Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the interstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 +/- 17 mg/d treated, 229 +/- 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
 ...
PMID:Contribution of angiotensin II to late renal injury after acute ischemia. 1086 84

The effect of enalapril and low prednisone doses on the urinary protein electrophoretic pattern was studied in 13 pediatric patients with glomerular diseases and steroid-resistant nephrotic syndrome. Enalapril was administered at doses of 0.2-0.6 mg/kg per day for 24-84 months, and prednisone was introduced 2 months later in 11 patients at doses of 30 mg/m2 on alternate days. The urine protein electrophoretic pattern showed a reduction of 80% and 70% in the total protein and albumin, respectively, after enalapril. Total urinary protein decreased from 5.46 to 1.1 g/m2 per day (P<0.001). A marked change from a pattern of non-selective urinary protein loss to an albumin-selective proteinuria was observed. Mean total plasma proteins increased from 4.7 to 5.43 g/dl (P<0.001). Four patients became free of proteinuria 24 months after enalapril was started, but only 2 remained free of proteinuria at 48 months of follow-up. The other 11 patients had persistent albuminuria of between 0.5 and 2.6 g/m2 per day with a selective urinary electrophoretic pattern. No additional decrease was observed after steroids were introduced. A clinical improvement in edema was observed in all children. Three patients developed transient acute renal failure, during the course of an infectious disease; 2 developed peritonitis and 1 pneumopathy. In these patients withdrawal of enalapril was necessary until a complete recovery of renal function was observed. Four patients were hypertensive on admission, achieving normal blood pressure 1 month after enalapril was started. No episodes of systemic arterial hypotension were seen. Creatinine clearance and serum potassium showed no statistically significant change.
 ...
PMID:Enalapril and prednisone in children with nephrotic-range proteinuria. 1104 92

This study was undertaken to determine whether angiotensin receptor blockers are as renoprotective as angiotensin-converting enzyme inhibitors in an experimental model of chronic interstitial renal disease. Groups of rats received one of the following treatments for 1 week: (1) enalapril, (2) diltiazem, (3) a cocktail of hydralazine, reserpine, and hydrochlorothiazide, or (4) irbesartan (an AT1 antagonist). The animals were injected with bromoethylamine (200 mg/kg), and antihypertensive treatment continued for 1 month. All drugs were effective in lowering the mean arterial pressure. The bromoethylamine-treated rats developed albuminuria and sustained a 40-50% decrease in creatinine clearance. Enalapril and irbesartan reduced albuminuria, but only enalapril partially prevented the decline in creatinine clearance and lowered the number of ED-1-positive cells. Diltiazem and cocktail had no effect on proteinuria, creatinine clearance, or ED-1 cells. In this experimental model, the effects of enalapril and irbesartan were not identical. Both drugs reduced proteinuria, but enalapril was more effective in protecting the renal function. The fact that the AT1 antagonist protected against albuminuria but did not affect the clearance of creatinine implies that the results seen with angiotensin-converting enzyme inhibition may be in part due to an effect on angiotensin II via AT2 receptor blockade or through an effect on bradykinin.
 ...
PMID:Differential effects of enalapril and irbesartan in experimental papillary necrosis. 1117 5

1. We have evaluated the effects of the angiotensin-converting enzyme inhibitor enalapril on renal function and oxidative status in the kidney of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous onset of type 2 diabetes mellitus. 2. Enalapril (5 mg/kg) or vehicle (distilled water) was given once daily by gavage to 22-week-old male OLETF rats for 32 weeks. Long-Evans Tokushima Otsuka (LETO) rats, the control animals for OLETF rats, received vehicle alone (n = 10 in each group). 3. Enalapril attenuated the rise in blood pressure mildly, but significantly. Enalapril significantly blunted the development of proteinuria without a significant effect on creatinine clearance. At the end of the study period, the lipid peroxide content in the renal cortex was significantly increased in OLETF compared with LETO rats, in which enalapril had no effect on lipid peroxide content. Enalapril enhanced the activity of catalase in the renal cortex of OLETF rats, but had no effect on the activity of either superoxide dismutase or glutathione peroxidase. 4. These results suggest that oxidative stress may be involved in the development of nephropathy in type 2 diabetes. Enalapril exhibited renoprotective effects without changing lipid peroxides in the kidney, suggesting that the beneficial effects of the compound on diabetic renal damage in OLETF rats may not be mediated through an anti-oxidative action.
 ...
PMID:Effect of enalapril on diabetic nephropathy in OLETF rats: the role of an anti-oxidative action in its protective properties. 1155 23

