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)

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria. 131 86

The nephrotic syndrome results from altered glomerular permselectivity, causing urinary protein loss, reduced albumin concentration, oncotic pressure (pi), and hyperlipidemia. Hepatic lipid and apolipoprotein synthesis increases and lipoprotein catabolism decreases. Decreased lipoprotein catabolism follows the onset of proteinuria but is not associated with hereditary analbuminemia [Nagase analbuminemic rat (NAR)] if proteinuria is absent. We measured plasma apolipoproteins (apo) AI, B, and E levels, their mRNA concentrations in liver, and the transcription rate of each mRNA in rats with Heymann nephritis (HN) or NAR to determine which alterations occurred in NAR alone without proteinuria. Plasma apo AI, B, and E were increased in both HN and NAR. Cholesterol and apo AI were inversely proportional to pi and independent of urinary protein loss or the presence of albumin in plasma. In contrast, triglycerides (TGs) were significantly greater in HN and were increased out of proportion to apo B. The concentration of apo AI mRNA increased in liver of both HN and NAR as did apo AI transcription. Apo E mRNA increased in neither HN nor NAR, whereas apo B mRNA increased only in HN. Transcription of neither apo B nor E increased. Plasma apo AI levels are likely to be regulated transcriptionally at the level of protein synthesis, whereas plasma apo B and E levels are regulated either posttranscriptionally, at the level of protein catabolism, or at both sites. Lipoproteins rich in TG and poor in apo B appear after the development of proteinuria but not as a consequence of analbuminemia alone. The accumulation of TG-rich apo B containing lipoproteins in rats with HN may result from impaired lipolysis occurring as a consequence of proteinuria.
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PMID:Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis. 159 Apr 20

In the Dahl S rat (DS), salt induces systemic and glomerular capillary hypertension associated with progressive glomerulosclerosis, while Dahl R rats (DR) remain normotensive, without glomerular abnormalities. Studies in experimental models have suggested that hypercholesterolemia may play a role in the development of glomerulosclerosis; however, it is unclear whether hypercholesterolemia alone, in the absence of hypertension, can initiate injury. To answer this question we induced hypercholesterolemia in salt-supplemented DS (DSC) and DR (DRC) by feeding a high cholesterol (4%) chow. Control rats (DS, DR) received high-salt, normal cholesterol chow. After eight weeks, DS and DSC developed equivalent hypertension (161 +/- 3 vs. 153 +/- 3 mm Hg, respectively, P = NS), while DR and DRC remained normotensive (138 +/- 5 vs. 131 +/- 5 mm Hg, P = NS; P less than 0.05 vs. DS and DSC). Cholesterol fed rats developed marked and equivalent hypercholesterolemia compared to controls (DS vs. DSC, 71 +/- 3 vs. 289 +/- 91 mg/dl, P less than 0.05; DR vs. DRC, 52 +/- 2 vs. 327 +/- 54 mg/dl, P less than 0.05). Hypertensive rats (DS, DSC) developed worse proteinuria and glomerular injury than normotensive rats (DR, DRC), but hypercholesterolemia exacerbated proteinuria and glomerulosclerosis only in DSC and not in DRC. Proteinuria significantly correlated with serum cholesterol in hypertensive rats (DS, DSC, P less than 0.05), but not normotensive rats (DR, DRC, P = NS). Furthermore, DSC had increased renal vascular resistance compared to DS, while no differences were found between DRC and DR. Thus, in the Dahl rat, hypercholesterolemia alone does not initiate glomerular injury. In this model, hypercholesterolemia is a pathogenetic factor in glomerular injury only when it coexists with systemic hypertension.
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PMID:Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury. 161 39

In order to obtain more information on the quality of metabolic control and presence of secondary complications in type 2 diabetic patients treated in a hospital outpatient-clinic, we studied 124 of our diabetic patients (56 males, 68 females, age 65 (SD 11) years, duration of diabetes 9, range 1-32 years). HbA1c levels were 7.9% in patients on oral hypoglycaemic agents (n = 56), and 8.2% in insulin-treated patients (n = 59). Cholesterol and triglyceride levels tended to be lower in the insulin-treated patients. The prevalence of vascular abnormalities was high: in comparison with a population of general practice patients more patients had hypertension (56% vs 38%), coronary artery disease (48% vs 40%), and cerebrovascular disease (15% vs 6%). In addition, 35% of our diabetics had signs of peripheral artery disease. Retinopathy was present in 35 patients, microalbuminuria was found in 31 patients, proteinuria in 18 patients. The presence of microalbuminuria and proteinuria was a strong indicator for cardiovascular disease, polyneuropathy and retinopathy. The use of cardiovascular medication was high: 57 patients used antihypertensive therapy, 37 used diuretics, and 26 long-acting nitrates. Only 25 patients took no medication apart from to their diabetes therapy.
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PMID:[Regulation of diabetes and late complications in the ambulatory treatment of patients with Type II diabetes mellitus]. 174 45

