Effects of Valsartan on the Progression of Chronic Renal Insufficiency in Patients with Nondiabetic Renal Diseases

Ishimitsu, Toshihiko; Kameda, Tomoko; Akashiba, Akira; Takahashi, Toshiaki; Ando, Norikazu; Ohta, Satoshi; Yoshii, Masayoshi; Inada, Hideki; Tsukada, Kohju; Minami, Junichi; Ono, Hitoshi; Matsuoka, Hiroaki

doi:10.1291/hypres.28.865

Cited by 18 publications

(10 citation statements)

References 28 publications

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“…As well as the animal experiments, an ARB has been shown to reduce proteinuria and slow the progression of renal dysfunction in patients with nondiabetic renal disease. 30) The COMB group in this study was given SPRL and a low-dose of TELM which did not significantly lower the blood pressure. However, the renal dysfunction, proteinuria, glomerular injuries, and perivascular lesions were improved comparably to the high-dose TELM group in which the blood pressure was significantly lowered.…”

Section: Discussionmentioning

confidence: 82%

Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-.GAMMA. and Decrease in TGF-.BETA.1

Takahashi

Ono

et al. 2007

Int. Heart J.

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SUMMARYTo investigate whether the receptor blockades of angiotensin II type 1 and aldosterone receptors can prevent renal tissue injury in relation to the renal tissue mRNA levels of peroxisome proliferation-activated receptors-γ (PPAR-γ) and transforming growth factor-β 1 (TGF-β 1 ) in spontaneously hypertensive rats (SHR) given N G -nitro-L-arginine methyl ester (L-NAME), which is considered a model of malignant hypertension.This study was performed in 5 groups of 17-week-old male SHR treated for 3 weeks as follows: group 1, control; group 2, L-NAME (50 mg/L in drinking); group 3, L-NAME plus aldosterone antagonist, spironolactone (SPRL, 100 mg/kg/day); group 4, L-NAME plus angiotensin II type 1 receptor blocker, telmisartan (TELM, 3 mg/kg/day); group 5, L-NAME plus combination therapy (COMB) with low-dose TELM (1 mg/kg/day) and SPRL (100 mg/kg/day).Urinary protein excretion and the glomerular injury score were significantly reduced in the SPRL, TELM, and COMB groups as compared with the L-NAME group, while significant blood pressure reduction was observed only in the TELM group. In the TELM and COMB groups, the perivascular cell infiltration and fibrosis area were significantly reduced together with the PPAR-γ mRNA increase and TGF-β 1 mRNA decrease. The urinary excretion of nitric oxides was significantly recovered and the wall to lumen ratio of the interlobular artery was significantly reduced only in the COMB group compared with the L-NAME group.Combined administration of 1 mg/kg/day telmisartan and 100 mg/kg/day spironolactone is thought to be effective in alleviating hypertensive renal injuries independently of blood pressure changes. The anti-inflammatory and antifibrotic effects due to PPAR-γ activation and TGF-β 1 inhibition may participate in the renoprotection of this combination therapy. (Int Heart J 2007; 48: 637-647)

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Section: Discussionmentioning

confidence: 82%

Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-.GAMMA. and Decrease in TGF-.BETA.1

Takahashi

Ono

et al. 2007

Int. Heart J.

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“…44) Multiple lines of clinical evidence have indicated that long-term inhibition of RAAS reduces proteinuria and attenuates the rate of deterioration of renal function in patients with diabetic and nondiabetic renal disease. [45][46][47][48] However, in SHR or patients with essential hypertension, detectable signs of renal injury do not occur until the later stage of life, 42) and it is not clear whether RAAS inhibitors can prevent or delay the onset of renal lesions in patients without pre-existing renal disease. In this respect, the present study demonstrated that lifelong antihypertensive therapy with an ARB can preserve renal function as indicated by creatinine clearance in SHR.…”

Section: Discussionmentioning

confidence: 99%

Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

et al. 2010

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SummaryMost previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year. Twelve SHR and 9 normotensive Wistar-Kyoto rats (WKY) were given normal tap water. Tail-cuff blood pressure was almost normalized by CS throughout 1 year (at 12-months: WKY 132 ± 3, SHR 229 ± 3, CS 137 ± 4 mmHg). After 1 year, cardiac ventricular weight (SHR +33%, CS -2% versus WKY) and aortic thickness (SHR +34%, CS +4% versus WKY) in the CStreated SHR rats were not different than those of WKY. Echocardiographic midwall fractional shortening (SHR -18%, CS -1% versus WKY) and left ventricular hydroxyproline content (SHR +47%, CS +11% versus WKY) were also improved by CS to the WKY level. With respect to kidney function, GFR (SHR -24%, CS +9% versus WKY) was preserved, proteinuria (SHR +312%, CS +12% versus WKY) was reduced, and the histological glomerular injury rate (SHR +186%, CS +6% versus WKY) was reduced by CS. These results suggest that long-term antihypertensive therapy with CS can completely prevent hypertensive cardiovascular and renal injuries in SHR. (Int Heart J 2010; 51: 359-364)

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“…Furthermore, African American Study of Kidney Disease and Hypertension (AASK) (27) suggested that ACE inhibitors slow renal disease progression in African American patients with hypertensive renal disease. Also as for the Asian population, we have reported that an ACE inhibitor and an ARB are effective in reducing proteinuria and slowing the deterioration of renal function in Japanese patients with chronic glomerulonephritis (28,29). Namely, an ACE inhibitor, benazepril, or an ARB, valsartan, inhibited the increase in serum creatinine and reduced proteinuria by 30-40% as compared with placebo ( Figure 7,8).…”

Section: Inhibitors Of Renin-angiotensin-aldosterone System In Antihymentioning

confidence: 89%

Blood Pressure Control in Patients with Glomerulonephritis

Ishimitsu¹

2011

An Update on Glomerulopathies - Clinical and Treatment Aspects

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Effects of Valsartan on the Progression of Chronic Renal Insufficiency in Patients with Nondiabetic Renal Diseases

Abstract: The present study tested the effects of valsartan, an angiotensin II receptor blocker, on the progression of renal insufficiency in patients with nondiabetic renal diseases. The study subjects were 22 patients with nondiabetic renal diseases whose serum creatinine (Cr) ranged from 1.

Cited by 18 publications

References 28 publications

Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-.GAMMA. and Decrease in TGF-.BETA.1

Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-.GAMMA. and Decrease in TGF-.BETA.1

Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

Blood Pressure Control in Patients with Glomerulonephritis

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