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)

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
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PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

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 precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain to be established. However, there is now evidence that renal disease clusters in families and that genetic factors are of central importance in determining liability. A predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Genetically controlled hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. This suggestion derives from the observation that the 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 sign of renal damage is the appearance of microalbuminuria and of a small elevation in arterial pressure, changes associated with significant mesangial expansion. Microalbuminuria is associated with abnormalities of lipoprotein profiles possibly as a consequence of insulin-resistance-induced hyperinsulinemia. It could be postulated that the environmental changes brought about by diabetes lead in susceptible individuals to increased systemic and intraglomerular pressure on the one hand and mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities would 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 of reduction in renal function, more hypertension, more proteinuria, more glomerular obsolence, more hyperlipidemia and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Mechanisms of diabetic renal and cardiovascular disease. 207 90

Twenty-three nonobese KK mice with abnormal tolerance to glucose, hyperinsulinemia with insulin resistance and human diabetic-like nephropathy were treated with either saline (12 mice) or glipizide, an oral hypoglycemic compound, 1 mg/kg, (11 mice) from 120 to 360 days of age. These mice develop significant increases in mesangial volume and matrix by 40 days of age. Oral glucose tolerance (OGTT), glucosyltransferase and N-acetyl-beta-glucosaminidase (enzymes involved in synthesis and degradation of kidney glycoproteins, respectively) in the kidney and serum, 24-hr proteinuria, and light microscopy studies of the kidney were performed. Glipizide-treated mice improved their OGTT. There was no difference in body weight; however, a 16% decrease (P less than 0.05) in kidney weight was observed in glipizide-treated mice. Both enzymes were significantly increased in the kidneys of mice treated with glipizide. No difference in serum enzymes was found between the two groups of mice. About 58% of the saline-treated mice had moderate glomerulosclerosis. By contrast, only 27% of glipizide-treated mice had moderate glomerulosclerosis. Also, a significant decrease in proteinuria was found in glipizide-treated mice. These data suggest that glipizide improves glucose metabolism, decreases kidney size, prevents kidney glycoprotein and mesangial matrix accumulation, and reduces proteinuria in type II diabetic KK mice. This indicates that good glycemic control prevents further progression of established diabetic nephropathy in animals.
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PMID:Diabetic microangiopathy in KK mice. VI. Effect of glycemic control on renal glycoprotein metabolism and established glomerulosclerosis. 214 55

Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel-Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease.
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PMID:Animal models of spontaneous diabetic kidney disease. 219 83

The SHR/N corpulent (cp) rat is a genetically obese rat that develops hyperglycemia, hyperinsulinemia, and proteinuria. This study was designed to evaluate the effects of high carbohydrate (CHO) intake on renal function and structure in this animal model and to determine whether the renal effects are related to the type of CHO ingested. Two groups of 5-wk-old obese male SHR/N-cp rats and lean male littermates were fed diets containing 54% CHO in the form of sucrose or starch. After 12 wk, renal function parameters, including creatinine clearance, urinary glucose excretion, and urinary protein excretion, were measured. Renal morphology was evaluated by semiquantitative light and electron microscopy. On either diet, obese rats had significantly higher urinary glucose and protein excretions than their lean littermates. Mean creatinine clearance (ml/min) in obese rats did not differ significantly from values observed in lean rats. When corrected for body weight, creatinine clearance (ml.min-1.kg-1) tended to be lower in obese than in lean rats, but the difference was significant (P less than .02) only for obese and lean sucrose-fed animals. Obese rats fed sucrose compared with their obese counterparts fed starch had higher body weight (+8%, P less than .05), glucose excretion (+63%, P less than .02), and protein excretion (+242%, P less than .005). In obese rats, protein excretion correlated with glucose excretion (r = .71, P less than .01). Glomerular lesions consisting of mesangial expansion and intercapillary nodules were found in obese but not in lean rats. Moreover, obese rats fed sucrose had a significantly greater number of involved glomeruli than obese rats fed starch.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of carbohydrate intake on kidney function and structure in SHR/N-cp rats. A new model of NIDDM. 272 22

