Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome

Shearer, Gregory C.; Stevenson, Frazier T.; Atkinson, David; Jones, Hardin B.; Staprãns, Ilona; Kaysen, George A.

doi:10.1046/j.1523-1755.2001.00478.x

Cited by 64 publications

(56 citation statements)

References 34 publications

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“…These observations are consistent with previous studies demonstrating that the daily steroid dose tended to be correlated with the total cholesterol levels in patients with SLE (17,29). However, SLE-related factors, in particular, renal disease and proteinuria, likely exacerbate the effect of steroids on total cholesterol levels (6,42,43).…”

Section: Sarkissian Et Alsupporting

confidence: 91%

“…Mean HDL cholesterol levels were significantly higher when patients were taking prednisone and the disease was inactive as compared with when patients were not taking prednisone but with active disease. The demonstration that prednisone treatment is associated with an increase in HDL cholesterol levels is consistent with previous reports (17,18,41,42) and may therefore be of benefit by increasing low levels of HDL cholesterol, which are associated with SLE.…”

Section: Sarkissian Et Alsupporting

confidence: 91%

“…A fall in triglyceride levels coincided with decreased disease activity as measured by the SLEDAI and a fall in proteinuria. Changes in proteinuria have been shown to modify triglyceride levels (42).…”

Section: Sarkissian Et Almentioning

confidence: 99%

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The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus

Sarkissian¹,

Beyenne²,

Feldman³

et al. 2006

Arthritis & Rheumatism

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Objective. To determine the prevalence of lipid abnormalities at different times and to determine the influence of both the disease and corticosteroid therapy on lipid abnormalities in pediatric patients with systemic lupus erythematosus (SLE).Methods. Lipid measurements were obtained in an inception cohort of 139 pediatric patients with SLE (114 females). Fasting levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and highdensity lipoprotein (HDL) cholesterol in the SLE patients were compared with those in age-and sex-matched control subjects. Disease activity levels and medication dosages were obtained at the time of lipid measurements.Results. At the time of diagnosis, the mean levels of total cholesterol, LDL cholesterol, and triglycerides were highest, whereas the mean levels of HDL cholesterol were lowest. The percentage of patients with abnormal triglyceride values was highest at diagnosis, decreased at year 1, and then remained relatively constant thereafter. The mean total cholesterol and LDL cholesterol levels decreased at year 1 as compared with the time of diagnosis and then remained relatively constant. The lowest mean HDL cholesterol levels were found at the time of diagnosis, and these values rose with time. Comparison of lipid levels at different prednisone dosages and disease activity levels revealed that changes in triglyceride levels were mainly associated with changes in disease activity, changes in both total cholesterol and LDL cholesterol levels were associated with changes in the prednisone dosage and not disease activity, and low levels of HDL cholesterol were associated with active SLE, whereas the prednisone dosage was associated with increased levels of HDL cholesterol.Conclusion. Factors intrinsic to SLE appear to alter lipid levels. Control of SLE may be the most important factor in improving abnormal lipid profiles, and paradoxically, prednisone therapy may improve abnormal lipid levels.

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Section: Sarkissian Et Alsupporting

confidence: 91%

Section: Sarkissian Et Alsupporting

confidence: 91%

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The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus

Sarkissian¹,

Beyenne²,

Feldman³

et al. 2006

Arthritis & Rheumatism

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“…The scarcity of cholesterol ester-rich HDL in nephrotic syndrome contributes to an impairment of VLDL and chylo micron metabolism, and limits the delivery of lipids to myocytes for energy production and to adipose tissue for storage 48 . The contribution of HDL abnormalities to the pathogenesis of impaired VLDL metabolism in nephrotic syndrome has been clearly demonstrated in vivo, where impaired endothelial binding and LPLmediated lipolysis of VLDL in nephrotic rats could be corrected by infusion of HDL from healthy animals 49,50 . These findings have been further supported by in vitro experiments that showed defective maturation of nascent VLDL in the presence of nephrotic HDL and its subsequent correction with the addition of normal HDL 40 .…”

Section: Consequences Hdl Abnormalitiesmentioning

confidence: 99%

HDL abnormalities in nephrotic syndrome and chronic kidney disease

2015

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| Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.