Spontaneously hypercholesterolemic (SHC) rats exhibit hypercholesterolemia, proteinuria and focal glomerulosclerosis with age, and they finally die as a result of renal failure. In this study, the renoprotective effects of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, and enalapril, an angiotensin I converting enzyme inhibitor, were examined in SHC rats. Candesartan cilexetil (0.1 and 1 mg /kg) and enalapril (10 mg/kg) were administered orally to 10-week-old SHC rats for a 6-week period. Candesartan cilexetil (1 mg/kg) and enalapril (10 mg/kg) significantly inhibited proteinuria and hypercholesterolemia to a similar extent. In untreated 16-week-old SHC rats, glomerulosclerosis, basophilic change, cast formation and interstitial mononuclear cell infiltration were observed. Candesartan cilexetil (1 mg/kg) inhibited all of these histological changes. Enalapril inhibited glomerulosclerosis and cast formation. These results show that candesartan cilexetil and enalapril have renal protective effects in SHC rats. Thus, angiotensin II might play an important role in renal pathogenesis in a model of focal glomerulosclerosis with hypercholesterolemia.
 ...
PMID:Renal protective effect of candesartan cilexetil in spontaneously hypercholesterolemic rats. 1194 85

We investigated the renal structural and functional consequences of nitric oxide (NO) deficiency co-treated with angiotensin-converting enzyme inhibitor (ACEi) in 20 adult male Wistar rats and 20 spontaneously hypertensive rats (SHR). The animals were separated into eight groups (n = 5) and treated for 30 days: Control, L-NAME (NO deficient group), Enalapril, L-NAME + Enalapril. The elevated blood pressure in NO deficient rats was partially reduced by enalapril. Serum creatinine was elevated in L-NAME-SHRs and effectively treated with enalapril. The proteinuria was significantly higher only in L-NAME-SHRs, and this was reduced by treatment with ACEi. The glomerular volume density (Vv(gl)) in L-NAME rats, both Wistar and SHR, was greater than in matched control rats, and enalapril treatment effectively prevented this Vv(gl) increase. No significant differences were observed in tubular volume density, Vv(tub), or tubular surface density, Sv(tub), in all Wistar groups. The Vv(tub) was smaller in L-NAME-SHRs than in control SHRs, and this tubular alteration was not prevented by enalapril. The Sv(tub) was not different among the SHR groups. In Wistar rats no changes were seen in vascular surface density, but a greatly increased cortical vascular volume density was seen in the enalapril treated rats. The vascular length density was greatly diminished in NO deficient rats that was effectively prevented with enalapril treatment. The vascular cortical renal stereological indices are normally reduced in SHRs. Administration of enalapril, but not L-NAME, changed this tendency. However, enalapril was not totally effective in preventing vascular damage in SHR NO deficient animals.
 ...
PMID:Kidney adaptation in nitric oxide-deficient Wistar and spontaneously hypertensive rats. 1470 68

Proteinuria in children with sickle cell anemia (SCA) is an early sign of sickle nephropathy, and portends the development of nephrotic syndrome and chronic renal failure. Enalapril has been shown to reduce proteinuria in adult patients with SCA, but the potential benefits of hydroxyurea in this clinical setting have not been reported. A single institution retrospective analysis was performed. Children with sickle nephropathy were identified, and the laboratory effects of enalapril and hydroxyurea therapy were evaluated in children with substantial proteinuria. Three children developed proteinuria at 8 +/- 1 years of age. Pre-treatment laboratory studies included a low serum albumin (2.8 +/- 0.8 g/dl) and a highly elevated urine protein/creatinine ratio (6.9 +/- 3.7, normal <0.2). Enalapril treatment for 3.0 +/- 1.3 years normalized serum albumin (3.9 +/- 0.3 g/dl) without significant changes in serum potassium, serum creatinine, or systolic blood pressure. However, urine protein/creatinine remained elevated in the nephrotic range (1.6 +/- 0.7). The addition of hydroxyurea therapy for 3.5 +/- 1.2 years increased fetal hemoglobin levels (7.0 +/- 3.6% to 21.0 +/- 3.2%) and was associated with a near-normal urine protein/creatinine ratio (0.5 +/- 0.1). Enalapril therapy for children with sickle nephropathy reduces urinary protein excretion and normalizes serum albumin. Hydroxyurea therapy may further normalize the urine protein/creatinine ratio. Combination therapy should be tested prospectively in children with sickle nephropathy.
 ...
PMID:Enalapril and hydroxyurea therapy for children with sickle nephropathy. 1570 13

