Beraprost sodium improves survival rates in anti-glomerular basement membrane glomerulonephritis and 5/6 nephrectomized chronic kidney disease rats

Yamaguchi, S.; Inada, Chifumi; Tamura, Mina; Sato, Nahoko; Yamada, Masahiro; Itaba, Shoichi; Okazaki, Seiji; Matsuura, Hirotoshi; Fujii, Shigeo; Matsuda, Fuko; Goto, Yasufumi; Mochizuki, Hidenori; Kurumatani, Hajimu; Miyamoto, M.

doi:10.1016/j.ejphar.2013.07.032

Cited by 25 publications

(28 citation statements)

References 24 publications

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“…Thus, inhibiting an increase in the sCr level might improve the prognosis of cats with CKD. BPS treatment has previously significantly improved survival in rat models of kidney disease . Further studies evaluating the potential effect of BPS on long‐term survival in cats with CKD are therefore needed.…”

Section: Discussionmentioning

confidence: 99%

“…Beraprost sodium (BPS) is an orally available prostacyclin analog that is used in humans to treat pulmonary arterial hypertension and atherosclerosis obliterans . BPS has a renoprotective effect in animal models of CKD . For instance, BPS inhibits the expression of inflammatory factors (notably monocyte chemoattractant protein‐1), inhibited apoptosis of renal microvascular endothelial and tubular epithelial cells, and inhibited tubulointerstitial fibrosis .…”

Section: Introductionmentioning

confidence: 99%

“…For instance, BPS inhibits the expression of inflammatory factors (notably monocyte chemoattractant protein‐1), inhibited apoptosis of renal microvascular endothelial and tubular epithelial cells, and inhibited tubulointerstitial fibrosis . Furthermore, BPS treatment improved the time to doubling of serum creatinine (sCr) and survival rates in 2 rat models of CKD . BPS improves renal hypoxia in a rat model of glomerulonephritis and is efficacious in humans with CKD .…”

Section: Introductionmentioning

confidence: 99%

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A Double‐blind, Placebo‐controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease

Takenaka¹,

Iio

Sato

et al. 2017

Veterinary Internal Medicne

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BackgroundChronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated.Hypothesis/ObjectivesTo evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo.AnimalsSeventy‐four client‐owned cats with naturally occurring CKD.MethodsDouble‐blind, placebo‐controlled, multicenter, prospective, randomized trial. The cats received BPS (55 μg/cat) or a placebo PO q12 h for 180 days. The primary endpoint was prospectively defined as a change in the serum creatinine (sCr), serum phosphorus‐to‐calcium ratio or urine specific gravity (USG).ResultsThe sCr increased significantly (P = 0.0030) in the placebo group (mean ± SD: 2.8 ± 0.7 to 3.2 ± 1.3 mg/dL) but not in the BPS group (2.4 ± 0.7 to 2.5 ± 0.7 mg/dL). The difference between the groups at day 180 was significant (0.8 mg/dL, 95% CI: 0.2 to 1.3 mg/dL, P = 0.0071). The serum phosphorus‐to‐calcium ratio was significantly (P = 0.0037) increased in the placebo group (0.46 ± 0.10 to 0.52 ± 0.21 mg/dL) but not in the BPS group (0.50 ± 0.08 to 0.51 ± 0.11 mg/dL). There was no significant change in the USG in either group. An adverse event judged as being treatment‐related included vomiting that occurred in 1 case in the placebo group. No clinically relevant change was observed in the CBC and other blood chemistry tests.Conclusions and Clinical ImportanceBeraprost sodium treatment was well tolerated and safe in cats with CKD. BPS inhibited the reduction in renal filtration function as measured by sCr increase.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Double‐blind, Placebo‐controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease

Takenaka¹,

Iio

Sato

et al. 2017

Veterinary Internal Medicne

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“…BPS, a new, stable, orally active PGI2 analogue, possesses antiplatelet and vasodilating properties [20]. Inada et al demonstrated that BPS improved survival in patients with CRD [21], while Shimamura et al suggested that certain dosages of BPS provided therapeutic efficacy in patients suffering from CRF [22]. In addition, BPS significantly inhibits glomerular hypertension and hyperfiltration, which may limit the progression of renal injury, while renal ablation causes hemodynamic changes in remnant nephrons, which engage in proinflammatory processes and profibrotic mechanisms, thereby amplifying nephron loss.…”

