ramipril and Proteinuria

ESRD represents a major health problem. The number of patients who enter kidney replacement programs has increased at an average of 7% per year in the past 10 yr. A large number of experimental and clinical studies have demonstrated that chronic nephropathies share common pathogenic mechanisms that contribute to renal disease progression, even independent of the original cause. Clinical studies found a significant correlation between the extent of urinary protein excretion and the rate of GFR decline in both diabetic and nondiabetic chronic nephropathies. Randomized trials, in particular the Ramipril Efficacy In Nephropathy (REIN) study, also showed that treatments that reduce proteinuria (namely angiotensin-converting enzyme [ACE] inhibitors) are renoprotective and limit progression to ESRD. Meta-analyses of randomized clinical trials also evaluated the role of proteinuria and of ACE inhibition therapy in chronic renal disease progression. Their findings were consistent with those of the REIN study and confirmed in larger series of patients the predictive value of proteinuria and the renoprotective effect of proteinuria reduction by ACE inhibition therapy. Thus, the meta-analyses may confirm and extend previous findings generated by randomized clinical trials. Conceivably, well-designed studies in properly selected and carefully monitored patients who are at increased risk continue to be the best approach to test novel hypotheses. The meta-analyses, however, represent a valuable tool to evaluate the consistency and generalizability of trial results to larger cohorts of patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Diet, Protein-Restricted; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Kidney Function Tests; Male; Prognosis; Proteinuria; Ramipril; Risk Assessment; Severity of Illness Index; Treatment Outcome

Ramipril is an angiotensin-converting enzyme inhibitor that has been extensively studied in randomised, controlled clinical trials in patients with cardiovascular diseases. Therapy with ramipril in patients with various cardiovascular disorders has demonstrated significant and clinically important reductions in cardiovascular death, myocardial infarction, stroke, congestive heart failure, progressive renal impairment and onset of diabetes. Ramipril is usually dosed at 2.5-10 mg/day. Beneficial effects of ramipril are observed in the treatment of hypertension and congestive heart failure, prevention of cardiovascular events in high-risk patients, prevention of congestive heart failure, diabetes and other vascular events.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Cardiovascular Diseases; Carotid Arteries; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Proteinuria; Ramipril; Randomized Controlled Trials as Topic; Renal Insufficiency; Tissue Distribution

Angiotensin receptor blockers (ARBs) have gained widespread use in clinical medicine during the past decade. Several large, prospective and randomized multi-center trials have led us to reconsider the role of ARBs in the treatment of hypertension. Firstly, in view of the favorable safety and side effect profile of ARBs, we recommend their use in hypertensive subjects in whom ACE inhibitors are indicated but are unable to tolerate agents of this type due to intractable cough. Secondly, in light of the results of the RENAAL and IDNT studies, we consider ARBs as the drug of choice in diabetic subjects with hypertension and proteinuria (> 300 mg/L). Thirdly, we view ACE inhibitors and ARBs as equally adequate for the treatment of diabetic patients with hypertension and microalbuminuria and recommend the use of the maximal allowable doses of these drugs in such patients. Finally, older hypertensive individuals with left ventricular hypertrophy should receive either ACE inhibitors or ARBs, as these drug classes presently appear to provide better overall protection than beta blockers or calcium channel blockers in this particular subgroup of patients.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetic Angiopathies; Humans; Hypertension; Proteinuria; Ramipril; Receptor, Angiotensin, Type 1

Topics: Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Female; Humans; Hypertension; Kidney Failure, Chronic; Kidney Glomerulus; Male; Proteinuria; Ramipril; Remission Induction; Renal Replacement Therapy

Ramipril is a long-acting, lipophylic angiotensin converting enzyme inhibitor, its principle action is to inhibit the conversion of angiotensin I to the active angiotensin II. Ramipril is indicated in the treatment of hypertension, congestive cardiac failure (including that following acute myocardial infarction), nephropathy (with and without diabetes mellitus) and now, following the findings of the HOPE study, in the prevention of cardiovascular events (including myocardial infarction) in high risk individuals. This article concentrates on reviewing the evidence supporting ramipril's use in these indications.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Diabetes Mellitus; Heart Failure; Humans; Hypertension; Myocardial Infarction; Proteinuria; Ramipril

Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD.. Phase 2, randomized, controlled, open-label, crossover trial.. After stratification by serum phosphate level, ≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period.. The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness.. Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer.. Short treatment duration, lower pretreatment proteinuria than expected.. 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria.. Sanofi (Milan, Italy).. Registered at ClinicalTrials.gov with study number NCT01968759.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chelating Agents; Cross-Over Studies; Drug Monitoring; Drug Therapy, Combination; Female; Fibroblast Growth Factor-23; Glomerular Filtration Rate; Humans; Hyperphosphatemia; Irbesartan; Male; Middle Aged; Phosphates; Proteinuria; Ramipril; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sevelamer; Treatment Outcome

The aim of the study was to determine the impact of using the win ratio approach and investigate whether this approach alters the interpretations or conclusions of a randomized trial in kidney transplantation.. We present an application of the win ratio approach in a kidney transplant trial that assessed the clinical effectiveness of ramipril treatment vs. placebo. The primary composite outcome included the time to death, kidney transplant failure, or doubling of serum creatinine. We compare the win ratio to a conventional hazard ratio (HR) from the original trial. A win ratio with a lower 95% confidence limit greater than 1 indicates a positive treatment effect with statistical significance.. For the primary composite end point, ramipril treatment resulted in a win ratio of 1.21 (95% confidence interval [CI], 0.55-2.59) vs. a HR of 0.76 (95% CI, 0.38-1.51). With extended follow-up (mean 48 months), ramipril was associated with a win ratio of 1.02 (95% CI, 0.54-1.83) vs. a HR of 0.96 (95% CI, 0.55-1.65).. The win ratio approach produced results similar to the original time-to-event analysis. Using this approach would not alter the conclusion of the original trial and lessens concerns associated with composite components of unequal clinical importance.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Confidence Intervals; Creatinine; Drug Administration Schedule; Endpoint Determination; Humans; Kidney Failure, Chronic; Kidney Transplantation; Placebos; Postoperative Complications; Proportional Hazards Models; Proteinuria; Ramipril; Time Factors; Treatment Failure

Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of end-stage renal disease and death in non-transplant patients with proteinuria. We examined whether ramipril would have a similar beneficial effect on important clinical outcomes in kidney transplant recipients with proteinuria.. In this double-blind, placebo-controlled, randomised trial, conducted at 14 centres in Canada and New Zealand, we enrolled adult renal transplant recipients at least 3-months post-transplant with an estimated glomerular filtration rate (GFR) of 20 mL/min/1·73m(2) or greater and proteinuria 0·2 g per day or greater and randomly assigned them to receive either ramipril (5 mg orally twice daily) or placebo for up to 4 years. Patients completing the final 4-year study visit were invited to participate in a trial extension phase. Treatment was assigned by centrally generated randomisation with permuted variable blocks of 2 and 4, stratified by centre and estimated GFR (above or below 40 mL/min/1·73 m(2)). The primary outcome was a composite consisting of doubling of serum creatinine, end-stage renal disease, or death in the intention-to-treat population. The principal secondary outcome was the change in measured GFR. We ascertained whether any component of the primary outcome had occurred at each study visit (1 month and 6 months post-randomisation, then every 6 months thereafter). This trial is registered with ISRCTN, number 78129473.. Between Aug 23, 2006, and March 28, 2012, 213 patients were randomised. 109 were allocated to placebo and 104 were allocated to ramipril, of whom 109 patients in the placebo group and 103 patients in the ramipril group were analysed and the trial is now complete. The intention to treat population (placebo n=109, ramipril n=103) was used for the primary analysis and the trial extension phase analysis. The primary outcome occurred in 19 (17%) of 109 patients in the placebo group and 14 (14%) of 103 patients in the ramipril group (hazard ratio [HR] 0·76 [95% CI 0·38-1·51]; absolute risk difference -3·8% [95% CI -13·6 to 6·1]). With extended follow-up (mean 48 months), the primary outcome occurred in 27 patients (25%) in the placebo group and 25 (24%) patients in the ramipril group (HR 0·96 [95% CI 0·55-1·65]); absolute risk difference: -0·5% (95% CI -12·0 to 11·1). There was no significant difference in the rate of measured GFR decline between the two groups (mean difference per 6-month interval: -0·16 mL/min/1·73m(2) (SE 0·24); p=0·49). 14 (14%) of patients died in the ramipril group and 11 (10%) in the placebo group, but the difference between groups was not statistically significant (HR 1·45 [95% CI 0·66 to 3·21]). Adverse events were more common in the ramipril group (39 [38%]) than in the placebo group (24 [22%]; p=0·02).. Treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, end-stage renal disease, or death in kidney transplant recipients with proteinuria. These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population.. Canadian Institutes of Health Research.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Proteinuria; Ramipril; Risk Factors

This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of ramipril on urinary protein excretion in renal transplant patients treated with sirolimus following conversion from a calcineurin inhibitor. Patients received ramipril or placebo for up to 6 weeks before conversion and 52 weeks thereafter. Doses were increased if patients developed proteinuria (urinary protein/creatinine ratio ≥0.5); losartan was given as rescue therapy for persistent proteinuria. The primary end point was time to losartan initiation. Of 295 patients randomized, 264 met the criteria for sirolimus conversion (ramipril, 138; placebo, 126). At 52 weeks, the cumulative rate of losartan initiation was significantly lower with ramipril (6.2%) versus placebo (23.2%) (p < 0.001). No significant differences were observed between ramipril and placebo for change in glomerular filtration rate from baseline (p = 0.148) or in the number of patients with biopsy-confirmed acute rejection (13 vs. 5, respectively; p = 0.073). One patient in the placebo group died due to cerebrovascular accident. Treatment-emergent adverse events were consistent with the known safety profile of sirolimus and were not potentiated by ramipril co-administration. Ramipril was effective in reducing the incidence of proteinuria for up to 1 year following conversion to sirolimus in maintenance renal transplant patients.

Topics: Antihypertensive Agents; Calcineurin Inhibitors; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Prospective Studies; Proteinuria; Ramipril; Risk Factors; Sirolimus; Tacrolimus

Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition.. In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32).. Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage.. Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).

Topics: Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Endothelium, Vascular; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Follow-Up Studies; Humans; Ischemia; Kidney Failure, Chronic; Male; Middle Aged; Phosphates; Proteinuria; Ramipril; Regression Analysis; Retrospective Studies

The treatment of immunoglobulin A (IgA) nephropathy with normal renal function and minimal proteinuria is unknown.. We randomly assigned 60 patients with IgA nephropathy, proteinuria <0.5 g/day, normal blood pressure and renal function to ramipril 2.5 mg daily or no treatment. Patients were followed for 5 years for the development of hypertension, proteinuria, or impaired renal function.. The blood pressure of the treatment group was marginally lower than the control group throughout the study period. At 60 months, the event-free survival was marginally higher for the treatment group as compared with the control group (81.1% vs 70.5%, P=.27). The proteinuria-free survival was similar at 82.9% and 79.3% for the treatment and control groups, respectively (P=.6); hypertension-free survival was 86.4% and 79.3% (P=.2). After 60 months of follow-up, the estimated glomerular filtration rate (GFR) was 108.1±29.0 mL/min/1.73 m(2) for the treatment group and 105.7±17.7 mL/min/1.73 m(2) for the control group (P=.7), but the difference was not statistically significant. None of the patients developed impaired renal function. The rate of GFR decline was similar between the treatment and control groups (-0.39±2.57 vs -0.59±1.63 mL/min/1.73 m(2) per year, respectively, P=.7). In general, the study medication was well tolerated. Two patients needed to stop prematurely because of cough and dizziness.. For early IgA nephropathy patients with minimal proteinuria, normal blood pressure, and normal renal function, treatment with 2.5 mg/daily of ramipril for 5 years does not offer any benefit.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Hypertension; Male; Middle Aged; Proteinuria; Ramipril

Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.. The trial ran from 2001 to 2007. After a 3-week run-in period, 25,620 participants were randomly assigned to ramipril 10 mg a day (n = 8,576), telmisartan 80 mg a day (n = 8,542), or to a combination of both drugs (n = 8,502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.. 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n = 1,147 [13.4%]) and ramipril (1,150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1,233 [14.5%]; HR 1.09, 1.01-1.18, p = 0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%];HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24,1.01-1.51, p = 0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m² vs -4.12 [17.4], p < 0.0001) or combination therapy (-6.11 [17.9], p < 0.0001). The increase in urinary albumin excretion was less with telmisartan (p = 0.004) or with combination therapy (p=0.001) than with ramipril.. In people at high vascular risk, telmisartans effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Clinical Trials as Topic; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Middle Aged; Multicenter Studies as Topic; Proteinuria; Ramipril; Telmisartan

