Treatment of IgA Nephropathy with ACE Inhibitors

Abstract

Abstract. Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria Ն 0.5 g/d, and serum creatinine (SCr) Յ 1.5 mg/dl were randomly assigned either to receive enalapril (n ϭ 23) or to a control group (n ϭ 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr Ͼ 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapriltreated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 Ϯ 37 mo in the enalapril group and 74 Ϯ 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P Ͻ 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P Ͻ 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr Ͼ 1.5 mg/dl at the last visit (P Ͻ 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P Ͻ 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.A considerable proportion (40 to 60% according to different series) of IgA nephropathy (IgAN) patients develop progressive renal insufficiency (1-4). Impairment in renal function, high BP, and proteinuria Ͼ 1 g/d are considered as the more important clinical predictors of an unfavorable evolution (1-6). With the exception of those patients who develop glomerular crescents or malignant hypertension, the rate of progression in IgAN patients with an unfavorable evolution is remarkably slow; end-stage renal failure develops in 20% of the cases after 10 yr and in 30% after 20 yr (1).Notwithstanding to be the most common type of glomerular disease in the world, surprisingly few prospective and controlled studies focused on the therapy of IgAN have been performed. Corticosteroids have shown a beneficial effect on the progression of IgAN in some randomized clinical trials (7,8), but concerns about its possible side effects in a disease with such a lengthy clinical course have been raised. Fish oil induced a decline in the rate of progression in a controlled study (9), but other studies failed to confirm this beneficial influence (10).Several multicenter and prospective studies have demonstrated that ACE inhibitors induce a significant renoprotective effect on the progression rate of both diabetic and nondiabetic chronic proteinuric nephropathies (11,12,13). This beneficial influence is closely related...

IgACE

“…While our enrollment was proceeding slowly, because ACE-I therapy was becoming a widely used treatment for patients with IgAN (even though not supported by evidence-based medicine), another group was performing an RCT in adults; this was published by Praga et al (26) in 2003. Compared with this study, our report has the advantages of being a placebocontrolled study (this is the first placebo-controlled RCT in IgAN), of being multicenter based, and of having well-defined selection criteria.…”

Clinical Trial to Evaluate Omega-3 Fatty Acids and Alternate Day Prednisone in Patients with IgA Nephropathy

“…Proposed therapies include corticosteroids (8 -20), fish oil (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), and angiotensin-converting enzyme (ACE) inhibitors (32,33). Although some studies of corticosteroids and omega-3 fatty acids (O3FA) have reported significant benefit, others showed no apparent benefit.…”

“…Possible explanations for the variable outcomes in patients who were treated with fish oil supplements include differences in the patient populations and variations in the dose or composition of the fish oil used. ACE inhibitors have been helpful in patients with a wide assortment of glomerulopathies, including patients with IgAN (32,33). This study was designed to evaluate whether a 2-yr course of alternate-day prednisone or of daily O3FA on a background of ACE inhibitor therapy in hypertension patients provides an effective means of preventing deterioration of GFR in young patients with IgAN.…”

Quantitative Appraisal of Treatment Options for IgA Nephropathy

“…cyturia using immunosuppressive drugs is unmatched by data from ACEI studies ( Figure 1). Only two randomized, controlled trials detailed prevalent BP: in our study of immunosuppressive drugs, mean arterial pressure (MAP), matching in both cohorts at 101 mmHg, was 135/85 or 140/80, 1 remarkably equal to levels achieved in the ACEI study 12 ; pressures in both were Ͻ10% above current recommendations: MAP 92 (125/75). However, the benefits of BP control, more so using ACEI and/or angiotensin receptor blockers (ARB), have an event ratio effect in preserving renal function in IgAN an order of magnitude lower than those of a combined immunosuppressive regimen (Table 1).…”

“…ACEI do not improve erythrocyturia, 12 and, typically, proteinuria is reduced only 50 to 70% with ACEI or combined ACEI/ARB, 13 reversing on withdrawal (Table 1). This striking contrast seems powerful confirmation that only immunosuppressive drugs can induce clinical remission in IgAN.…”