Lovastatin Preserves Renal Function in Experimental Diabetes

Inman, Sharon R.; Stowe, Nicholas T.; Cressman, Michael D.; Brouhard, Ben H.; Nally, Joseph V.; Satoh, Shigeru; Satodate, Ryoichi; Vidt, Donald G.

doi:10.1097/00000441-199904000-00001

Cited by 27 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 90%

Rosuvastatin-Induced Arrest in Progression of Renal Disease

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

Rosuvastatin-Induced Arrest in Progression of Renal Disease

et al. 2004

View full text Add to dashboard Cite

show abstract

“…This suggests that mere suppression of oxidant stress without acting at a "higher" (34) or different level might not be sufficient. This notion is particularly apparent in the pyridoxamine trial with diabetic rats in which pyridoxamine almost completely suppressed albuminuria and retinopathy, whereas ␣-lipoic acid, enalapril, and vitamin E had milder or no effect (35). One pronounced effect of pyridoxamine was its ability to markedly lower hyperlipidemia to levels not observed in other studies, thereby providing support for the proposed role of lipids in the pathogenesis of diabetic nephropathy (36).…”

Section: Discussionmentioning

confidence: 86%

Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Diabetic Rats

et al. 2005

View full text Add to dashboard Cite

We tested the hypothesis that green tea prevents diabetes-related tissue dysfunctions attributable to oxidation. Diabetic rats were treated daily with tap water, vitamins C and E, or fresh Japanese green tea extract. After 12 months, body weights were decreased, whereas glycated lysine in aorta, tendon, and plasma were increased by diabetes (P < 0.001) but unaffected by treatment. Erythrocyte glutathione and plasma hydroperoxides were improved by the vitamins (P < 0.05) and green tea (P < 0.001). Retinal superoxide production, acellular capillaries, and pericyte ghosts were increased by diabetes (P < 0.001) and improved by green tea and the vitamins (P variable). Lens crystallin fluorescence at 370/440 nm was ameliorated by green tea (P < 0.05) but not the vitamins. Marginal effects on nephropathy parameters were noted. However, suppressed renal mitochondrial NADH-linked ADP-dependent and dinitrophenol-dependent respiration and complex III activity were improved by green tea (P variable). Green tea also suppressed the methylglyoxal hydroimidazolone immunostaining of a 28-kDa mitochondrial protein. Surprising, glycoxidation in tendon, aorta, and plasma was either worsened or not significantly improved by the vitamins and green tea. Glucosepane cross-links were increased by diabetes (P < 0.001), and green tea worsened total cross-linking. In conclusion, green tea and antioxidant vitamins improved several diabetes-related cellular dysfunctions but worsened matrix glycoxidation in selected tissues, suggesting that antioxidant treatment tilts the balance from oxidative to carbonyl stress in the extracellular compartment. Diabetes 54:517-526, 2005

show abstract

“…It has been reported that inhibition of cholesterol synthesis by HMG-CoA reductase inhibitors (statins) and of triglyceride synthesis by peroxisome proliferator activated receptor-␣ agonists (fibrates) protect against diabetic and non-diabetic renal disease (13,49,50). A recent meta-analysis of several small scale interventional studies in diabetic and non-diabetic human subjects with glomerulosclerosis and proteinuria indicates that long term treatment with statins and/or fibrates significantly prevent the decline in glomerular filtration rate (29).…”

Section: Discussionmentioning

confidence: 99%

Diet-induced Obesity in C57BL/6J Mice Causes Increased Renal Lipid Accumulation and Glomerulosclerosis via a Sterol Regulatory Element-binding Protein-1c-dependent Pathway

Jiang

Wang

Proctor

et al. 2005

Journal of Biological Chemistry

333

280

View full text Add to dashboard Cite

Obesity and metabolic syndrome are associated with glomerulosclerosis and proteinuria, but the mechanisms are not known. The purpose of this study was to determine if there is altered renal lipid metabolism and increased expression of sterol regulatory elementbinding proteins (SREBPs) in a model of diet-induced obesity. C57BL/6J mice that were fed a high fat, 60 kcal % saturated (lard) fat diet (HFD) developed obesity, hyperglycemia, and hyperinsulinemia compared with those that were fed a low fat, 10 kcal % fat diet (LFD). In contrast, A/J mice were resistant when fed the same diet. C57BL/6J mice with HFD exhibited significantly higher levels of renal SREBP-1 and SREBP-2 expression than those mice with LFD, whereas in A/J mice there were no changes with the same treatment. The increases in SREBP-1 and SREBP-2 expression in C57BL/6J mice resulted in renal accumulation of triglyceride and cholesterol. There were also significant increases in the renal expression of plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), type IV collagen, and fibronectin, resulting in glomerulosclerosis and proteinuria. To determine a role for SREBPs per se in modulating renal lipid metabolism and glomerulosclerosis we performed studies in SREBP-1c ؊/؊ mice. In contrast to control mice, in the SREBP-1c ؊/؊ mice with HFD the accumulation of triglyceride was prevented, as well as the increases in PAI-1, VEGF, type IV collagen, and fibronectin expression. Our results therefore suggest that diet-induced obesity causes increased renal lipid accumulation and glomerulosclerosis in C57BL/6J mice via an SREBP-1c-dependent pathway.Obesity is a known risk factor for cardiovascular disease (1) and type-2 diabetes mellitus (2) and has been proposed to play a role in the pathogenesis of diabetic nephropathy (3). Obesity is one of the defining criteria of the metabolic syndrome as proposed by the National Cholesterol Education Program Adult Treatment Panel III (4) and the World Health Organization (5). The metabolic syndrome, which is characterized by the concurrent existence of obesity, dyslipidemia, hyperglycemia, hyperinsulinemia, and hypertension, has been shown to be a strong and independent risk factor for cardiovascular, and all cause mortality (6, 7) as well as the development of microalbuminuria and chronic kidney disease (8).Obesity is considered a major generator of metabolic syndrome (9). Early in the course of obesity-initiated metabolic syndrome, structural and functional changes similar to diabetic kidney disease occur (10). These changes include glomerular hyperfiltration, glomerular basement membrane thickening, mesangial cell proliferation, mesangial matrix thickening, and expansion of Bowman's capsule (10) and are considered precursors to more severe renal injury. Severe obesity has been associated with the eventual development of focal and segmental glomerulosclerosis (11). Although incompletely understood, several hemodynamic, hormonal, and metabolic factors have been proposed to contribute to t...

show abstract

Lovastatin Preserves Renal Function in Experimental Diabetes

Cited by 27 publications

References 26 publications

Rosuvastatin-Induced Arrest in Progression of Renal Disease

Rosuvastatin-Induced Arrest in Progression of Renal Disease

Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Diabetic Rats

Diet-induced Obesity in C57BL/6J Mice Causes Increased Renal Lipid Accumulation and Glomerulosclerosis via a Sterol Regulatory Element-binding Protein-1c-dependent Pathway

Contact Info

Product

Resources

About