beraprost and Kidney-Failure--Chronic

Inhibition of the renin-angiotensin system (RAS) has been used to treat diabetic nephropathy. However, RAS inhibition increases the risk of renal complications. In this study, we evaluated the effect of combining RAS inhibitor treatment with beraprost sodium (BPS), a prostaglandin I2 analog, in diabetic nephropathy with arteriosclerosis obliterans.. This study was a prospective, randomized, open-label study. Twenty-six Japanese patients (age >30 years) with diabetic nephropathy and arteriosclerosis obliterans were randomly assigned to the BPS group (n=13), which received the combination of an RAS inhibitor and BPS (120 μg/day) therapy, or the control group (n=13), which received only an RAS inhibitor. Patients were followed up for 1 year. The primary endpoint was the effect of BPS on renal function.. In the control group, serum creatinine (1.64±0.87 to 2.34±1.53 mg/dL, p<0.001), 1/creatinine (0.82±0.47 to 0.65±0.47, p=0.003) cystatin C (1.77±0.61 to 2.18±0.86 mg/L, p<0.001), and the estimated glomerular filtration rate (43.9±26.1 to 34.0±24.6 mL/min/1.73 m(2), p=0.004) were significantly worsened 48 weeks after the start of treatment. Conversely, in the BPS group, serum creatinine (1.71±0.75 to 1.66±0.81 mg/dL, p=0.850), 1/creatinine (0.66±0.19 to 0.71±0.25, p=0.577), cystatin C (1.79±0.55 to 1.80±0.57 mg/L, p=0.999), and the estimated glomerular filtration rate (35.8±10.8 to 38.7±14.4 mL/min/1.73 m(2), p=0.613) were unchanged.. Combination treatment with BPS and an RAS inhibitor prevented the progression of diabetic nephropathy. These observations should be confirmed in large-scale studies with long-term follow-up.

Topics: Aged; Arteriosclerosis Obliterans; Biomarkers; Creatinine; Cystatin C; Diabetic Nephropathies; Disease Progression; Epoprostenol; Female; Glomerular Filtration Rate; Humans; Japan; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renin-Angiotensin System; Time Factors; Treatment Outcome

To evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis.. Sixty-three patients with chronic renal failure due to chronic glomerulonephritis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group (n=20, with alprostadil injection at 10 µg/d for 2 weeks), sequential treatment group (n=21, with alprostadil injection at 10 µg/d for 2 weeks and oral beraprost sodium at 20 µg three times a day for 12 weeks), and strengthened sequential treatment group (n=22, with alprostadil injection at 20 µg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks). Urinary albumin excretion rate (UAER), cystatin C (Cys C), blood urea nitrogen, creatinine, fibrinogen, D-dimer, prothrombin time (PT), and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined.. The patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate (P<0.01) than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group (P<0.01). Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups (P<0.01). After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups (P<0.05) to a comparable level between the 3 groups (P>0.05), and prothrombin time (PT) or platelet showed no significant changes (P>0.05).. Sequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.

Topics: Adolescent; Adult; Aged; Alprostadil; Blood Urea Nitrogen; Chronic Disease; Creatinine; Drug Therapy, Combination; Epoprostenol; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Count; Prothrombin Time; Urological Agents; Young Adult

Renal blood flow decreases with the progression of chronic glomerulonephritis (CGN). This disease induces medullary ischemia and further renal dysfunction in patients with chronic renal insufficiency (CRI). Prostacyclin (PGI2), with its vasodilative action, increases renal blood flow (RBF) without increasing glomerular filtration rate (GFR). We therefore examined the possibility that PGI2 would mitigate the progression of renal dysfunction by increasing RBF in patients with CRI. Sixteen patients with progressive renal insufficiency (serum creatinine: 2.14+/-0.89 mg/dl) due to CGN were prospectively chosen for this study. The blood pressure was already under control using calcium channel blockers before and during this study in nine hypertensive patients. In the first 6 months the patients received a low-protein (0.6 g/kg/day) and low-salt (5.0 g/day) diet. In the next 6 months they received 60 microg/day of PGI2 analogue (Beraprost sodium) orally. GFR was determined by 24-hour creatinine clearance, and effective renal plasma flow (ERPF) was determined by 99mTc-MAG3 scintigraphy. Glomerular capillary pressure, the resistance ratio of afferent and efferent arterioles (R(A)/R(E)), and the other hemodynamic parameters from Gomez's estimation equation were determined at the start of this study, just before the administration of Beraprost and at the end of the study. The levels of GFR and ERPF were 34.6+/-12.4 and 140.6+/-52.1 ml/min at the start of this study respectively, and decreased to 28.0+/- 12.0 and 115.6+/-45.3 ml/min after the first 6 months without Beraprost. The levels of GFR and ERPF stayed at 28.1+/-15.7 and 119.2+/-57.6 ml/min after the next 6 months with Beraprost in the same patients. R(A)/R(E) increased in the first 6 months from 7.9+/-3.6 to 10.8+/-8.6, but remained constant during 6 months of Beraprost administration, at 10.5+/-8.0. These data indicate that PGI2 analogue diminishes the vascular resistance of glomerular afferent and efferent arterioles regulating the decrease of renal blood flow without glomerular hyperfiltration, thus mitigating the progression rate of renal dysfunction.

