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)

1. Both the angiotensin-converting enzyme inhibitor, lisinopril, and the non-steroidal anti-inflammatory drug, indomethacin, lower urinary protein excretion in renal disease and improve the selectivity of the residual proteinuria. Despite the clearly different renal haemodynamic profiles of the two drugs, we hypothesize that the antiproteinuric effect has a final common pathway that is a reduction in glomerular filtration pressure. 2. We studied the effects of lisinopril and indomethacin, separately and in combination, on urinary protein excretion, selectivity of proteinuria and renal haemodynamics in nine non-diabetic patients with overt proteinuria. 3. Urinary protein excretion was 5.4 +/- 2.5 g/24 h in the control period. Lisinopril monotherapy lowered urinary protein excretion by 53 +/- 26%. During indomethacin treatment urinary protein excretion was reduced by 63 +/- 24%. After adding indomethacin to lisinopril, urinary protein excretion fell by a further 58 +/- 23%, resulting in a 79 +/- 17% decrease during combined therapy. 4. Although both lisinopril and indomethacin monotherapy appeared to result in an improvement in glomerular protein permeselectivity, no further improvement was seen during the combination therapy. 5. The change in proteinuria were associated with changes in glomerular filtration rate, which showed a pronounced fall with combination therapy. The renal haemodynamic profiles during the different therapies suggest a post-glomerular vasodilatation by lisinopril and a pre-glomerular vasoconstriction by indomethacin, and the combination of both during the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Additive antiproteinuric effect of angiotensin-converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy: a clue to the mechanism of action. 165 38

Angiotensin converting enzyme (ACE) inhibitors are known to lower urinary protein excretion in human renal disease. This proteinuria lowering effect of ACE inhibition has been hypothesized to be a result of renal hemodynamic changes due to the inhibition of angiotensin II (Ang II) production. To test this hypothesis we studied the short-term effects of different doses of exogenous Ang II (5%, 10% and 20% of the pressor dose) on renal hemodynamics and urinary protein excretion in comparison with placebo infusion in six non-diabetic normotensive proteinuric patients, both before and after three months treatment with the ACE inhibitor, lisinopril. Lisinopril lowered proteinuria from 7.5 +/- 1.9 to 2.7 +/- 0.6 g/24 hr and induced a fall in blood pressure, renal vascular resistance and filtration fraction, whereas plasma Ang II levels were similar to the pre-treatment values. Ang II infusion induced typical effects which appeared to be similar before and during lisinopril treatment: a dose-related fall in renal plasma flow and rise in systemic blood pressure, renal vascular resistance and filtration fraction, while the glomerular filtration rate remained relatively stable. However, neither before nor during lisinopril therapy did any changes in urinary protein loss occur during the infusions of Ang II, despite the fact that Ang II reversed the long-term systemic and renal hemodynamic changes induced by the ACE inhibitor. We conclude that the long-term antiproteinuric effect of the ACE inhibitor, lisinopril, is neither mediated through changes in circulatory Ang II levels nor influenced by acute changes in systemic and renal hemodynamics, suggesting a non-hemodynamic mechanism of action.
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PMID:Angiotensin II does not acutely reverse the reduction of proteinuria by long-term ACE inhibition. 166 May 50

In a multicenter, parallel, double-blind study, lisinopril was compared with atenolol in the treatment of mild to moderate essential hypertension. Four hundred ninety patients were randomized to a once-a-day treatment with lisinopril 20 mg or atenolol 50 mg for 4 weeks, and the doses of lisinopril or atenolol were increased up to 80 mg or 200 mg, respectively, at 4-week intervals if sitting diastolic blood pressure (SDBP) was not well controlled. Hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added after 12 weeks, if necessary, and titrated upward after 4 weeks to a maximum dose of 25 or 50 mg/day. Lisinopril and atenolol reduced SDBP to a similar extent. All reductions from baseline in sitting diastolic and systolic blood pressure were significant (less than 0.01). Lisinopril produced a significant (less than 0.01) greater reduction in sitting systolic blood pressure (SSBP) than atenolol. Addition of HCTZ caused further blood pressure reductions (p less than 0.01). Five patients (1.7%) on lisinopril and four (2.0%) on atenolol developed skin rashes during weeks 1-12. Two patients (0.7%) on lisinopril 80 mg developed proteinuria (greater than 1 g/day). Cough occurred more often with lisinopril (4.5%), and elevated triglycerides occurred more often with atenolol (2.0%).
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PMID:The antihypertensive effect of lisinopril compared to atenolol in patients with mild to moderate hypertension. 244 51

