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)

Male Munich-Wistar rats were studied 18 weeks after 1 2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril, starting 1 week after ablation. Two additional groups received no therapy during the first 8 weeks, and then received ACE inhibitor or a low (12%) protein diet. Early ACE inhibitor therapy resulted in control of systemic and glomerular hypertension (HTN), and a striking limitation of proteinuria and glomerular sclerosis. During the first 8 weeks untreated rats developed severe systemic HTN and increasing proteinuria. After 8 weeks proteinuria increased further in untreated rats, and widespread sclerosis resulted. Late ACE inhibition reversed systemic HTN. Both late ACE inhibition and late protein restriction reversed glomerular HTN and prevented further increases in proteinuria and sclerosis. Thus, control of glomerular HTN can stabilize renal injury even when therapy is delayed until hypertension and glomerular injury are established.
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PMID:Reversing glomerular hypertension stabilizes established glomerular injury in renal ablation. 303 77

The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 +/- 5 mm Hg and serum creatinine of 128 +/- 9 mumol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria. Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 +/- 5 mm Hg compared with 176 +/- 7 mm Hg in untreated rats (p less than 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 +/- 9 mumol/l with enalapril treatment, compared with 159 +/- 21 mumol/l (p less than 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 +/- 3 mg/24 hr vs 85 +/- 22 mg/24 hr, p less than 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 +/- 0.08 vs 2.36 +/- 0.16, p less than 0.01). Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125I-hippurate clearance). At 6 wk, filtration fraction was 0.30 +/- 0.03 in enalapril treated and 0.48 +/- 0.03 in control rats (p less than 0.001). Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preservation of renal structure and function in the rat remnant kidney model of chronic renal failure by enalapril treatment. 303 69

Micropuncture and morphological studies were performed in three protocols assessing the renal hemodynamic and structural effects of angiotensin I-converting enzyme inhibitors (CEIs) in the progression of glomerular injury. In protocol I, rats were subjected to 5/6 renal ablation and received no therapy, enalapril (CEI), or triple-drug therapy (TRX) for 12 weeks. Control of systemic and glomerular hypertension with CEI resulted in prevention of glomerular capillary hypertension and protection against glomerular injury. Despite equivalent control of systemic BP, failure of TRX to control glomerular hypertension was associated with no protection against eventual proteinuria and glomerular sclerosis, values for these indexes being as abnormal as in rats receiving no therapy. In protocol II, rats were again subjected to 5/6 renal ablation and followed for 18 weeks. Early institution of CEI soon after ablation again prevented systemic and glomerular hypertension and largely limited glomerular injury. In a third group, enalapril therapy was delayed for 8 weeks after ablation until hypertension and proteinuria were established. Late institution of CEI resulted in prompt reduction in systemic and glomerular capillary hypertension and stabilization of glomerular disease. In protocol III, CEI was administered to normotensive, moderately hyperglycemic diabetic rats. A modest, 20-mm Hg reduction in systemic arterial pressure was associated with the normalization of glomerular capillary pressure and a striking reduction in the development of albuminuria and glomerular injury. These studies suggest that CEI effectively prevent glomerular capillary hypertension and thereby afford protection against glomerular injury in diverse models of progressive renal disease.
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PMID:Therapeutic implications of converting-enzyme inhibitors in renal disease. 303 94

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

Since their introduction in clinical practice in 1980, ACE inhibitors have been found useful in the treatment of hypertension and CHF. In hypertension, they are effective as monotherapy in 40% to 50% of the patients, and in combination with diuretics or calcium antagonists, they are effective in up to 85% of the patients. They are well tolerated, are not associated with depression, impotence, bronchospasm or metabolic derangements such as hypokalemia, hyperuricemia or hyperglycemia, and do not have adverse effects on the quality of life. As a result, they are preferred in hypertensive patients with CHF, left ventricular dysfunction, mental depression, older age, coronary artery disease, metabolic disorders, chronic destructive pulmonary disease, and peripheral vascular disease. In CHF they cause long-lasting hemodynamic and symptomatic improvement, improve exercise tolerance, and may lower mortality in certain patient subsets. Evolving new indications for ACE inhibitors include the diagnosis of renovascular hypertension, the prediction of surgical success, the treatment of scleroderma renal crisis, the reduction of proteinuria, renal protection, cardioprotection, the improvement of arterial compliance, in Bartter's syndrome and idiopathic edema, etc. ACE inhibitors are usually well tolerated but in some instances they may cause class-specific side effects such as hypotension; usually reversible azotemia or renal failure, especially in patients with renal artery stenosis or with CHF with low blood pressure; cough; angioedema; and hyperkalemia. Differences among ACE inhibitors are emerging and include chemical class (e.g., zinc ligand), biotransformation, potency, pharmacokinetics, prodrugs, tissue effects, additional pharmacologic properties, and drug interactions.
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PMID:Angiotensin converting enzyme inhibitors. II. Clinical use. 305 46