Obesity may increase the risk for progression of CKD, but the effect of established renoprotective treatments in overweight and obese patients with CKD is unknown. In this post hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, we evaluated whether being overweight or obese influences the incidence rate of renal events and affects the response to ramipril. Of the 337 trial participants with known body mass index (BMI), 105 (31.1%) were overweight and 49 (14.5%) were obese. Among placebo-treated patients, the incidence rate of ESRD was substantially higher in obese patients than overweight patients (24 versus 11 events/100 person-years) or than those with normal BMI (10 events/100 person-years); we observed a similar pattern for the combined endpoint of ESRD or doubling of serum creatinine. Ramipril reduced the rate of renal events in all BMI strata, but the effect was higher among the obese (incidence rate reduction of 86% for ESRD and 79% for the combined endpoint) than the overweight (incidence rate reduction of 45 and 48%, respectively) or those with normal BMI (incidence rate reduction of 42 and 45%, respectively). We confirmed this interaction between BMI and the efficacy of ramipril in analyses that adjusted for potential confounders, and we observed a similar effect modification for 24-hour protein excretion. In summary, obesity predicts a higher incidence of renal events, but treatment with ramipril can essentially abolish this risk excess. Furthermore, the reduction in risk conferred by ramipril is larger among obese than nonobese patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Body Mass Index; Chronic Disease; Comorbidity; Creatinine; Disease Progression; Female; Glomerular Filtration Rate; Humans; Incidence; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Overweight; Proteinuria; Ramipril; Treatment Outcome

Proteinuria is a common presentation of mesangioproliferative glomerulonephritis (MsPGN). No studies are available on the long-term effect of treatment by renin-angiotensin system (RAS) inhibitors on renal outcome in MsPGN patients. This study prospectively evaluates the effects of RAS inhibitors on renal outcome in patients with low risk MsPGN followed up for 10 years using historical patients with similar features at the time of presentation as untreated controls.. decrease of basal proteinuria>20% and loss>20% of basal glomerular filtrate rate (GFR) at the end of first year of observation. The patients were re-evaluated bimonthly during the first year and every 6 months thereafter.. Twenty-five patients fulfilled the selection criteria. After one year follow-up 19 patients reached the endpoint of proteinuria and no patient reached the endpoint of GFR. No significant change in blood pressure levels (BP) and GFR was registered, by contrast daily proteinuria decreased significantly (p<0.001), falling by 29% at sixth month and 47% at the end of the follow-up. The historical control group consisted of 15 untreated patients seen between 1987 and 1992. The two-way analysis of variance for repeated measures showed greater values of GFR (p<0.001) and lower levels of daily proteinuria (p<0.001) in treated patients as compared to untreated controls.. This 10-year follow-up study indicates that the early treatment with RAS inhibitors at low doses favourably influences the long-term renal outcome in proteinuric patients with MsPGN. Limitations were the small sample size and lack of randomization.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Disease Progression; Evidence-Based Medicine; Follow-Up Studies; Glomerular Filtration Rate; Glomerulonephritis, Membranoproliferative; Humans; Losartan; Prospective Studies; Proteinuria; Ramipril; Renin-Angiotensin System; Treatment Outcome; Young Adult

The renin-angiotensin system is involved in the progression of chronic renal disease of both diabetic and nondiabetic origin. The angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to reduce urinary protein excretion and attenuate the development of renal injury. This prospective, randomized, 12-month study assessed the effects of ramipril (N = 23) vs. valsartan (N = 22) vs. combination of ramipril and valsartan (N = 26) on proteinuria, renal function and metabolic profile in 71 patients with nondiabetic proteinuria with normal or slightly impaired renal function. Monotherapy with ramipril or valsartan and combination of these two drugs significantly reduced proteinuria, serum creatinine, cholesterol and triglycerides as well as systolic and diastolic arterial blood pressure. There was no significant difference among three study groups according to reduction of arterial blood pressure, serum cholesterol and triglycerides. At one year, a significant reduction in serum creatinine was recorded in all three study groups, whereas at 3 and 6 months a statistically significant reduction in serum creatinine was only observed in patients on combination therapy. In addition, at 3 months the reduction of proteinuria was significantly greater in patients on combination therapy than in those on either monotherapy. These results indicated the combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to be more efficacious than either monotherapy in reducing proteinuria and serum creatinine level in the first 3 (proteinuria and serum creatinine) or 6 (serum creatinine) months of treatment.

Topics: Adult; Aged; Angiotensin II Type 2 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Humans; Kidney; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Tetrazoles; Valine; Valsartan

The efficacy and safety of ACEI in adult patients with hypertension and proteinuria after renal transplantation is proven however data on the effectiveness of ACEI in transplanted children are rare. The aim of the present study was to investigate the effect of ramipril on proteinuria and BP in children after R-Tx. Twelve transplanted children (median age 15.3 yr, median time after R-Tx 4.5 yr) with proteinuria with or without hypertension were prospectively treated with ramipril for six months. Proteinuria was assessed as protein/creatinine ratio. Office BP was evaluated and hypertension defined as BP > or =95th centile. Graft function was assessed (Schwartz formula). The starting dose of ramipril was 1.5 mg/m(2)/24-h. Proteinuria declined in 92% of children from a median 39 to 22 mg/mmol creatinine (p < 0.01). The median decline of proteinuria was 9 mg/mmol creatinine, it reached 23% of the initial values. The prevalence of hypertension did not change significantly (50% initially vs. 33% after six months). Graft function and serum potassium level did not change significantly, two children developed mild hyperkalemia. Ramipril can reduce proteinuria in most transplanted children; its antiproteinuric effect is exhibited even without BP lowering effect.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Child; Humans; Hypertension; Kidney Transplantation; Prospective Studies; Proteinuria; Ramipril

Residual proteinuria is a strong modifiable risk factor for renal failure progression. We previously showed that the antiproteinuric effect of combined half doses of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) is increased by raising diuretic dosage. Methods. We tested whether uptitration of loop diuretics on top of combined half doses of ACEI and ARB would better decrease proteinuria than uptitration to combined full doses of ACEI and ARB in a randomized, crossover, three periods of 6-week controlled study. Eighteen patients with stable proteinuria over 1 g/day with combined ramipril at 5 mg/day and valsartan at 80 mg/day in addition to conventional antihypertensive treatments were randomized to receive combined ramipril at 5 mg/day and valsartan at 80 mg/day, or combined ramipril at 10 mg/day and valsartan at 160 mg/day, or combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage in random order. The primary end point was the mean urinary protein/creatinine ratio in two 24-hour urine collections at the end of the three treatment periods. Secondary end points included mean 24-hour proteinuria, home systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and estimated glomerular filtration rate (eGFR) levels.. The geometric mean urinary protein/creatinine ratio was lower with combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage compared to combined ramipril at 5 mg/day and valsartan at 80 mg/day, but also to combined ramipril at 10 mg/day and valsartan at 160 mg/day. These differences remained significant after adjustment for SBP, DBP or MAP and 24-hour natriuresis but not after adjustment on eGFR. Diuretic dosage uptitration did not increase the number of home systolic blood pressure measurements below 100 mmHg, but led to a statistically significant increase in the number of symptomatic hypotension episodes.. A cautious uptitration of loop diuretic dosage in addition to combined half doses of ACEI and ARB better decrease proteinuria in patients with CKD and high residual proteinuria than uptitration to full dose of combined ACEI and ARB. This antiproteinuric effect of diuretics was partly explained by an eGFR decrease, suggesting the contribution of haemodynamic modifications, whose safety on the long term still need to be addressed.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria; Ramipril; Tetrazoles; Treatment Outcome; Valine; Valsartan

Plasma visfatin levels are elevated in diabetic nephropathy in parallel to the severity of proteinuria and glomerular filtration rate. The aim of this study was to find out whether the renin-angiotensin-aldosterone system (RAAS) blockage has any effect on the plasma visfatin levels.. Thirty-two patients with diabetic proteinuria (>500 mg/day) with a normal glomerular filtration rate (GFR) and 33 healthy subjects were enrolled. Patients were treated with ramipril 5 mg daily for 2 months. Proteinuria, GFR, high-sensitivity C-reactive protein (hsCRP), visfatin, flow-mediated dilatation (FMD) and homeostasis model assessment of insulin resistance (HOMA-IR) index measurements were performed both before and after the treatment.. The plasma visfatin, and hsCRP levels of the patients were significantly higher and the FMD was significantly lower (P < 0.001 for all). The visfatin levels were significantly correlated to FMD, systolic and diastolic blood pressures, proteinuria, eGFR, HOMA-IR and hsCRP. Ramipril treatment resulted in a significant decrease in plasma visfatin, proteinuria, hsCRP, HOMA-IR and increase in FMD (P < 0.001) in patients (P < 0.001 for all).. The present study suggests that plasma visfatin levels are related to the endothelial functions, inflammation and the severity of proteinuria in diabetic nephropathy. Treatment with ramipril causes a significant decrease in visfatin levels along with the improvement of proteinuria, endothelial dysfunction and inflammatory state in diabetic nephropathy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Pressure; C-Reactive Protein; Cytokines; Diabetic Nephropathies; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Proteinuria; Ramipril; Renin-Angiotensin System; Time Factors; Treatment Outcome; Vasodilation

Currently, several therapeutic protocols exist for IgA nephropathy (IgAN); results in slowing the progression to end-stage renal disease (ESRD) are variable, but approximately 30-40% of patients require replacement therapy (dialysis or renal transplantation) by 20 years from the onset. The adverse effects brought by the chronic assumption of drugs can be a potential limit. Actually, the most used therapies for IgAN are renin-angiotensin system blockers (RASB), glucocorticoids and immunosuppressive agents. Trials with polyunsaturated fatty acids (PUFA) in IgAN have been done since the first successful attempt by Hamazaki in 1984, resulting in alternate answers, but no trials have ever been done testing the efficacy of combined therapy with RASB and PUFA.. We tested the effect of a 6-month course of PUFA (3 grams/day) in a group of 30 patients with biopsy-proven IgAN and proteinuria already treated with RASB randomized to receive PUFA supplementation or to continue their standard therapy. The primary end-point was the percent reduction of proteinuria from the baseline. Secondary end-points were modifications in glomerular filtration rate (GFR), blood pressure, serum triglycerides and erythrocyturia.. At the end of the 6-month trial, the percent reduction of proteinuria was 72.9% in the PUFA group and 11.3% in the RASB group (P < 0.001). A reduction of >or=50% of baseline proteinuria was achieved in 80.0% of PUFA patients and 20.0% of RASB patients (P = 0.002). Erythrocyturia was significantly lower in the PUFA group (P = 0.031). No significant changes in renal function, blood pressure and triglycerides were observed.. PUFA associated with RASB reduced proteinuria in patients with IgAN more than RASB alone.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Pressure; Docosahexaenoic Acids; Drug Synergism; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Hematuria; Humans; Irbesartan; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Ramipril; Renin-Angiotensin System; Tetrazoles; Triglycerides; Young Adult

Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD).. We analyzed data of 49 persons with stage 1 diabetic CKD and 32 healthy subjects in a prospective controlled trial. Endothelial dysfunction was determined by flow-mediated dilation (FMD). Serum PTX3, high-sensitivity C-reactive protein (hs-CRP) levels, and FMD were studied in baseline and after 12 wk of ramipril therapy. Stepwise multivariate regression analysis evaluated the association of FMD with clinical and serologic parameters.. Serum PTX3, hsCRP, and albumin levels and proteinuria were significantly decreased, and FMD levels were significantly increased, after ramipril treatment. FMD was negatively correlated with serum PTX3, 24-h proteinuria, and hsCRP levels and positively correlated to serum albumin both at baseline and after the 12-wk treatment period. Multivariate regression analysis revealed that PTX3 levels were independently related to FMD both before and after ramipril treatment.. Our study shows that serum PTX3 levels are associated with endothelial dysfunction in patients with stage 1 diabetic CKD, independent of CRP. In addition, short-term ACE-inhibitor treatment significantly improves FMD and normalizes PTX3, hsCRP, and urinary protein excretion. (NCT: The study was registered in clinicaltrials.gov as NCT00674596.).

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Proteinuria; Ramipril; Renin-Angiotensin System; Serum Amyloid P-Component; Severity of Illness Index; Time Factors; Treatment Outcome; Vasodilation

Immunoglobulin A nephropathy (IgAN) is the most common cause of chronic renal failure among primary glomerulonephritis patients. The best treatment for IgAN remains poorly defined. We planned a long-term, prospective, open-label, multicentre, centrally randomized controlled trial to assess whether the combination of prednisone and ramipril was more effective than ramipril alone in patients with proteinuric IgAN.. Ninety-seven biopsy-proven IgAN patients with moderate histologic lesions, 24-h proteinuria > or =1.0 g and estimated glomerular filtration rate (eGFR) > or = 50 ml/min/ 1.73 m(2) were randomly allocated to receive a 6-month course of oral prednisone plus ramipril (combination therapy group) or ramipril alone (monotherapy group) for the total duration of follow-up. The primary outcome was the progression of renal disease defined as the combination of doubling of baseline serum creatinine or end-stage kidney disease (ESKD). The secondary outcomes were the rate of renal function decline defined as the eGFR slope over time, and the reduction of 24-h proteinuria.. After a follow-up of up to 96 months, 13/49 (26.5%) patients in the monotherapy group reached the primary outcome compared with 2/48 (4.2%) in the combination therapy group. The Kaplan-Meier analysis showed a significantly higher probability of not reaching the combined outcome in the combination therapy group than in the monotherapy group (85.2% versus 52.1%; log-rank test P = 0.003). In the multivariate analysis, baseline serum creatinine and 24-h proteinuria were independent predictors of the risk of primary outcome; treatment with prednisone plus ramipril significantly reduced the risk of renal disease progression (hazard ratio 0.13; 95% confidence interval 0.03-0.61; P = 0.01). The mean rate of eGFR decline was higher in the monotherapy group than in the combination therapy group (-6.17 +/- 13.3 versus -0.56 +/- 7.62 ml/min/ 1.73 m(2)/year; P = 0.013). Moreover, the combined treatment reduced 24-h proteinuria more than ramipril alone during the first 2 years.. Our results suggest that the combination of corticosteroids and ramipril may provide additional benefits compared with ramipril alone in preventing the progression of renal disease in proteinuric IgAN patients in the long-term follow-up.

