Relationship between Hyperlipidemia, Lipid Mediators, and Progressive Glomerulosclerosis in the Nephrotic Syndrome

Kees-Folts, Deborah; Diamond, Jonathan R.

doi:10.1159/000168651

Cited by 32 publications

(11 citation statements)

References 46 publications

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“…Therefore, the action of supplementary micronutrients reducing microalbuminuria may be related to their antioxidant functions. Hypertension is well recognized as a risk factor for renal vascular and functional abnormalities (35,36), and antihypertensive therapies can halt the progression of renovascular disease and contribute to the preservation of renal function (37). Hypertension causes albuminuria, independent of diabetes, by a hemodynaminc mechanism of increased glomerular capillary hydrostatic pressure (38).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes

et al. 2005

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OBJECTIVE -The present study was designed to assess the effect of magnesium plus zinc, vitamins C plus E, and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -In a randomized, double-blind, placebocontrolled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months: group M (n ϭ 16), 200 mg Mg and 30 mg Zn; group V (n ϭ 18), 200 mg vitamin C and 100 IU vitamin E; group MV (n ϭ 17), minerals plus vitamins; and group P (n ϭ 18), placebo. Urinary albumin excretion and N-acetyl-␤-D-glucosaminidase activity (NAG) in urine were determined at the beginning and at the end of the trial. Treatment effects were analyzed by general linear modeling. RESULTS-Results indicate that after 3 months of supplementation, levels of urinary albumin excretion decreased in the V and MV groups (P ϭ 0.034 and P ϭ 0.005, respectively). Urinary NAG activity did not significantly change in any treatment groups. Levels of systolic, diastolic, and mean blood pressure significantly decreased in the MV group (P ϭ 0.008, P ϭ 0.017, and P ϭ 0.009, respectively). Also, combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose (P ϭ 0.035) and malondialdehyde concentrations (P ϭ 0.004) and in increasing HDL cholesterol and apolipoprotein A1 levels (P ϭ 0.019). There was no significant change in the levels of these parameters in the other three groups.CONCLUSIONS -In conclusion, the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium, zinc, and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients. Diabetes Care 28:2458 -2464, 2005D iabetic nephropathy is a serious complication of diabetes and a major cause of mortality and morbidity in these patients (1,2). Results of studies in animal models and humans have demonstrated that diabetes is associated with oxidative stress (3-5) and reduced levels of antioxidants (6). It has been well established that plasma magnesium levels in patients with diabetes is somewhat decreased (7,8). Numerous studies have found decreases in physiological measures of zinc status, hyperzincuria, and indications of zinc malabsorption in diabetic individuals (7,9). Levels of plasma ascorbic acid were found to be significantly lower in diabetic patients compared with nondiabetic control subjects in most studies (10 -12). Based on their results, the researchers observed that individuals with diabetes have significant defects of antioxidant protection, which may enhance their susceptibility to oxidative stress (12).Oxidative stress is hypothesized to play an important part in the development of late diabetes complications (6). Chronic hyperglycemia increases oxidative stress and considerably modifies the structure and function of proteins and lipids, due to glycoxidation and peroxidation...

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Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes

et al. 2005

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“…These alterations are likely to result in greater renal damage in a kidney exposed to both risk factors simultaneously. HC and HT are major risk factors for the development of end-stage renal disease 3 and are commonly present in combination. 4 Long-standing HT induces vascular and glomerular damage, including arteriolosclerosis and glomerulosclerosis, 22,23 with a progressive decline in renal function.…”

Section: Discussionmentioning

confidence: 99%

“…1 Hypertension (HT) 2 and hypercholesterolemia (HC) or atherosclerosis 3 are major risk factors for renal vascular and functional abnormalities and are commonly present in combination in a clinical setting. Clinical studies have shown that the coexistence of dyslipidemia and HT greatly increases the incidence of cardiovascular morbidity and mortality 4 and likely modulates the deterioration of renal function as well.…”

