ramipril and Glomerulonephritis--IGA

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

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

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

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

The early suspension of Altitude trial in recent years has induced most nephrologists and cardiologists to abandon Aliskiren use. Consequently, the potential usefulness of the direct renin inhibition in IgA glomerulonephritis remained an under-investigated therapeutic option.. We report the case of a 53 years old IgA GMN patient unresponsive to all conventional anti-angiotensin-2 agents, steroids and immunosuppressants, in which the administration of Aliskiren permitted to achieve and maintain a complete proteinuria remission in the absence of any adverse event.. Aliskiren might represent a valid and safe therapeutic option in IgA GMN, although further investigations would be needed to confirm this conclusion.

Topics: Amides; Biopsy, Needle; Drug Administration Schedule; Drug Resistance, Multiple; Drug Therapy, Combination; Follow-Up Studies; Fumarates; Glomerulonephritis, IGA; Humans; Immunohistochemistry; Immunosuppressive Agents; Irbesartan; Male; Middle Aged; Prednisone; Ramipril; Retreatment; Time Factors; Treatment Outcome

Topics: Adrenal Cortex Hormones; Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Drug Therapy, Combination; Glomerulonephritis, IGA; Humans; Prednisone; Ramipril; Randomized Controlled Trials as Topic; Survival Rate; 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