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)

The present study investigated the development of hypertension and the functional and morphological changes in the kidney in Dahl salt-sensitive (Dahl S) rats fed with a normal salt diet during aging. Furthermore, the effects of calcium channel antagonists nitrendipine and nicardipine on these changes were examined. The rats showed proteinuria from 6 weeks of age and gradually developed hypertension accompanied by the decrease in the glomerular filtration rate during aging. Glomerular screlosis and degeneration of the renal tubule were found by histological examinations at 17 weeks of age. Nitrendipine (20 mg/kg chow), given from 7 weeks of age for 10 weeks, inhibited the elevation in systolic blood pressure from 3 weeks after the dosing, whereas nicardipine (20 mg/kg chow) inhibited it only at 5 weeks after dosing. Both drugs decreased glomerular sclerosis, but did not affect the glomerular filtration rate, urine volume, urinary excretion of protein and N-acetyl-beta-D-glucosaminidase and serum concentrations of creatinine and urea nitrogen. These results demonstrated that Dahl S rats fed with a normal salt diet spontaneously developed the renal disorder in the early stage of hypertension and reinforce the validity of nitrendipine for the treatment of hypertensive patients with renal failure.
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PMID:[Effects of nitrendipine on the development of hypertension and renal failure in Dahl salt-sensitive rats]. 1067 98

Hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) have a faster progression to end-stage renal disease (ESRD) than their normotensive counterparts. The aim of this prospective, randomized study is to compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor enalapril as first-line therapy on blood pressure, renal function, and urinary albumin excretion in hypertensive patients with ADPKD. Twenty-four patients with ADPKD with hypertension with creatinine clearances (Ccrs) greater than 50 mL/min/1.73 m(2) were included in the study. Twelve patients received amlodipine (mean dose, 9 mg/d), and 12 patients received enalapril (mean dose, 17 mg/d). The patients were followed up for 5 years. Baseline mean arterial pressures, which were 109 +/- 3 mm Hg in the amlodipine group and 108 +/- 3 mm Hg in the enalapril group, decreased significantly after 1 year of follow-up (amlodipine, 96 +/- 3 mm Hg; P < 0.005; enalapril, 89 +/- 2 mm Hg; P < 0.0005) and remained stable at year 5 (amlodipine, 97 +/- 3 mm Hg; P < 0.0005 versus baseline; enalapril, 94 +/- 3 mm Hg; P < 0.005 versus baseline). Ccrs, which were 83 +/- 5 mL/min/1.73 m(2) in the amlodipine group and 77 +/- 6 mL/min/1.73 m(2) in the enalapril group, remained stable after 1 year of follow-up and decreased significantly at year 3 in both groups (amlodipine, 67 +/- 5 mL/min/1.73 m(2); P < 0.01 versus year 1 and baseline; enalapril, 58 +/- 4 mL/min/1.73 m(2); P < 0.05 versus year 1 and P < 0.0005 versus baseline) with no significant change thereafter. No change was observed in urinary albumin-creatinine ratio in the amlodipine group (baseline, 68 +/- 21 mg/g; year 1, 52 +/- 21 mg/g; year 5, 148 +/- 74 mg/g), whereas it decreased significantly in the enalapril group at year 1 (baseline, 23 +/- 4 mg/g; year 1, 13 +/- 3 mg/g; P < 0.05) and remained stable until the end of the study at year 5 (14 +/- 6 mg/g). The investigators concluded that blood pressure was similar in both groups but only enalapril had a significant effect to sustain decreased urinary albumin excretion for a 5-year follow-up. Although proteinuria has been considered a surrogate of renal disease progression, further studies will be necessary to confirm this hypothesis in ADPKD, because after 5 years, no differences in renal function were observed between the enalapril and amlodipine groups. In comparison with patients with ADPKD with uncontrolled hypertension, effective control of blood pressure, as undertaken in the present study, should delay the onset of ESRD by approximately 15 years.
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PMID:Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. 1069 86

