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The increase in urinary albumin excretion rate (AER), a hallmark of both diabetic nephropathy and hypertension, has also been described in patients affected with diffuse psoriasis. The aim of this study was to investigate whether such an increase is independent of the coexistence of diabetes or hypertension and whether it may be related to the extension and severity of skin lesions. Median AER, determined by radioimmunoassay, was significantly higher in a group of 32 normotensive nondiabetic psoriatic patients than in 36 age- and sex-matched controls (9.6 vs. 5.3 micrograms/min; p = 0.0006). AER was related with grading of skin involvement (r = 0.65; p = 0.001); patients with the most widespread skin lesions (psoriasis area and severity index: PASI greater than 11) were characterized by a significantly raised median AER (14.9 micrograms/min) compared with those with PASI scores between 4 and 11 (9.8 micrograms/min) or less (5.6 micrograms/min) and controls (F = 10.58; p = 0.0001), independent of other covariates such as age, sex and blood pressure (p = 0.001). This latter finding was confirmed by the prevalence of microalbuminuria (AER greater than 10 micrograms/min) which was present in 2 out of 8 patients with PASI less than 4, 0 out of 12 patients with PASI ranging between 4 and 11 and in 5 out of 12 psoriatics with PASI greater than 11 (p = 0.038 by two-tailed Fisher's exact test).
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PMID:Relation between urinary albumin excretion and skin involvement in patients with psoriasis. 142 37

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
Hypertension 1992 Nov
PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

Increases in urine concentration of specific proteins have been proposed as early indicators of deleterious changes in kidney function. Four urinary proteins (albumin, superoxide dismutase, transferrin and N-acetyl-beta-D-glucosaminidase) were measured in workers exposed to heavy metals and solvents. None of the workers had clinical evidence of renal disease or hypertension. Workers exposed to mercury had a significant increase in urinary transferring, superoxide dismutase levels were slightly increased in workers exposed to solvents and lead, follow-up of these workers is needed to confirm that these changes predict late clinical deterioration of kidney functions.
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PMID:Early detection of changes in kidney function in workers exposed to solvents and heavy metals. 142 16

To evaluate the relationship between urinary albumin excretion and left ventricular hypertrophy in essential hypertension, we studied, cross-sectionally, 64 subjects with essential hypertension and no diabetes. Urinary albumin excretion and Sokolow index correlated significantly (r = 0.483; P = 0.0001). Five subjects were positive for microalbuminuria (> 30 mg/24 h) and Sokolow index (> 35 mm); 43 were negative for both, with a concordance rate of 77 percent (chi-squared test 11.1; P = 0.0009). Stepwise multivariate regression analysis indicated two independent determinants for urinary albumin excretion: Sokolow index (F = 18.29), and diastolic blood pressure (F = 12.23). The relationships between urinary albumin excretion, Sokolow index, and blood pressure were not different in the 18 subjects taking angiotensin I-converting enzyme inhibitors and in the 46 others. The close relationship between urinary albumin excretion and Sokolow index observed in this study suggests that left ventricular hypertrophy due to hypertension may account for the increased cardiovascular mortality observed in non diabetic subjects with microalbuminuria.
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PMID:[Microalbuminuria and left ventricular hypertrophy in essential arterial hypertension. A study in non-diabetic patients]. 143 89

Although calcium antagonists have long been introduced into antihypertensive treatment, little is known of their renal long-term action in patients with diabetes mellitus, diabetic nephropathy, or hypertension. Much of the current information concerning this issue is from short-term studies. While urinary albumin excretion, a major indicator of glomerular damage in patients with diabetes mellitus, remains unchanged or even increases during short-term calcium antagonist treatment in type 1 diabetic patients, it is mostly reduced in type 2 diabetic patients, especially by diltiazem and nicardipine. There have been discrepant observations in studies lasting 6-months or longer. In many of the studies, urinary albumin excretion is not decreased by calcium antagonist treatment, although blood pressure is well controlled. Albuminuria is markedly reduced, however, after nitrendipine or diltiazem treatment. While calcium antagonists such as diltiazem, nicardipine, or nitrendipine may be as efficacious as converting enzyme inhibitors in preventing the progression of diabetic kidney disease in diabetic patients, the beneficial efficacy of others is less apparent. Reduced albuminuria may be more difficult to attain in macroalbuminuric patients with advanced nephropathy. However, considerations on the potential effects of calcium antagonist long-term treatment on cardiovascular morbidity or mortality in diabetic patients should not be overlooked when their renal action is under discussion. Thus, further studies are needed to define the role of calcium antagonists more precisely in the long-term treatment of diabetic patients with hypertension or diabetic nephropathy.
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PMID:Renal long-term effects of calcium antagonist treatment in patients with diabetes mellitus. 145 Jun 19

Abnormalities in sodium homeostasis and in atrial natriuretic peptide (ANP) behavior could play a role in determining and accelerating the development of glomerular hypertension, hypertension, and microalbuminuria in insulin-dependent diabetes. The aim of the present study was to investigate in 32 hypertensive insulin-dependent diabetic patients (HD) with an altered albumin excretion rate the natriuretic response and ANP release to saline load (2 mmol/kg 90 min, and the effects angiotensin converting enzyme inhibitor therapy 2.5 to 5.0 mg cilazapril, once daily), and calcium antagonists (sustained release verapamil: 120 to 240 mg Isoptin Press, once daily, and long acting nifedipine: 20 to 40 mg Adalat AR, twice daily) on sodium homeostasis and albumin excretion rate. Eight normal subjects matched for sex, age, and weight served as controls. The 32 HD patients showed a blunted response in ANP release and sodium excretion during saline infusion in comparison with controls. The cilazapril and verapamil treatments were tested in 16 of the 32 HD patients and were both effective in ameliorating natriuretic and ANP response to saline load and in decreasing albumin excretion rate. The combined cilazapril and verapamil treatment further improved both these parameters in these patients, although blood pressure levels were comparable. The other 16 HD patients underwent sequential verapamil and nifedipine treatment. Verapamil was more effective than nifedipine in improving natriuresis and ANP release to saline load and in lowering the albumin excretion rate. The results of the present study demonstrate that sodium homeostasis and ANP release are altered in hypertensive nephropathic patients, and both cilazapril and verapamil are more effective than nifedipine in ameliorating natriuresis, ANP release, and albumin excretion rate.
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PMID:Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action and on albumin excretion rate in hypertensive insulin-dependent diabetic patients. 145 87

