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)

We have recently reported that a lipid-lowering agent, probucol, reduces proteinuria in puromycin aminonucleoside (PA)-induced nephrotic rats (PAN). In this study, we examined whether a long-term treatment of hyperlipidemia with probucol can suppress the development of focal and segmental glomerulosclerosis (FSGS) in chronic PAN. A chronic PAN model was made with repeated intraperitoneal injections of PA (initially 100 mg/kg body weight followed by 25 mg/kg 5 times at 2-week intervals). Two weeks after the first injection of PA, either normal rat chow with or without 1% probucol was given to the nephrotic rats for 10 weeks. Chronic PAN exhibited remarkable proteinuria, hypoalbuminemia and severe hyperlipidemia with all lipoprotein fractions increased. Probucol treatment significantly reduced the lipid concentration in all major lipoproteins, significantly reduced proteinuria and increased plasma albumin concentration. Plasma albumin inversely correlated with cholesterol or phospholipid in low-density and high-density lipoproteins, suggesting that the lipid-lowering effect of probucol may ameliorate the hypoalbuminemia associated with nephrosis. In light microscopic examination, various degrees of FSGS with tubulointerstitial lesions were observed in the renal cortex from chronic PAN. The degree of FSGS was scored from grades 1 to 4 according to severity. One half of the untreated PAN (4/8) was classified into grade 4 and the other into grades 2 or 3, whilst one half of treated PAN (4/8) was classified either into grade 1 or 2. The grading of FSGS correlated negatively with plasma albumin concentration. These results demonstrate that probucol is highly effective upon nephrotic hyperlipidemia and suggest that a long-term treatment of secondary hyperlipidemia can suppress progressive renal injury associated with chronic nephrosis.
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PMID:Treatment of hyperlipidemia with probucol suppresses the development of focal and segmental glomerulosclerosis in chronic aminonucleoside nephrosis. 158 21

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

Diabetic patients who develop proteinuria show a marked increase in cardiovascular morbidity and mortality. The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain, in part, obscure. However, there is now evidence that renal disease clusters in families and that genetic factors may be of central importance in determining susceptibility. Predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. Interestingly, fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first clinical signs of renal involvement are the appearance of microalbuminuria and a small elevation in arterial pressure. Mesangial expansion accompanies these changes. Microalbuminuria is associated with abnormalities of lipoprotein profiles and higher Na+/Li+ countertransport rates. The environmental changes brought about by diabetes could lead in susceptible individuals to increased systemic and intraglomerular pressures on the one hand and to mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered, involving reduction in renal function, further hypertension, proteinuria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Risk factors for renal and cardiovascular disease in diabetic patients. 165 64

We sought to determine whether systemic administration of proteases ameliorates membranous nephritis induced in rats by immunization and challenge with cationic bovine gamma globulin, and whether targeting of protease to glomerular capillaries increases efficacy. Proteases substituted with biotin were targeted via the cationic protein avidin A, which by virtue of its charge has affinity for the glomerular basement membrane. Despite identical pretreatment proteinuria, rats given untargeted protease (biotin-conjugated without avidin, or unconjugated plus avidin) had significantly less proteinuria than saline-treated controls and nephrotic rats given avidin plus biotin-conjugated (targeted) protease had even less proteinuria and reduced glomerular rat IgG and C3. Among more severely nephrotic rats, targeted protease was again more effective than untargeted protease at reducing proteinuria, and also decreased the size of electron-dense glomerular deposits, hypercholesterolemia, and creatininemia. Inactivated targeted proteases had no effect on proteinuria, hypercholesterolemia, or azotemia. Finally, active targeted protease did not affect proteinuria in the nonimmune mediated nephrosis induced by puromycin aminonucleoside. We conclude that systemic protease can specifically diminish glomerular immune deposits, proteinuria, hyperlipidemia, and creatininemia associated with experimental immune complex glomerulonephritis but not toxic nephrosis, and that targeted protease is more effective than untargeted protease.
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PMID:Targeted enzyme therapy of experimental glomerulonephritis in rats. 170 86

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.
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PMID:Pathophysiology of hyperlipidemia in diabetes mellitus. 171 Jul 39

Nephrotic syndrome is defined as proteinuria sufficiently severe to result in hypoalbuminaemia, oedema and hyperlipidaemia. The early modern history of this illness was characterised by the serendipitous development of renal biopsy technique at approximately the same time as the use of corticosteroids for nephrotic syndrome. The coincidence of these events set the stage for evaluating therapeutic response to corticosteroids and cytotoxic agents in relation to renal histology and ultimate clinical outcome. The International Study of Kidney Disease in Children (ISKDC) was initiated in the 1960s as a multicentre study examining these relationships in children. Over the next decade this study, as well as contributions from other investigators, helped define optimum therapy for these children. It was determined that a child with nephrotic syndrome under the age of 6 years, who did not present with hypertension, azotaemia, hypocomplementaemia or signs of systemic illness, had an approximately 85% chance of responding to corticosteroid therapy. If only those children who had minimal change histology on biopsy were considered, 94% responded. The original regimen which is still used today, was 60 mg/m2 bsa/day prednisone administered on a 3 times per day dosage schedule for 4 weeks, followed by an additional 4 weeks of therapy at a dose of 40 mg/m2 bsa given as a single oral dose every other day. Of those who respond roughly one-third will have no relapses, while almost half will have frequent relapses (greater than or equal to 2 in 6 months) and the rest will have infrequent relapses. Patients in relapse are treated as at presentation but are usually converted to the 40 mg/m2 bsa dose when the urine has been free of protein for 3 days, and are then tapered off or maintained on this dose for several weeks, depending on the individual's history of relapses and incidence of side effects from corticosteroids. For those children who are suffering frequent relapses and severe corticosteroid side effects (e.g. growth failure, morbid obesity, aseptic necrosis of bone), cytotoxic agents were identified as providing long term remission. After inducing remission with conventional corticosteroid dosages, cyclophosphamide is administered at a dose of 2 mg/kg/day given as a single dose for 8 weeks. This regimen was shown to lead to approximately 70% of patients being in remission 2 years after completion of this course of therapy. Chlorambucil given at a dose of 0.2 mg/kg/day as a single oral dose has been equally efficacious.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of nephrotic syndrome in childhood. 171 84