Numerous trials have shown the efficacy of ACE-inhibitors in moderate and severe essential hypertension. Their use must be regarded as very promising. They lower peripheral vascular resistance without influencing cardiac index and heart rate. Additionally, they maintain serum potassium and do not effect plasma lipids or provoke diabetes mellitus or gout. In 20-30% of hypertensive patients ACE-inhibitors have to be combined with diuretics and/or calcium antagonists. The addition of beta-blockers is useful in patients with resting tachycardia. In mild hypertension the use of ACE-inhibitors as first-line drugs is indicated in patients with adverse reactions to beta-blockers or diuretics. In bilateral renovascular hypertension, ACE-inhibitors may induce a strong blood pressure fall; in bilateral stenosis they contribute to a deterioration of renal function with reversible renal insufficiency. In renoparenchymal hypertension, ACE-inhibitors may attenuate the progression of renal insufficiency; in addition, proteinuria is lowered. In systolic hypertension in the elderly, one must be aware of a marked first-dose hypotensive effect. ACE-inhibitors decrease exaggerated exercise-induced elevation of blood pressure and heart rate and therefore lower myocardial oxygen consumption. In patients with hypertension and diabetes mellitus, antihypertensive treatment should be initiated for blood pressure levels above 140/90 mmHg, to attenuate the progression of vascular damage in the kidney. In patients with severe left ventricular hypertrophy, ACE-inhibitors reduce left ventricular mass within three months by about 30%. In hypertension and coronary heart disease, recent studies report benefits of ACE-inhibitors on coronary circulation. Presently available ACE-inhibitors and those in preparation do not differ in pharmacodynamic, but in pharmacokinetic properties, concerning the beginning and duration of blood pressure lowering. A hypotensive first-dose effect can be observed in diuretic pretreated patients, in severe (malignant) and renovascular hypertension. ACE-inhibitors should not be used during pregnancy or in patients with autoimmune diseases or those undergoing treatment with immunosuppressive drugs, due to the side effects of neutropenia and proteinuria, which are more often seen under these conditions. Results from long-term studies on the influence of ACE-inhibitor treatment on cardiovascular risk in mild hypertension have not been available until now. In the decision to treat mild hypertension with ACE-inhibitors as first-line drug therapy, the costs of therapy in comparison to cheaper antihypertensives must be taken into account.
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PMID:[The value of angiotensin-converting enzyme inhibitors in the treatment of hypertension]. 306 60

When captopril was first introduced, it was used in high doses for severe hypertension, often in the presence of renal insufficiency, and side effects such as proteinuria, rash, neutropenia, and altered taste sensation were noted. Upon analysis, these effects were most commonly seen in patients with renal disease, autoimmune disease, or collagen vascular disease. These complications usually reversed rapidly upon discontinuation of treatment. In contrast, the growing use of the angiotensin converting enzyme inhibitors, captopril and enalapril, for treating mild to moderate hypertension and the trend toward the use of lower doses has shown these agents to be well tolerated with a low frequency of troublesome adverse effects. In fact, the original spectrum of adverse effects has virtually disappeared with the use of lower doses in patients with uncomplicated hypertension. In low doses, the converting enzyme inhibitors produce remarkably few incidences of symptomatic discomfort; the most common is skin rash, which often responds to dosage reduction. Cough and rare occurrences of angioedema have also been reported. Moreover, evidence is evolving that indicates that the converting enzyme inhibitors may sometimes decrease proteinuria and improve renal function; these effects may be especially important in diabetic hypertensive patients. Of note, these drugs can also attenuate the unwanted metabolic side effects of concurrent diuretic treatment.
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PMID:Safety issues during antihypertensive treatment with angiotensin converting enzyme inhibitors. 306 5