The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus. 145 61

Diabetic nephropathy is a serious complication of insulin-dependent diabetes mellitus (IDDM) that affects 30% to 40% of IDDM patients with a predictable time of onset. Epidemiologic data suggest that either a genetic susceptibility, perhaps for hypertension (HTN), or an environmental exposure selects out that subset of IDDM patients and destines them to develop diabetic nephropathy. Hopefully, assessing glomerular hyperfiltration, urinary albumin excretion rate (AER), glycemic control, mean arterial pressure (MAP), and perhaps early morphologic changes will allow early identification of this high-risk group of IDDM patients before overt nephropathy is present. Once nephropathy appears, renal function inexorably declines, although the natural history of this progression may be changing with earlier therapeutic intervention. IDDM patients with nephropathy suffer a high mortality rate compared with IDDM patients without nephropathy or with nondiabetic end-stage renal disease patients. This is primarily due to malignant atherosclerotic disease manifested as coronary, peripheral, and cerebral arterial disease. Therapeutic interventions of demonstrated benefit in slowing the rate of decline of glomerular filtration rate (GFR) include blood pressure control and low-protein diets. Strict blood sugar control or treatment with aldose reductase inhibitors, converting enzyme inhibitors (CEIs), or inhibitors of advanced glycosylation end-product formation are of possible benefit, but are awaiting clinical trial results.
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PMID:Diabetic nephropathy in insulin-dependent patients. 146 80

Regional 125I-albumin permeation and glomerular structural changes were assessed in male Sprague-Dawley rats with diabetes and/or hypertension. All rats underwent unilateral nephrectomy 2 weeks after induction of diabetes with streptozotocin. At the same time, one-half of the nondiabetic and diabetic animals were placed on 1% saline drinking water and given weekly intramuscular injections of deoxycorticosterone acetate to induce hypertension (systolic blood pressure greater than 150 mm Hg). Vascular permeability studies were performed after 1 and 3 months of hypertension. Hypertension, alone or in combination with diabetes, had no effect on weight gain, plasma glucose, or food consumption, but did increase 24-h urine volume in nondiabetics. In normotensive diabetics and in nondiabetic hypertensive rats, vascular 125I-albumin permeation was increased in eyes, aorta, and new granulation tissue (formed in a subcutaneous fabric implant), and glomerular basement membranes were thickened without any change in the fractional volume of the glomerulus occupied by mesangium. Urinary albumin and IgG excretion in nondiabetic hypertensive rats was increased much more than in normotensive diabetics. Hypertension and diabetes were additive in their effects on 125I-albumin permeation in eyes, aorta, and granulation tissue, and on glomerular basement membrane thickening, but were synergistic in their effects on urinary albumin excretion and mesangial fractional volume. The magnitude of the increase in vascular albumin permeation and urinary albumin and IgG excretion between and 1 and 3 months was much larger in diabetic hypertensive rats than in rats with hypertension or diabetes alone. Neither diabetes nor hypertension, alone or in combination, had any effect on albumin permeation in skeletal muscle, skin, heart, or brain. These findings demonstrate that hypertension and diabetes increase vascular albumin permeation in rats preferentially in tissues that correspond to sites of clinically significant vascular disease in human diabetics. They also attest to an important interaction between blood pressure-induced and diabetes-induced increases in vascular permeability in these tissues and in structural changes in the glomerular vasculature.
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PMID:Interactions between hypertension and diabetes on vascular function and structure in rats. 147 45

In this study, 52 nonproteinuric Japanese patients with non-insulin-dependent diabetes (NIDDM) were followed from 1985 to 1990 to investigate the rate of development and progression of microalbuminuria and the factors which influence it. In 1985, 34 patients were normoalbuminuric, and 18 patients were microalbuminuric. Five years later, 11 of 34 initially normoalbuminuric patients (32.4%) developed microalbuminuria, and 6 of 18 initially microalbuminuric patients (33.3%) developed overt proteinuria. At the beginning of the study, hypertension existed more frequently in the patients who later developed microalbuminuria (8 of 11, 72.7%) than in the patients who stayed normoalbuminuric (4 of 23, 17.4%). Age-adjusted values of mean blood pressure (+/- SEM) at the beginning of the study in the patients who developed microalbuminuria (98.2 +/- 3.4 mm Hg, n = 11) were significantly higher than those in the patients who stayed normoalbuminuric (87.3 +/- 2.4 mm Hg, n = 23). In six patients who developed overt proteinuria, initial urinary albumin excretion rates (AER) were higher than those in the patients who stayed microalbuminuric, and four patients who presented with initial AER greater than 100 micrograms/min all developed overt proteinuria. These results indicate that, in Japanese patients with NIDDM, the rate of development of microalbuminuria is faster than that reported in Caucasian IDDM, and preexisting hypertension with relatively poor control of blood pressure may be a risk factor for the development of microalbuminuria.
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PMID:High blood pressure is a risk factor for the development of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes mellitus. 147 44


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