UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACE inhibitors have been shown to worsen the kidney damage occurring distal to a renal artery stenosis. To determine if this effect was due to the decrease of arterial pressure or to an inhibition of the formation of angiotensin, we compared the effects of equihypotensive doses of an angiotensin converting enzyme inhibitor (enalapril) and a long-acting calcium antagonist (Ro 40-5967) in 2K-1C rats. The rats were treated for five weeks with either enalapril, Ro 40-5967, or were left untreated. A group of sham operated rats was used as control. At the end of the five-week treatment period, proteinuria, plasma urea and creatinine were measured and quantitative morphometry of the clipped and unclipped kidneys was performed. Ro 40-5967, despite an absence of inhibition of the renin-angiotensin system, worsened the lesions of the clipped kidney to the same extent as enalapril. In contrast, the effects of both drugs on the unclipped kidney were different. Ro 40-5967, and not enalapril, increased the weight and the glomerular surface area of the unclipped kidney. Ro 40-5967 did not change the glomerulosclerosis index, which was improved by enalapril. In contrast with enalapril, Ro 40-5967 decreased plasma urea and creatinine concentrations. Only enalapril decreased proteinuria which originated from the unclipped kidney as shown by nephrectomy experiments. We conclude that during ACE inhibition the fall in renal perfusion pressure seems to be the main determinant of the renal damage distal to a renal artery stenosis, independently of a blockade of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium blockade versus ACE inhibition in clipped and unclipped kidneys of 2K-1C rats. 796 54

In 47 patients with diabetic nephropathy (29 type I, 18 type II) renal function and blood pressure (BP) (treated with or without an angiotensin-converting enzyme [ACE] inhibitor, enalapril [10 mg], in 38 hypertensive patients) were followed over 4 years. A percutaneous renal biopsy was performed in all patients initially and repeated in a representative 19 patients with treated hypertension after 4 years. Mean glomerular volume (MGV), interstitial fibrosis (IF), capillary volume, and sclerosed glomeruli (GS) were measured histomorphometrically. Mean fall in creatinine clearance (CCr) was 11.8% after 4 years with no difference between treatment groups or type of diabetes. BP both initially and during treatment correlated with initial and final serum creatinine and CCr (P < 0.01). There were no histomorphometric differences between type I and type II patients or hypertension treatment groups. Initial IF correlated with initial and final serum creatinine and CCr (P < 0.05) in all patients and type I patients alone, MGV correlated inversely with CCr in type I patients (P < 0.05). After 4 years, IF (24.8 vs. 30.0%, P < 0.01) and GS (26 vs. 37%, P < 0.05) increased significantly, and increase in IF correlated with fall in CCr (P < 0.01). Proteinuria and HbA1 did not correlate with indexes of function or structure. In this longitudinal study of patients with diabetic nephropathy, there was a close relation between BP and renal function but no difference between treatment with enalapril and other hypertensive agents. The correlations between renal function and histology at entry and after 4 years suggest that IF is a co-determinant of renal function in diabetic nephropathy.
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PMID:Clinical and histological correlations of decline in renal function in diabetic patients with proteinuria. 803 99

Eight patients with biopsy-proven primary nephrotic syndrome were included in an open, prospective, two-year study of lovastatin. One patients was withdrawn after 6 months due to an asymptomatic rise in creatinine phosphokinase, which was rapidly reversed after interruption of lovastatin. In the remaining patients, treatment was well-tolerated and produced no side effects. After 2 years of treatment, these 7 patients had decreases in total cholesterol from 446 +/- 165 to 250 +/- 57 mg/dl (p < 0.001), LDL cholesterol from 343 +/- 121 to 174 +/- 49 mg/dl (p < 0.001), Apo B lipoprotein from 162 +/- 60 to 108 +/- 42 mg/dl (p < 0.05), triglycerides from 336 +/- 273 to 182 +/- 71 mg/dl (p < 0.04). There was no change in HDL cholesterol. The LDL/HDL cholesterol and the total/HDL cholesterol ratios fell from 15.0 +/- 12.1 and 19.1 +/- 17.2 mg/dl before the study to 4.4 +/- 1.2 and 6.3 +/- 1.6 mg/dl, respectively, at 2 years. A decrease in proteinuria from 8.6 +/- 4.6 to 5.0 +/- 3.7 g/24 h (p < 0.02) was noted in 4 patients on concomitant ACE inhibitor therapy. Renal function remained stable in all patients throughout the study, except for one whose moderate impairment progressed to end-stage renal failure requiring dialysis 3 months poststudy. We conclude that long-term lovastatin in patients with primary nephrotic syndrome is an effective and generally safe treatment for accompanying dyslipidemia.
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PMID:Long-term effect of lovastatin on lipoprotein profile in patients with primary nephrotic syndrome. 805 Feb 7

