Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lecithin-cholesterol acetyltransferase (LCAT) is involved in the synthesis of plasma cholesteryl esters and is pivotal in the maturation of plasma high-density lipoprotein (HDL) and conversion of HDL3 to HDL2. In nephrotic syndrome (NS), the ratio of HDL2 to HDL3 is low even though the total concentration of HDL is generally normal. We hypothesize that the reduced HDL2/HDL3 ratio in NS is due to urinary losses of LCAT, leading to plasma LCAT deficiency. To test this hypothesis, Sprague-Dawley rats were randomized to NS (given 130 mg puromycin aminonucleoside on day 1 and 60 mg ip on day 14) or control groups and were studied on day 30. To dissect the effect of proteinuria from hypoalbuminemia, a group of Nagase rats with inherited hypoalbuminemia was included. Hepatic LCAT and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA abundance and plasma and urine LCAT activity were measured. The NS group showed a fourfold rise in serum cholesterol and triglycerides, a fivefold rise in free cholesterol, and a fourfold fall in the HDL-to-total cholesterol ratio. Despite severe hypoalbuminemia, the Nagase rats showed only a mild elevation of serum cholesterol and triglycerides with a normal serum free cholesterol and HDL-to-total cholesterol ratio. The NS group exhibited a normal hepatic LCAT-to-GAPDH mRNA ratio, a marked reduction in plasma LCAT activity, and a significant increase in urinary LCAT excretion. LCAT/GAPDH mRNA and plasma and urine LCAT were normal in Nagase rats. Thus NS led to heavy urinary losses and reduced plasma concentration of LCAT, despite normal hepatic LCAT mRNA abundance. However, hypoalbuminemia, per se, without proteinuria as seen in the Nagase rats had no effect on plasma LCAT or the HDL-to-total cholesterol ratio. Therefore, proteinuria, not hypoalbuminemia, causes LCAT deficiency and a depressed HDL-to-total cholesterol ratio in NS.
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PMID:Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome. 1129 24

The purpose of this study was to assess the prevalence of dyslipoproteinemia and to analyze the clinical variables that are associated with it in a sample of premenopausal systemic lupus erythematosus (SLE) patients. We studied 53 premenopausal (34.5 y) SLE outpatients and 45 controls. Clinical variables studied included patient age, weight, height, body mass index (BMI), age at disease onset, disease duration, clinical activity of SLE, renal involvement and drug therapy. Total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides were measured using standard enzymatic techniques. Apolipoproteins (apo) A-I and B were determined by radial immunodiffusion. Twenty-nine patients (55%) and 14 controls (30%) had dyslipoproteinemia. An increase in TC, triglycerides, HDL3-C, apo A-I and apo B, and a decrease in HDL2-C and HDL-C/TC index was found in SLE patients in comparison with controls. TC (P = 0.007), apo B (P = 0.02), LDL-C (P = 0.03) and triglycerides (P = 0.0001) were significantly correlated with proteinuria. Patients on prednisone therapy had higher triglycerides levels (P = 0.03) than untreated patients. TC (P = 0.01), LDL-C (P = 0.006) and triglycerides (P = 0.04) were also correlated with the dose of prednisone. Dyslipoproteinemia is a common feature in adult SLE premenopausal patients which is characterized by an increase in TC, triglycerides and apo B, and an abnormal distribution of HDL subclasses. Corticosteroid therapy and proteinuria are the best predictors of dyslipoproteinemia in these patients.
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PMID:Lipid and lipoprotein levels in premenopausal systemic lupus erythematosus patients. 1140 67

Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL.
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PMID:Cubilin maintains blood levels of HDL and albumin. 2435 74

Renal diseases have been recognized as a major cause of secondary dyslipidemia since the late 1950's. Two main pathological conditions of renal diseases, impaired renal function and severe proteinuria (nephrotic syndrome), are individually or conjointly associated with altered lipid metabolism depending on the primary diseases. An impaired renal function causes reductions in lipoprotein and hepatic TG lipase activity, the VLDL recep- tor abundance, and ApoC-II to apoC-III ratio, as well as in ApoA-I and LCAT activities. These alterations result in reduced VLDL clearance and the disturbance of HDL synthesis and maturation, leading to uremic dyslipidemia: increased levels of TG, IDL-C, and small-dense LDL-C and decreased levels of HDL-C. Lipid disorders in nephrotic syndrome (NS) are characterized by increased levels of LDL-C and/or TG. NS-induced hypoalbuminemia enhances the synthesis of cholesterol, cholesterol ester, and ApoB, leading to the increased production of LDL and VLDL. Recently, two intriguing molecules were newly identified as inhibitors of lipoprotein clearance. Pro-protein Convertase Subtilisin/Kexin type 9 (PCSK9) is upregulated in NS, and decreases LDL clearance via prompting degradation of the LDL receptor, while angiopoietin-like 4 (Angptl4) is also induced in NS and restricts VLDL clearance via inhibiting lipoprotein lipase. NS impairs HDL maturation from HDL3 to HDL2 due to a reduction of LCAT, with HDL-C levels preserved. Finally, considering that diabetic nephropathy is representative of progressive renal disease and that gluco- corticoids are an anchor drug for the treatment of NS, diabetes- or drug-associated dyslipidemia is occasional- ly superimposed on the original renal dyslipidemia. [Review].
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PMID:[Renal Dyslipidemia]. 3069 62


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