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Enyu Imai

Publications and source records attributed to Enyu Imai.

At least 19 recordsLinked to original sources
PubMed2006

Prospective randomized study evaluating the efficacy of the spherical adsorptive carbon AST-120 in chronic kidney disease patients with moderate decrease in renal function.

AIMS: We studied whether adding the spherical adsorptive carbon AST-120 to conventional treatments is effective in inhibiting progression of chronic kidney disease (CKD) at the stage of moderate decrease in renal function. METHODS: 43 CKD patients with moderately impaired renal function indicated by glomerular filtration rate (GFR) of 20-70 ml/min as measured by non-radiolabeled iothalamate clearance method were enrolled in the study. 26 patients showing a decrease of GFR by 5 ml/min during a 1-year observation period were randomized to receive ongoing treatments only (control group, 12 cases) or with AST-120 co-administered with ongoing treatment (AST-120 group, 14 cases). The intervention period was 1 year and the change in GFR was the primary evaluation variable. RESULTS: The mean changes of GFR per month (DeltaGFR) in the intervention period were not significantly different between both groups. However, when comparing the DeltaGFR in the observation and intervention periods for each group, the rate of decline in GFR was significantly retarded (p < 0.001) in the AST-120 group while no significant difference was observed in the control group. CONCLUSION: These results suggest that co-administration of AST-120 with conventional treatments retards decline in renal function in CKD patients with moderate decrease in renal function.

Administration, Oral↗
PubMed2006

Risedronate, an effective treatment for glucocorticoid-induced bone loss in CKD patients with or without concomitant active vitamin D (PRIUS-CKD).

BACKGROUND: Recent post hoc analysis proved the efficacy and tolerability of risedronate in osteoporotic patients with renal impairment, but the combination of active vitamin D in chronic kidney disease (CKD) patients taking glucocorticoids remains unknown. METHODS: We conducted a prospective study enrolling 114 CKD patients (creatinine clearance > or =30 ml/min/1.73 m(2)) receiving glucocorticoid therapy for > or =6 months. Eighty-eight subjects who had received active vitamin D (aVD) were randomly assigned to either a group treated with aVD only (group A), or to a group also receiving risedronate 2.5 mg/day (group B). The remaining patients (group C) received risedronate only. RESULTS: After 1 year 100 subjects were analysed. Risedronate was effective on the lumbar spine, but not on the femoral neck. The lumbar bone mineral density (BMD) significantly increased by 2.8 and 2.5% in groups B and C, respectively, but decreased by 1.0% in group A. Serum N-terminal telopeptides of type I collagen (S-NTX) and bone alkaline phosphatase (ALP) fell significantly in groups B and C at 3 and 6 months, respectively, while in group A S-NTX remained unchanged and bone ALP significantly increased. There was no significant difference between groups B and C regarding BMD and bone markers. The reduction rate of S-NTX (bone ALP) at 6 months predicted the increase in lumbar BMD at 1 year with a sensitivity of 73% (34%) and a specificity of 46.2% (100%). CONCLUSIONS: Risedronate is effective in increasing BMD with or without aVD in CKD patients receiving long-term glucocorticoid therapy. Bone markers are of some use in predicting the response to anti-resorptive therapy.

Adult↗
PubMed2006

Smooth muscle alpha-actin deficiency in myofibroblasts leads to enhanced renal tissue fibrosis.

Myofibroblasts are a major source of proinflammatory cytokines and extracellular matrix in progressive tissue fibrosis leading to chronic organ failure. Myofibroblasts are characterized by de novo expression of smooth muscle alpha-actin (SMalphaA), which correlates with the extent of disease progression, although their exact role is unknown. In vitro cultured myofibroblasts from kidney of SMalphaA knock-out mice demonstrate significantly more prominent cell motility, proliferation, and type-I procollagen expression than those of wild-type myofibroblasts. These pro-fibrotic properties are suppressed by adenovirus-mediated SMalphaA re-expression, accompanied by down-regulation of focal adhesion proteins. In interstitial fibrosis model, tissue fibrosis area, proliferating interstitial cell number, and type-I procollagen expression are enhanced under SMalphaA deficiency. In mesangioproliferative glomerulonephritis model, cell proliferation in the mesangial area is also enhanced in SMalphaA knock-out mice. Adenoviral SMalphaA introduction into renal interstitium obviously ameliorates tissue fibrosis in interstitial fibrosis model. These results indicate that SMalphaA suppresses the pro-fibrotic properties of myofibroblasts, highlighting the significance of smooth muscle-related proteins in moderating chronic organ fibrosis under pathological conditions.

