The pancreas in experimental hypercholesterolemia in normal and in subdiabetic rabbits

Wellmann, Klaus F.; Volk, Bruno W.

doi:10.1007/bf00548970

Cited by 29 publications

(31 citation statements)

References 18 publications

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“…It has been recognized that lipid nephrotoxicity is involved in the development of DN since the 1970s [19]. Previous studies have shown that dyslipidemia facilitates glomerulosclerosis under diabetic conditions.…”

Section: Impairment Of the Renal Function By Lipidsmentioning

confidence: 99%

Dyslipidemia in diabetic nephropathy

2016

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Diabetic nephropathy (DN) not only is a major cause of end-stage renal disease (ESRD) in developing and developed countries but also plays a critical role as a risk factor for cardiovascular disease. The pathogenesis of DN is multifactorial and remains to be elucidated. It is well known that dyslipidemia is frequently complicated with diabetes. Recently, dyslipidemia has been recognized to be involved in the progression of DN. In general, diabetic dyslipidemia is caused by impaired action of lipoprotein lipase (LPL) that is localized to the endothelial cells, resulting in increased serum levels of increased triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C). Smaller size and modified low-density lipoprotein (LDL), such as glycated and oxidized LDL, play important roles to induce vascular and renal cellular dysfunction. Previous studies demonstrated that dyslipidemia enhances macrophage infiltration and excessive extracellular matrix (ECM) production in the glomeruli under diabetic conditions, leading to the development of DN. Clinical studies have demonstrated that lipid-lowering therapy shows a protective effect on the renal function. It is well known that statins reduce albuminuria in patients with DN. A series of our studies indicated that this effect is mediated by Rho-kinase inhibition. Rho-kinase plays a key role in the pathogenesis of DN by activating the inflammatory pathway, including oxidative stress, NF-κB, and hypoxia inducible factor (HIF)-1. Intriguingly, Rho-kinase inhibitors have been shown to attenuate glomerulosclerosis as well as atherosclerosis. Therefore, Rho-kinase could be a promising therapeutic target for both DN and cardiovascular disease.

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Section: Impairment Of the Renal Function By Lipidsmentioning

confidence: 99%

Dyslipidemia in diabetic nephropathy

2016

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“…In a number of animal models, lipogenic diets worsen whereas cholesterollowering medications ameliorate renal injury (23)(24)(25)(26)(27). Fried et al (28) performed a meta-analysis that examined the role of lipid-lowering therapy on renal function in humans.…”

Section: Lipid and Lipoprotein Profile And Progression Of Kidney Diseasementioning

confidence: 99%

Apolipoprotein A-IV Predicts Progression of Chronic Kidney Disease

Boes¹,

Fliser²,

Ritz³

et al. 2006

Journal of the American Society of Nephrology

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It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n ‫؍‬ 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m 2 ; P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P ‫؍‬ 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype ⑀2/⑀4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.

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“…Recently, hypercholesterolemia was related to a more rapid decline in the glomerular filtration rate (GFR) in DN [23,30], and cholesterol-lowering therapy was shown to retard the progression of DN [19]. Clinical observations suggesting that hypercholesterolemia increases the risk of DN were substantiated by experimental data [16,28].…”

Section: Introductionmentioning

confidence: 53%

Apolipoprotein E Gene Polymorphism, Hypercholesterolemia and Glomerular Filtration Rate in Type 2 Diabetic Subjects: A 9-Year Follow-Up Study

et al. 2003

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Objective: To study the association between apolipoprotein E (apoE) genotype and the rate of decline in glomerular filtration rate (GFR) in type 2 diabetic patients in a 9-year prospective study. Methods: GFR was determined in 84 type 2 diabetic patients by plasma clearance of ⁵¹Cr-EDTA at baseline and after 9 years of follow-up. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme HhaI digestion and designated as Ε4 allele group (apoE4/2, 4/3 and 4/4 genotypes; n = 20) and non-Ε4 allele group (apoE3/3 and E3/2 genotypes; n = 64). We focused our analysis on those patients who were more likely to progress to diabetic renal disease, i.e. whose GFR fell more than expected in the normal course of ageing [1 ml × min^–1 × (1.73 m²)^–1 per year]. Results: In the whole population, the decline in the GFR did not differ statistically significantly between the apoE genotype groups [p = 0.65 with analysis of variance for repeated variables (RANOVA) for interaction between apoE genotype group and time point]. However, among patients whose GFR changed more than 9 ml × min^–1 × (1.73 m²)^–1, GFR showed a statistically significantly greater decline in the Ε4 allele group (n = 11) than in the non-Ε4 allele group (n = 43) [from 116 ± 36 to 80 ± 29 ml × min^–1 × (1.73 m²)^–1 vs. from 119 ± 20 to 96 ± 18 ml × min^–1 × (1.73 m²)^–1; p = 0.005 with RANOVA]. Conclusion:ApoE allele Ε4 may speed up the rate of decline of the GFR in patients with progressive diabetic renal disease.

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The pancreas in experimental hypercholesterolemia in normal and in subdiabetic rabbits

Cited by 29 publications

References 18 publications

Dyslipidemia in diabetic nephropathy

Dyslipidemia in diabetic nephropathy

Apolipoprotein A-IV Predicts Progression of Chronic Kidney Disease

Apolipoprotein E Gene Polymorphism, Hypercholesterolemia and Glomerular Filtration Rate in Type 2 Diabetic Subjects: A 9-Year Follow-Up Study

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