Topics: Adrenal Cortex Hormones; Adult; Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerulonephritis, IGA; Humans; Male; Prednisone; Prospective Studies; Proteinuria; Ramipril; Survival Rate; Time Factors; Treatment Outcome

Although inhibition of the renin-angiotensin system delays the progression of renal failure in adults with chronic kidney disease, the blood-pressure target for optimal renal protection is controversial. We assessed the long-term renoprotective effect of intensified blood-pressure control among children who were receiving a fixed high dose of an angiotensin-converting-enzyme (ACE) inhibitor.. After a 6-month run-in period, 385 children, 3 to 18 years of age, with chronic kidney disease (glomerular filtration rate of 15 to 80 ml per minute per 1.73 m(2) of body-surface area) received ramipril at a dose of 6 mg per square meter of body-surface area per day. Patients were randomly assigned to intensified blood-pressure control (with a target 24-hour mean arterial pressure below the 50th percentile) or conventional blood-pressure control (mean arterial pressure in the 50th to 95th percentile), achieved by the addition of antihypertensive therapy that does not target the renin-angiotensin system; patients were followed for 5 years. The primary end point was the time to a decline of 50% in the glomerular filtration rate or progression to end-stage renal disease. Secondary end points included changes in blood pressure, glomerular filtration rate, and urinary protein excretion.. A total of 29.9% of the patients in the group that received intensified blood-pressure control reached the primary end point, as assessed by means of a Kaplan-Meier analysis, as compared with 41.7% in the group that received conventional blood-pressure control (hazard ratio, 0.65; confidence interval, 0.44 to 0.94; P=0.02). The two groups did not differ significantly with respect to the type or incidence of adverse events or the cumulative rates of withdrawal from the study (28.0% vs. 26.5%). Proteinuria gradually rebounded during ongoing ACE inhibition after an initial 50% decrease, despite persistently good blood-pressure control. Achievement of blood-pressure targets and a decrease in proteinuria were significant independent predictors of delayed progression of renal disease.. Intensified blood-pressure control, with target 24-hour blood-pressure levels in the low range of normal, confers a substantial benefit with respect to renal function among children with chronic kidney disease. Reappearance of proteinuria after initial successful pharmacologic blood-pressure control is common among children who are receiving long-term ACE inhibition. (ClinicalTrials.gov number, NCT00221845.)

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Child; Child, Preschool; Creatinine; Disease Progression; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hypertension; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Proteinuria; Ramipril; Renal Insufficiency, Chronic

Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.. The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.. 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril.. In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney; Middle Aged; Proteinuria; Ramipril; Telmisartan

Proteinuria may cause a worsening of accompanying renal disease or even lead to glomerulosclerosis. There is no data about the effect of carvedilol on patients with proteinuric (>0.5 g/day) glomerulonephritis. This study aimed to compare the effects of carvedilol with ramipril and losartan in patients with proteinuric glomerulonephritis.. Twenty-one glomerulonephritis patients were followed for 12 months. Patients were divided into three groups. All patients were treated with losartan 50 mg once daily for two weeks. After two weeks (baseline), patients were given additional medications: 50 mg losartan, 5 mg ramipril, and 25 mg carvedilol were given additionally to the patients in groups 1, 2, and 3 respectively.. Baseline mean proteinuria values of patients in groups 1, 2 and 3 were 1.6 +/- 1.1 g/day, 2.1 +/- 1.3 g/day, and 1.4 +/- 1.2 g/day, respectively. These values decreased to 0.5 +/- 0.7 g/day, 0.6 +/- 0.7 g/day, and 0.9 +/- 0.9 g/day, respectively, at the end of the 12th month. These results were statistically significant only in group 1 (p = 0.04). The rational variation of proteinuria between the first and 12th month of losartan, ramipril, and carvedilol were -61%, -62%, and -27%, respectively. The decreases in blood pressures between baseline and the first, sixth, and twelfth-month measurements were significant in all groups.. Thee results showed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (AT1ras) provide marked decreases in proteinuria, making their use indisputable in patients with glomerulonephritis. Carvedilol was not found to be as effective as ACEIs and AT1ras in decreasing proteinuria and preserving renal function.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Carbazoles; Carvedilol; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Glomerulonephritis; Humans; Losartan; Propanolamines; Proteinuria; Ramipril; Treatment Outcome; Vasodilator Agents

The aim of this study was to find out whether the beneficial effects of the renin-angiotensin-aldosterone system (RAS) blockage in chronic kidney disease (CKD) has any relation with the alteration of asymmetric dimethylarginine (ADMA) levels.. Sixty-six nondiabetic patients with CKD and proteinuria and 36 healthy subjects were enrolled. Patients were treated with either ramipril 5 mg daily or valsartan 160 mg daily for 3 months. Proteinuria, ADMA, symmetric dimethyl arginine (SDMA), flow-mediated dilatation (FMD) and HOMA index measurements were performed both before and after the treatment.. ADMA, SDMA, hsCRP levels, HOMA index and proteinuria of patients were significantly higher (p < 0.001 for all) and FMD, L-arginine and L-arginine/ADMA ratio in CKD were significantly lower than controls. According to the multiple regression analysis, proteinuria levels were independently related to ADMA and SDMA levels.. Both drugs were equally effective in reducing elevated ADMA levels and improving endothelial dysfunction in CKD patients.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Arginine; Biomarkers; Blood Glucose; C-Reactive Protein; Female; Glomerular Filtration Rate; Hemorheology; Humans; Insulin Resistance; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Proteinuria; Ramipril; Renin-Angiotensin System; Tetrazoles; Valine; Valsartan; Vasodilation

To evaluate the impact of microalbuminuria (MAU) or tubular proteinuria (TPU) on cardiovascular and cerebrovascular events and all-cause mortality, and to assess whether a normalization of MAU and/or TPU induced by angiotensin-converting enzyme-inhibitor-based antihypertensive treatment with ramipril improves cerebrovascular prognosis in essential hypertensive patients without diabetes mellitus.. A prospective, controlled, multicenter study was performed involving 3529 hypertensive participants (average follow-up 42.5 months). Ramipril was the basic antihypertensive medication. Proteinuria analysis (albumin, alpha 1-microglobulin, SDS electrophoresis) was performed by quantitative measurement every year. Ambulatory blood pressure monitoring was performed once yearly. The main outcome determined was cardiovascular and cerebrovascular events and all-cause mortality.. In patients with TPU and/or MAU, the risk for endpoints increased significantly compared with normal (TPU, 30.0%; MAU, 54.7%; MAU + TPU, 64.0%; macroproteinuria, 74.4%). A change of protein excretion either from pathologic to normal or from normal to pathologic showed a clear trend to correlate with cerebrovascular endpoints (P = 0.056 and P = 0.055). Normal protein excretion at baseline and during follow-up indicated a significantly better prognosis than pathologic proteinuria at baseline and during follow-up. (P < 0.0001). TPU normalized in 31.9%, MAU in 30.6%, MAU + TPU in 29.3%, and macroproteinuria in 10.2% of patients. A total of 445 (25.4%) patients with normal protein excretion developed pathologic proteinuria during follow-up.. In non-diabetic hypertensive patients, MAU as well as TPU increases the incidence of cardiovascular events. Normalization of MAU, TPU or macroproteinuria during angiotensin-converting enzyme-inhibitor-based treatment correlates with a reduction of cardiovascular events. Beyond blood pressure control, normalization of MAU and TPU should be considered as a further therapeutic goal. There is a need for further studies to optimize treatment if proteinuria is unresponsive to angiotensin-converting enzyme inhibitors.

Topics: Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Stroke

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics may exert synergistic antiproteinuric effects. Eighteen patients with a proteinuria >1 g/24 h after 6 mo of treatment with ramipril at 5 mg/d were assigned to receive in random order ramipril at 10 mg/d, valsartan at 160 mg/d, or combined ramipril at 5 mg/d and valsartan at 80 mg/d in addition to their antihypertensive treatment. The treatment periods lasted 4 wk and were separated by a 4-wk washout with ramipril at 5 mg/d. At the end of this crossover sequence, patients received combined ramipril at 5 mg/d, valsartan at 80 mg/d, and an increased furosemide dosage for an additional 4-wk period. The primary end point was the urinary protein/creatinine ratio for two 24-h urine collections at the end of each treatment period. No significant differences were noted between the study end points of the ramipril 10, valsartan 160, and combined ramipril 5 and valsartan 80 treatment groups. However, the urinary protein/creatinine ratio was lower with combined ramipril 5 and valsartan 80-increased furosemide dosage than with valsartan 160 and combined ramipril 5 and valsartan 80, with a similar tendency compared with ramipril 10. Combined ramipril 5 and valsartan 80-increased furosemide dosage decreased systolic home BP and increased serum creatinine but did not significantly increase the number of symptomatic hypotension cases compared with the other three treatments. Thus, in patients with severe proteinuria and hypertension, a cautious increase in diuretic dosage in addition to combined angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decreases proteinuria and BP but may expose the patient to prerenal failure.

Topics: Adult; Aged; Antihypertensive Agents; Cross-Over Studies; Diet, Sodium-Restricted; Diuretics; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Reference Values; Risk Assessment; Severity of Illness Index; Tetrazoles; Treatment Outcome; Valine; Valsartan

The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Creatinine; Enalapril; Follow-Up Studies; Humans; Hypertension; Kidney Function Tests; Kidney Transplantation; Losartan; Proteinuria; Ramipril; Renal Artery; Renin-Angiotensin System; Tetrazoles; Time Factors; Valine; Valsartan

The magnitude of proteinuria is associated with a graded increase in the risk of progression to end-stage renal disease and cardiovascular events. The objective of this study was to relate baseline and early changes in proteinuria and glomerular filtration rate (GFR) to long-term progression of hypertensive nondiabetic kidney disease.. Post hoc analysis of a randomized 3 x 2 factorial trial. A total of 1094 African Americans with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were followed up for a median of 3.8 years. Participants were randomized to a mean arterial pressure goal of 102 to 107 mm Hg (usual) or 92 mm Hg or less (lower) and to initial treatment with a beta-blocker (metoprolol), an angiotensin-converting enzyme inhibitor (ramipril), or a dihydropyridine calcium channel blocker (amlodipine). Baseline proteinuria and GFR predicted the rgate of GFR decline. For each 10-mL/min per 1.73 m(2) lower baseline GFR, an associated mean +/- SE 0.38 +/- 0.08-mL/min per 1.73 m(2) per year greater mean GFR decline occurred, and for each 2-fold higher proteinuria level, a mean +/- SE 0.54 +/- 0.05-mL/min per 1.73 m(2) per year faster GFR decline was observed (P < .001 for both). In multivariate analysis, the effect of baseline proteinuria GFR decline persisted. Initial change in proteinuria from baseline to 6 months predicted subsequent progression, with this relationship extending to participants with baseline urinary protein levels less than 300 mg/d.. The change in the level of proteinuria is a predictor of subsequent progression of hypertensive kidney disease at a given GFR. A prospective trial is needed to confirm this observation.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Black or African American; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Male; Metoprolol; Middle Aged; Prognosis; Proteinuria; Ramipril; Risk Factors; Treatment Outcome; United States

The African American Study of Kidney Disease and Hypertension examined the effect on renal function decline of 2 blood pressure (BP) goals (low mean arterial pressure [MAP] < or =92 versus usual MAP 102 to 107 mm Hg) and 3 antihypertensives (ramipril versus amlodipine versus metoprolol). We previously reported that in all drug groups combined the BP intervention had similar effects on the primary outcome of glomerular filtration rate (GFR) slope or the main secondary clinical composite outcome of end-stage renal disease (ESRD), death, or GFR decline by 50% or 25 mL/min per 1.73 m2. This report examines the effect of the BP intervention separately in the 3 drug groups. The BP effect was similar among the drug groups for either GFR slope or the main clinical composite. However, the BP effect differed significantly among the drug groups for the composite of ESRD or death (P=0.035) and ESRD alone (P=0.021). Higher event rates for amlodipine patients assigned to the usual BP goal (0.087 per patient-year for ESRD or death and 0.064 per patient-year for ESRD) were seen compared with the remaining groups of the factorial design (range, 0.041 to 0.050 for ESRD or death; and range, 0.027 to 0.036 for ESRD). The low BP goal was associated with reduced risk of ESRD or death (risk reduction 51%; 95% confidence interval, 13% to 73%) and ESRD (54%; 8% to 77%) for amlodipine patients, but not for patients assigned to the other drug groups. These secondary analyses suggest a benefit of the low BP goal among patients assigned to amlodipine, but they must be interpreted cautiously.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black or African American; Blood Pressure; Calcium Channel Blockers; Double-Blind Method; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Failure, Chronic; Metoprolol; Middle Aged; Proteinuria; Ramipril; Treatment Outcome

While the antihypertensive and renoprotective potency of angiotensin-converting enzyme (ACE) inhibitors is well-established in adults with hypertension and/or chronic renal failure, little experience exists in pediatric chronic kidney disease.. As part of a prospective assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure (BP) control, 397 children (ages 3 to 18 years) with chronic renal failure [CRF; glomerular filtration rate (GFR) 11 to 80 mL/min/1.73 m2] and elevated or high-normal BP received ramipril (6 mg/m2) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors. Drug efficacy was assessed by two monthly office BP and proteinuria assessments, and by ambulatory BP monitoring at start and after 6 months of treatment.. In the 352 patients completing six months of treatment, 24-hour mean arterial pressure (MAP) had decreased by a mean of 11.5 mm Hg (-2.2 SDS) in initially hypertensive subjects, but only by 4.4 mm Hg (-0.8 SDS) in patients with initially normal BP. A linear correlation was found between MAP at baseline and the change of MAP during treatment (r= 0.51; P < 0.0001). The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease. BP was reduced with equal efficacy during day- and nighttime. Urinary protein excretion was reduced by 50% on average, with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies. The magnitude of proteinuria reduction depended on baseline proteinuria (r= 0.32, P < 0.0001), and was correlated with the antihypertensive efficacy of the drug (r= 0.22, P < 0.001). The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period. Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia. Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter.. Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension. The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children.