Actins↗
PubMed2006

Targeting of interstitial cells using a simple gene-transfer strategy.

BACKGROUND: Interstitial fibroblasts are central to the inflammatory response during the progression of tubulointerstitial fibrosis. We examined the efficiency of a new gene transfer method that targets interstitial cells by using parenchymal injection of DNA followed by electroporation. METHODS: Fluoresceinisothiocyanate-labelled oligodeoxynucleotides (FITC-ODNs) or expression vectors were directly injected into the cortex of the kidney, followed by electroporation. RESULTS: Transfection with FITC-ODNs or the EGFP expression vector resulted in efficient transfection in interstitial fibroblasts, but not in tubular epithelial cells or glomerular cells. Transfection efficiency was optimal after using a total of 150 microg of DNA in 1000 microl of PBS, combined with clamping of the renal vessels prior to electroporation. Gene expression peaked at 4 days after transfection and decreased by two orders of magnitude at 6 weeks post-transfection; however, expression recovered to near peak levels after parenchymal or intraperitoneal injection of FR901228, a histone deacetylase inhibitor. CONCLUSION: We demonstrated that direct parenchymal injection of DNA combined with electroporation enables gene transfer into interstitial fibroblasts.

Animals↗
PubMed2006

Serum NTX is a practical marker for assessing antiresorptive therapy for glucocorticoid treated patients with chronic kidney disease.

INTRODUCTION: In chronic kidney disease (CKD) patients, serum concentration of type I collagen N-telopeptide (S-NTX) increases as renal function declines because of perturbed bone metabolism by renal dysfunction itself and impaired urinary excretion of NTX. Glucocorticoid (GC), which is often used for the treatment of kidney disease, may enhance bone resorption. We studied the bone resorption state in GC-treated CKD patients and the effects of bisphosphonate on S-NTX. METHODS: We measured S-NTX and creatinine clearance (Ccr) in 48 non-diabetic patients with declining renal function who had never received GC, vitamin D, calcium or bisphosphonate (reference group). Bone markers including S-NTX and BSAP (bone specific alkaline-phosphatase) in 144 patients receiving GC (prednisone equivalent of > or =2.5 mg/day) for more than 6 months (GC-treated group) were measured. We compared the GC-treated group to the reference group in a cross-sectional study. In a longitudinal study, we further followed 55 patients from the GC-treated group, whose Ccr was more than 60 mL/min (CKD stage 1 or 2) for 1 year after 2.5 mg/day of risedronate was commenced. RESULTS: In the reference group, S-NTX was correlated with Ccr (S-NTX = 456.6/Ccr + 4.5, r = 0.797, P < 0.0001). S-NTX values in the GC-treated group were higher than those found in the reference group at any Ccr. We defined the resorption index (RI) as a ratio of measured S-NTX to estimated NTX given by the correlation curve. Whereas BSAP did not change significantly, S-NTX decreased significantly by risedronate treatment. RI decreased from 1.59 (baseline) to 1.54, 1.25 (P < 0.01, versus baseline) and 1.23 (P < 0.01) at 1, 3 and 6 months after the start of therapy, respectively, which means that S-NTX values approached the correlation curve. Percent changes of S-NTX at 3 months were larger in patients with higher pretreatment S-NTX. CONCLUSION: Higher S-NTX in the GC-treated group suggests that bone resorption is enhanced by GC. In CKD patients with mild renal dysfunction, S-NTX is a practical and useful marker for monitoring bone resorption during GC treatment.

Adolescent↗
PubMed2005

Cyclooxygenase-1-deficient mice have high sleep-to-wake blood pressure ratios and renal vasoconstriction.