There is a growing body of evidence suggesting that calcium channel blockers (CCB) exert beneficial effects on kidney transplant survival. However, it is not completely understood if these agents act independently of blood-pressure reduction. In the present study, the 5-yr follow-up of 45 kidney transplant recipients receiving CCB during the 60-month follow-up period was compared to that of recipients with lower blood pressure and an antihypertensive treatment without CCB. During the whole follow-up, systolic (127.4 +/- 2.5 vs. 139.4 +/- 2.1 mmHg, p < 0.05) as well as diastolic blood pressure (78.8 +/- 1.1 vs. 84.8 +/- 1.8 mmHg, p < 0.05) was higher in the group receiving CCB. Moreover, in CCB-treated recipients, a significant (p < 0.05) higher increase in proteinuria was detected (from 759 +/- 120 to 1690 +/- 359 mg/24 h vs. 180 +/- 45 to 340 +/- 45 mg/24 h). Despite higher blood pressure and higher proteinuria, the increase in serum creatinine in the group of CCB-treated recipients was significantly lower (0.01 mg/dL/month) in comparison to that of the controls (0.02 mg/dL/month, p < 0.05). Moreover, the 5-yr transplant survival was significantly higher in CCB-treated recipients (62.3 vs. 31.8%, p < 0.05). The results of the present study further support the beneficial effects of CCB in kidney transplant recipients, which are independent of blood-pressure reduction.
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PMID:The beneficial effects of calcium channel blockers on long-term kidney transplant survival are independent of blood-pressure reduction. 1083 Oct 86

That systemic hypertension is involved in the progression of human renal disease is mostly suggested by the way anti-hypertensive treatment affects the course of the disease. Clinical evidence has been obtained from observational studies as well as from studies of dietary protein restriction. In addition, several trials have compared the effects of different antihypertensive agents. The angiotensin-converting-enzyme inhibitors have the best renoprotective effect when compared to conventional agents and calcium channel blockers. In most studies, ACE-inhibitors approximately halved the risk of progressive renal functional deterioration in patients with non-diabetic nephropathies; this protection was associated with a significant reduction in systemic blood pressure and proteinuria. Statistical analysis, however, also suggests a direct effect of ACE-inhibitors on the kidney.
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PMID:Hypertension and progression of renal disease. 1092

The important contribution of hypertension to the progression of renal failure is well realized. However, it have been less discussed which drugs are suitable for the different stages of progressive renal failure. The present study examined the effects of timing of antihypertensive therapy using calcium channel blocker and angiotensin converting enzyme inhibitor in 5/6 nephrectomized spontaneously hypertensive rats (SHRs). Forty male 6 week old SHRs were divided into 5 groups (n=8 in each group), and they were placed on a high salt diet after 5/6 nephrectomy. Group 1, high salt diet without any drug. Group 2 received 0.2 mg/kg/day of amlodipine and group 3 received 0.2 mg/kg/day of enalapril mixed in the high salt diet from week 6 respectively. Similarly group 4 received the same doses of amlodipine, and group 5 received the same doses of enalapril from week 10. Each drug protected from increasing blood pressure in 4 groups, and no significant difference was observed between the effects of amlodipine and enalapril. Proteinuria was reduced with both drugs. In histopathological evaluation, glomerulosclerosis was controlled only in group 2, and arterio/olosclerosis was significantly suppressed in all treated groups except group 5. From these results, both amlodipine and enalapril are renal protective in early stage of renal failure with hypertension. However, in advanced stage of renal failure, amlodipine is superior in its renal protective effect.
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PMID:Influence of the timing of initiating antihypertensive therapy in hypertensive rats with renal failure. 1093 42