Topics: Adolescent; Antihypertensive Agents; Blood Pressure; Child; Child, Preschool; Humans; Hypertension, Renal; Kidney Failure, Chronic; Prospective Studies; Proteinuria; Ramipril; Treatment Outcome

The objective of our study was to evaluate the changes of blood pressure (BP), urinary protein excretion (PRT/Cr) and renal function (GFR) after long-term administration of ACE inhibitor, ramipril. This prospective trial, a part of the European Multicentric Escape Study, included 14 patients (5 girls and 9 boys), mean-age 11 years, with congenital renal malformations. The basic inclusion criteria were stable chronic renal failure (CRF) and mean arterial pressure (MAP) above 50 percentile defined by 24-hour ABPM or earlier antihypertensive medication. The patients were studied 6 months before and up to 36 months after the introduction of ramipril therapy. The dosage of ramipril ranged from 4.7 to 7.7 mg/ m2 SBA, mean 37.8 (+/- 4.03) mg/m2 SBA. The patients were controlled every two months for BP, proteinuria and GFR, while 24-hour ABPM was performed in 6 months. The significant decrease of regular and 24-hour ambulatory blood pressure (ABP), systolic, diastolic and MAP, was found within the first months of treatment, while ramipril-induced reduction of proteinuria and slowing down of GFR were delayed. BP did not differ significantly among patients, but antiproteinuric effect and influence on GFR showed large individual variations. Antiproteinuric and antihypertensive effects of ramipril correlated with underlying proteinuria, GFR and blood pressure. However, there was no constant relationship between changes of proteinuria and BP. Ramipril has been shown to: lower BP significantly, decrease proteinuria slowly, and significantly decelerate GFR after 18 months of treatment. Considering favorable preliminary results of lower BP, decrease of proteinuria and decelerated GFR, an optimal renal protection by long-term therapy with ACE inhibitors may be expected in children with CRF caused by congenital renal malformations.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Child; Child, Preschool; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Male; Proteinuria; Ramipril

Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined.. We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone.. Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).. In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biphenyl Compounds; Creatinine; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Irbesartan; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Renin-Angiotensin System; Tetrazoles; Treatment Outcome

Findings that early changes in proteinuria independently predict long-term glomular filtration rate (GFR) decline (Delta GFR) would highlight proteinuria as a major determinant of progression in chronic renal disease.. We investigated whether percent changes (3 months vs. baseline) in proteinuria (adjusted for concomitant changes in GFR) and residual proteinuria at 3 months, predicted Delta GFR [over a median (IQ range) follow up of 31.3 (24.5 to 50.3) months] in 273 patients with proteinuric chronic nephropathies enrolled in the Ramipril Efficacy In Nephropathy (REIN) study.. Short-term changes and residual proteinuria (r = -0.23, P = 0.0001 for both) significantly correlated with Delta GFR and, at multivariate analyses, independently predicted Delta GFR (beta = -0.23, P = 0.0002; beta = -0.21, P = 0.0004, respectively). For comparable levels of residual proteinuria, patients with greater short-term reduction had slower Delta GFR (-0.28 +/- 0.04 mL/min/1.73 m2/ vs. -0.53 +/- 0.07 mL/min/1.73 m2/month, P = 0.04). On ramipril and conventional treatment, specular short-term changes in proteinuria (-18.2 +/- 3.5% vs. 24.2 +/- 6.7%, P < 0.0001, respectively) were associated with significantly different Delta GFRs. However, similar changes in proteinuria resulted in a difference in Delta GFR (ramipril, 0.39 +/- 0.07 mL/min/1.73 m2/month; conventional therapy, 0.74 +/- 0.11 mL/min/1.73 m2/month; P < 0.01) that was sevenfold higher (0.35 vs. 0.05 mL/min/1.73 m2/month) in patients with basal proteinuria > or =3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours (ramipril, 0.25 +/- 0.06 mL/min/1.73 m2/month; conventional therapy, 0.30 +/- 0.07 mL/min/1.73 m2/month; P = NS).. Regardless of blood pressure control and treatment randomization, short-term changes in proteinuria and residual proteinuria reliably predict long-term disease progression. Reducing proteinuria is renoprotective, particularly in nephrotic patients. As for arterial hypertension, proteinuria should be a specific target for renoprotective treatment.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Proteinuria; Ramipril; Sensitivity and Specificity

The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury.. We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks.. All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period.. Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Cross-Over Studies; Diabetic Nephropathies; Female; Glomerulonephritis, IGA; Humans; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Renin-Angiotensin System; Tetrazoles; Transforming Growth Factor beta

Despite the accumulating evidence of their efficacy, angiotensin-converting enzyme inhibitors (ACEi) still provide imperfect renoprotection. Up-titration above conventional doses and combined therapy with other antiproteinuric agents may serve to achieve renoprotection in patients at risk of rapid disease progression.. The effect of maximum tolerated ACEi doses (ramipril 15 mg/day, range 5 to 20) alone or combined with indomethacin (75 mg x 2/day) on urinary protein excretion (UPE) and glomerular barrier size-selective function was evaluated in 19 patients with chronic non-diabetic nephropathies and persistent proteinuria.. Maximum ramipril doses decreased UPE more effectively than non-ACEi therapy. Proteinuria reduction was associated with significant reduction (>50%) of the non-selective glomerular membrane shunt, but did not correlate with concomitant changes in arterial pressure and renal hemodynamics, nor was it influenced by treatment duration. The reduction in UPE and sieving coefficient of the largest neutral dextrans exceeded by twofold the reduction achieved by conventional ACEi doses in historical controls with similar renal dysfunction and proteinuria, previously studied under identical experimental conditions. Indomethacin did not influence renal effects of maximum ramipril doses and was prematurely withdrawn in six patients because of reversible side effects. Serum potassium significantly increased only in combination with indomethacin and never required treatment withdrawal.. Up-titration to maximally tolerated doses safely increases ACEi antiproteinuric effect and may serve to achieve maximum renoprotection in the long-term. Combination with indomethacin is poorly tolerated and ineffective. Innovative approaches are needed to use ACEi more effectively.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Dextrans; Drug Therapy, Combination; Female; Humans; Indomethacin; Kidney Failure, Chronic; Kidney Glomerulus; Male; Middle Aged; Proteinuria; Ramipril

Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.. To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.. Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.. A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.. Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.. Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.. Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.. No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black or African American; Blood Pressure; Calcium Channel Blockers; Disease Progression; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Male; Metoprolol; Middle Aged; Proportional Hazards Models; Proteinuria; Ramipril

Albuminuria has been shown to identify patients with an increased cardiovascular risk, and in clinical studies ACE inhibitors reduce the urinary protein excretion. It was the primary aim of this intensified monitoring project to determine whether these results can be reproduced in a clinical practice setting. Micro- (2.7-22.6 mg albumin/mmol creatinine) or macroalbuminuria (>22.6 mg/mmol) was confirmed by a central laboratory in 598 out of 773 patients with hypertension who had albuminuria >50 mg/l on a Micral Test II performed by 147 general practitioners. Coronary heart disease (prevalence rates 15% in patients with normalbuminuria, 33% in patients with microalbuminuria, and 40% in patients with macroalbuminuria), heart failure (prevalence rates 19, 29, and 32%, respectively), left ventricular hypertrophy (prevalence rates 30, 42, and 38%, respectively), and peripheral vascular disease (prevalence rates 7, 15, and 20%, respectively) were significantly more common in patients with elevated urinary albumin excretion. 230 patients with microalbuminuria and 202 subjects with macroalbuminuria were treated with the angiotensin-converting enzyme inhibitor ramipril for 6 months. The treatment significantly lowered mean arterial blood pressure (from a median value of 120 mm Hg, quartiles 113-125 mm Hg, to 103 mm Hg, quartiles 100-109 mm Hg) as well as urinary albumin excretion (from a median value of 18 mg/mmol creatinine, quartiles 7.2-54.6 mg/mmol creatinine, to 6.5 mg/mmol creatinine, quartiles 1.6-23.1 mg/mmol creatinine). The treatment efficacy was unaffected by age, body mass index, and smoking status. Patients with diabetes mellitus type II and heart failure also had a significant, although less pronounced reduction of albuminuria. In summary, we conclude that ramipril is able to reduce the urinary albumin excretion in a clinical practice setting, as has been shown in clinical studies. However, the treatment response is not completely uniform, as special patient populations seem to be more resistant to therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Austria; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Creatinine; Female; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Monitoring, Physiologic; Proteinuria; Ramipril; Risk Factors

Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans.. To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression.. Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000.. Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals.. The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death.. Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001).. Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black or African American; Calcium Channel Blockers; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Male; Metoprolol; Middle Aged; Nephrosclerosis; Proportional Hazards Models; Proteinuria; Ramipril

In the Ramipril Efficacy in Nephropathy study, ramipril decreased the rate of GFR decline (deltaGFR) and progression to end-stage renal disease (ESRD) in 352 patients with proteinuric chronic nephropathies. This study investigated whether in these patients disease outcome and response to treatment were affected by gender or insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. deltaGFR (0.43 +/- 0.05 versus 0.48 +/- 0.08 ml/min per 1.73 m2) and incidence of ESRD (23 and 22%, respectively) were comparable in male and female patients. However, compared to conventional treatment, ramipril decreased deltaGFR (-52% versus -19%) and progression to ESRD (-74% versus -40%) more effectively in women than in men. Thus, the relative risk (95% confidence interval [CI]) of events (ESRD) between conventional and ramipril treatment was 5.52 (1.59 to 19.17, P = 0.003) in women, but only 1.80 (1.08 to 2.97, P = 0.02) in men. This gender-related effect of ramipril was associated with more reduction in proteinuria (-7.8 +/- 4.2% versus -21.9 +/- 5.7%, P = 0.05) and was still evident even after correction for potentially confounding factors such as baseline GFR, daily sodium intake, ramipril dose, BP control, and concomitant treatment with diuretics or dihydropyridinic calcium channel blockers (adjusted RR [95% CI]: women, 5.07 [1.26 to 20.38], P = 0.02; men, 1.44 [0.85 to 2.44], P = 0.17). Ramipril uniformly decreased deltaGFR and incidence of ESRD in women with either DD (-39% and - 100%) or II + ID (-71% and -82%) genotype, and in men (-25% and -50%) with the DD genotype, but had no beneficial effect in men with the II + ID genotype (+18% and +34%). Thus, the relative risk of events (ESRD) between conventional and ramipril-treated men was higher in subjects with the DD genotype (1.85; 0.69 to 4.94) and lower in those with the II +/- ID genotype (0.71; 0.28 to 1.80). Again, in parallel with deltaGFR and events, proteinuria decreased in women with DD (-23.3 +/-8.0%) or II + ID (-16.0 +/- 9.5%) genotype and in men with the DD genotype (-14.8 +/- 7.0%), but did not change in men with II + ID genotype (+ 1.0 +/- 7.8%). Of note, the ACE genotype-related effect of ramipril was still evident even after correction for the above potentially confounding factors (adjusted RR [95% CI]: DD, 2.52 [0.83 to 7.63], P = 0.10; II + ID, 0.35 [0.12 to 1.01], P = 0.05). Thus, among patients with chronic proteinuric nephropathies, men are at increased risk of pro

Topics: Adolescent; Adult; Age Distribution; Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Base Sequence; Chronic Disease; Cohort Studies; Comorbidity; Confidence Intervals; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Kidney Failure, Chronic; Male; Mice; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Predictive Value of Tests; Prospective Studies; Proteinuria; Ramipril; Risk Factors; Sex Distribution; Sex Factors