High--resolution two--dimension electrophoresis technique for protein with silver staining was used to characterise urinary high density lipoprotein (HDL)--apolipoproteins. Sequential ultracentrufugation method was used to isolate urinary lipoprotein particles of the same density as serum HDL. Immunostaining of electroblotted proteins further confirmed the presence of HDL--Apos in urine. HDL--Apolipoprotein A--1, A--11 and C were identified in urine of normal subjects, diabetic patients and patients with biopsy proven glomerular proteinuria. An in-house ELISA method was used to quantify urinary HDL--Apo A--1. Selectivity indices were also determined. A high degree of association was found between selectivity index and urinary HDL--Apo A--1 (r = 0.87) and also between HFL--APO A--1 loss/24 h and total protein loss/24 h (r = 0.91). This appear to indicate that HDL loss in urine was a function of glomerular selectivity. Urinary HDL--Apo A--1 levels were significantly raised in the patients with glomerular proteinuria (p less than 0.01). HDL--Apo A--1 levels appear to be a marker for glomerular proteinuria. Consistent with glomerular proteinuria serum lipids and protein loss were significantly higher in patients with glomerular proteinuria (p less than 0.001) but HDL--Cholesterol was lower (p less than 0.001).
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PMID:Urinary high density lipoprotein--a possible marker for glomerular proteinuria. 181 5

Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol + 1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak = 11.52 +/- 1.09 mmol l-1 vs. 4.73 +/- 0.31 on control diet, P less than 0.001) and triglyceride concentrations (peak = 2.31 +/- 0.27 mmol l-1 vs. 1.41 +/- 0.29, P less than 0.05) and a marked increase in beta-migrating lipoproteins. The severity of hypercholesterolaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, P less than 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, P less than 0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (P less than 0.05). The kidney total cholesterol content was increased from 29.2 +/- 0.8 to 47.7 +/- 3.3 mumols g-1 dry weight (P less than 0.0001), with esterified cholesterol increasing from 7.5 +/- 0.4% to 14.5 +/- 2.1% of total (P less than 0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition (rs = 0.7195, P less than 0.0001) and tissue total cholesterol content (rs = 0.6053, P less than 0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable.
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PMID:The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy. 210 41

The present study provides a histochemical analysis of the macromolecular and cellular composition of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) in the rat with special reference to the different types of lipids present and to the participation of monocytes. FSGHS was induced in male Wistar rats by unilateral nephrectomy (UN) or puromycin aminonucleoside (PAN) injections. Histochemical analysis of glomeruli with FSGHS in both models after 20 weeks of proteinuria revealed massive deposits of lipids. These lipid accumulations were shown to consist mainly of free and esterified cholesterol; triglycerides and phospholipids were present in small amounts. Monocytes, identified by the alpha-naphthyl acetate method for non-specific esterase activity were scanty in glomeruli affected by FSGHS with an average glomerular count of 0.1 in UN- and 0.2 in PAN-treated rats. When present, no preferential localization of monocytes in the lesions was observed. The progressive glomerular damage occurring once the process of hyalinosis and sclerosis has started may be related to the paucity of "scavenging" monocytes. Cholesterol may be one of the substances involved in the development of these glomerular changes.
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PMID:Glomerular sclerotic lesions in the rat. Histochemical analysis of their macromolecular and cellular composition. 287 25