Elevated serum levels of the atherogenic and thrombogenic lipoprotein (a) (Lp(a)) have been recognized as a feature of the nephrotic syndrome associated hyperlipidaemia. To examine a possible relationship between serum Lp(a) concentration and proteinuria, serum albumin, or blood pressure, we studied nine patients with nephrotic-range proteinuria both at baseline and after various forms of antihypertensive and antiproteinuric treatment. In fixed order, patients received conventional antihypertensive treatment (either alpha-methyldopa or clonidine), subsequently ACE-inhibition therapy (lisinopril), ACE inhibition combined with an NSAID (indomethacin), and finally NSAID plus conventional antihypertensive therapy. Measurements were performed at the end of each 2-month study period. When compared to controls (n = 29), proteinuric patients before treatment showed increased levels of total cholesterol, very-low and low-density lipoprotein (VLDL+LDL) cholesterol, triglycerides and apolipoprotein B (apoB), while high-density lipoprotein (HDL) HDL cholesterol was lower. Lp(a) was significantly higher in patients (107 (95% CI: 55-208) mg/l) as compared to controls (25 (13-49) mg/l, P < 0.01). Conventional antihypertensive treatment did not reduce proteinuria, while Lp(a) remained unaffected. ACE-inhibitor treatment lowered proteinuria, raised serum albumin, while La(a) tended to fall (-11 +/- 8%). Addition of an NSAID induced a further fall in proteinuria and a rise in serum albumin. Lp(a) now fell by 40 +/- 5% from baseline values (P < 0.01). Both serum total, HDL and VLDL+LDL cholesterol fell significantly. Finally, during subsequent single therapy with NSAID most parameters, including proteinuria and Lp(a), returned towards values obtained during single therapy with ACE inhibiton.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Symptomatic antiproteinuric treatment decreases serum lipoprotein (a) concentration in patients with glomerular proteinuria. 805 29

A multicentre, randomized, placebo-controlled study was performed in 39 adult patients with biopsy-proven IgA nephropathy with the aim of comparing the effects of the ACE inhibitor fosinopril and placebo on proteinuria. All patients had normal blood pressure and normal renal function. Proteinuria ranged from 1.0 to 2.5 g/24 h. After a 3-month run-in period, fosinopril and placebo were randomly administered in two 4-month sequences separated from cross-over treatment by a 1-month interval. The mean values of creatinine clearance did not change during either the placebo or the treatment sequences. The mean values of mean arterial pressure (MAP) were significantly lower during the fosinopril sequence (90.4 +/- 9.0 mmHg) than in basal conditions (92.8 +/- 9.1 mmHg) (P = 0.034). The mean basal values of proteinuria were 1.74 +/- 0.84 g/24 h. They were unchanged during the placebo sequence (1.79 +/- 1.20) and fell to 1.37 +/- 0.98 g/24 h after 4 months of fosinopril treatment. Using a multivariate statistical analysis, the treatment effect by time on proteinuria was significantly evident only in the fosinopril sequence (Wilks test, P = 0.033). Changes in protein excretion were not correlated with changes in MAP, baseline plasma renin activity, and urinary sodium excretion. This controlled study shows that fosinopril can significantly reduce proteinuria even in normotensive patients with IgA nephropathy. Obviously, the results of treatment with ACE inhibitors on long-term renal prognosis remain to be elucidated.
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PMID:ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. 805 32

The authors evaluate in a retrospective study the effect of prednisone, cyclophosphamide, small doses of acetylsalicylic acid, conventional antihypertensive drugs and ACE inhibitors on the course of primary chronic proliferative types of glomerulonephritis. The group comprised 44 patients, incl. 16 with normal blood pressure and 28 with hypertension. All were at first given prednisone and cyclophosphamide--for an average of 18 months--and the patients with systemic hypertension conventional antihypertensive drugs. At the termination of treatment proteinuria in the whole group was significantly lower, while glomerular filtration was unaltered, i.e. normal. When the results in normotonic and hypertonic patients were evaluated separately, it was obvious that normotonic patients have a significantly lower proteinuria and a glomerular filtration significantly higher than hypertonic patients. After termination of immunosuppression the authors started to administer to all patients acetylsalicylic acid (1/4 tablet Anopyrin in 24 hours) and in hypertensive patients the conventional antihypertensive drugs were replaced by ACE inhibitors, combined in some with Ca channel blockers. Antiaggregation therapy persists now for more than three years, treatment with ACE inhibitors for more than two years. The results at the end of the investigation indicate that there is no significant difference between normotonic and hypertonic subjects. All have proteinuria lower than 2.0 g/24 hours, stabilized glomerular filtration and after 15 years of glomerulonephritis none of the patients suffers from chronic renal failure. The authors assume that combined immunosuppression, antiaggregation therapy and treatment of hypertension with ACE inhibitors can contribute to the stabilization of chronic glomerulonephritis.
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PMID:[Present possibilities of treatment of primary chronic glomerulonephritis]. 807 42

The primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria. 815 85

1. The relationship between vasopressin and the progression of renal failure has been proposed, but not intensively investigated because of a lack of orally available, selective vasopressin antagonists. 2. The effects of novel, orally available vasopressin V1 and V2 receptor antagonists on several indices of the progression of chronic renal failure, i.e. blood pressure, urinary protein excretion, sodium balance and renal histopathology, were investigated by using Wistar rats with adriamycin-induced nephropathy accelerated by deoxycorticosterone acetate-salt hypertension. Groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as the control. To block the effects of vasopressin efficaciously, V1 and V2 antagonists were simultaneously administered (group 4). 3. At week 6, 2 weeks after the beginning of administration of deoxycorticosterone acetate-salt and vasopressin antagonists after the second injection of adriamycin, V1 and V2 antagonists given either alone or in combination significantly reduced the systolic blood pressure as compared with the control, and urine volume was increased in groups 3 and 4. The proteinuria was also decreased at week 10 in groups 2, 3 and 4. Differences in sodium excretion between all groups were not significant. Histopathological alterations in the kidneys of group 4 were significantly ameliorated. 4. These results suggest that a combination of V1 and V2 antagonists can have therapeutic effects in certain types of chronic renal failure.
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PMID:Effects of vasopressin V1 and V2 receptor antagonists on progressive renal failure in rats. 816 33

Superoxide (O2-) production and Fc alpha R antigen expression of circulating polymorphonuclear leukocytes (PMNL) isolated from patients with IgA nephropathy (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN) and healthy volunteers were investigated to establish their biological importance in the immunopathogenesis of mesangial proliferative glomerulonephritis. PMNL from both patient groups showed increased O2- production when stimulated with N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA). The increased O2- generation demonstrated a positive correlation with the degree of proteinuria. Aggregated IgA caused enhanced O2- production only in patients with IgAN who also showed a significant correlation with proteinuria. Increased expression of Fc alpha R on circulating PMNL was observed in IgAN patients as determined by flow cytometric analysis. The amount of Fc alpha R on PMNL was positively correlated with O2- generation triggered with IgA aggregates. These results suggest that: 1. Circulating PMNL may potentially be participating in the pathogenesis of glomerular injury in mesangial proliferative glomerulonephritis, and 2. IgA aggregates/immune complexes may contribute to the immunopathogenesis of IgAN through augmenting the Fc alpha receptor-mediated generation of superoxide anion.
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PMID:Fc alpha R expression on polymorphonuclear leukocyte and superoxide generation in IgA nephropathy. 819 90

In rat membranous nephropathy, complement C5b-9 induces glomerular epithelial cell (GEC) injury and proteinuria. In cultured rat GEC, C5b-9 stimulates a phosphoinositide-directed phospholipase (PL) C and products of PLC downregulate C5b-9-mediated GEC injury. We now report that C5b-9-induced hydrolysis of phosphatidylcholine (PC) provides an additional source of 1,2-diacylglycerol (DAG). PC was labeled in intact GEC by brief incubation with 1-O-[alkyl-3H]2-lyso-PC. Assembly of C5b-9 stimulated an increase in PC-derived [3H]DAG (173 +/- 18% control), which was reduced in GEC depleted of protein kinase C (PKC) by prolonged preincubation with phorbol 12-myristate 13-acetate (PMA). Similar to C5b-9, [3H]DAG was released from PC after brief incubation of GEC with Ca2+ ionophore A23187 plus PMA. The increases in [3H]DAG induced by C5b-9 and A23187 plus PMA were paralleled by increases in DAG mass. C5b-9 also increased [3H]phosphatidic acid (PA; 182 +/- 37% control), but there was no significant interconversion of DAG and PA. Thus DAG probably originated via PLC. PC-directed PLC activity was also studied in GEC homogenates by release of [14C]DAG from exogenous 1-palmitoyl-2-[arachidonoyl-14C]PC. PLC activity was present at physiological Ca2+ concentration (200-1,200 nM), and PMA stimulated PLC activity in cell homogenates (in presence of ATP). These results demonstrate directly that PMA stimulates release of DAG from PC and are in keeping with the effect of PMA in [3H]lyso-PC-labeled GEC. Thus GEC contain a PC-directed PLC, whose activity is physiologically regulated and is present at nanomolar Ca2+ concentration. C5b-9 stimulates PC-directed PLC, leading to production of DAG. This DAG might trigger a mechanism for limiting injury during complement attack.
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PMID:Phosphatidylcholine-directed phospholipase C: activation by complement C5b-9. 823 84

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