Table III compares metabolic and morphologic characteristics of different species of control and KK mice. The C57BL/6J demonstrates no significant metabolic, clinical or histologic abnormalities. Our two highly inbred Swiss albino groups I and II also do not show significant glomerular lesions, although we found striking intolerance to glucose, hyperinsulinism, and obesity among them. Thus a genetic predisposition may be necessary in addition to various environmental factors to produce microangiopathy in KK mice. The yellow AY mouse is included in this table, since it is strikingly hyperinsulinemic and obese without concomitant vasculopathy such as the other mentioned control strains have. In conclusion, the KK mice develop chemical diabetes preceded by a stage of prediabetes and also demonstrate renal, retinal and neurologic complications similar to those seen in human diabetes. Of particular interest is the development of mild to moderate glomerulosclerosis in the prediabetic stage; with progression to severe glomerulosclerosis and attendant proteinuria later in life. With proper back-crossing, both hyperglycemia and glomerulosclerosis can be transmitted to normal control mice, suggesting that a specific genetic background is necessary for the development of diabetes and diabetic-like microangiopathy. We therefore suggest that the KK mouse serves as an ideal genetic animal for the study of non-insulin-dependent diabetes mellitus and its complications for rational prevention and therapy.
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PMID:Hereditary diabetes in the KK mouse: an overview. 307 69

The pathogenesis of hypertension associated with diabetes mellitus (DM) involves an interplay of hereditary and acquired mechanisms. A familial trait for essential hypertension appears to be a risk factor for the development of both hypertension and nephropathy in type I DM and coexists commonly with impaired insulin sensitivity, relative hyperinsulinemia, and dyslipidemia, which can already be detected before the appearance of hypertension, obesity, or upper abdominal redistribution of body fat. The latter finding helps explain the frequent development of hypertension as well as dyslipidemia and/or type II DM in given individuals. Obesity is an important factor promoting these complications. Type I or II DM but not uncomplicated essential hypertension is characteristically accompanied by excess body Na+. This abnormality complements a tendency toward vascular hyperreactivity and a presumably morphologic and functional vasculopathy, thereby promoting the pathogenesis of hypertension in diabetic patients. For the treatment of hypertension in diabetic patients, nonpharmacologic measures are indispensable. If drugs are needed, angiotensin-converting enzyme (ACE) inhibitors and some but not all calcium antagonists are the preferred agents. Monotherapy or a combination of these drug types allows effective blood pressure control in most diabetic patients without further metabolic impairment; ACE inhibitors even tend to improve glucose control. Ketanserin may be a potential alternative, and if a diuretic is also needed, the metabolically neutral indapamide is a reasonable choice. If these agents do not allow satisfactory blood pressure highly selective beta 1-blockers or alpha 1-blockers may be introduced as a second choice. In diabetic patients with nephropathy, effective antihypertensive therapy can reduce proteinuria and slow the progression of the nephropathy; ACE inhibitors may improve diabetic proteinuria even at unchanged systemic blood pressure levels. Unless diuretics are needed for reasons other than hypertension, the treatment of diabetic patients with thiazides or loop diuretics in conventional dosage should probably be avoided until clarification of their influence on prognosis. Nevertheless, whether and to what extent other agents and nonpharmacologic measures can modify the prognosis in diabetic patients is also unclear, and the approach to antihypertensive therapy is therefore still largely empiric.
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PMID:Pathogenesis and treatment of hypertension associated with diabetes mellitus. 848 Jun 21