We used cyclooxygenase-1 (COX-1)-deficient mice to test the hypothesis that COX-1 regulates blood pressure (BP) and renal hemodynamics. The awake time (AT) mean arterial pressures (MAPs) measured by telemetry were not different between COX-1(+/+) and COX-1(-/-) (131+/-2 versus 126+/-3 mm Hg; NS). However, COX-1(-/-) had higher sleep time (ST) MAP (93+/-1 versus 97+/-2 mm Hg; P<0.05) and sleep-to-awake BP ratio (+8.6%; P<0.05). Under anesthesia with moderate sodium loading, COX-1(-/-) had higher MAP (109+/-5 versus 124+/-4 mm Hg; P<0.05), renal vascular resistance (23.5+/-1.6 versus 30.7+/-1.7 mm Hg . mL(-1) . min(-1) . g(-1); P<0.05) and filtration fraction (33.7+/-2.1 versus 40.2+/-2.0%; P<0.05). COX-1(-/-) had a 89% reduction (P<0.0001) in the excretion of TxB2, a 76% reduction (P<0.01) in PGE2, a 40% reduction (P<0.0002) in 6-ketoPGF1alpha (6keto), a 27% reduction (P<0.02) in 11-betaPGF2alpha (11beta), a 35% reduction (P<0.01) in nitrate plus nitrite (NOx), and a 52% increase in metanephrine (P<0.02). The excretion of normetanephrine, a marker for sympathetic nervous activity, was reduced during ST in COX-1(+/+) (6.9+/-0.9 versus 3.2+/-0.6 g . g(-1) creatinine . 10(-3); P<0.01). This was blunted in COX-1(-/-) (5.1+/-0.9 versus 4.9+/-0.7 g . g(-1) creatinine . 10(-3); NS). Urine collection during ST showed lower excretion of 6keto, 11beta, NOx, aldosterone, sodium, and potassium than during AT in both COX-1(+/+) and COX-1(-/-), and there were positive correlations among these parameters (6keto versus NOx; P<0.005; 11beta versus NOx; P<0.005; and NOx versus sodium; P<0.005). In conclusion, COX-1 mediates a suppressed sympathetic nervous activity and enhanced NO, which may contribute to renal vasodilatation and a reduced MAP while asleep or under anesthesia. COX-1 contributes to the normal nocturnal BP dipping phenomenon.

Aldosterone↗
PubMed2005

Impact of lowering dialysate calcium concentration on serum bone turnover markers in hemodialysis patients.

Loss of renal function perturbs bone metabolism because kidney is a vital organ maintaining homeostasis of calcium and phosphate. In hemodialysis patients, bone diseases are serious complications resulting in fractures and extraosseous calcification. The latest clinical practice guidelines by the National Kidney Foundation (New York, US) recommend a dialysate calcium concentration (D-Ca) of 2.5 mEq/L rather than 3.0 mEq/L to avoid excess calcium load and to prevent subsequent vascular calcification. However, there is no perfect agreement yet about which concentration should be chosen because lowering D-Ca might enhance uncoupled bone resorption. Here, we studied effects of lowering D-Ca from 3.0 to 2.5 mEq/L on bone metabolism in 67 patients. Doses of vitamin D and phosphate binders were kept constant for a 2-month period beginning 1 month before the change in D-Ca, and were adjusted thereafter. In group A [intact parathyroid hormone (iPTH) < 100 pg/ml before the study], serum cross-linked N-terminal telopeptide of type I collagen (NTx) increased immediately after lowering D-Ca and then remained stable. Intact osteocalcin (iOC) increased later along with iPTH, suggesting the improvement of adynamic bone disease which shows a marked decrease in bone turnover without osteoid accumulation. Vitamin D was not dosed up in this group. In group B (100 < or = iPTH < 300), serum NTx increased transiently, which is followed by an increase of iOC but not by a change of iPTH. In group C (300 < or = iPTH), lowering D-Ca allowed us to increase the dose of vitamin D without hypercalcemia, leading to a significant decrease in NTx and iPTH. Overall, serum phosphate increased from 5.4 +/- 1.6 to 6.1 +/- 1.6 mg/dL (P < 0.0001) and serum NTx increased by 1.5-fold (P < 0.0001) 1 month after lowering D-Ca. Over a 3-month period after that, serum phosphate and serum NTx decreased to their basal levels. These indicate that bone resorption predominated over formation for only a short period. In conclusion, a D-Ca of 2.5 mEq/L with adjustment of vitamin D ameliorates metabolic abnormalities of bone which develop under 3.0 mEq/L.

