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)

The hypothesis that increased cholesterol synthesis provides a mechanism that contributes to nephrotic syndrome-associated hyperlipidemia is mainly based on experimental evidence. The serum level of the cholesterol precursor, lathosterol (expressed per millimole cholesterol), is a reliable marker of whole-body cholesterol synthesis in normocholesterolemia and primary hypercholesterolemia. Serum lathosterol and lipoprotein levels were measured in 11 moderately hyperlipidemic patients with nephrotic-range proteinuria and 22 matched controls. The proteinuric patients were evaluated before and during three antiproteinuric treatment periods with angiotensin-converting enzyme (ACE) inhibition therapy (n = 6) or a low-protein diet (n = 5) alone, in combination, and again as a single treatment. In untreated patients, serum total cholesterol, very-low-density (VLDL) and low-density (LDL) lipoprotein cholesterol, apolipoprotein B (apo B), and lipoprotein (a) [Lp(a)] levels were higher than in controls (P < .01 to P < .001), but the lathosterol to cholesterol ratio tended to be lower in patients (0.99 +/- 0.43 micromol/mmol) as compared with controls (1.29 +/- 0.41 micromol/mmol, P < .10). During combined antiproteinuric treatment, total and VLDL + LDL cholesterol, apo B, and Lp(a) decreased (P < .02 to P < .01), but remained higher than levels in controls. Yet the serum lathosterol to cholesterol ratio changed little and was even lower (P < .05) in treated patients than in controls. Serum total cholesterol (r = -.82, P < .01) and apo B (r = -.84, P < .01) were inversely correlated with serum albumin in untreated patients, whereas the serum lathosterol to cholesterol ratio was not (r = -.01, NS). In the patient group, multiple regression analysis showed that changes in the lathosterol to cholesterol ratio during the study were only related to changes in the dietary polyunsaturated to saturated fatty acids ratio (P:S) coinciding with the low-protein diet (P < .01). In contrast, the decrease of VLDL + LDL cholesterol, apo B, and Lp(a) was independently related to reduction of proteinuria (P < .02 to P < .001), but not to changes in the lathosterol to cholesterol ratio. In conclusion, the present data, based on the serum lathosterol to cholesterol ratio, do not support the concept that increased cholesterol synthesis plays an important role in the maintenance of human nephrotic syndrome-associated hypercholesterolemia. Moreover, it appears unlikely that the decrease of apo B-containing lipoproteins with antiproteinuric treatment is attributable to inhibition of cholesterogenesis. These findings warrant further documentation of cholesterol synthesis in human nephrotic syndrome by direct methods.
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PMID:The serum lathosterol to cholesterol ratio, an index of cholesterol synthesis, is not elevated in patients with glomerular proteinuria and is not associated with improvement of hyperlipidemia in response to antiproteinuric treatment. 863 47

Lipoprotein(a) [Lp(a)] is a plasma lipoprotein whose structure and composition closely resemble that of low-density lipoproteins, but contains an additional protein called apolipoprotein(a) [apo(a)]. Factors which modulate plasma Lp(a) concentrations are poorly understood. The influence of nephrotic syndrome on Lp(a) levels was investigated in 103 patients with nephrotic syndrome: 72 with primary kidney disease and 31 with diabetic nephropathy. Nephrotic patients had significantly higher Lp(a) levels (mean 63 +/- 7 mg/dl; median 42 mg/dl) compared with controls (mean 22 +/- 2 mg/dl; median 8 mg/dl). Fifty-seven percent of the patients and 22% of the controls had values greater than 30 mg/dl. Within all apo(a) isoform classes, higher concentrations of Lp(a) were seen in the nephrotic patients compared with controls. In 17 patients with primary kidney disease remission of the nephrotic syndrome was induced by immunosuppressive treatment and Lp(a) concentration dropped in parallel with the reduction of proteinuria (pretreatment mean, 98 +/- 9 mg/dl vs. remission mean, 25 +/- 5 mg/dl). In 9 patients where multiple measurements were done, multiple regression analysis showed a strong relation of Lp(a) with the amount of proteinuria (p < 0.01). We conclude that most patients with the nephrotic syndrome have Lp(a) concentrations which are substantially elevated compared with control subjects of the same apo(a) isoform. Because Lp(a) concentrations are substantially reduced when remission of the nephrotic syndrome is induced by immunosuppressive drugs, it is likely that nephrotic syndrome directly results in elevation of Lp(a). The high levels of Lp(a) in nephrotic syndrome could potentially cause glomerular injury as well as increase the risk of atherosclerosis and thrombotic events associated with this disorder.
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PMID:Lipoprotein(a) in patients with the nephrotic syndrome: influence of immunosuppression and proteinuria. 867 20