A series of 166 American Indian renal biopsy specimens from 1971 to 1989 showed a very high proportion with mesangial proliferative glomerulonephritis with mesangial immunoglobulin deposition (Ig-pos mesGN). This disease comprised 68.7% of all the biopsies and 83.8% of all primary GN, proportions much greater than those (23.5% and 37.7%, respectively) of a local contemporaneous biopsy series from non-Indians (P < 0.001). These proportions and the extrapolated population-based incidence rates of mesGN are the highest yet described in any population. Males and females were equally represented in the Indian Ig-pos mesGN series. Biopsy was most commonly performed in early adulthood, but duration of suspected disease prior to biopsy was often many years. Mesangial glomerulonephritis often occurred in family clusters. It was occasionally associated with rashes, arthralgias, and/or a history of alcohol abuse. Due to different surveillance and biopsy practices, the spectrum of severity was different in Zunis and Navajos, allowing examination of clinicopathologic correlations over a broad range of disease. Early disease was manifest by microscopic hematuria alone, but rates of severe disease, with hypertension, heavy proteinuria, and renal insufficiency, were very high. Clinical severity increased with age, with extension of pathology beyond the mesangium, and with scarring and vascular change. Changing patterns of deposition of mesangial immunoglobulin and of electron-dense deposits in sequential biopsy specimens, recurrence of disease in kidney transplants, and biopsy diagnosis of disease in asymptomatic relatives of afflicted subjects were all observed. Five-year renal failure rates were estimated at 41%, much higher than in most other series. This disease constituted most biopsied cases of GN-end stage renal disease in Navajos, and largely determined the young age of Navajo GN-end stage renal disease subjects compared with their US-wide counterparts. To reconcile the diversity of clinical and morphologic findings in such homogeneous ethnic groups, and in individual families within such groups, we propose a unifying hypothesis for a broader spectrum of mesGN than traditionally defined by immunoglobulin subtype deposition. We also argue against a major role for IgA aggregates or immune complexes in initiating or propagating the mesangial inflammatory process, and propose that mesangial pathology of another, independent cause might be primary. Hyperinsulinemia, or insulin resistance, which is common in these populations and in other transitional populations with similar GN and ESRD patterns, might be one such mesangiopathic factor.
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PMID:Mesangial proliferative glomerulonephritis in southwestern American Indians. 848 16

Triamcinolone or triiodothyronine (T3) was administered to rats with nephrosis induced by aminonucleoside of puromycin and to control nontreated rats. Triamcinolone produced hyperglycemia, hyperinsulinemia and liver glycogen deposition in control rats and to a lesser extent in nephrotic rats. Triamcinolone treatment did not affect plasma protein and albumin levels but increased the level of plasma triglycerides and cholesterol in the very low density lipoprotein (VLDL) and LDL but not high density lipoprotein fractions. The exacerbation of hyperlipoproteinemia was attributed both to increase hepatic lipid synthesis and delayed removal, since it was associated with the induction of hepatic acetyl-CoA carboxylase, the regulatory enzyme of lipogenesis, as well as with marked suppression of adipose tissue lipoprotein lipase (LPL). The hepatic lipase activity was found to be elevated in nephrotic rats but was suppressed by triamcinolone treatment, indicating a reduced capacity of VLDL to LDL conversion. T3 treatment resulted in serum glucose and insulin increases similar to triamcinolone, but more moderate in nephrotic vs. control rats, and in marked reduction in liver glycogen content. Plasma protein levels were not affected, but contrary to control rats, T3 treatment produced an elevation in serum triglycerides and cholesterol in nephrotic rats. The activity of several hepatic lipogenic enzymes, including acetyl-CoA carboxylase, was markedly elevated, as was the activity of gluconeogenic enzymes. Thus, the hyperlipoproteinemia on T3 treatment appeared to be mainly due to predomination of lipid synthesis over removal, since the activities of enzymes responsible for plasma lipid disposal, adipose tissue LPL and hepatic lipase were enhanced both in control and nephrotic rats. It is remarkable that both T3 and triamcinolone induce the lipogenic enzymes and apolipoproteins in the liver of nephrotic rats, already pronouncedly stimulated to replace the excreted plasma proteins. Thus, the nephrotic liver is able to respond to hormonal stimulation with further specific protein and lipid synthesis. It is also pertinent that the recovery from immunosuppressive treatment of human nephrosis, developing on an immune background, may result in more impressive amelioration of proteinuria and hypoproteinemia than of hyperlipoproteinemia because of the lipidemic effect of glucocorticoids.
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PMID:Hyperlipoproteinemia of aminonucleoside-induced nephrotic syndrome--modulation by glucocorticoids and triiodothyronine. 868 44


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