 0.927 [0.873-0.959], and SOFA 0.813 [0.733-0.873], p <.05). Conclusions: Our results suggest that urinary L-type fatty acid-binding protein can be a useful biomarker for sepsis complicated with acute kidney injury for detecting its severity. © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Nakamura T.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | Ueda Y.,Dokkyo University | Yamada S.,Shino Test Corporation | Koide H.,Koto Hospital
Blood Purification | Year: 2011

This case report describes polymyxin B-immobilized fiber (PMX-F) treatment of septic shock caused by pyelonephritis in a 68-year-old woman with autosomal dominant polycystic kidney disease. She was admitted for severe lower left abdominal pain, high fever (40°C) and gross hematuria. Her endotoxin and high-mobility group box-1 protein (HMGB1) levels were extremely elevated. Her blood pressure was 68/36 mm Hg. Urinalysis revealed innumerable white blood cells (WBCs). Blood and urine cultures were positive for Klebsiella pneumoniae and Pseudomonas aeruginosa. Plain abdominal radiography showed large kidney shadows and calcium deposition. Septic shock with endotoxemia was diagnosed. Her symptoms of septic shock persisted for 3 days with antibiotics, γ-globulin and dopamine. Direct hemoperfusion was performed twice with a PMX-F column. The patient's body temperature, WBC count and C-reactive protein level decreased. Her blood endotoxin level and blood HMGB1 level also decreased to an almost normal level. She was discharged on day 23 after admission. Copyright © 2011 S. Karger AG, Basel.


Nakamura T.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Fujiwara N.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | And 4 more authors.
Clinical Cardiology | Year: 2011

Background: There is a growing body of evidence that advanced glycation end products (AGE) and their receptor (RAGE) system are implicated in chronic kidney disease (CKD). We have previously found that a long-acting calcium channel blocker, azelnidipine, but not amlodipine, improves renal injury in CKD patients. However, little is known about the effect of azelnidipine on the AGE-RAGE axis in humans. In this study, we examined whether azelnidipine addition could have renoprotective properties in hypertensive CKD patients by reducing serum levels of AGE and soluble form of RAGE (sRAGE). Thirty nondiabetic stage I or II CKD patients who had already been treated with angiotensin II receptor blockers were enrolled in this study. Hypothesis: We hypothesized that azelnidipine treatment could limit renal injury partly by blocking the AGE-RAGE axis. Methods: Patients were randomly divided into 2 groups; one group was treated with 16 mg azelnidipine and the other with 5 mg amlodipine once daily. They were followed up for 6 months. Results: Proteinuria was positively correlated with circulating AGE and sRAGE levels in our subjects. Both drugs exhibited comparable and significant blood pressure (BP)-lowering effects. Although neither of them affected glucose, glycated hemoglobin, lipid levels, and estimated glomerular filtration rate, treatment with azelnidipine, but not amlodipine, decreased circulating AGE, sRAGE, proteinuria, and urinary levels of liver-type fatty acid binding protein, a marker of tubular injury, in a BP-lowering-independent manner. Conclusions: Our present results suggest that azelnidipine may exert renoprotective properties in nondiabetic hypertensive CKD patients via its unique inhibitory effects on the AGE-RAGE axis. © 2011 Wiley Periodicals, Inc.


Nakamura T.,Shinmatsudo Central General Hospital | Fujiwara N.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Ueda Y.,Dokkyo University | And 2 more authors.
Kidney and Blood Pressure Research | Year: 2010

Background: There is increasing evidence that inhibition of the renin-angiotensin system provides renoprotection independent of blood pressure lowering. The aim of the present study was to determine whether various angiotensin II receptor blockers (ARBs) affect urinary albumin excretion (UAE), urinary liver-type fatty acid-binding protein (L-FABP) and 8-hydroxy-2′- deoxyguanosine (8-OHdG) levels in early-stage diabetic nephropathy patients with microalbuminuria. Methods: Sixty-eight diabetic nephropathy patients with microalbuminuria were randomly allocated to 1 of 4 treatment groups: losartan 100 mg/day (group A), candesartan 12 mg/day (group B), olmesartan 40 mg/day (group C), or telmisartan 80 mg/day (group D). Treatment was continued for 12 months. UAE, L-FABP and 8-OHdG excretion, serum creatinine, and 24-hour creatinine clearance (Ccr) were measured. Results: The serum creatinine and 24-hour Ccr were not affected during the experimental period in any of the groups. Systolic and diastolic blood pressures, UAE, urinary L-FABP and 8-OHdG excretion were significantly reduced after 6 and 12 months compared with baseline in any of the groups. ΔL-FABP and Δ8-OHdG were significantly greater in group D than in the other 3 groups after 12 months. Conclusions: ARBs have renoprotection and this effect of telmisartan appears to be more potent than that of losartan, candesartan, or olmesartan in early-stage diabetic nephropathy patients. Copyright © 2010 S. Karger AG.


Nakamura T.,Shinmatsudo Central General Hospital | Sato E.,Shinmatsudo Central General Hospital | Fujiwara N.,Shinmatsudo Central General Hospital | Kawagoe Y.,Shinmatsudo Central General Hospital | And 3 more authors.
American Journal of the Medical Sciences | Year: 2012

BACKGROUNDS: Autosomal dominant polycystic kidney disease (ADPKD) progresses more quickly to end-stage renal disease in patients with hypertension than in their normotensive counterparts. The authors investigated the effect of telmisartan versus enalapril on systolic and diastolic blood pressure (SBP and DBP), urinary albumin excretion (UAE), serum high mobility group box-1 protein (HMGB1), serum interleukin (IL)-6 and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with hypertensive ADPKD. METHODS: Twenty patients with hypertensive ADPKD with good renal function were randomly assigned to 1 of 2 treatments: telmisartan 80 mg once daily (n = 10) or enalapril 10 mg once daily (n = 10). Treatment lasted 12 months. SBP, DBP, serum creatinine, UAE, HMGB1, IL-6 and urinary 8-OHdG levels were measured before and 6 and 12 months after treatment. RESULTS: Both SBP and DBP were significantly reduced after treatment (P < 0.001) in both groups. Serum creatinine changed little during the experimental period in either group. UAE, serum HMGB1, serum IL-6 and urinary 8-OHdG levels were significantly decreased after treatment (UAE, HMGB1 and IL-6, P < 0.001; and 8-OHdG, P < 0.01 versus baseline levels) in both groups. However, the decreases in UAE, serum HMGB1 and serum IL-6 were significantly greater in the telmisartan group than in the enalapril group at 6 months (P < 0.05, P < 0.01 and P < 0.01, respectively) and 12 months (all, P < 0.05). CONCLUSIONS: Telmisartan seems to be equivalent to enalapril in lowering BP, but telmisartan has more potent renoprotective, anti-inflammatory and antioxidative effects than enalapril in patients with hypertensive ADPKD. © Copyright 2012 Southern Society for Clinical Investigation.

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