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“…H yperlipidemia in the nephrotic syndrome is a result of increased synthesis (1,2) and decreased catabolism (1,3,4). VLDL levels are increased predominantly as a consequence of decreased catabolism both in rats with the nephrotic syndrome (4) and in humans (5).…”

mentioning

confidence: 99%

Graded Effects of Proteinuria on HDL Structure in Nephrotic Rats

Shearer

Newman

Hammock

et al. 2005

Journal of the American Society of Nephrology

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Nephrotic syndrome is characterized by increased triglycerides resulting from decreased clearance of VLDL and chylomicrons. These triglyceride-rich lipoproteins are structurally altered by interaction with HDL derived from animals with proteinuria and not as a consequence of hypoalbuminemia. HDL isolated from rats with massive proteinuria is depleted in apolipoprotein E (apoE). It is unknown at what threshold of urinary albumin loss HDL structure is altered, and it is unknown what effects proteinuria has on apolipoproteins other than apoE. Two models of albuminuria were used in Sprague-Dawley rats: Adriamycin and passive Heymann nephritis (HN). The adriamycin group was divided into minimal albumin excretion (MAE) and intermediate albumin excretion (MAE, 1 to 40; intermediate albumin excretion, 60 to 210 mg/d per 100 g body wt). Urinary albumin excretion exceeded 300 mg/d per 100 g body wt in the HN rats. HDL apolipoprotein composition was analyzed with SDS-PAGE densitometry and liquid chromatography-time of flight mass spectrometer mass spectrometry. HDL apoA-IV content relative to apoA-I was reduced at all levels of albuminuria (P < 0.0001). ApoE was not reduced in MAE but was significantly reduced in IAE (72%; P < 0.001). By contrast, apoA-II and apoC-III were each significantly increased with increasing UAE. ApoA-IV and apoE were decreased to approximately 10% of control in HDL isolated from rats with HN, whereas apoA-II, apoC-II, and apoC-III were each significantly increased relative to apoA-I. HDL is structurally altered by levels of albuminuria that are insufficient to change serum albumin levels and is progressively altered as albuminuria increases.J H yperlipidemia in the nephrotic syndrome is a result of increased synthesis (1,2) and decreased catabolism (1,3,4). VLDL levels are increased predominantly as a consequence of decreased catabolism both in rats with the nephrotic syndrome (4) and in humans (5). VLDL from nephrotic rat plasma does not bind normally to vascular endothelial cells, a consequence of reduced apolipoprotein E (apoE) content. Nascent VLDL functions normally when secreted by nephrotic livers but acquires a structural and functional defect through interaction with nephrotic HDL after VLDL secretion (6). The alteration in HDL structure and function results directly from proteinuria (3,6) and not from hypoalbuminemia.We have shown that defective clearance of VLDL in nephrotic rats requires interaction with HDL from proteinuric animals and that hypoalbuminemia does not deleteriously affect HDL structure. Although we have analyzed the effect of nephrotic range albuminuria on HDL structure, the effects of lesser amounts of albuminuria have not been well examined. Even small amounts of albuminuria are associated with increased relative risk for vascular disease in both diabetes (7,8) and hypertension (9,10). This association is generally believed to reflect underlying endothelial dysfunction in patients with microalbuminuria, causing both the renal albumin leak and the association with vasc...

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Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome

Cited by 64 publications

References 34 publications

The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus

The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus

HDL abnormalities in nephrotic syndrome and chronic kidney disease

Graded Effects of Proteinuria on HDL Structure in Nephrotic Rats

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