Lipids and the kidney.

Kasiske, Bertram L.; O’Donnell, Michael P.; Cowardin, W; Keane, William F.

doi:10.1161/01.hyp.15.5.443

Cited by 69 publications

(29 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Glomerulosclerosis was increased in the kidneys exposed to systemic hypertension and reduced in the clipped kidneys. Similarly, Kasiske et al 10 showed exacerbation of proteinuria in two-kidney, one clip rats fed a high-cholesterol diet compared with rats subjected to either experimental maneuver alone. Glomerulosclerosis was increased in kidneys exposed to hypertension, whereas morphological protection was observed in the clipped kidney.…”

mentioning

confidence: 85%

Combined antihypertensive and lipid-lowering therapy in experimental glomerulonephritis.

et al. 1994

View full text Add to dashboard Cite

We examined the interrelation between systemic hypertension, hyperlipidemia, and progressive renal injury in experimental glomerulonephritis. Induction of nephrotoxic serum nephritis in Sprague-Dawley rats led to systemic hypertension and hyperlipidemia. Four groups of rats were studied over a 16-week period: (1) untreated nephritic rats; (2) nephritic rats treated with hydralazine, reserpine, and lasix (AH); (3) nephritic rats treated with lovastatin (4 mg/kg) (Lova); and (4) nephritic rats treated with combined antihypertensive/lipidlowering therapy (AH/Lova). Systolic blood pressure rose progressively in untreated rats (152±4 mm Hg at 16 weeks ). Glomerular injury score was significantly reduced by antihypertensive therapy (P<.01) and lipid-lowering therapy (f<.05). Glomerular injury score was lowest in animals receiving combined therapy, reflecting an interaction between these therapies (P<.01) (untreated, 173±29; Lova, 128±24; AH, 111±22; AH/Lova, 48±11). Our results suggest that both hypertension and hyperlipidemia accelerate glomerular sclerosis in experimental glomerulonephritis and that combined therapy of these disorders may best limit progressive renal injury. (Hypertension. 1994^3:92-95.) Key Words • hyperlipidemia • glomerulonephritis • hypertension C omplex interrelations exist between systemic hypertension, hyperlipidemia, and progressive renal injury. Recent evidence indicates that hyperlipidemia may be associated with accelerated renal damage in experimental glomerular disease and that lipid-lowering therapy ameliorates progressive renal injury in many of these models. 13 Moreover, it has been suggested that pathogenetic mechanisms responsible for the evolution of fatty streak lesions in blood vessels are analogous to those responsible for the development of glomerulosclerosis.1 ' 2 We have previously shown that systemic hypertension exacerbates renal injury in experimental glomerulonephritis. 4 Similarly, other investigators have demonstrated acceleration of atherosclerotic vascular lesions when experimental hypertension is combined with an atherogenic diet or superimposed on hereditary hyperlipidemia. 58 We hypothesize that factors predisposing to atherosclerotic vascular lesions, most notably systemic hypertension and hyperlipidemia, may have similar importance in the development of glomerular sclerosis. In fact, several studies suggest that hypertension and hyperlipidemia may have additive or perhaps synergistic effects on the development and progression of glomerular injury, as reflected by proteinuria and glomerular sclerosis. 912 In this context, we undertook a study to determine the relative efficacy of antihypertensive and cholesterol-lowering therapy in ameliorating progressive renal injury in nephrotoxic serum nephritis in the rat, a model characterized by both hypertension and hyperlipidemia. Our results suggest that both hypertension and hyperlipidemia accelerate glomerular sclerosis in experimental glomerulonephritis and that combined therapy of these disorders best l...

show abstract

mentioning

confidence: 85%

Combined antihypertensive and lipid-lowering therapy in experimental glomerulonephritis.

et al. 1994

View full text Add to dashboard Cite

show abstract

“…There is a body of evidence linking hyperlipidemia to progressive renal injury in various experimental models (25)(26)(27), and the injury is believed to be mediated via oxidized LDL (28,29). We evaluated the role of oxidative stress in ZDF rat kidneys that contained abundant lipid deposits by assessing HNE, a marker of lipid peroxidation.…”

