Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells

Quaschning, Thomas; Königer, M.; Krämer-Guth, Annette; Greiber, S.; Pavenstädt, Hermann; Nauck, Markus; Schollmeyer, P.; Wanner, C

doi:10.1093/ndt/12.12.2528

Cited by 15 publications

(11 citation statements)

References 5 publications

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“…Although no differences in renal tissue AmB concentra- tions were observed following Doc-AmB administration to cholesterol-fed rabbits, AmB's increased level of association with the TRL fraction may decrease AmB's ability to inflict renal damage at the cellular level. This may be because receptor-mediated uptake of apolipoprotein B-and E-rich lipoproteins (namely, LDL and TRL) by human glomerular epithelial cells (11,24) is downregulated in cholesterol-fed rabbits (11). Thus, most TRL-associated AmB, although delivered to the renal tissue, would not interact with kidney cells and would not cause damage.…”

Section: Discussionmentioning

confidence: 99%

Amphotericin B Lipid Complex or Amphotericin B Multiple-Dose Administration to Rabbits with Elevated Plasma Cholesterol Levels: Pharmacokinetics in Plasma and Blood, Plasma Lipoprotein Levels, Distribution in Tissues, and Renal Toxicities

Ramaswamy

Peteherych

Kennedy

2001

Antimicrob Agents Chemother

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The purpose of the present study was to determine if a relationship exists between the plasma cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the pharmacokinetics of AmpB in plasma in hypercholesterolemic rabbits administered multiple doses of amphotericin B (AmB) deoxycholate (Doc-AmB) and AmB lipid complex (ABLC). After 7 days of administration of a cholesterolenriched diet (0.50% [wt/vol]) or a regular rabbit diet, each rabbit was administered a single intravenous bolus of Doc-AmB (n ‫؍‬ 8) or ABLC (n ‫؍‬ 10) (1.0 mg/kg of body weight) daily for 7 consecutive days (a total of eight doses). Blood samples were obtained daily before and 24 h after the administration of each dose and serially thereafter following the administration of the last dose for the assessment of pharmacokinetics in plasma, kidney toxicity, plasma lipoprotein levels, and drug distribution in tissue. The pharmacokinetics of AmB in blood following the administration of ABLC were also determined in rabbits fed cholesterol-enriched and regular diets (n ‫؍‬ 3 each group). Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total, low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) cholesterol levels in plasma compared with the levels in rabbits on a regular diet. No significant differences in total plasma triglyceride levels were observed. Significant increases in plasma creatinine levels were observed in rabbits fed a cholesterol-enriched diet (P < 0.05) and rabbits fed a regular diet (P < 0.05) when administered AmB. However, the magnitude of this increase was twofold greater in rabbits fed a regular diet than in rabbits fed a cholesterol-enriched diet. An increase in plasma creatinine levels was observed only in rabbits on a cholesterol-enriched diet administered ABLC. The pharmacokinetics of AmB were significantly altered in rabbits on a cholesterol-enriched diet administered Doc-AmB or ABLC compared to those in rabbits on a regular diet administered each of these compounds. The pharmacokinetics of AmB in blood were significantly different following ABLC administration but not following Doc-AmB administration in both rabbits fed cholesterolenriched diets and rabbits fed regular diets compared to their corresponding pharmacokinetics in plasma. An increased percentage of AmB was recovered in the TRL fraction when Doc-AmB was administered to rabbits fed a cholesterol-enriched diet than when it was administered to rabbits fed a regular diet. Furthermore, an increased percentage of AmB was recovered in the LDL and TRL fractions when ABLC was administered to rabbits fed a cholesterol-enriched diet rabbits fed a regular diet. These findings suggest that an increase in plasma cholesterol levels modifies the pharmacokinetics of AmB and renal toxicity following the administration of multiple intravenous doses of Doc-AmB and ABLC.Disseminated fungal infections such as candidiasis, histoplasmosis, and aspergillosis are on the rise, particularly in patients with ...