Most researchers have found increases of lipoprotein (a) [Lp(a)] in uremic patients, as well as in those undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). The mechanisms for this increase remain unclear. We studied 71 patients undergoing CAPD, 48 men and 23 women. According to the time spent on CAPD, the patients were divided into three groups: group 0: 29 patients at the starting off point of dialysis treatment; group I: 22 patients with an average stay of 15.2 months; group II: 20 patients with an average stay of 69.3 months on CAPD. We have only observed significant increases of Lp(a) levels in those patients initiating the dialysis, but no significant differences are found in the other groups undergoing CAPD for longer periods when compared to the control group. We found no significant relation between Lp(a) levels and peritoneal protein loss, and not with absorption of glucose from the dialysate either. We have found a positive and significant correlation between Lp(a) levels and urinary protein loss (r = 0.41; p < 0.001). It is possible that an element associated with proteinuria might have an effect on the metabolism of Lp(a) in CAPD patients.
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PMID:Lipoprotein (a) levels in patients undergoing continuous ambulatory peritoneal dialysis. 872 99

Hyperlipoproteinemia is frequently observed in patients after renal transplantation and contributes to cardiovascular morbidity and mortality. In addition, it was recently shown that hypercholesterolemia accelerates the progression of renal disease. In a renal transplant recipient (RTR) with severe coronary heart disease, familial hypercholesterolemia and decreased renal function, immunospecific LDL-apheresis was instituted since dietary restrictions failed to sufficiently improve hyperlipoproteinemia and medication had to be avoided due to drug interactions. Over a period of 36 months 145 LDL-apheresis treatments were performed at weekly intervals. The desorption of 5600 ml plasma volume allowed a mean reduction of total cholesterol by 56.6% (from 256 mg/dl to 110 mg/dl), of LDL-cholesterol by 63.0% (from 163 mg/dl to 58 mg/dl), of Lp(a) by 68.3% (from 34 mg/dl to 11 mg/dl) and of triglycerides by 49.6% (from 332 mg/dl to 163 mg/dl). Although temporarily decreasing during each apheresis session by 9.0%, HDL-cholesterol values increased during the first 9 months of treatment and remained within the normal range (> 45 mg/dl) thereafter. Cyclosporine A blood trough values were decreased by 32% during LDL-apheresis. Symptoms of angina pectoris rapidly improved and disappeared after 8 months of apheresis treatment. Initial coronary angiography exhibited serious three-vessel-disease, without the possibility of bypass grafting. Coronary angiography repeated after two years of therapy showed a regression of the disease. Serum creatinine levels declined during treatment (from 2.7 mg/dl to 1.8 mg/dl) and proteinuria did not increase further. This is the first report to show that long-term LDL-immunoadsorption is a safe and highly effective treatment of severe hyperlipidemia and coronary heart disease in a RTR, resulting in regression of vascular pathology. Moreover, amelioration of hyperlipidemia may have improved transplant function. Multicenter studies are necessary to confirm our results.
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PMID:Regression of coronary atherosclerosis and amelioration of renal function during LDL-immunoadsorption therapy in a renal transplant recipient. 878 84