The Ramipril Efficacy in Nephropathy (REIN) study found that angiotensin-converting enzyme (ACE) inhibitors effectively decreased proteinuria, glomerular filtration rate (GFR) decline (DeltaGFR), and incidence of end-stage renal disease (ESRD) in patients with proteinuric chronic nephropathies. In this study, we prospectively investigated the main clinical determinants of progression and response to treatment in the 352 patients enrolled into the REIN study. Mean DeltaGFR (0.56 +/- 0.05 [SEM] versus 0.21 +/- 0.05 mL/min/1.73 m(2)/mo; P = 0.0001) and incidence of ESRD (30% and 10%; P = 0.0001) were more than twice that in patients with proteinuria of 2 g/24 h or greater of protein compared with those with protein less than 2 g/24 h (relative risk [RR], 4.07; 95% confidence interval [CI], 2.20 to 7.52), as well as in patients with hypertension compared with normotension (mean DeltaGFR, 0.48 +/- 0. 05 versus 0.22 +/- 0.05 mL/min/1.73 m(2)/mon; P = 0.0006; ESRD, 25% versus 10%; P = 0.004; RR, 3.18; 95% CI, 1.38 to 7.32). Hypertension at study entry (P = 0.038), greater mean blood pressure on follow-up (P = 0.002), and urinary protein excretion rate (P = 0.0001) were independent predictors of faster DeltaGFR. DeltaGFR was approximately twofold faster in patients with type 2 diabetes than in those with primary glomerular disease (P = 0.002; including immunoglobulin A [IgA] nephropathy, P = 0.009); nephrosclerosis (P = 0.03), adult polycystic kidney disease (APKD), or chronic interstitial nephritis (P = 0.006). Diabetes at study entry (P = 0. 02) and greater mean blood pressure (P = 0.0001) and urinary protein excretion rate (P = 0.0001) on follow-up were independent predictors of faster DeltaGFR. After correction for baseline covariates, diabetes was also associated with an increased risk for progression to ESRD (RR, 2.39; 95% CI, 1.01 to 5.68; P < 0.05). At multivariate analyses, ramipril significantly decreased DeltaGFR (regression coefficient,-0.23 +/- 0.11 [SEM]; P = 0.036) and ESRD (RR, 2.08; 95% CI, 1.21 to 3.57; P = 0.008) in patients with baseline proteinuria of 2 g/24 h or greater of protein, and the renoprotective effect increased for increasing levels of proteinuria. Ramipril decreased DeltaGFR to a similar extent in normotensive and hypertensive patients (-0.14 +/- 0.11 versus -0.14 +/- 0.09) and significantly limited ESRD in hypertensive patients (RR, 2.03; 95% CI, 1.26 to 3. 26; P = 0.004). DeltaGFR was decreased by 42% in primary glomerular disea

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cohort Studies; Confidence Intervals; Diabetic Nephropathies; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Incidence; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Proteinuria; Ramipril; Treatment Outcome

Angiotensin-converting enzyme (ACE) inhibitors are increasingly administered to patients with chronic renal disease. One issue of concern with the use of ACE inhibitors in patients with impaired renal function is the possible development of hyperkalemia. We reasoned that the impact of ACE inhibitors on plasma potassium could be minimized by administering these agents at very low doses. To examine this issue, we investigated the effect of a low dose of ramipril (1.25 mg orally once daily) and an eight-fold higher dose (10 mg orally once daily) on plasma potassium in 13 patients with proteinuria and mild chronic renal insufficiency. The study was divided into four phases: placebo (4 weeks), low-dose ramipril (8 weeks), high-dose ramipril (8 weeks), and washout phase (4 weeks). With the low dose of ramipril, urinary protein excretion decreased significantly as early as after 1 week of administration (from 4.4 +/- 0.5 to 3.7 +/- 0.4 g/24 h; P < 0.025) and did not decrease any further thereafter even when the dose was increased eight-fold. Mean arterial blood pressure and plasma potassium did not change significantly with the low dose of ramipril, whereas with the higher dose, mean arterial blood pressure decreased significantly (from 107 +/- 2.0 to 100 +/- 2.0 mm Hg, P < 0.005), and plasma potassium increased significantly (from 4.53 to 4.78 mEq/L, P < 0.05). We conclude that a low dose of ramipril can reduce proteinuria to the same extent as an eight-fold higher dose without significantly lowering blood pressure or increasing plasma potassium. This latter feature may be advantageous for the treatment of patients at risk for hyperkalemia who require ACE inhibitors.

Topics: Adult; Aged; Aldosterone; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Drug Administration Schedule; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptidyl-Dipeptidase A; Potassium; Proteinuria; Ramipril; Renin; Treatment Outcome

Topics: Angiotensin-Converting Enzyme Inhibitors; Combined Modality Therapy; Double-Blind Method; Humans; Kidney Failure, Chronic; Kidney Function Tests; Proteinuria; Ramipril

Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h.. In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months.. The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2.. In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Ramipril; Treatment Outcome

We investigated the predictors of the rate of glomerular filtration rate decline (delta GFR) and progression to end-stage renal failure (ESRF) in the 352 patients with proteinuric non-diabetic chronic nephropathies [urinary protein excretion rate (UProt) > or = 1 g/24 hr, creatinine clearance 20 to 70 ml/min/1.73 m2] enrolled in the Ramipril Efficacy In Nephropathy (REIN) study. Overall the GFR declined linearly by 0.46 +/- 0.05 ml/min/1.73 m2/month (mean rate +/- SEM) over a median follow-up of 23 months (range 3 to 64 months), and progression to ESRF was 17.3%. Using multivariate analysis, higher UProt and mean arterial pressure (MAP) independently correlated with a faster delta GFR (P = 0.0001 and P = 0.0002, respectively) and progression to ESRF (P = 0.0001 and P = 0.003, respectively). Mean UProt and systolic blood pressure during follow-up were the only time-dependent covariates that significantly correlated with delta GFR (P = 0.005 and P = 0.003, respectively) and ESRF (P = 0.006 and P = 0.0001, respectively). After stratification for baseline UProt, patients in the lowest tertile (UProt < 1.9 g/24 hr) had the slowest delta GFR (0.16 +/- 0.07 ml/min/1.73 m2/month) and progression to ESRF (4.3%) as compared with patients in the middle tertile (UProt 2.0 to 3.8 g/24hr; delta GFR, 0.55 +/- 0.09 ml/min/1.73 m2/month, P = 0.0002; ESRF, 15.3%, P = 0.0001) and in the highest tertile (UProt 3.9 to 18.8 g/24 hr; delta GFR, 0.70 +/- 0.11 ml/min/1.73 m2/month, P = 0.0001; ESRF, 32.5%, P = 0.0001). Both delta GFR (P = 0.01) and progression to ESRF (P = 0.01) significantly differed even between the middle and the highest tertiles. On the contrary, stratification in tertiles of baseline MAP failed to segregate subgroups of patients into different risk levels. Patients with the highest proteinuria and blood pressure were those with the fastest progression (delta GFR, 0.91 +/- 0.23; ESRF 34.7%). Of interest, at each level of baseline MAP, a higher proteinuria was associated with a faster delta GFR and progression to ESRF. On the other hand, at each level of proteinuria, a faster delta GFR was associated with MAP only in the highest tertile (> 112 mm Hg) and the risk of ESRF was independent of the MAP. Thus, in chronic nephropathies proteinuria is the best independent predictor of both disease progression and ESRF. Arterial hypertension may contribute to the acceleration of renal injury associated with enhanced traffic of plasma proteins. Antihypertensive drugs th

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Time Factors

In diabetic nephropathy, angiotensin-converting-enzyme (ACE) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate (GFR). Whether this difference applies to progression of nondiabetic proteinuric nephropathies is not clear. The Ramipril Efficacy in Nephropathy study of chronic nondiabetic nephropathies aimed to address whether glomerular protein traffic influences renal-disease progression, and whether an ACE inhibitor was superior to conventional treatment, with the same blood-pressure control, in reducing proteinuria, limiting GFR decline, and preventing endstage renal disease.. In this prospective double-blind trial, 352 patients were classified according to baseline proteinuria (stratum 1: 1-3 g/24 h; stratum 2: > or = 3 g/24 h), and randomly assigned ramipril or placebo plus conventional antihypertensive therapy targeted at achieving diastolic blood pressure under 90 mm Hg. The primary endpoint was the rate of GFR decline. Analysis was by intention to treat.. At the second planned interim analysis, the difference in decline in GFR between the ramipril and placebo groups in stratum 2 was highly significant (p = 0.001). The Independent Adjudicating Panel therefore decided to open the randomisation code and do the final analysis in this stratum (stratum 1 continued in the trial). Data (at least three GFR measurements including baseline) were available for 56 ramipril-assigned patients and 61 placebo-assigned patients. The decline in GFR per month was significantly lower in the ramipril group than the placebo group (0.53 [0.08] vs 0.88 [0.13] mL/min, p = 0.03). Among the ramipril-assigned patients, percentage reduction in proteinuria was inversely correlated with decline in GFR (p = 0.035) and predicted the reduction in risk of doubling of baseline creatinine or endstage renal failure (18 ramipril vs 40 placebo, p = 0.04). The risk of progression was still significantly reduced after adjustment for changes in systolic (p = 0.04) and diastolic (p = 0.04) blood pressure, but not after adjustment for changes in proteinuria. Blood-pressure control and the overall number of cardiovascular events were similar in the two treatment groups.. In chronic nephropathies with proteinuria of 3 g or more per 24 h, ramipril safely reduces proteinuria and the rate of GFR decline to an extent that seems to exceed the reduction expected for the degree of blood-pressure lowering.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Ramipril; Risk

In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function. Treatment regimens which reduce proteinuria and hypertension improve prognosis. The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest.. The studied cohort consisted of 11 patients with CGN, hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks, doubly blinded and randomized according to a "Latin-square design": Celiprolol (beta-1-antagonist, beta-2-agonist, 200 mg/d), Atenolol (selective beta-1-antagonist, 50 mg/d), Ramipril (ACE-inhibitor, 2.5 mg/d) and placebo. There was a two-week wash-out phase between each of the four treatment phases. At the end of each treatment phase glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-amino-hippuric acid (PAH) clearance. Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase. During this period blood pressures were measured with a continuous 24-hour blood pressure monitor.. Mean arterial blood pressure (MAP) was significantly reduced, compared with placebo, by all three antihypertensives (108 +/- 9 mm Hg with placebo, 98 +/- 12 mg Hg with atenolol, 101 +/- 11 mm Hg with celiprolol and 98 +/- 8 mm Hg with ramipril; P < 0.01). Celiprolol produced a significant rise In ERPF (322 +/- 109 ml/min with placebo, 391 +/- 110 ml/min with celiprolol: P < 0.05). GFR was slightly, but not significantly, reduced by celiprolol and atenolol. Filtration fraction remained unchanged with atenolol and celiprolol, while it was slightly, but not significantly, reduced with ramipril. Compared with the placebo, all three drugs significantly reduced proteinuria (P < 0.05): 1.8 +/- 1.3 g/24 h with placebo, 1.2 +/- 1.2 g/24 h with atenolol, 1.2 +/- 1.1 g/24 h with celiprolol and 1.4 +/- 1.4 g/24 h with ramipril.. These data indicate that, in addition to ACE inhibitors, the new generation of beta-receptor blockers in particular, because of their vasodilator action, favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Celiprolol; Chronic Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Inulin; Male; Middle Aged; p-Aminohippuric Acid; Proteinuria; Ramipril; Renal Circulation; Renal Plasma Flow, Effective; Treatment Outcome

A prospective double-blind, randomized study was conducted to compare the effects of the beta 1 antagonist, beta 2 agonist celiprolol (200 mg daily) on renal hemodynamics and protein excretion with those of the beta 1 antagonist atenolol (50 mg daily), the ACE-inhibitor ramipril (2.5 mg daily), and placebo in 11 patients with proteinuria > 400 mg/24 h due to chronic glomerulonephritis. All 4 substances were given in a double-blind, randomized manner according to a latin-square design over a period of 4 weeks with a wash-out period of 2 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and PAH clearance. Proteinuria was assessed by urine sampling at the end of each treatment period. Mean arterial pressure (MAP) was reduced significantly (p < 0.01) by all 3 drugs compared to placebo (108 +/- 9 mmHg placebo, 98 +/- 12 mmHg atenolol, 101 +/- 11 mmHg celiprolol, and 98 +/- 8 mmHg ramipril). Celiprolol induced a significant increase in ERPF compared to placebo (322 +/- 109 ml/min under placebo versus 391 +/- 110 ml/min under celiprolol, p < 0.05). GFR was slightly but insignificantly increased under atenolol and celiprolol. Filtration fraction (FF) remained unchanged in case of atenolol and celiprolol treatment and was slightly but not significantly reduced by ramipril. Proteinuria was significantly (p < 0.05) reduced compared to placebo by all 3 drugs (1.8 +/- 1.3 g/24 h under placebo, 1.2 +/- 1.2 g/24 h under atenolol, 1.2 +/- 1.1 g/24 h under celiprolol, and 1.4 +/- 1.4 g/24 h under ramipril). These data demonstrate that new beta-blocking agents show favorable effects on proteinuria and renal blood flow in patients with chronic glomerulonephritis and arterial hypertension. This may be attributed to their vasodilating properties.

Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Atenolol; Blood Pressure; Celiprolol; Chronic Disease; Double-Blind Method; Female; Glomerulonephritis; Humans; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Renal Circulation; Vasodilator Agents

Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuminuria; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Creatinine; Cross-Over Studies; Diabetes Mellitus; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Renal Plasma Flow

Microalbuminuria and proteinuria are strong independent predictors for increased cardiovascular mortality in non-insulin-dependent diabetic (NIDDM) patients. In such patients, angiotensin converting enzyme (ACE) inhibition improves the evolution of diabetic nephropathy; however, no data are currently available on the effects of such intervention on cardiovascular morbidity and mortality. The aim of the Diab-Hycar study is to test the hypothesis that ACE inhibition with a low daily dose of 1.25 mg ramipril, which has no significant effect on blood pressure, may reduce cardiovascular morbidity and/or mortality in normotensive or hypertensive NIDDM patients with persistent albuminuria. Selected and followed by general practitioners, 4000 patients will receive their usual oral antidiabetic treatment and if necessary antihypertensive treatment (ACE inhibitors excluded). In addition in a randomized, double-blind trial they will be given either a placebo or 1.25 mg ramipril daily. The follow-up is currently scheduled to last 3 years. The efficacy of ACE-inhibition will be assessed by the following major end-points: cardiovascular death, sudden death, myocardial infarction, stroke, renal replacement therapy. The Diab-Hycar study started on 3 February 1995. By 1 September 1995, 11,000 urine samples were tested. The prevalence of persistent albuminuria was 23%, 964 patients were initially included in the study, with 619 eligible patients included soon after. Different strategies have been developed to record cardiovascular events correctly and to minimize the number of patients lost to follow-up.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Clinical Protocols; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Patient Selection; Proteinuria; Ramipril

The antiproteinuric pharmacokinetics of Ramipril in response to different doses and modalities of administration has been poorly investigated so far.. Prospective, open-label and not placebo controlled study.. 40 Caucasian adult patients having GFR ≥ 50 mL/min, proteinuria 1-3 g/day; SBP/DBP ≤ 150/90 mmHg were recruited between June 2014 and November 2014.. Impact on 24 h proteinuria and fractioned proteinuria of Ramipril given at different dosages (2.5 mg/day or Ramipril 5 mg/day or Ramipril 10 mg/day) and with different daily administration modalities (single or two divided doses) for cycles of 10 days.. At the end of each cycle, 24 h and fractioned proteinuria on three timed urinary collections (morning, afternoon and night) were measured.. Compared to baseline, Ramipril significantly reduced 24 h proteinuria at each dose and modality of administration. In particular, the greatest effects were evident with the higher and divided dose of the drug. The analysis of the fractioned proteinuria showed that the greatest reduction was obtained in the night urinary collection by administering Ramipril 10 mg/day in two divided doses.. Small sample size.. Ramipril reduces proteinuria at any of the tested doses. Although the using of high and divided doses seems to maximize the antiproteinuric effect of the drug, possibly due to a better pharmacological coverage of the nocturnal period.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Prospective Studies; Proteinuria; Ramipril; Time Factors

Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular and structural markers of glomerular and tubulointerstitial renal damage, were studied in a rat model of normotensive nephropathy induced by adriamycin and treated with PPARγ agonist pioglitazone (12mg/kg, po), angiotensin converting enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone had no effect on systolic blood pressure, marginally reduced glycemia and improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone prevented the development of proteinuria and focal glomerulosclerosis to the similar extent as blood-pressure lowering ramipril. Renoprotection provided by either treatment was associated with a reduction in the cortical expression of profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing endothelin-1, and a limitation of interstitial macrophage influx. Treatment with PPARγ agonist, as well as ACE inhibitor comparably affected renal expression of the renin-angiotensin system (RAS) components, normalizing increased renal expression of ACE and enhancing the expression of Mas receptor. Interestingly, combined pioglitazone and ramipril treatment did not provide any additional renoprotection. These results demonstrate that in a nondiabetic renal disease, such as adriamycin-induced nephropathy, PPARγ agonist pioglitazone provides renoprotection to a similar extent as an ACE inhibitor by interfering with the expression of local RAS components and attenuating related profibrotic and inflammatory mechanisms. The combination of the both agents, however, does not lead to any additional renal benefit.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Blood Pressure; Disease Progression; Doxorubicin; Endothelium, Vascular; Gene Expression Regulation; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Pioglitazone; PPAR gamma; Proteinuria; Ramipril; Rats; Rats, Wistar; Renin-Angiotensin System; Thiazolidinediones

Proteinuria is the hallmark of renal disease. In essential hypertension the onset of de novo proteinuria is associated with faster rate of progression of disease. Some authors have suggested that the DD genotype of the angiotensin-converting enzyme (ACE) gene would be an adverse renal prognosis factor. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. Observations on the association between the ACE gene polymorphism and hypertension have been inconsistent, which might be due to ethnic and geographical variations. In this study was to investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (ramipril) and to evaluate the possible association between I/D polymorphism and hypertension. We recruited 66 hypertensive patients (male 42, female 24) with overt proteinuria (urinary protein excretion over 500 mg/day). Patients were classified into three groups in accordance with ACE genotypes (17 DD; 35 ID; 14 II). They were treated with ramipril and prospectively followed up for one year. Various clinical parameters including age, body mass index (BMI), 24-h urine protein, creatinine, creatinine clearance (Ccr), systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP) were measured in the pre- and post-treatment periods. The ACE gene insertion/deletion(I/D) polymorphisms in intron 16 were determined by PCR. Results showed that there were no significant differences in the clinical parameters such as age, gender, serum creatinine, Ccr, SBP, DBP, MAP, and daily urinary excretion of protein among three groups (P > 0.05). ID genotype patients were found to have lower BMI (p = 0.031). ACE inhibition significantly reduced proteinuria in all genotype groups (p < 0.05). The percentage reductions of 24-h urinary excretion of protein were significantly different between the genotype groups (p = 0.042) and for DD genotype were significantly greater than in ID (79.2 +/- 28.9% vs 49.2 +/- 64.8%, P = 0.015). The slope of SBP was the main factor related to the slope of the percentage reduction of proteinuria, however, a significant negative correlation coefficient between these parameters was found (rs = -0.382, p = 0.002). We failed to find significant difference in outcomes of treatments with ACE inhibitor between male and female according the I/D polymorphism of the ACE gene. D allele in the ACE genotype could be a useful genetic marker with

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Female; Genetic Predisposition to Disease; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Proteinuria; Ramipril; Risk Factors

High sodium intake limits the antihypertensive and antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors in patients with CKD; however, whether dietary sodium also associates with progression to ESRD is unknown. We conducted a post hoc analysis of the first and second Ramipril Efficacy in Nephropathy trials to evaluate the association of sodium intake with proteinuria and progression to ESRD among 500 CKD patients without diabetes who were treated with ramipril (5 mg/d) and monitored with serial 24-hour urinary sodium and creatinine measurements. Urinary sodium/creatinine excretion defined low (<100 mEq/g), medium (100 to <200 mEq/g), and high (≥200 mEq/g) sodium intake. During a follow-up of >4.25 years, 92 individuals (18.4%) developed ESRD. Among those with low, medium, and high sodium intakes, the incidence of ESRD was 6.1 (95% confidence interval [95% CI], 3.8-9.7), 7.9 (95% CI, 6.1-10.2), and 18.2 (95% CI, 11.3-29.3) per 100 patient-years, respectively (P<0.001). Patients with high dietary sodium exhibited a blunted antiproteinuric effect of ACE inhibition despite similar BP among groups. Each 100-mEq/g increase in urinary sodium/creatinine excretion associated with a 1.61-fold (95% CI, 1.15-2.24) higher risk for ESRD; adjusting for baseline proteinuria attenuated this association to 1.38-fold (95% CI, 0.95-2.00). This association was independent from BP but was lost after adjusting for changes in proteinuria. In summary, among patients with CKD but without diabetes, high dietary salt (>14 g daily) seems to blunt the antiproteinuric effect of ACE inhibitor therapy and increase the risk for ESRD, independent of BP control.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Ramipril; Sodium; Sodium, Dietary

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Kidney Failure, Chronic; Male; Proteinuria; Ramipril; Sodium, Dietary

Pierson syndrome, caused by mutations in the LAMB2 gene, was originally described as a combination of microcoria and congenital nephrotic syndrome, rapidly progressing to end-stage renal failure.. We report a minor variant of Pierson syndrome in a teenage girl with severe myopia since early infancy and proteinuria first detected at age 6. At the age of 11 she was found to carry a unique homozygous non-truncating LAMB2 mutation in exon 2: c.T240G (p.S80R). Renal biopsy revealed mild diffuse mesangial sclerosis and residual expression of laminin β2. Today at age 14, on treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, she continues to have nephrotic range proteinuria, but a normal glomerular filtration rate.. LAMB2 mutations should be considered in all patients with glomerular proteinuria and abnormal ocular phenotype, irrespective of age and disease severity.

Topics: Abnormalities, Multiple; Adolescent; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Eye Abnormalities; Female; Glomerular Filtration Rate; Humans; Kidney; Laminin; Losartan; Mutation; Mutation, Missense; Myasthenic Syndromes, Congenital; Myopia; Nephrotic Syndrome; Phenotype; Proteinuria; Pupil Disorders; Ramipril; Retinal Detachment; Vision Disorders

Topics: Angiotensin-Converting Enzyme Inhibitors; Body Mass Index; Chronic Disease; Comorbidity; Creatinine; Disease Progression; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Failure, Chronic; Obesity; Proteinuria; Ramipril; Treatment Outcome

Alterations within the RAS (renin-angiotensin system) are pivotal for the development of renal disease. ACE2 (angiotensin-converting enzyme 2) is expressed in the kidney and converts the vasoconstrictor AngII (angiotensin II) into Ang-(1-7), a peptide with vasodilatory and anti-fibrotic actions. Although the expression of ACE2 in the diabetic kidney has been well studied, little is known about its expression in non-diabetic renal disease. In the present study, we assessed ACE2 in rats with acute kidney injury induced by STNx (subtotal nephrectomy). STNx and Control rats received vehicle or ramipril (1 mg. kg (-1) of body weight . day (-1), and renal ACE, ACE2 and mas receptor gene and protein expression were measured 10 days later. STNx rats were characterized by polyuria, proteinuria, hypertension and elevated plasma ACE2 activity (all P<0.01) and plasma Ang-(1-7) (P<0.05) compared with Control rats. There was increased cortical ACE binding and medullary mas receptor expression (P<0.05), but reduced cortical and medullary ACE2 activity in the remnant kidney (P<0.05 and P<0.001 respectively) compared with Control rats. In STNx rats, ramipril reduced blood pressure (P<0.01), polyuria (P<0.05)and plasma ACE2 (P<0.01), increased plasma Ang-(1-7) (P<0.001), and inhibited renal ACE(P<0.001). Ramipril increased both cortical and medullary ACE2 activity (P<0.01), but reduced medullary mas receptor expression (P<0.05). In conclusion, our results show that ACE2 activity is reduced in kidney injury and that ACE inhibition produced beneficial effects in association with increased renal ACE2 activity. As ACE2 both degrades AngII and generates the vasodilator Ang-(1-7), a decrease in renal ACE2 activity, as observed in the present study, has the potential to contribute to the progression of kidney disease.

Topics: Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Female; Gene Expression; Hypertension; Kidney; Nephrectomy; Peptidyl-Dipeptidase A; Polyuria; Proteinuria; Proto-Oncogene Mas; Proto-Oncogene Proteins; Ramipril; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled

Renin-angiotensin system (RAS) blockade improves proteinuria and the endothelial functions in diabetic nephropathy. Plasma asymmetric dimethylarginine (ADMA), abundant in the cell than in the plasma, is also improved by RAS blockage. We hypothesized that RAS blockade may reduce ADMA by reducing injurious cell death.. In a hypothesis-generating study, we assessed circulating levels of apoptotic signalling peptides in incident chronic kidney disease (CKD) stage 1 patients (aged >18 years with diabetes mellitus type 2 as the only cause of nephropathy) not previously prescribed statins or RAS blockade. Ninety-three (29 M, 47 ± 5 years) patients with CKD 1 diabetic nephropathy and 38 healthy subjects (20 M, 47 ± 5 years) were enrolled. Ramipril was given (5 mg daily for 12 weeks), and circulating ADMA, soluble Fas (sFas), myostatin and endothelial function [flow-mediated vasodilation (FMD); ultrasound)] were measured.. After the study, ADMA, sFas, myostatin, insulin resistance, high-sensitive C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), blood pressure and proteinuria levels were decreased, and FMD and serum albumin levels increased (P < 0.05 for all). ADMA and sFas levels were independently related to FMD levels both before (rho = -0.33; P < 0.005 and rho = -0.26; P < 0.02, respectively) and after (rho = -0.39; P < 0.001 and rho = -0.28; P < 0.002, respectively) ramipril treatment. Changes in sFas and ADMA were related to the change in FMD (-0.32; P > 0.004 and -0.31; P < 0.004, respectively).. A reduction of proteinuria in CKD 1 diabetic kidney disease is accompanied by lower circulating sFas, myostatin and ADMA, suggesting that increased cell death may contribute to ADMA formation and endothelial dysfunction in diabetic CKD.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Arginine; Chronic Disease; Diabetic Nephropathies; fas Receptor; Female; Humans; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Myostatin; Proteinuria; Ramipril

We studied the effect of the combined treatment with an angiotensin-converting enzyme (ACE) inhibitor (ramipril) and eplerenone compared with ramipril alone in streptozocin-induced diabetic rats.. Wistar rats were divided into 4 groups: nondiabetic controls, streptozocin-treated diabetic rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg) and diabetic rats treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for 8 weeks. Our model produced early-stage diabetic nephropathy.. The diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by creatinine clearance) and histopathological evidence of renal injury including glomerular hypertrophy and mesangial expansion. Ramipril reduced proteinuria but its combination with eplerenone did not produce any greater benefit. Both treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to ramipril prevented glomerular hyperfiltration.. Whether eplerenone should be used in addition to an ACE inhibitor or an angiotensin receptor blocker at an early stage of diabetic nephropathy remains questionable.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Creatinine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Drug Therapy, Combination; Eplerenone; Glomerular Mesangium; Hypertrophy; Kidney Glomerulus; Male; Mineralocorticoid Receptor Antagonists; Proteinuria; Ramipril; Random Allocation; Rats; Rats, Wistar; Severity of Illness Index; Spironolactone

Recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation with nephrotic syndrome is a serious problem with a high risk of graft loss. The therapeutic role of renin-angiotensin-system (RAS) blockers in recurrent FSGS is not clear. We present the safety and efficacy of an intensified triple RAS blockade with an ACE-inhibitor, an AT 1 receptor blocker and the direct renin inhibitor aliskiren in a 29-year-old renal transplant recipient with biopsy proven recurrence of FSGS and relapsing severe nephrotic syndrome. We subsequently used full dose ramipril, candesartan and aliskiren under a close monitoring of kidney function and electrolytes and examined the effect on proteinuria, clinical course and tolerability over 12 months. We found a significant and sustained antiproteinuric effect under triple RAS blockade. RAS blockade was generally well tolerated. This can offer a new therapeutic approach in selected hypertensive patients with recurrent FSGS.