Exogenous obesity is characterized hemodynamically by expanded intravascular (plasma) volume associated with an increased cardiopulmonary volume and cardiac output. In contrast, essential hypertension is related to an increased total peripheral resistance that is more or less uniformly distributed throughout the component organ circulations associated with a contracted plasma volume in proportion to the height of arterial pressure. Thus, both cardiac output and total peripheral resistance are elevated in obesity hypertension, and both impose a load on the left ventricle, resulting in both a volume and a pressure overload left ventricular hypertrophy. Although renal vascular resistance is not as increased as it is in lean hypertensive patients, these patients are subjected to hyperfiltration and proteinuria. Additionally, these hemodynamic alterations coexist with carbohydrate intolerance, hyperinsulinemia, hyperlipidemia, and hyperuricemia. With weight reduction and associated pressure reduction, the hemodynamic and metabolic changes reverse toward normal. However, should this not be achievable, the angiotensin converting enzyme inhibitors and calcium antagonists provide rational physiological approaches to drug therapy. With these agents pressure reduction is achieved through a fall in vascular resistance without intravascular volume expansion, and this is associated with reduced left ventricular mass and preserved cardiac and renal function, and without exacerbation of preexisting metabolic perturbations. Hence, these two classes of antihypertensive agents may provide a rational and physiological means for reversing the pathophysiological alterations of hypertensive disease in those obese patients in whom weight control is not possible.
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PMID:Obesity hypertension. Converting enzyme inhibitors and calcium antagonists. 173 Apr 48

The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism. Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipid-lowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in poly- and monounsaturates fatty acids, has been recently tested by the author, with very promising results.
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PMID:Lipid changes in the nephrotic syndrome: new insights into pathomechanisms and treatment. 175 84

The hyperlipidemic Imai rat was originally developed as an animal model of spontaneous hyperlipidemia. We report the natural course of the Imai rat up to 32 weeks of age focusing on renal pathology. The degree of proteinuria, which first appeared at 8 weeks, increased with age, and all Imai rats developed heavy proteinuria (mean, 228 mg/24 h) with impaired renal function (mean BUN, 78.7 mg/dl) at 32 weeks. Histologic changes of the glomeruli were characterized by focal and segmental sclerosis and hyalinosis. Both the percentage of affected glomeruli and the severity of each affected glomerulus were progressively increased with age. The immunofluorescence and electron-microscopic findings were also comparable to those of focal glomerulosclerosis (FGS) in humans. The serum levels of total cholesterol, triglyceride, and phospholipid in Imai rats were significantly higher than those in normal Sprague-Dawley rats at 8 weeks of age, and progressively increased thereafter. The proteinuria, glomerular involvements, and hyperlipidemia were generally less severe in the females than in the males. We conclude that the hyperlipidemic Imai rat, a naturally occurring animal model of FGS, is useful in studying the pathogenesis of FGS and the renal effects of hyperlipidemia in humans.
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PMID:Renal lesions of hyperlipidemic Imai rats: a spontaneous animal model of focal glomerulosclerosis. 175 40

Recent reports of risk factors for and survival of patients with diabetic retinopathy do not include exudative maculopathy as a separate entity. We therefore studied a group of hypertensive Type II diabetic subjects with exudative maculopathy (n = 26) compared to a carefully matched hypertensive diabetic comparison group without retinopathy (n = 26) over seven years. Diabetic maculopathy patients had higher mean diastolic blood pressure (101.6 +/- 14 versus 94.8 +/- 10 mmHg, p less than 0.05), serum cholesterol (6.65 +/- 2.2 versus 5.9 +/- 1.31 mmol/l), HDL2 subfraction levels (0.46 +/- 0.23 versus 0.32 +/- 0.18 mmol/l) and a higher prevalence of hyperlipidaemia (54% versus 35%) compared to the comparison group. After seven years, the maculopathy group showed a strikingly higher prevalence of renal failure and nephrotic syndrome (42% versus 8%, p less than 0.05) and of macroproteinuria (58% versus 15%, p less than 0.01) compared to the comparison group. Mortality and cardiovascular disease event rate was 12% and 38% in the maculopathy and 15% and 31% respectively in the comparison group. We conclude that although mortality is not significantly higher in diabetics with exudative maculopathy, proteinuria, renal failure and nephrotic syndrome may be associated features on long term follow-up. Hypertension and hypercholesterolaemia may also be risk factors in the development of diabetic maculopathy.
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PMID:Long-term follow-up of and underlying medical conditions in patients with diabetic exudative maculopathy. 180 Jan 69


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