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confidence: 99%

Combination of Hypercholesterolemia and Hypertension Augments Renal Function Abnormalities

et al. 2001

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Abstract-Hypercholesterolemia and hypertension are both risk factors for end-stage renal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hemodynamics and function in response to vasoactive challenges with acetylcholine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (nϭ10) or hypercholesterolemic (nϭ10) diet, renovascular hypertension (nϭ7), or combined hypercholesterolemiaϩhypertension (nϭ6). The hypercholesterolemic and hypercholesterolemicϩhypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemicϩhypertensive groups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filtration rates were similar among the groups. In response to acetylcholine, cortical perfusion increased in normal animals (15.6Ϯ4.7%, Pϭ0.002) but not in hypercholesterolemic or hypertensive animals (8.0Ϯ7.4% and 8.2Ϯ5.9%, respectively; PϾ0.05). Moreover, in the hypercholesterolemicϩhypertensive group, cortical perfusion response was further attenuated (2.5Ϯ4.8%, Pϭ0.02) and significantly different from the group fed a normal diet (PϽ0.05). The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemicϩhypertensive group. The functional abnormalities in hypercholesterolemia or hypertension were associated with a decrease in systemic and/or renal tissue levels of oxygen radical scavengers that was again accentuated in hypercholesterolemiaϩhypertension. These results demonstrate that concurrent hypercholesterolemia and hypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially augment renal functional impairment and play a role in the initiation and progression of renal injury in hypertension and atherosclerosis. Clinical studies have shown that the coexistence of dyslipidemia and HT greatly increases the incidence of cardiovascular morbidity and mortality 4 and likely modulates the deterioration of renal function as well. 5 Indeed, both antihypertensive and lipid-lowering therapies can halt the progression of renovascular disease and contribute to the preservation of renal function. 6 The onset of renal injury is detectable after a relatively short exposure to cardiovascular risk factors, inasmuch as experimental HC and HT have each been linked to alterations of vascular and tubular function. We have previously shown that experimental HC was associated with alterations in the renal vascular response to challenge both in vivo 7 and in vitro 8 and abnormal tubular dynamics in vivo. 7 Similarly, HT has been shown to induce abnormalities of renal vascular 9 and tubular 10 function. One of the mechanisms...

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“…Moreover, understanding the pathogenesis of vessel injury in atherosclerosis has provided insights into mechanisms that lead to kidney injury, as hyperlipidemia accelerates the rate of glomerulosclerosis, and reductions in lipid levels reverse this effect [4, 5, 6, 7]. In blood vessel walls that become atherosclerotic, circulating lipids bind to and become trapped by extracellular matrix molecules [8], where they undergo oxidation [9].…”

Section: Introductionmentioning

confidence: 99%

Cellular Lipid Metabolism and the Role of Lipids in Progressive Renal Disease

Abrass¹

2004

Am J Nephrol

241

180

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Dyslipidemia contributes to the rate of progression of atherosclerosis and chronic kidney disease. Also, chronic kidney disease leads to the development of secondary abnormalities in lipid metabolism that contribute to increased cardiovascular morbidity and mortality. This review presents the mechanisms that underlie this risk. The mechanisms of normal cellular lipid metabolism and the abnormalities that develop in association with inflammation are reviewed. There is a special emphasis on foam cells in the kidney and on lipid-mediated changes in intrinsic kidney cells that lead to glomerulosclerosis and interstitial fibrosis. Correlates to studies performed in whole animals and humans are included.

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Relationship between Hyperlipidemia, Lipid Mediators, and Progressive Glomerulosclerosis in the Nephrotic Syndrome

Cited by 32 publications

References 46 publications

Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes

Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes

Combination of Hypercholesterolemia and Hypertension Augments Renal Function Abnormalities

Cellular Lipid Metabolism and the Role of Lipids in Progressive Renal Disease

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