Topics: Adult; Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Benzimidazoles; Biphenyl Compounds; Drug Therapy, Combination; Female; Fumarates; Glomerulosclerosis, Focal Segmental; Humans; Hypertension, Renal; Kidney Transplantation; Nephrotic Syndrome; Plasma Exchange; Proteinuria; Ramipril; Recurrence; Renin; Renin-Angiotensin System; Rituximab; Tetrazoles

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Disease Progression; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Kidney; Multicenter Studies as Topic; Proteinuria; Ramipril; Randomized Controlled Trials as Topic; Telmisartan

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Child; Child, Preschool; Disease Progression; Drug Therapy, Combination; Humans; Hypertension; Proteinuria; Ramipril; Renal Insufficiency, Chronic

Topics: Adolescent; Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cataract; Female; Hearing Loss, Sensorineural; Humans; Kidney Diseases; Losartan; Male; Molecular Motor Proteins; Mutation; Myosin Heavy Chains; Proteinuria; Ramipril; Renin-Angiotensin System; Syndrome; Telmisartan; Thrombocytopenia

Inhibition of the renin angiotensin aldosterone system (RAAS) produces protective effects on cardio-renal injury in type 2 diabetes. Vasopeptidase inhibitors (VPI) represent a new pharmacological tool, acting by simultaneous inhibition of the RAAS and neutral endopeptidase. We examined the effects of chronic VPI on renal function and morphology in experimental type 2 diabetes as compared to angiotensin converting enzyme inhibition (ACE-I). Zucker diabetic fatty rats aged 13 weeks were treated with either VPI (AVE7688, ZDF-VPI, n = 8) or ACE-I (Ramipril, ZDF-ACE-I, n = 7) or placebo (ZDF, n = 8). Heterozygous rats served as non-diabetic controls (Ctr, n = 8). Both treatments led to a similar decrease in blood pressure. After 10 weeks of treatment, ZDF developed marked albuminuria. The latter was significantly attenuated in ZDF-VPI as compared to ZDF and ZDF-ACE-I. Renal histology revealed a significant expansion in the glomerular tuft area in all ZDF groups. However, expression of glomerular desmin, which has been recognized as a sensitive marker of early podocyte damage, was significantly increased in ZDF as compared to Ctr. Desmin was reduced in ZDF-VPI but not in animals treated with ACE-I. There was a correlation between albumin excretion and desmin-positive glomerular area. In experimental type 2 diabetes, albuminuria correlates to podocyte damage. These hallmarks of diabetic nephropathy are attenuated by VPI to a greater extent than by ACE-I alone. These findings suggest that podocyte damage is an early critical step in the progression of diabetic nephropathy, and that VPI is a promising pharmacological tool in the treatment of diabetic renal disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Heterocyclic Compounds, 3-Ring; Male; Microscopy, Polarization; Neprilysin; Podocytes; Protease Inhibitors; Proteinuria; Ramipril; Rats; Rats, Zucker; Renin-Angiotensin System; Triglycerides; Weight Gain

Economic analyses of drug therapies are highly dependent on the clinical indications for treatment. The cost effectiveness of ramipril has been evaluated in numerous studies, usually based on the results of one specific clinical trial. We estimated the cost effectiveness of this drug across a range of currently accepted therapeutic indications, using a single health economic model and adjusted for quality of life, to compare the different outcomes observed in four clinical trials.. The cardiovascular life expectancy model, a validated Markov model, was calibrated to accurately forecast the results of four trials including AIRE, HOPE, Micro-HOPE, and REIN. We then extrapolated these results over the remaining life expectancy of the patients enrolled in each study and adjusted for the quality of life associated with the observed outcomes. The cost per quality-adjusted life-year (QALY) was then calculated from the perspective of the Canadian healthcare system incorporating the estimated direct healthcare costs associated with treatments and outcomes.. After discounting all costs and outcomes 3% annually, the benefits associated with ramipril ranged from 0.74 QALYs in the AIRE study to 1.22 QALYs in Micro-HOPE. Treatment was estimated to be cost-saving for some patient groups, such as those in REIN. The highest cost-effectiveness ratio was observed among individuals enrolled in HOPE ($Can20 000 per QALY in 2002).. Treatment with ramipril appears to be economically attractive across a wide range of patient groups, including those with increased coronary risk and/or diabetes mellitus (HOPE and Micro-HOPE), those with congestive heart failure (AIRE), and those with non-diabetic nephropathy (REIN).

Topics: Angiotensin-Converting Enzyme Inhibitors; Canada; Cardiovascular Diseases; Clinical Trials as Topic; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Models, Economic; Proteinuria; Quality of Life; Quality-Adjusted Life Years; Ramipril; Treatment Outcome

Angiotensin (ANG) II can be associated with gene expression regulation. Thus we studied the possible role of ANG II in the regulation of AT(2) mRNA and protein expression. We utilized sham-operated renal ablation rats as well as renal ablation rats pretreated during the first 7 days of the development of renal damage with either the angiotensin-converting inhibitor ramipril, the AT(1) receptor antagonist losartan, or the AT(2) receptor antagonist PD-123319. Renal tissue was analyzed for histological changes and expression of AT(2) receptor mRNA (by RT-PCR) and protein (by immunohistochemistry). To explore the physiological role of AT(2) receptor overexpression in the development of renal damage, blood pressure, urinary protein excretion, and renal damage were evaluated. A time-dependent increase in the expression of AT(2) receptor mRNA and protein was observed at 7, 15, and 30 days after renal ablation. Because these effects were already evident at day 7, the effects of ramipril, losartan, or PD-123319 were tested at this time. The ramipril group and the PD-123319-pretreated group showed inhibition of AT(2) receptor expression, whereas the losartan-pretreated group showed a further increase in AT(2) receptor expression. Inhibition of the AT(2) receptor during renal ablation was associated with increased renal damage and a further increase in the blood pressure. This suggests that overexpression of AT(2) receptors after renal ablation is modulated by ANG II through its own AT(2) receptor and that functional expression of this effect may represent a counterregulatory mechanism to modulate the renal damage induced by renal ablation.

Topics: Angiotensin II; Angiotensin II Type 2 Receptor Blockers; Animals; Blood Pressure; Diuresis; Gene Expression Regulation; Imidazoles; Kidney; Ligation; Losartan; Male; Nephrectomy; Proteinuria; Pyridines; Ramipril; Rats; Rats, Wistar; Receptor, Angiotensin, Type 2; Renal Artery; RNA, Messenger

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) reduces proteinuria and the rate of renal function deterioration in diabetic nephropathy and other glomerular diseases, but its role in quiescent lupus nephritis has not been established. We conducted a retrospective study to investigate the effects of ACEI/ARB on proteinuria and renal function in patients with persistent proteinuria (>1 g/day) despite resolution of acute lupus nephritis following immunosuppressive treatment. Fourteen out of 92 patients were included. The duration of treatment with ACEI/ARB was 52.1 +/- 35.7 months. The levels of proteinuria, serum albumin, serum creatinine, systolic and diastolic blood pressure were 1.10 to 6.90 g/day, 35.8 +/- 3.6 g/L, 102.54 +/- 34.48 micromol/L, 137.6 +/- 10.9 and 81.9 +/- 9.2 mmHg at baseline. Proteinuria and serum albumin showed significant sustained improvements after 6 and 24 months of treatment. Comparison of slopes for serial proteinuria, albumin and reciprocal of serum creatinine before and after treatment showed significant improvements in six (43%), eight (57%) and two patients, respectively. At last follow-up proteinuria remained significantly lower (0.36 g/day, P = 0.043) and albumin higher (41.3 +/- 2.2 g/L, P = 0.023). Eleven (78.6%) patients had proteinuria improved by >50%, and five had insignificant proteinuria at last follow-up. Systolic blood pressure was significantly reduced from 6 months onwards, but this did not correlate with proteinuria reduction. Diastolic blood pressure, serum creatinine, creatinine clearance, anti-dsDNA, C3 and haemoglobin were not altered. We conclude that ACEI/ARB effectively reduces proteinuria and improves serum albumin in patients with persistent proteinuria despite quiescent lupus nephritis.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Creatinine; Enalapril; Female; Follow-Up Studies; Humans; Losartan; Lupus Nephritis; Male; Proteinuria; Ramipril; Retrospective Studies; Serum Albumin

Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension. The efficacy and safety of ramipril in adults has been proved; however, data on effectiveness of ramipril in children are few. The aim of the present study was to investigate the effect of ramipril on blood pressure (BP) and proteinuria in children with chronic kidney diseases.. A total of 31 children (median age 11.3 years, range 1.9-19.8 years) with various chronic nephropathies and hypertension or proteinuria were prospectively treated with ramipril for 6 months. Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children. Proteinuria was defined as protein excretion > or =100 mg/m(2)/24 h. The starting dose of ramipril was 1.5 mg/m(2)/24 h once daily. In 27 children it was given as monotherapy.. The median decrease in ambulatory BP was 11 mm Hg for daytime systolic, 10 mm Hg for daytime and nighttime diastolic, and 8 mm Hg for nighttime systolic BP. Hypertension normalized in 55% of the children. Proteinuria decreased in 84% of the children with pathologic proteinuria; the median decrease was 51%. A positive correlation was found between initial proteinuria and change of proteinuria (r = 0.95, P <.001). Glomerular filtration rate and serum potassium level did not change significantly. One child developed a cough that was believed to be related to ramipril.. Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension, proteinuria, or both.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Child; Child Welfare; Child, Preschool; Chronic Disease; Circadian Rhythm; Diastole; Female; Humans; Hypertension; Infant; Kidney Diseases; Male; Prospective Studies; Proteinuria; Ramipril; Severity of Illness Index; Statistics as Topic; Systole; Treatment Outcome

It is not known whether physical exercise increases daily proteinuria in patients with proteinuric nephropathies, thus accelerating progression of the renal lesion. This study evaluates the acute effects of physical exercise on proteinuria in young adults with immunoglobulin A (IgA) nephropathy.. Changes induced by intense physical exercise on quantitative and qualitative proteinuria were evaluated in basal conditions and after 10 days of ramipril therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate (GFR), proteinuria between 0.8 and 1.49 g/24 h, and "glomerular" microhematuria before and after the end of a maximal treadmill Bruce test (B-test). The basal study also was performed in 10 age- and sex-matched healthy volunteers.. At rest, GFR averaged 141 +/- 23 mL/min; it increased by 16.3% +/- 3.3% (P < 0.005) and 7.1% +/- 1.6% at 60 and 120 minutes after the B-test, respectively. At rest, GFR-corrected proteinuria averaged protein of 0.76 +/- 0.21 mg/min/100 mL GFR; it increased to 1.55 +/- 0.28 mg/min/100 mL GFR after 60 minutes (P < 0.001) and declined to 0.60 +/- 0.11 mg/min/100 mL GFR at 120 minutes after the end of the B-test. The pattern of urinary proteins remained unchanged, as did microhematuria. Daily proteinuria was not different from the basal value on the day of the B-test. After ramipril therapy, patients showed a reduction in GFR, but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or hematuria.. The increase in proteinuria after exercise in our patients is significant and is not prevented by ramipril therapy, but lasts less than 120 minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not support the need to reduce acute physical activity in patients with nonnephrotic renal diseases.