Renal disease patients often exhibit alterations in the lipid profile which may become an important risk of accelerated atherosclerosis and contribute to disease progression. Among such alterations, increased levels of lipoprotein(a) [Lp(a)] are common and may be related, in part, to the degree of proteinuria. Omega-3 polyunsaturated fatty acids (omega-3 FA) have been reported to decrease Lp(a) concentrations in nonrenal subjects. In addition, they have recently been shown to reduce proteinuria in patients with chronic glomerular disease. We therefore tested the hypothesis that omega-3 FA treatment in patients with chronic glomerular disease may reduce Lp(a) concentrations. Eight patients (2 with membranous glomerulonephritis, 6 with focal glomerular sclerosis) were submitted to a total of 13 six-week courses of treatment with omega-3 FA, at a dose of 3 g/day with a triglyceride preparation (n = 4) and of 7.7 g/day with an ethyl-ester preparation (n = 9). Both treatments significantly increased the proportions of omega-3 to omega-6 FA in total serum lipids, documenting compliance to treatment. Both treatments were also effective in decreasing serum thromboxane (from mean 490 +/- (SEM) 70 to 325 +/- 49 ng/ml, p < 0.05, in the high-dose group) and prolonging the bleeding time (from 5.8 +/- 0.4 to 7.7 +/- 0.5 min, p < 0.05, in the high-dose group), thus documenting the biological efficacy of treatment. However, despite a significant reduction in serum triglyceride levels (from 137 +/- 20 to 104 +/- 19 mg/dl in the high-dose group), Lp(a) concentrations did not change (292 +/- 120 U/l before, 315 +/- 130 U/l after the high-dose therapy). Treatment-related changes in proteinuria (from 2.9 +/- 0.5 to 2.1 +/- 0.7 g/24 h) were not related at all to changes in Lp(a) levels. We conclude that omega-3 FA do not decrease Lp(a) concentrations in renal patients with chronic glomerular diseases and that Lp(a) levels are unlikely to be related to the degree of proteinuria within the short-term modifications induced by omega-3 FA.
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PMID:Omega-3 fatty acid supplementation and lipoprotein(a) concentrations in patients with chronic glomerular diseases. 885 84

Chronic renal failure is frequently accompanied by elevated plasma levels of lipoprotein (a) [Lp(a)]. Elevated Lp(a) levels have been proposed to contribute not only to increased risk of atherosclerotic and thrombotic complications but also to the progression of renal insufficiency. To investigate whether higher Lp(a) plasma concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of Lp(a) with the progressive decline of renal function in an observational study of human chronic renal disease. Forty-nine non-diabetic patients (40 men, nine women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.1 years, and the mean rate of decline in glomerular filtration rate (51Cr-EDTA clearance) was -2.8 (SD 4.1) ml/min/1.73 m2. The mean plasma concentration of Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100 ml with a median value of 12.2 mg/100 ml. There was no association between the initial plasma concentration of Lp(a) and the rate of progression as assessed by linear regression analysis. Furthermore, the progression rate in patients within the highest quartile of the Lp(a) distribution (> or = 30 mg/100 ml) did not differ from that in patients with lower levels of Lp(a). In contrast, increased levels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Based on these results, it was concluded that elevated plasma levels of Lp(a) are not associated with an increased rate of progression of renal insufficiency in human chronic renal disease. However, the results of this study suggest that other apoB-containing lipoproteins may play a significant role in this process.
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PMID:Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure. 894 84

Cardiac involvement, evaluated by echo-doppler-cardiography, occurred in 41 of 50 (82%) patients with systemic lupus erythematosus (SLE). Valvular pathology with aortic cusp sclerosis was the most prevalent finding irrespective of age. This finding, suggestive of atherosclerotic heart disease, was supported by increased levels of cholesterol and triglycerides in these patients. There was no significant increase in Lp(a) in the whole patient group, but Lp(a) was raised in patients with proteinuria. Forty percent of the SLE patients had pericarditis. Twelve patients with hypertension and/or mitral regurgitation had increased dimensions of left ventricle, left atrium or interventricular septum while 15 of 50 patients had isolated increase of these parameters. Localized hypokinesia was found in nine patients. Reduced cardiac index was found in five patients with SLE. There was no association between valvular disease, increased pulmonary artery pressure, and anticardiolipin antibodies.
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PMID:Echocardiographic findings, lipids and lipoprotein(a) in patients with systemic lupus erythematosus. 909 95