Section: Discussionmentioning

confidence: 99%

Beraprost Sodium, a Stable Analogue of PGI2, Inhibits the Renin-Angiotensin System in the Renal Tissues of Rats with Chronic Renal Failure

Wang¹,

Zhang²,

Lu³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Chronic renal failure (CRF) is a prolonged kidney condition characterized by decreased kidney function that can eventually develop into total kidney failure. The renin-angiotensin system (RAS) helps to regulate the balance between human bodily fluids and electrolytes. The aim of the present study was to investigate the effects of a prostacyclin analogue (beraprost sodium [BPS]) on the expression of key factors associated with local RAS activities in the renal tissues of rats with CRF. Methods: After a CRF rat model was successfully established, the levels of BUN, SCr, phosphorus, and calcium were detected by an automatic biochemistry analyzer. Furthermore, the activities of malondialdehyde (MDA) and superoxide dismutase (SOD) in rat renal tissues were measured using a colorimetric method, while the activity of angiotensin-converting enzyme (ACE) was determined by ultraviolet (UV) spectrophotometry. In situ hybridization was employed to determine the expression of angiotensin II type 1 receptor (AT). Finally, the positive expression rates of cells expressing important apoptotic proteins (Bax and Bcl-2) were determined, and the protein and mRNA levels of phosphatidylinositol 3-kinase (AKT) and key factors involved in the RAS (AT1, AT2, angiotensin ACE and angiotensinogen [AGT]) were evaluated by RT-qPCR and western blot analysis. Results: Initial observations revealed that treatment with BPS decreased the levels of BUN, SCr and phosphorus but increased calcium levels in the renal tissues of CRF rats. Additionally, BPS reduced the levels of MDA while increasing the levels of SOD, ACE activity, and AT1 expression in the renal tissues of CRF rats. BPS inhibited glomerular hypertension and hyperfiltration; increased the mRNA and protein levels of AKT and AT2; and decreased the mRNA and protein levels of AT1, AGT, and ACE in the renal tissues of CRF rats. Conclusion: The results of this study demonstrate that BPS, a PGI2 analogue, inhibits the expression of key factors involved in the local RAS, resulting in a delay in the occurrence and development of CRF. The key findings of the present study ultimately highlight the potential of this PGI2 analogue as a promising therapeutic strategy for treating CRF.

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“…Prostacyclin analog Beraprost-Na delayed the doubling of creatinine in 5/6 rat nephrectomy model [138], anti-GBM model [138,139] and has a possible effects in humans with chronic glomerulonephritis [140]. Urinary PGI 2 showed no relationship with the development of hemolytic uremic syndrome and was not protective [141].…”

Section: Amelioration Of Hyperfiltration-induced Glomerular Dysfunmentioning

confidence: 99%

Hyperfiltration-associated biomechanical forces in glomerular injury and response: Potential role for eicosanoids

Sharma

McCarthy

et al. 2017

Prostaglandins & Other Lipid Mediators

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Hyperfiltration is a well-known risk factor in progressive loss of renal function in chronic kidney disease (CKD) secondary to various diseases. A reduced number of functional nephrons due to congenital or acquired cause(s) results in hyperfiltration in the remnant kidney. Hyperfiltration-associated increase in biomechanical forces namely pressure-induced tensile stress and fluid flow-induced shear stress (FFSS) determine cellular injury and response. We believe the current treatment of CKD yields limited success because it largely attenuates pressure-induced tensile stress changes but not the effect of FFSS on podocytes. Studies on glomerular podocytes, tubular epithelial cells and bone osteocytes provide evidence for a significant role of COX-2 generated PGE2 and its receptors in response to tensile stress and FFSS. Preliminary observations show increased urinary PGE2 in children born with a solitary kidney. FFSS-induced COX2-PGE2-EP2 signaling provides an opportunity to identify targets and, for developing novel agents to complement currently available treatment.

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Beraprost sodium improves survival rates in anti-glomerular basement membrane glomerulonephritis and 5/6 nephrectomized chronic kidney disease rats

Cited by 25 publications

References 24 publications

A Double‐blind, Placebo‐controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease

A Double‐blind, Placebo‐controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease

Beraprost Sodium, a Stable Analogue of PGI2, Inhibits the Renin-Angiotensin System in the Renal Tissues of Rats with Chronic Renal Failure

Hyperfiltration-associated biomechanical forces in glomerular injury and response: Potential role for eicosanoids

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