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Section: Discussionmentioning

confidence: 99%

Amphotericin B Lipid Complex or Amphotericin B Multiple-Dose Administration to Rabbits with Elevated Plasma Cholesterol Levels: Pharmacokinetics in Plasma and Blood, Plasma Lipoprotein Levels, Distribution in Tissues, and Renal Toxicities

Ramaswamy

Peteherych

Kennedy

2001

Antimicrob Agents Chemother

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“…Finally, lipid-lowering therapy has been shown to improve glomerulosclerosis in the Zucker rat, a model of diabetes complicated with dyslipidemia [22]. Mesangial cells and glomerular epithelial cells (podocytes) have been shown to express receptors for TG-rich lipoproteins (TGRLs) [23][24][25][26]. TGRLs stimulate inflammatory pathways via the secretion of proinflammatory cytokines such as TNF-α, transforming growth factor (TGF)-β, and interleukin (IL)-6 [27], which results in the production of reactive oxygen species (ROS), leading to excessive ECM production.…”

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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“…In fact, glomerular cells like mesangial or epithelial cells have been shown in vitro to express lipoprotein receptors and to take up LDL comparably to fibroblasts and hepatocytes. 46 It is, however, completely unclear whether the kidney plays a significant role in LDL catabolism in vivo. Perfusion studies in rat kidneys indicated that virtually no intact LDL is cleared from the circulation by the kidney.…”

Section: Ikewaki Et Al Delayed Catabolism Of Idl and Ldl In Hemodialymentioning

confidence: 99%

Delayed In Vivo Catabolism of Intermediate-Density Lipoprotein and Low-Density Lipoprotein in Hemodialysis Patients as Potential Cause of Premature Atherosclerosis

Ikewaki

Schaefer

Frischmann

et al. 2005

ATVB

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Objective-Premature cardiovascular disease is the leading cause of death in patients with end-stage renal disease treated by hemodialysis (HD). Low-density lipoprotein (LDL) levels are not generally increased in HD patients, but their LDL metabolism is still poorly understood. We therefore investigated the in vivo metabolism of apoB-containing lipoproteins in two different ethnic populations of HD patients and controls. Methods and Results-We performed stable isotope kinetic studies using a primed constant infusion of deuterated leucine in 12 HD patients and 13 healthy controls. Tracer/tracee ratio of apoB was determined by means of gas chromatography/mass spectrometry, and the modeling program SAAMII was used to estimate the fractional catabolic rate (FCR) of apoB. Mean LDL-apoB plasma concentrations were almost identical in both groups (HD: 95Ϯ30 mg/dL, controls: 91Ϯ40 mg/dL), whereas LDL-apoB FCR was 50% lower in HD patients as compared with controls (0.22Ϯ0.12 days Ϫ1 versus 0.46Ϯ0.20 days Ϫ1 , Pϭ0.001) with concomitantly decreased production rates of LDL. T hirty yeas ago, Lindner and colleagues recognized in their seminal report the excessive risk of cardiovascular disease for hemodialysis (HD) patients. 1 The prevalence and incidence of cardiovascular disease is much higher in HD patients, and current mortality rates are Ϸ10 to 20 times greater than the general population with rates even higher at young ages. 2 A remarkable number of factors, including dyslipoproteinemia, chronic inflammation, hypertension, oxidative stress, elevated homocysteine, and anemia, that may contribute to this increased frequency of atherosclerotic complications have been identified. 3,4 HD patients are characterized by a complex plasma dyslipoproteinemic profile. 5 The most notable quantitative abnormalities are elevated plasma triglyceride and very lowdensity lipoprotein (VLDL) levels with a prevalence of 25% to 75%, 6,7 increased levels of atherogenic intermediate density lipoprotein (IDL) 8 and lipoprotein(a) 9 particles, and decreased high-density lipoprotein (HDL) levels. 10 Interestingly, total and low-density lipoprotein (LDL) cholesterol plasma levels are usually normal or even subnormal in HD patients as compared with healthy controls. 11,12 In addition to quantitative changes in lipoprotein particles, numerous compositional and qualitative lipoprotein changes have been demonstrated as well. These include accumulation of small dense LDL 13 as well as oxidation, glycation, and carbamylation of LDL. The association of small dense LDL Original

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Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells

Cited by 15 publications

References 5 publications

Amphotericin B Lipid Complex or Amphotericin B Multiple-Dose Administration to Rabbits with Elevated Plasma Cholesterol Levels: Pharmacokinetics in Plasma and Blood, Plasma Lipoprotein Levels, Distribution in Tissues, and Renal Toxicities

Amphotericin B Lipid Complex or Amphotericin B Multiple-Dose Administration to Rabbits with Elevated Plasma Cholesterol Levels: Pharmacokinetics in Plasma and Blood, Plasma Lipoprotein Levels, Distribution in Tissues, and Renal Toxicities

Dyslipidemia in diabetic nephropathy

Delayed In Vivo Catabolism of Intermediate-Density Lipoprotein and Low-Density Lipoprotein in Hemodialysis Patients as Potential Cause of Premature Atherosclerosis

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