The goals of antihypertensive therapy are to lower blood pressure and prevent end-organ damage without side effects, which affect quality of life. The antihypertensive drugs, regardless of class, all lower blood pressure, but they vary in their mechanisms of action, side-effect profiles, suitability for patients with other comorbid conditions, and ability to protect against the long-term sequelae of hypertension. The Sixth Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure (JNC-VI) recommends diuretics and beta-blockers as first-line therapy for uncomplicated hypertension, with diuretics also being strongly preferred for patients with isolated systolic hypertension or hypertension and heart failure and beta-blockers being strongly preferred for patients who have had a myocardial infarction (MI) and those with hypertension and angina, atrial tachycardia, or atrial fibrillation. Because angiotensin-converting enzyme (ACE) inhibitors have been shown to be cardioprotective and renoprotective in patients with diabetes or impaired left ventricular (LV) function, the JNC-VI recommends them as first-line therapy in patients with diabetes with proteinuria, heart failure, and MI complicated by LV dysfunction. It recommends calcium channel blockers for hypertensive patients with angina, long-acting dihydropyridines for those with isolated systolic hypertension, and the nondihydropyridines for those with atrial tachycardia or fibrillation, diabetes, and proteinuria. The angiotensin II receptor blockers (ARBs) share many of the organ-protective effects of ACE inhibitors when studied in animal models. They are effective in lowering blood pressure and have a very benign side-effect profile; however, these agents have not been available long enough to ascertain their efficacy in protecting against long-term complications.
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PMID:Clinical overview of antihypertensive classes--clinically relevant differences: myths or facts? Based on a presentation by Alan H. Gradman, MD. 1097 60

Cyclosporine (CsA) (45 mg/kg/day for 7 days) administration in female Wistar rats induced significant decrease in creatinine clearance (Ccr) and body weight loss (BWL). Urine volume (V) was not altered and proteinuria (PU) not provoked. These changes were associated with increased urinary endothelin 1 (ET-1) and thromboxane B(2)(TXB(2)) concentrations, and decreased urinary ratios of prostaglandin (6ketoPGF(1 alpha)and PGE(2)) to TXB(2)excretions. Nifedipine (NFD) (0.1 mg/kg/day for 7 days), a calcium channel blocker, administrated in addition to CsA, to another group of animals, significantly augmented Ccr and urine V but did not prevent BWL in comparison to CsA-only treated rats. The urinary ET-1 and TXB(2)concentrations displayed significant and non-significant decrease respectively, while the urinary excretion ratios of 6ketoPGF(1 alpha)/TXB(2)and PGE(2)/TXB(2)were significantly enhanced.These observations indicate that the partial protection of NFD in CsA-induced nephrotoxicity could be attributed to augmented urinary prostanoid ratios of renal vasodilators (6ketoPGF(1 alpha)and PGE(2)) to vasoconstrictor (TXB(2)) excretions, and also to reduced release of rather renal origin ET-1, the most potent mamalian vasoconstrictor peptide known to date. In a previous study, we found that NFD only slightly prevented structural renal damage, induced by CsA. So, the NFD protection refers only to functional toxicity and not to structural damage, mediated at least in part by the preservation of relatively high renal TXB(2)levels. However, other nephrotoxic factors and additional mechanisms could also be implicated in this CsA-induced syndrome.
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PMID:Effect of nifedipine in cyclosporine-induced nephrotoxicity in rats: roles of the thromboxane and endothelin systems. 1109 Feb 52

Hypertension plays a critical role in causing a high rate of cardiovascular events in patients with diabetes mellitus. Large trials show that lowering blood pressure in the patient with diabetes who has hypertension has profoundly favorable effects. This review discusses recent trials to answer the question of how low patients' blood pressure should go and which agents should be used to achieve this goal. The National Institutes of Health's guidelines, published in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, call for a blood pressure goal of <130/85 mmHg in patients with diabetes. Based on data from the recent trials, an even lower blood pressure of <130/80 mmHg in patients with diabetes and hypertension appears to be appropriate. Observational studies show that the lowest cardiovascular event rate is observed in patients with diabetes whose systolic blood pressure is <120 mmHg. Thus, goal blood pressure in patients with diabetes who have hypertension may need to be revised lower, to <120/80 mmHg. In patients with overt proteinuria of 1 g/d or more, mean arterial pressure of <92 mmHg is recommended. Available evidence justifies the use of angiotensin-converting enzyme (ACE) inhibitors as first-line agents and angiotensin receptor blockers in those patients who are intolerant to ACE inhibitors. Because the blood pressure goal is lower in patients with diabetes who are hypertensive, these patients require the use of multiple agents. Diuretics or long-acting calcium channel blockers are logical second choices because of their synergistic blood pressure reduction effect observed with ACE inhibitors. Alpha-blockers should be used with caution, however. In patients with renal disease, loop diuretics may be required to reduce sodium and volume overload and to improve blood pressure control.
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PMID:Treatment of hypertension in patients with diabetes: lessons from recent trials. 1117 14