The antihypertensive efficacy and safety of lisinopril, a long-acting angiotensin-converting enzyme inhibitor, were assessed in 40 elderly patients (aged 65 years or over) with mild to moderate systolic/diastolic or isolated systolic hypertension, in an open study of 12 weeks' duration. Lisinopril was given orally in single daily doses. The starting dose was 5 mg in patients with glomerular filtration rate (GFR) of 30-60 ml/min and 10 mg in patients with GFR greater than 60 ml/min. The dose of lisinopril could be titrated upwards to a maximum of 40 mg daily according to blood pressure response. A thiazide diuretic was then added if blood pressure was not controlled. Thirty-six patients completed the study. Mean sitting blood pressure was significantly reduced by lisinopril treatment. There was no significant alteration in the heart rate, and postural hypotension did not occur. The median dose of lisinopril given was 20 mg daily (range 5-40 mg daily), and only two patients had a diuretic added to the lisinopril. One patient was withdrawn from the study because of unstable angina, and another was discontinued from lisinopril treatment because of anorexia and facial flushing. One patient was withdrawn after 8 weeks because of interruption of lisinopril therapy for a transurethral resection of the prostate, and one patient was lost to follow-up. No clinically significant haematological or biochemical changes were observed. The mean glomerular filtration rate was unchanged during the study. Proteinuria did not occur de novo, nor did established proteinuria increase. Thus lisinopril was well-tolerated and effective therapy in a group of elderly hypertensive patients.
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PMID:Lisinopril in elderly patients with hypertension. 244 57

Lisinopril is a new, nonsulfhydryl angiotensin-converting enzyme inhibitor approved for the treatment of hypertension. After oral administration, 25-29 percent of the dose is absorbed intact; biotransformation is not required for pharmacological activity. Onset of action occurs one to two hours after administration, with effects still present 24 hours later. The major route of elimination is through renal excretion and an elimination half-life of 12.6 hours has been reported in normotensive individuals. In patients with impaired renal function (creatinine clearance less than or equal to 30 ml/min) a longer half-life and accumulation have been observed. Lisinopril 20-80 mg/d has been shown to be as effective as hydrochlorothiazide, nifedipine, and beta-blocking agents in the treatment of essential hypertension. Its efficacy in renovascular hypertension has also been demonstrated. In congestive heart failure (CHF) doses of 2.5-20 mg/d appear to provide hemodynamic effects comparable to those of captopril. Dizziness and cough have been the most frequently reported side effects; rash and proteinuria have also been reported in a small number of patients. Interactions with diuretics, potassium supplements, and possibly with nonsteroidal antiinflammatory agents may occur. Lisinopril appears to be similar in efficacy to other antihypertensive agents in the treatment of essential hypertension and to captopril in the treatment of CHF. Whether lisinopril is safer or more effective than captopril or enalapril in the treatment of hypertension or CHF requires further investigation. Prolonged duration of action of lisinopril allows once daily dosing, unlike captopril for which dosing is required every 8-12 hours or enalapril which may necessitate twice daily dosing.
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PMID:Lisinopril: a new angiotensin-converting enzyme inhibitor. 283 26

The effects of the angiotensin converting enzyme (ACE) inhibitor lisinopril on blood pressure, proteinuria and renal hemodynamics were evaluated in 13 patients with renal disease of different origin. A comparison was made with the effects of conventional antihypertensive therapy. Both drug regimens significantly lowered blood pressure, while only after 12 weeks of treatment with lisinopril, blood pressure was significantly lower than during conventional therapy. Lisinopril reduced proteinuria (by 61 +/- 40%), whereas conventional therapy had no significant effect on protein excretion. During the first eight weeks of treatment with lisinopril, there was a comparable degree of blood pressure reduction with both treatment regimens, whereas urinary protein loss was significantly less during ACE inhibition. There was only a nearly-significant positive correlation between the fall in proteinuria during lisinopril and the concomitant decrease in mean arterial pressure. Glomerular filtration rate decreased from 26.3 +/- 11.6 to 20.6 +/- 9.4 ml/min during treatment with lisinopril. This decrease was not correlated with the fall in proteinuria. A significant positive correlation existed between the fall in urinary protein excretion and both the decrease in overall renal vascular resistance, and the fall in filtration fraction. Although blood pressure lowering by itself could contribute to the antiproteinuric effect of lisinopril, our results suggest that this effect of ACE inhibition is also due to efferent (postglomerular) vasodilation. We conclude that the ACE inhibitor lisinopril effectively reduces blood pressure and proteinuria in renal disease. The latter effect is not only the result of a lower blood pressure, but is probably also due to a fall in intraglomerular capillary pressure.
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PMID:Reduction of proteinuria by angiotensin converting enzyme inhibition. 304 Oct 97

