The combination of lovastatin and enalapril in a model of progressive renal disease

Brouhard, Ben H.; Takamori, Hiroki; Satoh, Shigeru; Inman, Sharon R.; Cressman, Michael D.; Irwin, Kimberly C.; Berkley, V.; Stowe, Nicholas T.

doi:10.1007/bf00856524

Cited by 23 publications

(12 citation statements)

References 18 publications

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“…Our observation of a lack of progression of renal disease is also consistent with data obtained from numerous investigations using animal models of progressive renal disease [26, 27, 28, 29, 30, 31]. In these preclinical studies, statins have been shown to reduce progression of both the diabetic and nondiabetic forms of renal disease.…”

Section: Discussionsupporting

confidence: 80%

Rosuvastatin-Induced Arrest in Progression of Renal Disease

et al. 2004

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Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor^®) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants were initially included in controlled clinical trials that evaluated the lipid-lowering efficacy and safety of rosuvastatin when compared with placebo or other lipid-lowering agents (i.e., atorvastatin, simvastatin, pravastatin, cholestyramine, fenofibrate or extended-release niacin). The median duration of treatment with the various doses of statins in these trials was approximately 8 weeks. Following completion of a controlled clinical trial, patients were permitted to enter an open-label extension trial and received rosuvastatin treatment. These data permitted assessment of renal function in a diverse group of over 10,000 patients who received rosuvastatin in its recommended dose range (5–40 mg) for up to 3.8 years. Mean serum creatinine concentrations were lower when compared with baseline both early and later in the course of rosuvastatin treatment. In contrast, no change in mean serum creatinine was observed with placebo. Mean glomerular filtration rates (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) equation were higher when compared with baseline both early and later in the course of rosuvastatin treatment. No change in GFR was observed in the placebo group. Among patients who received long-term rosuvastatin treatment (≧96 weeks), GFR was unchanged or tended to increase, rather than decrease, when compared with baseline irrespective of age, gender, hypertensive or diabetic status, level of renal function (GFR ≧60 vs. <60 ml/min/1.73 m²) at entry or urine dipstick protein status prior to or during the period of treatment. These findings suggest that rosuvastatin may arrest the progression of renal disease.

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Section: Discussionsupporting

confidence: 80%

Rosuvastatin-Induced Arrest in Progression of Renal Disease

et al. 2004

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“…Reducing arterial hypertension and proteinuria results in slowing of the progression of renal insufficiency which is a characteristic of many chronic and therapy-resistant nephropathies. These important features have been clearly established in various experimental models, such as subtotal nephrectomy [2,3], streptozocin-induced diabetes mellitus [1] and puromycin-induced nephrotic syndrome [4,5]. The same renoprotective effect of ACEI has been observed in adult patients with different kinds of chronic renal diseases, especially diabetic nephropathy, different primary glomerular diseases, such as focal glomerulosclerosis, membranous and membranoproliferative glomerulonephritis and IgA nephritis, and also in reflux nephropathy, polycystic kidney disease and nephroangiosclerosis [5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 93%

Long-term therapy with enalapril in patients with nephrotic-range proteinuria

1996

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The effect of enalapril on urinary protein excretion and renal function was studied in six paediatric patients with various renal diseases causing nephroticrange proteinuria. In three younger children (aged 7-9 years) with steroid-resistant nephrotic syndrome, enalapril at a dose of 0.5 mg/kg per day given for 24 months yielded a temporary reduction of proteinuria in one child, a moderate and steady decrease in another and a complete disappearance of proteinuria in the third. Three adolescents, aged 17 years, took enalapril for 24 months at a dose of 20 mg/day. We observed no effect on proteiuria in one patient with Alport syndrome, a complete disappearance of urinary protein in one patient with membranoproliferative glomerulonephritis and a moderate decrease in the third patient who had idiopathic steroid-resistant nephrotic syndrome. Enalapril therapy resulted in an important reduction of proteinuria in two patients and a moderate decrease in three others. However this therapy was accompanied by a fall in glomerular filtration in all subjects, which was very marked in two patients. This fall in glomerular filtration may, however, simply reflect the natural course of the disease.

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“…By interfering with prenylation of Ras and Rho family small GTP-binding proteins, they block the activation of mitogen-activated protein kinase signaling pathways and transcription factors including NF-B and AP-1 (29 -31), which regulate the expression of inflammatory, vasoactive, and fibrogenic genes critical to renal disease progression. Combining ACEi with a statin had more renal protective effect than single therapy in rats with puromycin-induced nephrotic syndrome (32) as well as in rats subjected to 5/6 nephrectomy (33). We have recently documented that in severe passive Heymann nephritis (PHN) resistant to ACEi alone, combination of lisinopril with simvastatin given from month 4 to 10 of disease prevented proteinuria from worsening and also limited tubulointerstitial damage (10).…”

mentioning

confidence: 99%

How To Fully Protect the Kidney in a Severe Model of Progressive Nephropathy

Zoja¹,

Corna²,

Camozzi³

et al. 2002

Journal of the American Society of Nephrology

155

124

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Abstract. The current therapy for chronic proteinuric nephropathies is angiotensin-converting enzyme inhibitors (ACEi), which slow, but may not halt, the progression of disease, and which may be not effective to the same degree in all patients. In accelerated passive Heymann nephritis (PHN), this study assessed the effect of combining ACEi with angiotensin II receptor antagonist (AIIRA) and with statin that, besides lowering cholesterol, influences inflammatory and fibrogenic processes. Uninephrectomized PHN rats were divided into four groups (n ϭ 10 each) and daily given oral doses of the following: vehicle; 40 mg/L lisinopril; 100 mg/L lisinopril plus L-158,809; 0.3 mg/kg lisinopril plus L-158,809 plus cerivastatin. Treatments started at 2 mo when rats had massive proteinuria and signs of renal injury and lasted until 10 mo. Increases in BP were equally lowered by treatments. ACEi kept proteinuria at levels comparable to pretreatment and numerically lower than vehicle. The addition of AIIRA to lisinopril was more effective, being proteinuria reduced below pretreatment values and significantly lower than vehicle. When cerivastatin was added on top of ACE inhibition and AIIR blockade, urinary protein regressed to normal values and renal failure was prevented. Renal ACE activity was increased threefold in PHN, it was inhibited by more than 60% after ACEi, and decreased below control values with triple therapy. Cerivastatin inhibited ACE activity by 30%. Glomerulosclerosis, tubular damage and interstitial inflammation were ameliorated by ACEi alone or combined with AIIRA, and prevented by addition of statin. TGF-␤ 1 mRNA upregulation in PHN kidney was partially reduced after ACEi or combined with AIIRA and almost normalized after adding statin. Cerivastatin inhibited TGF-␤ 1 gene upregulation by 25%. These data suggest a possible future strategy to induce remission of proteinuria, lessen renal injury, and protect from loss of function in those patients who do not fully respond to ACEi therapy.

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The combination of lovastatin and enalapril in a model of progressive renal disease

Cited by 23 publications

References 18 publications

Rosuvastatin-Induced Arrest in Progression of Renal Disease

Rosuvastatin-Induced Arrest in Progression of Renal Disease

Long-term therapy with enalapril in patients with nephrotic-range proteinuria

How To Fully Protect the Kidney in a Severe Model of Progressive Nephropathy

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