Section: -Hydroxy-2-nonenal (Hne) Immunoexpression Compared With Agementioning

confidence: 99%

Nephropathy in Zucker Diabetic Fat Rat Is Associated with Oxidative and Nitrosative Stress

Chander¹,

Gealekman²,

Brodsky³

et al. 2004

Journal of the American Society of Nephrology

163

109

View full text Add to dashboard Cite

Abstract. Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia develop focal and segmental sclerosis. The role of oxidative and nitrosative stress in the nephropathy in ZDF was studied. Renal histology, function, and immunohistologic and biochemical parameters of oxidative and nitrosative stress were evaluated at 8 and 22 wk of age in ZDF and Zucker lean (ZL) rats and after chronic treatment with ebselen, an antioxidant and peroxinitrite scavenger. At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephropathy, but higher levels of dihydrobiopterin and 3-nitrotyrosine (3-NT)-modified proteins compared with agematched ZL rats. At 22 wk, ZDF rats developed focal and segmental sclerosis, proteinuria, decreased creatinine clearance, and renal tissue levels of glutathione and tetrahydrobiopterin with further elevation in dihydrobiopterin and 3-NTmodified proteins, in contrast to age-matched ZL rats. Renal immunohistologic expression of lipid peroxidation products and 3-NT-modified proteins also increased in 22-wk-old ZDF but not in ZL rats. Chronic ebselen treatment of ZDF rats restored renal tissue levels of glutathione and tetrahydrobiopterin; prevented significant accumulation of dihydrobiopterin, lipid peroxidation products, and 3-NT-modified proteins; and ameliorated focal and segmental sclerosis, proteinuria, and fall in creatinine clearance without affecting mean BP, body weight, and blood glucose, compared with the untreated ZDF rats. Chronic ebselen therapy also ameliorated vasculopathy with lipid deposits and tubulointerstitial scarring, inflammation, and upregulated ␣-smooth muscle actin expression. These findings suggest that ZDF rats develop a progressive nephropathy with glomerular, vascular, and tubulointerstitial pathology. Oxidative and nitrosative stress predates the nephropathy, which is improved by peroxinitrite scavenger ebselen, and thus considered its cause and not consequence.The growing population of patients with the metabolic syndrome and with obesity-associated type 2 diabetes has resulted in a dramatic increase in the number of patients who have ESRD and require dialytic life support (1,2). This challenge is being met by interdisciplinary efforts to elucidate the characteristics and mechanisms of nephropathy and to develop animal models and therapeutic tools. The Zucker diabetic fat (ZDF) rat represents a well-characterized model of the metabolic syndrome. Developed more than three decades ago (3), the pathophysiologic mechanism of this model has recently been attributed to the missense mutation of leptin receptor (4). The evolution of the metabolic syndrome in the ZDF rat is associated with the development and progression of nephropathy, together with obesity, insulin resistance, hyperglycemia, and hyperlipidemia (5-10). Focal and segmental sclerosis (FSGS) develops at the age of 18 wk, although severe hyperlipidemia, hyperglycemia, and obesity predate it (8).Previous studies suggested the role of oxidative stress and endothelial dysfunction in the pathoph...

show abstract

“…Dietas ricas em colesterol podem causar albuminúria e glomerulosclerose em várias espécies animais, particularmente quando combinada com hipertensão arterial (36,37). A hiperlipidemia presente favorece a deposição de lípides nas células mesangiais glomerulares, o que contribuiria para a progressão da glomerulosclerose (38).…”

Section: Discussionunclassified

“…Agentes redutores dos lípides melhoram as lesões renais em vários modelos experimentais de nefropatia (36,37), sugerindo que o diagnóstico e o tratamento da dislipidemia poderiam ser úteis na prevenção da lesão renal. Em pacientes com DM1, associação entre a hiperlipidemia e déficit de função renal já foi detectada (33).…”