Renal transplantation is frequently accompanied by systemic hypertension. In the present study we evaluated the effect of 2.5 mg lisinopril in 12 hypertensive and proteinuric renal graft recipients with stable graft function over 3 months. Only patients with absence of renal artery stenosis, at least as judged by technetium-scan imaging, were included. Lisinopril was effective in lowering systemic blood pressure. Mean arterial pressure was unchanged despite reduction of concomitant antihypertensive medication. Mean serum creatinine was unchanged during the study (1.95 +/- 0.8 mg/dl in the pretreatment period vs. 1.77 +/- 0.76 mg/dl in the intervention period, n.s.). Glomerular filtration rate remained stable (62.75 +/- 21.96 vs. 60.17 +/- 18.27 ml/min/1.73 m2, n.s.) whereas renal plasma flow increased (224.75 +/- 91.66 vs. 244.92 +/- 94.13 ml/min/1.73m2, P < 0.01), leading to a drop in filtration fraction (31.4 +/- 12.4 vs. 26.8 +/- 8.6, n.s.). Renal vascular resistance was significantly reduced following angiotensin-converting enzyme (ACE) inhibitor therapy (26,447 +/- 14,574 vs. 23,425 +/- 12,430 dyne sec cm-5/1.73 m2, P < 0.01). Mean daily proteinuric decreased significantly (2.98 +/- 2.06 vs. 2.06 +/- 2.29 g, P < 0.01) whereas in a group of patients with comparable blood pressure but without ACE inhibitor therapy and similar degree of proteinuria, 24-hr proteinuria remained stable. No severe side effects were observed--in particular, mean serum potassium showed only a slight increase and no clinically significant hyperkalemic condition was observed. When lisinopril therapy was withdrawn after 3 months, blood pressure increased in all patients, requiring reinstitution of additional antihypertensive medication. Renal hemodynamic parameters and daily proteinuria returned to baseline values. We conclude that 2.5 mg lisinopril daily was safe and effective in this group of renal transplant recipients and showed a good antihypertensive as well as antiproteinuric effect.
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PMID:The effects of lisinopril on renal function in proteinuric renal transplant recipients. 839 Jul 33

1. The mechanism of renal protection by angiotensin-converting enzyme inhibition is still the subject of debate. Inhibition of proteinuria might play a role. If so, a good antiproteinuric response to angiotensin-converting enzyme inhibition should predict subsequent protection against renal structural damage. This hypothesis has not been tested in models where treatment is started after the renal disease is well established, i.e. models that mimic the clinical situation. 2. We therefore investigated this hypothesis in 96 male Wistar rats with established adriamycin nephrosis. Reduction of proteinuria was achieved by lisinopril (0, 2, 5 and 10 mg day-1 kg-1) on two different sodium diets (0.3% and 0.05% NaCl). Therapy started 6 weeks after adriamycin (at stable proteinuria) and was continued for 6 weeks. 3. Lisinopril reduced blood pressure by 32 +/- 4% and proteinuria by an average of 72 +/- 7%, with stabilization after 2 weeks. Considerable interindividual differences in antiproteinuric response was found. Glomerulosclerosis score was reduced by 15 +/- 5%. All the effects of angiotensin-converting enzyme inhibitors were enhanced by sodium depletion, but sodium depletion in itself did not affect blood pressure (124 +/- 4 mmHg), proteinuria (664 +/- 68 mg/day) or glomerulosclerosis score (30 +/- 5%). Interestingly, the more proteinuria was reduced initially in an individual rat, the less sclerosis was found in the long term in that rat. 4. In conclusion, angiotensin-converting enzyme inhibition lowers proteinuria and prevents glomerulosclerosis in established adriamycin nephrosis. These effects are enhanced by sodium depletion. The individual short-term antiproteinuric effect predicts the protection against ultimate glomerular damage. This is consistent with the hypothesis that reduction of proteinuria is a mechanism by which angiotensin-converting enzyme inhibitors exert renoprotection.
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PMID:Antiproteinuric effect predicts renal protection by angiotensin-converting enzyme inhibition in rats with established adriamycin nephrosis. 866 77

The therapeutic effects of angiotensin converting enzyme inhibitor, lisinopril, on puromycin aminonucleoside (PAN)-induced nephrosis were investigated using unilaterally nephrectomized rats. Lisinopril showed potent dual effects on PAN nephrosis. Lisinopril treatment (50 mg/l in drinking water) from day 5 or day 9 reduced urinary protein excretion and suppressed the development of glomerular sclerosis at 8 weeks after PAN injection (150 mg/kg, i.p.), indicating a therapeutic effect on the nephrosis. Recovery of decreased anionic charge sites on the glomerular basement membrane was involved, at least in part, in the therapeutic action of lisinopril against proteinuria. On the other hand, oliguria and progressive azotemia derived from continuous deterioration of the renal function was induced if the treatment of lisinopril was started on the same day as PAN injection. The renal dysfunction induced by simultaneous administration of lisinopril with PAN could be abolished by combination dosing with sarcosine, an angiotensin II (AII)-receptor agonist. These results indicate that lisinopril treatment attenuates proteinuria by ameliorating the anionic charge barrier on the glomerular basement membrane and that it also protects against the development of chronic renal disease with segmental glomerular sclerosis, although AII depletion during the acute nephrotic stage exacerbates the renal damage in PAN nephrosis of unilaterally nephrectomized rats.
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PMID:Dual effects of lisinopril on puromycin aminonucleoside nephrosis in unilaterally nephrectomized rats. 916 71

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.
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PMID:Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients. 940 9


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