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria, hypoalbuminemia, and eventual edema formation. Although the mechanisms underlying this phenomenon are not yet fully clarified, it is well accepted that nephrin and podocin are involved in the development of proteinuria. The effects of early treatment with various antiproteinuric therapies on proteinuria and glomerular staining of nephrin and podocin in rats with experimental NS have not been previously studied. Proteinuria and glomerular nephrin and podocin immunofluorescence were examined in rat kidneys with adriamycin-induced NS and the effects of antiproteinuric drug therapies during 5 wk with enalapril, losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on these parameters were assessed. Injection of adriamycin caused a significant increase in daily (from 21.8 +/- 1.4 to 983.1 +/- 45.8 mg/day, P < 0.01) and cumulative protein excretion (from negligible values to 22,490 +/- 931 mg, P < 0.001) during 5 wk. Early treatment with enalapril significantly decreased the daily (641.7 +/- 82.4 mg/day, P < 0.0023) and cumulative proteinuria (15,727 +/- 2,204 mg, P < 0.001). A similar effect, although to a lesser extent, was obtained after omapatrilat treatment: cumulative proteinuria was reduced to 18,706 +/- 1,042 mg, P < 0.001. In contrast, losartan treatment did not significantly influence the cumulative proteinuria that remained comparable (20,351 +/- 1,360 mg, P > 0.05) to that observed in untreated NS rats. Unexpectedly, when losartan was given in combination with enalapril, it abolished the beneficial effects of the latter. Pretreatment with mycophenolate mofetil exerted a moderate antiproteinuric effect, which appeared only during the last week of the experimental treatment. Nephrotic rats exhibited severe disruption of slit diaphragm structure as seen by rapid and profound loss of nephrin and podocin. Beneficial effects of enalapril, omapatrilat, and mycophenolate mofetil paralleled the preservation of nephrin, as determined immunohistochemically, and enabled prediction of significant antiproteinuric responses. Enalapril alone or in combination with losartan resulted in significant preservation of podocin. Pretreatment with enalapril, and to a lesser extent omapatrilat, is superior to losartan in reducing proteinuria in NS rats. A combination of ACE inhibitors with ANG II receptor blockers does not provide any advantageous antiproteinuric therapy in these animals. Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction. Not all the drugs which restore podocin reduce urinary protein in NS.
 ...
PMID:Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome: different effects of antiproteinuric therapies. 1594 45

An important explanatory theory for the mechanism of postexercise proteinuria is that angiotensin II could be inhibited by angiotensin converting enzyme inhibitors. Because of the kininase effect of the angiotensin converting enzyme, it is unclear whether the kallikrein-kinin system contributes to the effect of angiotensin converting enzyme inhibitors on postexercise proteinuria. The aim of this study was to evaluate any possible involvement of the kallikrein-kinin system in the therapeutic effect of angiotensin converting enzyme inhibitors on postexercise proteinuria. We evaluated urinary protein levels in exhausted rats receiving an angiotensin converting enzyme inhibitor (enalapril) or an angiotensin II type I receptor antagonist (losartan). Enalapril (30 mg/kg/day, two days) or losartan (20 mg/kg/day, two days) were given to animals using an intragastric catheter. Urinary protein levels increased (41 %) in rats which were exhausted via treadmill running (p < 0.05). In animals that received drug treatment (enalapril or losartan), but did not exercise to exhaustion, urinary protein levels were not different from the control group. Urinary protein levels were found to be significantly lower (p < 0.05) in animals which performed acute exhaustive exercise after enalapril or losartan administration, compared to rats which were exhausted without drug administration. Inhibition of postexercise proteinuria by either enalapril or losartan suggested that angiotensin II plays an important role in postexercise proteinuria, however, it appears the kallikrein-kinin system is not involved in angiotensin converting enzyme inhibitors effect.
 ...
PMID:Angiotensin II inhibition attenuates postexercise proteinuria in rats. 1623 14

A retrospective study was performed in 68 patients diagnosed as having idiopathic nephrotic syndrome with steroid-dependent, steroid-resistant or frequent relapse subtypes at the Department of Pediatrics, Siriraj Hospital during Jan 1996-Dec 2004. Male to female ratio was 3.3:1 and mean age (+/- SD) was 8.4 +/- 3.5 years. Mean follow up time (+/- SD) was 47.4 +/- 30.5 months. Renal biopsy was done in 60 patients, showing IgM nephropathy in 73.3%. Fifty-four patients (79.4%) received cyclophosphamide at a dose (+/- SD) of 2.2 +/- 0.5 mg/kg/d for 11.6 +/- 3.4 weeks. Negative proteinuria at 1 year was found in 70% and prednisolone was discontinued in 52%. Leucopenia was found in 9.2%. At last follow up, 34% of the patients were still in remission. Enalapril was prescribed in 50 patients for 12.4 +/- 10.0 months. Thirty-six patients also received cyclophosphamide. Remission at 1 year was achieved in 66% and prednisolone discontinued in 28%. Twelve patients (24%) were still in remission at last follow up. The results of 3 regimens: cyclophosphamide, enalapril, and cyclophosphamide plus enalapril were compared using chi-square test. Remission was significantly better in cyclophosphamide group (p = 0.014). Dipyridamole was prescribed in 14 patients due to thrombocytosis. Only 2 of 14 patients achieved remission although 11 patients received cyclophosphamide plus enalapril, and another 2 patients received only cyclophosphamide. Complications included hypertension (44%), cataract (40%), glaucoma (15%), short stature (17.6%), and obesity (5.9%). Recurrent infection was found in 69%, including dental caries (16.29%), urinary tract infection (14.7%), intestinal parasitic infestration (10.3%), respiratory tract infection (8.8%), and skin infection (7.4%). Chronic renal failure was found in 3 patients and portal vein thrombosis was found in 1 patient. We suggest that cyclophosphamide should be used as first line drug in difficult-to-treat nephrotic syndrome patients. Enalapril may be beneficial in some patients. Thrombocytosis may be associated with poor response to both medications. Difficult-to-treat patients also need long-term follow up and surveillance for complications due to disease and/or treatment.
 ...
PMID:Difficult-to-treat nephrotic syndrome: management and outcome. 1685 34


<< Previous 1 2 3 4 5 6 7 Next >>