Although most patients respond well to loop diuretics, poor response is sometimes a problem and some underlying mechanisms were addressed in this study. The renal response to continuous infusion of furosemide was investigated in eight healthy volunteers during controlled isotonic dehydration and after full restoration of volume losses. A rapidly reversible acute tolerance developed in parallel with dehydration and activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS). Dehydration also reduced the renal clearance of furosemide substantially, but only decreased the urinary delivery rate of the drug (the principal determinant of the diuretic effect) to a minimal extent. Delayed tolerance to an i.v. bolus dose of furosemide was found in 12 healthy volunteers after 1 week of oral furosemide treatment with and without angiotensin converting enzyme inhibition. No pharmacokinetic changes were seen. This type of tolerance was not related to dehydration or activation of RAAS. Thus, the induced decrease in renal sensitivity to furosemide was probably due to an intrarenal (structural?) adaptation. The pharmacokinetics and pharmacodynamics of piretanide were studied in six healthy volunteers and 22 patients with chronic renal failure (glomerular filtration rate 1-28 ml/min). Poor response to the diuretic action of the drug was found in the patients. This was entirely due to a decrease in the fraction of piretanide excreted unchanged in the urine, and the renal sensitivity to the drug was normal. Multiple daily doses of piretanide of maximally 24 mg are recommended for optimal efficiency in renal failure. Substantial changes in pharmacokinetics of furosemide were found after manipulation of plasma albumin in five patients with nephrosis, while the urinary delivery of the drug scarcely changed. Neither the induced alterations in proteinuria nor those in plasma volume influenced the renal sensitivity to furosemide significantly. Some methodological observations proved to be of significance. Creatinine was found to be an unreliable marker of GFR because of its substantial tubular secretion and reabsorption, both of which were related to the degree of hydration. Likewise, lithium was considered an unreliable marker of proximal tubular reabsorption, since there were reasons to suspect furosemide-sensitive distal lithium reabsorption.
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PMID:Mechanisms of reduced effects of loop diuretics in healthy volunteers and in patients with renal disease. 320 Nov 62

The effect of angiotensin converting enzyme inhibition with captopril therapy (3 x 12.5 mg/d) on heavy proteinuria and kidney function was investigated in 10 insulin-treated diabetic patients over a period of 6 months. Urinary protein excretion increased from 3706 mg/day (SD 1491) to 5405 (SD 2699) after 6 months of treatment (p = 0.05); serum creatinine rose from 248 mumol/l (SD 163) to 283 (SD 186) (p less than 0.01), whereas there was no significant difference in blood pressure before (150/80 mm Hg--SD 23/6) and after therapy (150/90 mm Hg--SD 23/10). HbA1c as a marker of metabolic long-term control decreased from 8.3% (SD 1.0) to 7.3% (SD 1.0) (p less than 0.05). No beneficial effects of low dose angiotensin converting enzyme inhibition on heavy proteinuria could be demonstrated in this group of patients with advanced diabetic nephropathy. In particular, progressive deterioration of kidney function was not influenced by the captopril treatment. In diabetic patients with incipient diabetic nephropathy presenting with microalbuminuria, further studies concerning a possible therapeutic effect are necessary.
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PMID:[Lack of effect of ACE inhibition on severe proteinuria in diabetic nephropathy--a 6-month-long study]. 327 75

An examination of the principal physiological actions of angiotensin II should make it clear why in vivo attempts to inhibit the rate of angiotensin II generation have been an attractive avenue in pursuing control of high blood pressure. The major physiological effect of angiotensin II relates to its direct pressor effect, but there are supplementary blood pressure regulating actions. Therefore, if we limit the rate of angiotensin II generation by inhibiting the angiotensin converting enzyme (ACE) we should expect to control high blood pressure in a number of clinical syndromes. This paper reviews the future of ACE inhibitors in the treatment of conditions such as hypertension associated with unilateral renal artery stenosis, essential hypertension and severe and previously unresponsive hypertension, with respect not only to efficacy but also to the side-effect profile and ancillary properties. Side effects seen with this class of drug are cough, rashes (both morbilliform and urticarial) and, rarely, angio-oedema. Proteinuria, nephrotic syndrome, leukopenia and taste disturbance were previously reported with captopril but only taste disturbance, and that less frequently, is apparent at the lower doses now employed. Several studies have examined the 'quality-of-life' aspects of ACE therapy and have usually but not always reported favourably. There are features of the ACE inhibitors which make them attractive drugs, and while we should be cautious because of limited experience, we should critically and creatively examine their properties over the next years.
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PMID:Angiotensin converting enzyme inhibition in hypertension. 331 25


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