Patients with chronic renal failure (CRF) have an increased risk of cardiovascular disease (CVD). Elevated lipoprotein(a) (LP(a)) levels have been shown to be an important risk factor for CVD. This study examined Lp(a) changes during the progression of renal disease in patients following different dietary regimens. Fifty-seven patients with CRF of different etiology and degree (mean age 58 +/- 10 yrs) were divided into four groups according to their serum creatinine (sCr) levels. The first group had sCr 1.5-3; the second 3-6; the third > 6, all on a conventional low-protein diet (CLPD), and the fourth had sCr > 6 on a supplemented vegetarian diet (SVD). Lp(a), apoproteins AI, B, E, CII, CIII, CII/CIII, Apo A/Apo B ratios and the lipid pattern (total cholesterol (TC) and its fractions LDL, HDL, HDL3 and triglycerides) were investigated. Patients with diabetes, proteinuria > 1.5 g/24 h, hepatic disease or taking contraceptives or lipid lowering drugs were excluded. Results were compared with a reference group (N = 12) with sCcr < 1. Lp(a) concentrations increased with the progression of renal failure, and a significant correlation was observed with sCr. Despite the elevated sCr levels, patients on the SVD had an almost normal Lp(a) concentration. Only 15% of the reference group had Lp(a) levels > 30 mg/dl, compared to 33%, 50% and 78% of the 1st, 2nd and 3rd groups and 38% of the 4th group. No relationship was found between Lp(a), lipids or apoproteins. Our results indicate that renal function influences Lp(a) levels and suggest a SVD helps to lower them. This might be ascribed to some antioxidant factors in the SVD.
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PMID:Lp(a) levels: effects of progressive chronic renal failure and dietary manipulation. 924 24

Lipoprotein(a) [Lp(a)] may be elevated in patients with the nephrotic syndrome and patients on hemodialysis or continuous ambulatory peritoneal dialysis. High levels of Lp(a) are due to proteinuria or an activated acute-phase response. Serum concentrations greater than 30 mg/dl are independently associated with coronary heart disease. Data from cell culture studies suggest that it is not uptake of Lp(a) by mesangial cells but trapping by matrix proteins that contributes to the generation of glomerular apo(a) deposits. Lp(a) alters mesangial cell DNA synthesis and stimulates the generation of reactive oxygen species. Prolonged exposure to Lp(a) causes mesangial cell death in vitro culture' experiments. Lp(a) does not alter autocrine transforming growth factor-beta transcription in human mesangial cells and has, unlike low-density lipoprotein, no effect on the production of the extracellular matrix protein fibronectin. Future cell culture studies on the role of Lp(a) in renal disease have to address whether Lp(a) induces cell death via apoptosis and to what extent the generation of oxygen radicals is involved in this process.
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PMID:Lipoprotein(a) in nephrotic syndrome and end-stage renal disease. 938 8

To study the relationship of the concentration of serum lipoprotein (a) [Lp(a)] with diabetic complications in non-insulin dependent diabetes mellitus (NIDDM), 100 non-diabetics with 150 patients with NIDDM were compared. There was no difference in Lp(a) concentration (P > 0.5) between the two groups. Lp(a) concentration was not significantly correlated with the levels of total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, apolipoprotein A-I, apolipoprotein B in both groups. In NIDDM group, patients with hypertension, macro- and microangiopathy had higher levels of Lp(a) than those without these complications (P < 0.001 and P = 0.002 respectively). Lp(a) level was positively related to presence of macroangiopathy (r = 0.185, P = 0.024) and proteinuria (r = 0.316, P < 0.001) in NIDDM.
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PMID:[Lipoprotein (a) and non-insulin dependent diabetes mellitus]. 938 40


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