Section: Discussionunclassified

Benefícios da atividade física no perfil lipídico de pacientes com diabetes tipo 1

Khawali

Andriolo

Ferreira

2003

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

RESUMOAvaliamos a resposta do perfil lipídico a uma intervenção não-farmacológica de curta duração, e investigamos se alterações nas lipoproteí -nas estavam presentes, antes da nefropatia diabética (ND) clínica, em 46 pacientes jovens com diabetes tipo 1 (DM1), com idade de 15,5±1,5 anos submetidos a um programa de 8 dias de dieta apropriada e exercícios, durante controle glicêmico estável (glicemia média 110,3±27,1mg/dl e HbA1c 6,9±1,3%). No início, 65% dos jovens apresentavam colesterol total ≥160mg/dl (IC 95% 0,51-0,78), enquanto que ao final somente 38% (IC 95% 0,24-0,51) tinham tais níveis. A melhora no perfil lipídico foi ainda melhor para a fração LDL, considerando que inicialmente 67% mostravam valores acima de 100mg/dl (IC 95% 0,55-0,78) e 24% (IC 95% 0,12-0,36) ao final. Valores de HDL-colesterol subnormais (≤ 40mg/dl) ocorreram em 38% (95% IC 0,24-0,51) e 11% (IC 95% 0,02-0,20) deles, no início e final do período. A razão albumina/creatinina média foi 9,0±8,0mg/g de creatinina. Encontramos fracas correlações entre a razão albumina/creatinina e os níveis de colesterol total (r= 0,21), LDL (r= 0,24), VLDL (r= 0,30), HDL (r= -0,17) e de triglicérides (r= 0,31). Dentro da faixa de referência de albuminúria, não foi encontrada nenhuma associação entre a excreção urinária de albumina e os níveis de lípides nos pacientes com DM1 estável. Um programa de exercícios regulares é eficaz em otimizar o perfil lipídico nestes pacientes, independentemente do controle glicêmico. Nossos dados não apoiam a hipótese de que mudanças no metabolismo lipídico precederiam a microalbuminúria no curso da ND. We assessed the response of lipid profile to short-term non-pharmacological intervention and investigated if lipoprotein abnormalities were present before overt diabetic nephropathy (DN) in 46 type 1 diabetic (DM1) youngsters aged 15.5±1.5 yrs. They were submitted to a 8-day program of adequate diet and exercise, during stable glycemic control (mean glycemia 110.3±27.1mg/dl and HbA1c 6.9±1.3%) to minimize the influence of disturbed glucose homeostasis on urinary albumin excretion and lipid profile. Mean albumin-to-creatinine ratio was 9.0±8.0mg/g creatinine. At the beginning of the program, 65% of the subjects had total cholesterol ≥ 160mg/dl (95% CI 0.51-0.78), whereas only 38% (95% CI 0.51-0.24) maintained such levels at the end. The improvement in lipid profile was even better concerning LDL fraction, considering that initially 67% of the subjects showed values ≥ 100mg/dl (95% CI 0.55-0.78) and 24% (95% CI 0.12-0.36) at the end. Initial HDL-cholesterol was ≤ 40mg/dl in 38% (95% CI 0.24-0.51) and in 11% (95% CI 0.02-0.20) at the end. In addition, HDLcholesterol increased significantly. Poor correlations were found between albumin-to-creatinine ratio and total cholesterol (r= 0.21), LDL (r= 0.24), VLDL (r= 0.31), HDL (r= -0.17) and triglycerides levels (r= 0.31). A regular exercise program is effective on optimizing lipid profile in DM1 artigo original

show abstract

Lipids and the kidney.

Cited by 69 publications

References 60 publications

Combined antihypertensive and lipid-lowering therapy in experimental glomerulonephritis.

Combined antihypertensive and lipid-lowering therapy in experimental glomerulonephritis.

Nephropathy in Zucker Diabetic Fat Rat Is Associated with Oxidative and Nitrosative Stress

Benefícios da atividade física no perfil lipídico de pacientes com diabetes tipo 1

Contact Info

Product

Resources

About