Hyperlipidemia in Nephrotic Syndrome

Wheeler, David C.; Varghese, Z.; Moorhead, John F.

doi:10.1159/000168044

Cited by 22 publications

(8 citation statements)

References 42 publications

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“…The presence of interstitial and glomerular foam cells correlates with the duration, but not with the intensity of proteinuria in glomerulopathies [38]. Thus, control of hyperlipidaemia in persistent nephrotic syndromes [39] could have the aim not only of preventing generalised atheroma, but also of preventing entry into renal failure, or at least slowing its progression ( fig. 7).…”

Section: Indirect Mechanisms Of Proteinuric Glomerular Damage: Hyperlmentioning

confidence: 99%

Proteinuria and Progression in Human Glomerular Diseases

Js¹

1990

Am J Nephrol

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Proteinuria is characteristic of many glomerular conditions, and often exceeds 2–3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from ‘overload’ proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinura leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in haematuric conditions. Therapies designed to reduce proteinura per se may have a role in the treatment of glomerulopathies.

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Section: Indirect Mechanisms Of Proteinuric Glomerular Damage: Hyperlmentioning

confidence: 99%

Proteinuria and Progression in Human Glomerular Diseases

Js¹

1990

Am J Nephrol

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“…There has been an accumulation of clinical and experi mental data which indicate that glomerular function and morphology may be influenced by lipids, and that hyperlip idemia may enhance the development of renal injury [1][2][3][4]. Analogous to the role of lipids in atherosclerosis, glomeru lar lipid accumulation has been implicated in the develop ment of glomerular sclerosis [1].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Hyperlipidemia with Probucol Suppresses the Development of Focal and Segmental Glomerulosclerosis in Chronic Aminonucleoside Nephrosis

Hirano

Morohoshi²

1992

Nephron

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We have recently reported that a lipid-lowering agent, probucol, reduces proteinuria in puromycin aminonucleoside (PA)-induced nephrotic rats (PAN). In this study, we examined whether a long-term treatment of hyperlipidemia with probucol can suppress the development of focal and segmental glomerulosclerosis (FSGS) in chronic PAN. A chronic PAN model was made with repeated intraperitoneal injections of PA (initially 100 mg/kg body weight followed by 25 mg/kg 5 times at 2-week intervals). Two weeks after the first injection of PA, either normal rat chow with or without 1% probucol was given to the nephrotic rats for 10 weeks. Chronic PAN exhibited remarkable proteinuria, hypoalbuminemia and severe hyperlipidemia with all lipoprotein fractions increased. Probucol treatment significantly reduced the lipid concentration in all major lipoproteins, significantly reduced proteinuria and increased plasma albumin concentration. Plasma albumin inversely correlated with cholesterol or phospholipid in low-density and high-density lipoproteins, suggesting that the lipid-lowering effect of probucol may ameliorate the hypoalbuminemia associated with nephrosis. In light microscopic examination, various degrees of FSGS with tubuloin-terstitial lesions were observed in the renal cortex from chronic PAN. The degree of FSGS was scored from grades 1 to 4 according to severity. One half of the untreated PAN (⁴/₈) was classified into grade 4 and the other into grades 2 or 3, whilst one half of treated PAN (⁴/₈) was classified either into grade 1 or 2. The grading of FSGS correlated negatively with plasma albumin concentration. These results demonstrate that probucol is highly effective upon nephrotic hyperlipidemia and suggest that a long-term treatment of secondary hyperlipidemia can suppress progressive renal injury associated with chronic nephrosis.

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“…The precise contribution of increased lipogenesis and decreased lipid catabolism to hyperlipidemia, and their relationship to urinary protein loss, hypoalbuminemia, and reduced serum oncotic pressure, remain controversial. Although proteinuria, hypoalbuminemia, and edema are regularly seen, hyperlipidemia is not universally present, even in adults with NS [21]. It is always present in MCNS, with 95% of children having serum cholesterol greater than 250 mg/dl.…”

Section: Resultsmentioning

confidence: 99%

Oxidative damage of erythrocyte membrane in nephrotic syndrome

Mocan

Aksoy

Uydu

et al. 1999

Pediatric Nephrology

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Erythrocytes are target cells for peroxidative damage. Abnormal susceptibility of erythrocyte lipids to peroxidation is believed to reflect a similar abnormality in other organs and tissues. The changes in erythrocyte lipid peroxidation [measured by malonyldialdehyde (MDA) concentration] and erythrocyte membrane cholesterol (EMC) and their correlation with plasma lipid changes were studied in 36 children with steroid-responsive minimal change nephrotic syndrome (MCNS) (16 in relapse, 20 in remission) and 30 matched healthy controls. Erythrocyte MDA levels were significantly higher in relapse [126.3+/-40.6 nmol/g hemoglobin (Hb)] compared with remission (101.2+/-21.3 nmol/g Hb, P<0.02) and in controls (95.4+/-20.4 nmol/g Hb, P<0.001). Plasma MDA levels in relapse were also higher than in remission (4.26+/-1.19 nmol/ml vs. 3.16+/-1.18 nmol/ml, P<0.01), and in controls (2.49+/-0.86 nmol/ml, P<0.001). The EMC content changed significantly during remission (1.22+/-0.15 mg/10(10) cells in relapse, 1.09+/-0.19 mg/10(10) cells in remission, P<0.04). These results show an increased sensitivity of red cells to lipid peroxidation in patients with steroid-sensitive nephrotic syndrome without the development of renal failure and anemia. Lipid peroxidation of plasma lipids and erythrocyte membrane may be a primary phenomenon, but this should be confirmed by investigation of peroxidation of renal lipids.

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Hyperlipidemia in Nephrotic Syndrome

Cited by 22 publications

References 42 publications

Proteinuria and Progression in Human Glomerular Diseases

Proteinuria and Progression in Human Glomerular Diseases

Treatment of Hyperlipidemia with Probucol Suppresses the Development of Focal and Segmental Glomerulosclerosis in Chronic Aminonucleoside Nephrosis

Oxidative damage of erythrocyte membrane in nephrotic syndrome

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