Topics: Adult; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Creatinine; Disease Progression; Exercise Test; Exercise Tolerance; Female; Glomerulonephritis, IGA; Hematuria; Humans; Kidney Tubules, Proximal; Male; Proteinuria; Ramipril; Renin

Alport syndrome (AS) is a common hereditary cause of end-stage renal failure in adolescence due to defects in type IV collagen genes. Molecular genetics allows early diagnosis, however, no preventive strategy can be offered. Using the COL4A3 -/- mouse, an animal model for human AS, we evaluated therapy with ramipril in mice.. One hundred and twenty-two Alport-mice were treated with 10 mg/kg/day ramipril added to drinking water. Proteinuria, serum-urea and lifespan were monitored. Renal matrix was characterized by immunohistochemistry, light- and electron microscopy, and Western blot.. Untreated COL4A3 -/- mice died from renal failure after 71 +/- 6 days. Early therapy starting at four weeks of age and continuing to death delayed onset and reduced the extent of proteinuria. Uremia was postponed by three weeks in treated animals. Lifespan increased by more than 100% to 150 +/- 21 days (P < 0.01). In parallel, decreased deposition of extracellular matrix and lessened interstitial fibrosis as well as reduced amounts of renal transforming growth factor-beta1 (TGF-beta1) could be demonstrated. Late therapy starting at seven weeks decreased proteinuria, however, lifespan did not increase significantly.. The results indicate an antiproteinuric and antifibrotic nephroprotective effect of ramipril in COL4A3 -/- mice is mediated by down-regulation of TGF-beta1. This effect in mice is enhanced by initiation of therapy during pre-symptomatic disease. The data in COL4A3 -/- mice as an animal-model for Alport syndrome suggest that ramipril might as well delay renal failure in humans with AS. Early diagnosis and preemptive treatment also may be crucial in humans.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Autoantigens; Basement Membrane; Collagen Type IV; Disease Models, Animal; Extracellular Matrix; Fibrosis; Kidney; Kidney Glomerulus; Longevity; Mice; Mice, Knockout; Nephritis, Hereditary; Proteinuria; Ramipril; Renal Insufficiency; Transforming Growth Factor beta; Transforming Growth Factor beta1; Uremia

Topics: Angiotensin-Converting Enzyme Inhibitors; Dose-Response Relationship, Drug; Humans; Proteinuria; Ramipril

The present study examined non-insulin-treated streptozotocin (STZ)-induced diabetic rats to determine the role of kinins in diabetic nephropathy. Their involvement in the renoprotective effect of the angiotensin-converting enzyme inhibitor (ACEI) ramipril was investigated using the bradykinin (BK) B(2)-receptor antagonist, icatibant (HOE 140), or a combination of the two drugs.Although, none of the treatments prevented the decline of the glomerular filtration rate (GFR) in diabetic rats, ramipril (3 mg/kg/day), but not icatibant (HOE 140; 500 microg/kg/day), prevented proteinuria in these animals. However, the antiproteinuric effect of ramipril was reduced by 45% when combined with icatibant. To explore whether the renal kallikrein-kinin system (KKS) belongs to the underlying mechanisms of these findings, we also determined urinary BK levels, renal kallikrein (KLK) and angiotensin-converting enzyme (ACE) activity as well as renal cortical mRNA levels of neutral endopeptidase 24.11 (NEP) and low-molecular weight (LMW) kininogen. STZ led to a reduction of renal KLK and ACE activity and NEP expression and to a three-fold increase of urinary BK excretion and renal kininogen expression. Icatibant given alone had no effect on these parameters. In contrast, ramipril treatment normalized urinary protein and BK excretion as well as kininogen mRNA expression without affecting NEP mRNA expression or KLK and ACE activity. Our data demonstrate that renal BK is increased in severe STZ-induced diabetes mellitus, but may affect glomerular regulation only to a minor degree under this condition. However, kinins are partly involved in the antiproteinuric action of ACEI at this stage of diabetic nephropathy.

Topics: Actins; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Bradykinin; Bradykinin B2 Receptor Antagonists; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Hypertension, Renal; Hypoglycemic Agents; Insulin; Kallikrein-Kinin System; Kidney Cortex; Kidney Function Tests; Kininogens; Kinins; Male; Neprilysin; Peptidyl-Dipeptidase A; Proteinuria; Ramipril; Rats; Rats, Wistar

We studied the effect of ramipril on proteinuria and mild hypertension in a 21-year-old patient affected by glycogen storage disease type I non-A. After few months of therapy we obtained a decrease in total urine protein excretion that later re-increased in spite of the high dose of ACE inhibitor. Even if ACE inhibitors are the only effective therapy for GSD I nephropathy, further studies are requested.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Glucose-6-Phosphatase; Glycogen Storage Disease Type I; Humans; Hypertension, Renal; Kidney Diseases; Male; Proteinuria; Ramipril

Our objectives were to predict the long-term cost and efficacy of the angiotensin-converting enzyme, ramipril, in patients with nondiabetic chronic nephropathies.. The time to end-stage renal disease (ESRD) was predicted by two different models based on the rate of glomerular filtration rate decline (DeltaGFR) and incidence of ESRD (events) measured during the Ramipril Efficacy in Nephropathy Trial in 117 and 166 patients, respectively, randomized to comparable blood pressure control with ramipril or conventional therapy. Direct medical costs of conservative and renal replacement therapy were estimated by a payer perspective, and cases more and less favorable to ramipril were computed by a sensitivity analysis. The study took place at the Clinical Research Center for Rare Diseases, "Aldo & Cele Daccò," Bergamo, Italy. Patients included those with chronic, nondiabetic nephropathies and persistent urinary protein excretion rate >/=3 g/24 h. Time to ESRD, survival, and direct costs of conservative and renal replacement therapy are discussed.. Both in the DeltaGFR-based or events-based models, ramipril delayed progression to ESRD and prolonged patient survival by 1.5 to 2.2 and 1.2 to 1.4 years, respectively, and saved $16,605 to $23,894 lifetime and $2, 422 to $4203 yearly direct costs per patient. Even in the less favorable hypotheses, ramipril allowed lifetime and yearly cost savings that exceeded 10 to 11 and 20 to 40 times, respectively, the additional costs related to prolonged survival.. In our study population, ramipril prolongs life while saving money because of its beneficial effect on the course of nondiabetic chronic nephropathies.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cost-Benefit Analysis; Disease Progression; Drug Costs; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Ramipril; Sensitivity and Specificity; Survival Analysis; Treatment Outcome

The MICRO-HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service.. Non-proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO-HOPE substudy.. Non-proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty-nine percent were already taking an angiotensin-converting enzyme inhibitor. The remaining 764 patients were similar to ramipril-treated participants in the MICRO-HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively.. Of non-proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin-converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Middle Aged; Proteinuria; Ramipril; Risk Factors

In this post hoc, secondary analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, an angiotensin-converting enzyme (ACE) inhibition risk/benefit profile was assessed in 322 patients with nondiabetic, proteinuric chronic nephropathies and different degrees of renal insufficiency. The rate of GFR decline (Delta GFR) and the incidence of end-stage renal disease (ESRD) during ramipril or non-ACE inhibitor treatment were compared within three tertiles of basal GFR. Delta GFR was comparable in the three tertiles, whereas the incidence of ESRD was higher in the lowest tertile than in the middle and highest tertiles. Ramipril decreased Delta GFR by 22%, 22%, and 35% and the incidence of ESRD by 33% (P < 0.05), 37%, and 100% (P < 0.01) in the lowest, middle, and highest tertiles, respectively. Delta GFR reduction was predicted by basal systolic (P < 0.0001), diastolic (P = 0.02), and mean (P < 0.001) BP and proteinuria (P < 0.0001) but not by basal GFR (P = 0.12). ESRD risk reduction was predicted by basal proteinuria (P < 0.01) and GFR (P < 0.0001) and was strongly dependent on treatment duration (P < 0.0001). Adverse events were comparable among the three tertiles and within each tertile in the two treatment groups. Thus, disease progression and response to ACE inhibition do not depend on severity of renal insufficiency. The risk of ESRD and the absolute number of events saved by ACE inhibition is highest in patients with the lowest GFR. However, renoprotection is maximized when ACE inhibition is started earlier and when long-lasting treatment may result in GFR stabilization and definitive prevention of ESRD.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Administration Schedule; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Ramipril; Renal Insufficiency

We studied the effect of ramipril on urinary protein excretion and arterial pressure in a 27-year-old patient with GSD Ia and heavy proteinuria (2-3 g /24 h). Ramipril therapy resulted in an important reduction of proteinuria (0.3-0.5 g/24 h): no changes were observed in arterial pressure and renal function during the 12-month follow-up. We conclude that treatment with ramipril can be employed effectively and safely in GSD Ia patients with nephrotic-range proteinuria.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Glycogen Storage Disease Type I; Humans; Kidney Function Tests; Male; Nephrosis; Proteinuria; Ramipril

Diabetic nephropathy is a glomerular disease, which causes most of premature mortality observed in diabetic patients. The risk of diabetic nephropathy is not entirely accounted for by diabetes duration and control. Diagnosis has been improved by sensitive assays for urinary albumin (microalbuminuria). Treatment relies up on early and liberal use of several antihypertensive agents. Among them, angiotensin I converting enzyme inhibitors rank first, because of their efficacy.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Primary Prevention; Prognosis; Prospective Studies; Proteinuria; Ramipril; Renin-Angiotensin System; Risk Factors; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Humans; Kidney Diseases; Kidney Failure, Chronic; Proteinuria; Ramipril

Fifty patients with stable slight and moderate uncomplicated essential hypertension, treated by ramipril, atenolol, or isradipine, were examined. Total protein and urinary excretion of individual proteins were studied before and after treatment. Urinary concentrations of apolipoproteins A1 and B1, alpha 1-acid glycoprotein, alpha 1-antitrypsin, prealbumin, albumin, beta 2-microglobulin, transferrin, haptoglobin, IgG and IgA, and C3 and C4 complement components were measured. Index of proteinuria selectiveness was calculated for each portion of urine. All three drugs exerted a nephroprotective effect, atenolol being the most active of them. Apolipoproteins, IgG, and complement components were the most valuable for diagnosis. Their excretion correlated with the severity of arterial hypertension and efficiency of treatment. Use of protein markers helps reliably assess the renal function and monitor the treatment efficiency.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Apolipoproteins; Atenolol; Biomarkers; Complement C3; Complement C4; Female; Haptoglobins; Humans; Hypertension; Immunoglobulin G; Immunoglobulins; Isradipine; Kidney; Male; Middle Aged; Models, Theoretical; Monitoring, Physiologic; Prealbumin; Proteinuria; Ramipril; Transferrin

Random, nontimed blood pressure (BP) measurements in the outpatient clinic may fail to provide reliable information on actual daily BP control in renal patients on chronic antihypertensive therapy.. In a cohort of 163 patients with proteinuric chronic nephropathies followed prospectively with repeated BP and glomerular filtration rate (GFR) measurements, we compared baseline and follow-up pretreatment, morning ("trough," measured by standard procedures, and "0 minutes," measured by an automatic device) and post-treatment (120 minutes) measurements, with BP monitored up to 600 minutes after treatment administration. We then evaluated which BP value most reliably predicted GFR decline (delta GFR) and progression to end-stage renal failure (ESRF) over a median (interquartile range) follow-up of 20 (9 to 25) months.. GFR decline was more reliably predicted by systolic as compared with diastolic BP and by pretreatment as compared to post-treatment BP, regardless of the timing and method of measurement, respectively. In particular, at the 120-minute baseline and follow-up measurements, systolic BP had no predictive value in patients with less severe renal insufficiency and baseline diastolic BP, regardless of the level of renal dysfunction. The BP predictive value was remarkably higher in ramipril than in conventionally treated patients. All follow-up-but no baseline-measurements reliably predicted the risk of ESRF in the entire study group.. In patients with progressive chronic nephropathies, systolic BP and pretreatment morning BP measurements are the most reliable predictors of disease outcome and may serve to guide antihypertensive therapy in routine clinical activities and in prospective controlled trials, particularly in patients on angiotensin-converting enzyme inhibitor therapy. Reliability and relevance of single measurements taken at different times after treatment administration are questionable.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Multicenter Studies as Topic; Prognosis; Prospective Studies; Proteinuria; Ramipril; Randomized Controlled Trials as Topic

Topics: Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Disease Progression; Humans; Kidney Failure, Chronic; Prognosis; Proteinuria; Ramipril

Topics: Angiotensin-Converting Enzyme Inhibitors; Confidence Intervals; Glomerular Filtration Rate; Humans; Proteinuria; Ramipril

To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Blood Pressure; Bridged Bicyclo Compounds; Creatinine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Glomerular Filtration Rate; Hypertension; Male; Nephrectomy; Proteinuria; Ramipril; Rats; Sodium, Dietary

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet. 2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period. 3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P less than 0.001). 4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P less than 0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160 +/- 30 mg/day in Group 1, 240 +/- 50 mg/day in Group 2, and 60 +/- 11 mg/day in Group 3. 5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.

Topics: Animals; Blood Pressure; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Diabetes Mellitus, Experimental; Glomerular Filtration Rate; Male; Proteinuria; Ramipril; Rats; Rats, Inbred SHR; Sodium, Dietary; Streptozocin; Time Factors

Topics: Adult; Blood Pressure; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypertension, Renal; Kidney Function Tests; Male; Middle Aged; Nephrotic Syndrome; Proteinuria; Ramipril; Renin