Topics: Creatinine; Disease Progression; Epoprostenol; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Kinetics; Male; Middle Aged; Renal Circulation; Renal Plasma Flow, Effective; Vasodilator Agents

This study aimed to evaluate the efficacy of beraprost sodium (BPS) or clopidogrel (CL) using vascular thromboembolic events (VTEs) of arteriovenous fistula as a primary endpoint in patients with end-stage renal disease (ESRD) undergoing arteriovenous fistula surgery.. We performed a multicentre, retrospective cohort study from August 2012 to August 2016. We studied patients with ESRD who underwent arteriovenous fistula surgery and received peroral administration of 40 µg BPS, three times per day, for 1 month, or 75 mg CL (initial dose of 300 mg), one time per day, for 1 month. The time to first on-study VTE was the primary endpoint.. The BPS-treated cohort had a significantly delayed time to first VTE compared with the CL-treated cohort (hazard ratio 0.33, 95% confidence interval 0.18-0.56). An increased incidence of VTEs was detected in the 1-month follow-up, with rates of 2.4% and 8.7% for BPS and CL, respectively. This difference persisted over time, with rates of 8.0% and 18.1% at the final follow-up, respectively.. CL-treated patients with ESRD have a greater risk of VTEs compared with BPS-treated patients. CL-treated patients also tend to experience a VTE within the first month after cessation of oral administration.

Topics: Administration, Oral; Adult; Arteriovenous Fistula; Clopidogrel; Drug Administration Schedule; Epoprostenol; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Renal Dialysis; Retrospective Studies; Uremia; Venous Thromboembolism

To assess the time to first on-study vascular thromboembolic events (VTEs) of clopidogrel (CL) or beraprost sodium (BPS) in Chinese population with end-stage renal disease (ESRD) treated with arteriovenous fistula (AVF) surgery.. From Jan 2009 to May 2015, 346 ESRD cases suffering an AVF surgery and undergoing oral administration of 75 mg CL (initial dose of 300 mg), 1 time/day, for 4 weeks or 40 μg BPS, 3 times/day, for 4 weeks were retrospectively assessed. The primary outcome was time to first on-study VTE.. In total, 222 ESRD cases (CL, n = 112; BPS, n = 110) were assessed, with a median follow-up time of 38.1 months (range, 37-40 months). The mean time to first on-study VTE was 1.2 weeks (0.5-2.3) and 1.8 weeks (1.2-3.8) for CL and BPS, respectively (HR 0.27, 95% CI 0.16-1.45; P = 0.00). An increased incidence of VTEs was found during the 1th-month follow-up, with rates of 14.2 and 5.5% for CL and BPS, respectively (P = 0.03). The difference persisted over time, with rates of 24.1 and 11.8% at final follow-up, respectively (P = 0.02).. CL with an increased risk of VTEs tended to have a VTE within the 1st month after cessation compared with BPS.

Topics: Adult; Aged; Arteriovenous Shunt, Surgical; China; Clopidogrel; Constriction, Pathologic; Epoprostenol; Female; Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation Inhibitors; Renal Dialysis; Retrospective Studies; Thrombosis; Time Factors; Young Adult

Hemodialysis vascular access dysfunction, mostly attributed to neointimal hyperplasia, is a major cause of morbidity and hospitalization in patients on hemodialysis. It has been reported that prostaglandin I. Fifty-five patients with end-stage renal disease who were on hemodialysis were prospectively selected for this study. Twenty-three patients were assigned to be treated with 120 µg/day of beraprost sodium, while remaining patients (n = 32) were assigned to a control group. The primary outcome was primary unassisted vascular access patency at 2 years.. The incidence of primary unassisted patency at 2 years was 83% in the beraprost sodium group and 38% in the control group (p = 0.001). Analysis of covariables indicated that this effect occurred mainly as a result of beraprost sodium administration. No life-threatening adverse event or severe bleeding was recorded in any of the groups.. Our data indicated that an oral prostaglandin I

Topics: Aged; Arteriovenous Shunt, Surgical; Epoprostenol; Female; Humans; Hyperplasia; Kidney Failure, Chronic; Male; Middle Aged; Neointima; Platelet Aggregation Inhibitors; Prospective Studies; Renal Dialysis; Secondary Prevention; Time Factors; Vascular Patency