Aged↗
PubMed2005

Prevalence of human polyoma virus (BK virus and JC virus) infection in patients with chronic renal disease.

BACKGROUND: Polyoma virus infection in renal transplant patients is sometimes critical in graft survival. But, to date, polyoma virus infection or reactivation has not been checked before renal transplantation. The prevalence of polyoma viruses (BK virus and JC virus) was investigated in 45 patients with renal disease who were future candidates as renal graft recipients. METHODS: Because these viruses are excreted in urine, the urine of these 45 patients was analyzed by polymerase chain reaction (PCR). The urine of 37 age-matched normal subjects (control group) was also investigated. RESULTS: In the control group, 13.5% of the normal subjects were positive for BK virus and 24.3% were positive for JC virus. In the patients with renal disease, 33.3% were positive for BK virus and 33.3% were positive for JC virus; the prevalence of BK virus infection was significantly higher than that in the normal subjects. Patients with renal disease with corticosteroid therapy revealed an especially high prevalence of BK virus infection (55.6%), indicating the possibility of viral reactivation by corticosteroid therapy. CONCLUSIONS: More attention should be paid to polyoma virus infection in candidates for renal transplantation with a previous therapeutic history of corticosteroid administration.

Adrenal Cortex Hormones↗
PubMed2005

Different routes bridging calcium in Japanese hemodialysis patients.

There is growing evidence that not only serum calcium concentration but also excess calcium load is associated with vascular calcification and mortality in hemodialysis patients. Calcium load in hemodialysis patients cumulatively comes from three different routes: oral intake of calcium including calcium-based phosphate binders, traffic of calcium from/to dialysate, and calcemic action of vitamin D. The K/DOQI guidelines recommend sevelamer hydrochloride instead of calcium-containing phosphate binders to control serum phosphate concentration. However, in Japan, both kinds of phosphate binders are used concomitantly, mainly because Japanese patients are prone to a higher incidence of sevelamer-associated adverse events such as gastrointestinal symptoms. Regarding the calcium concentration of dialysate (D-Ca) in Japan, 3.0 mEq/L is more popular than 2.5 mEq/L. Calcium loaded through 3.0 mEq/L dialysate may lead to metastatic calcification rather than to bone formation because serum phosphate concentration rebounds several hours after the end of each hemodialysis session when plasma pH is still high. In contrast, use of 2.5 mEq/L dialysate may result in an unfavorable increase of intact parathyroid hormone particularly when the amount of oral calcium intake is reduced. Although a higher dose of vitamin D is required to counteract the stimulation of parathyroid glands, hypercalcemia is less likely with 2.5 mEq/L dialysate. As the new K/DOQI guidelines are released, it is time to discuss the appropriate D-Ca as well as doses and kinds of phosphate binders and vitamin D for the comprehensive management of Japanese hemodialysis patients.

Bone and Bones↗
PubMed2005

[Diuretics; their characteristics and future development].

We review the diuretics regarding the mechanism of action, way of clinical use and their adverse effects. Recent progress of molecular biology revealed the molecular target of diuretics and thereby, the molecular mechanism of diuretic action became clear to understand. Loop diuretics and thiazides are the most widely used diuretics and the physiologic adaptation to their prolonged use are mentioned. Carbonic anhydrase inhibitors are not used as diuretics but for correction of metabolic alkalosis and treatment of glaucoma. Potassium-sparing diuretics have modest natriuresis but the combination with loop diuretics or thiazides results in strong natriuresis. Adenosine type 1 receptor antagonist has been developed for treatment of edema in chronic heart failure. Vasopressin type 2 receptor antagonists are developed for a new type of diuretics to increase the free water clearance in cases of chronic heart failure and SIADH. The recombinant atrial natriuretic polypeptide is recently used as diuretics in acute heart failure. Knowledge of pharmacological action of diuretics could help the appropriately clinical use of diuretics, in particular the diuretics-resistant edema.

Diuretics↗