In recent years in conjunction with medicamentous treatment of renoparenchymatous hypertension in particular two problems were discussed: target blood pressure values and renoprotective effects of antihypertensive drugs. Prospective studies revealed that a blood pressure reading of < 130/80 mm Hg significantly retards the progression of nephropathy whereby patients with proteinuria > 1 g/d benefit from even lower BP readings. In diabetic nephropathy the drugs of choice are inhibitors of angiotensin converting enzyme (ACEI), already in the incipient stage and also in normotensive patients. The importance of ACEI in the treatment of non-diabetic nephropathies was confirmed recently by controlled prospective studies AIPRI and REIN. A maximal renoprotective effect of ACEI probably calls for larger doses than those needed for normalization of BP. Long-term investigations of the renoprotective effect of antagonists of angiotensin AT1 receptors and comparative studies with ACEI resp. are not available. Dihydropyridine blockers of calcium channels with a short-term action (nifedipine) may have a negative influence on the progression of diabetic nephropathy, the effect of dihydropyridines of the second generation is tested in prospective studies. Non-dihydropyridine calcium channel blockers have a renoprotective action in diabetic nephropathy. In cca two thirds of the patients combined treatment with ACEI and diuretics or with calcium channel blockers is necessary. As to other antihypertensive drugs, vasodilatating beta-blockers and perspectively antagonists of endothelin receptors are useful.
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PMID:[Treatment of renal hypertension]. 1122 86

Fixed verapamil SR/trandolapril combinations 180/1 mg and 180/2 mg (Tarka, Knoll AG) have a significantly superior antihypertensive effect compared to equal dosages of either agent alone. Verapamil SR/trandolapril 180/2 mg combination produces the best dose-response ratio of different dose combinations of these two drugs. Combination therapy has the most pronounced effect on blunting the early morning rise in blood pressure. Thus, verapamil SR/trandolapril combination therapy may be an appropriate treatment option in patients with moderate essential hypertension, particularly in those who have a tendency toward the early morning rise in blood pressure. The adverse effect profile of the fixed combination of verapamil SR/trandolapril includes the typical side effects of its monocompounds. The fixed combination of verapamil SR/trandolapril is also effective and safe in the treatment of hypertension in the elderly. The fixed low-dose combination therapy with verapamil SR/trandolapril 180/2 mg is a suitable treatment option for patients with moderate essential hypertension and Type 2 diabetes mellitus, because it improves parameters of carbohydrate metabolism and uricaemia and does not alter the lipid profile. The insulin-sensitising effect of angiotensin converting enzyme (ACE) inhibitor monotherapy with its theoretical risk of hypoglycaemia is completely neutralised in the combination with verapamil SR. Comparative studies have shown that the low-dose combination of verapamil SR/trandolapril may be a suitable alternative to combinations containing a thiazide diuretic or a beta-blocking agent for the long-term management of hypertensive patients for whom combination therapy is indicated. The combination of an ACE inhibitor with a non-dihydropyridine calcium channel blocker reduces proteinuria to a greater extent than either agent alone. A combination of an ACE inhibitor and a calcium channel blocker may provide additional benefit in inducing the regression of left ventricular hypertrophy. Combination therapy leads to a significant increase in left ventricular ejection fraction, improvement of wall motion index and increases exercise duration time in patients with coronary heart disease and left heart failure. It also improves the ratio of exercise to rest rate-pressure product and decreases the number of angina attacks. These findings support the hypothesis that the combination of verapamil and trandolapril might be useful in patients with attenuated left ventricular function and angina pectoris. Thus, Tarka is an effective and well-tolerated antihypertensive agent with a good safety profile and positive metabolic effects.
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PMID:The fixed combination of verapamil SR/trandolapril. 1124 35

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