The Strong Heart Study, a study of cardiovascular disease among American Indians, was conducted to determine cardiovascular disease rates and the prevalence of risk factors among members of 13 tribal groups in South Dakota/North Dakota (SD/ND), southeastern Oklahoma, and Arizona. From 1989 to 1992, 4,549 tribal members aged 45-74 years (62% of eligible participants) were surveyed and examined for cardiovascular disease and its risk factors. Mean total cholesterol concentrations were over 20 mg/dl lower among the men and 27 mg/dl lower among the women than national mean levels for the same age groups. Cholesterol levels varied by tribal group; Arizona Indians had mean levels more than 20 mg/dl lower than those of SD/ND Indians. The prevalence of hypercholesterolemia was almost twice as high among SD/ND Indians as among Arizona Indians, but the rates for all three groups were much lower than total US rates (all races). Mean levels of high density lipoprotein cholesterol were lower among Indian men and women than in the US population as a whole. The prevalence of hypertension among Arizona and Oklahoma Indians was higher than that for the entire United States. SD/ND Indians had significantly lower mean blood pressures and prevalence rates of hypertension than Oklahoma and Arizona Indians and the United States as a whole. The prevalence of cigarette smoking was higher for all Indian groups except Arizona women in comparison with US rates. Smoking rates were highest in SD/ND and lowest in Arizona. Indian smokers smoked fewer cigarettes per day than the average US smoker. Arizona Indians had the highest prevalence of diabetes mellitus; over 60% of those participants were diabetic. In Oklahoma and SD/ND, one third of the men and over 40% of the women were diabetic. In addition, 13-20% of the participants had impaired glucose tolerance. Proteinuria was also a common problem; almost half of the Arizona Indians had micro- or macroalbuminuria, and 20% of Oklahoma and SD/ND Indians had significant proteinuria. The prevalence of obesity was high in all three groups, with Arizona Indians having the highest rates and the highest mean body mass indices. The prevalence of current alcohol use was lower among Indians than in the nation as a whole, but binge drinking was common among those who used alcohol. These results indicate that cardiovascular disease risk factors vary significantly among tribal groups. Prevention programs tailored toward decreasing the prevalence of risk factors are recommended for long-term reduction of cardiovascular disease rates in American Indian communities.
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PMID:Cardiovascular disease risk factors among American Indians. The Strong Heart Study. 763 31

Ischemic nephropathy encompasses renal insufficiency due to 3 different diseases, namely renal artery stenosis, so-called benign nephrosclerosis, and renal cholesterol embolism. All 3 disease entities may lead to a progressive loss of renal excretory function. If a patient presents with renal failure of unknown origin, renal artery stenosis should be looked for by color-coded duplex scanning or arteriography. The clinical presentation of benign nephrosclerosis in caucasians has no typical clues. Usually, a renal biopsy identifies this renal disorder in a patient with long-standing hypertension, moderate proteinuria and renal insufficiency. Cholesterol embolism typically affects several arterial trees, and is induced by arteriography in patients with arteriosclerosis of the aorta. The best treatment for ischemic nephropathy due to renal artery stenosis [conservative, angioplasty, surgery] is unknown because appropriately controlled trials are lacking. Invasive therapy should be considered in patients with bilateral renal artery stenosis or stenosis of a single functioning kidney, particularly if the affected kidney is not contracted. Arguments in favor of invasive therapy include the progressive nature of renal artery stenosis and the poor outcome of dialysis patients with this diagnosis as underlying renal disease.
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PMID:[Ischemic nephropathy]. 778 95

Lp(a) was measured in 64 normoalbuminuric, 52 microalbuminuric, and 37 proteinuric Type 1 diabetic patients and 54 healthy subjects. Microalbuminuric and proteinuric Type 1 diabetic patients had higher median Lp(a) values (133 (16-1932) and 169 (17-1149) mg l-1) than patients with normal AER (73 (15-1078) mg l-1; p = 0.048 and p = 0.027). Lp(a) in healthy subjects (110 (15-1630)mg l-1) did not differ from the diabetic subgroups. The frequency of Lp(a) values in the upper quarter of the normal distribution was similar in the diabetic groups and did not differ between diabetic and control subjects. The cumulative distribution of Lp(a) was similar in all groups. Lp(a) concentrations were not related to AER, age, gender, duration of diabetes, body mass index, glycaemic control, serum creatinine, free insulin or systolic blood pressure. Cholesterol, LDL-cholesterol, triglycerides, and apo B were higher in microalbuminuric and proteinuric than in normoalbuminuric Type 1 diabetic patients. Lp(a) was independently related to diastolic blood pressure, fibrinogen, and macroangiopathy. In conclusion, median Lp(a) concentrations tend to be higher in Type 1 diabetic patients with early and established renal disease, although the differences are small and the overlap between groups large. Lp(a) is related to diastolic blood pressure and fibrinogen, and this association of powerful risk factors suggests that Lp(a) may play a role in the pathogenesis of cardiovascular disease in Type 1 diabetic patients with proteinuria. Whether Lp(a) is an independent determinant of increased cardiovascular risk in these patients needs to be elucidated by prospective studies.
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PMID:Lipoprotein(a) in type 1 diabetic patients with renal disease. 789 61


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