We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Effect of combining ACE inhibitor and statin in severe experimental nephropathy.
- Authors
Zoja, Carla; Corna, Daniela; Rottoli, Daniela; Cattaneo, Dario; Zanchi, Cristina; Tomasoni, Susanna; Abbate, Mauro; Remuzzi, Giuseppe
- Abstract
Effect of combining ACE inhibitor and statin in severe experimental nephropathy. Background. Angiotensin-converting enzyme (ACE) inhibitor therapy given soon after disease induction uniformly prevents proteinuria in virtually all models of disease progression. This does not necessarily apply to patients with proteinuric nephropathies, who might be referred late in the course of their disease. Here we used a severe rat model of passive Heymann nephritis (PHN), which may mimic advanced phases of human membranous nephropathy, to study the response to ACE inhibitor alone or in combination with a HMG CoA reductase inhibitor (statin) that independently of the cholesterol-lowering effect influences pathways involved in inflammatory and fibrogenic processes. Therapies started when animals had massive proteinuria and renal lesions. Methods. PHN was accelerated by uninephrectomy seven days after IV injection of rabbit anti-FX1A antibody. Four months later, when massive proteinuria and renal lesions were present, the rats were divided into five groups and daily given orally: vehicle; lisinopril 40 mg/L; lisinopril 400 mg/L; simvastatin 2 mg/kg b.i.d; or lisinopril 40 mg/L plus simvastatin. Six normal rats served as controls. Animals were sacrificed at 10 months. Results. By the end of the study three PHN rats died in the vehicle group, four in the group given lisinopril at 40 mg/L and two in the group at 400 mg/L, whereas all rats on simvastatin or combined therapy were alive. Blood pressure increased during time in PHN and was normalized by treatment with ACE inhibitor and combined therapy. Even at the high dose lisinopril failed to reduce proteinuria. Simvastatin only partially affected proteinuria. However, combining lisinopril with simvastatin had a remarkable antiproteinuric effect, such that at 10 months the urinary proteins were comparable to pre-treatment values and significantly lower than either the vehicle or lisinopril groups. Hypercholesterolemia of PHN rats...
- Subjects
ACE inhibitors; EPITHELIAL cells; KIDNEY diseases
- Publication
Kidney International, 2002, Vol 61, Issue 5, p1635
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00332.x