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The renin-angiotensin system in lupus: physiology, genes and practice, in animals and humans

Immunology/Allergy Unit, Rabin Medical Center, Petah Tiqwa, Israel, teplit{at}zahav.net.il

Y Shoenfeld

Department of Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel

A Tanay

Rheumatology, and Immunology and Allergy Unit, Wolfson Medical Center, Holon Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Although multiple studies suggest a potential role for angiotensin II in inflammation, most were performed either in vitro or in animals with non-immune-complex-mediated diseases. Extrapolation of these findings to humans, particularly patients with lupus, which involves multiple immunoregulatory pathways, is unclear. In autoimmune-prone MRL/lpr mice, angiotensin-converting-enzyme (ACE) inhibition improved survival although to a lesser degree than cyclophosphamide and diminished the glomerular histopathologic damage, proteinuria, lymphoid hyperplasia, dermatitis, and hypergammaglobulinemia, with a reduction in TGF-beta1 and beta 2 expression in the kidneys and renal chemokine mRNA expression. Spleen levels of IL-4 and IL-10 were also reduced. Uncontrolled studies in patients with treatment-refractory lupus nephritis showed a significant reduction in proteinuria with ACE-inhibitors and Angiotensin receptor blockers treatment. The ‘masking’ effect of ACE-inhibitors should be taken into consideration, as an exacerbation of lupus nephritis may be missed when estimated by the magnitude of proteinuria, which is decreased by these treatments. No single ACE genotype was consistently associated with subsets of SLE patients. In retrospective analyses, ACE-inhibitor use predicted a favourable outcome in 94 cases of pauci-immune vasculitis. The attenuating effect of angiotensin II inhibitors on the progression of chronic renal disease is well recognized. The data on the role of this intervention in lupus is limited.

Key Words: ACE inhibitors • angiotensin • angiotensin receptor antagonist • lupus nephritis • SLE • systemic lupus erythematosus

Lupus, Vol. 15, No. 6, 319-325 (2006)
DOI: 10.1191/0961203306lu2306rr


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