Reversal of renal disease: is it enough to inhibit the action of angiotensin II?

Abstract

Over the last years, evidence emerged demonstrating that the progression of renal fibrosis is reversible in experimental models. The present review summarizes the new insights concerning the mechanisms of progression and regression of renal disease and examines this novel evidence under the light of feasibility and transfer to human nephropathies. The involved mechanisms are discussed with particular emphasis on the fibrotic role of vasoactive peptides such as angiotensin II and endothelin, and growth factors such as transforming growth factor b (TGFb). The possibility of regression is introduced by presenting the in vivo efficiency of anti-hypertensive treatments and of systems that antagonize the fibrogenic action of TGFb such as bone morphogenic protein-7 (BMP-7) and hepatocyte growth factor. Finally, we provide a brief description of the promising future directions and clinical considerations about the applications of the experimental data to humans.

Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist

“…On the other hand, some authors have reported ACE inhibition is more effective than ETA blockade in prevention of renal and cardiac dysfunctions in type 2 diabetes (Gross et al, 2004(Gross et al, , 2003a(Gross et al, , 2003b. Similarly in the L-NAME induced hypertensive model, although bosentan reversed renal fibrosis, such effects were found to be less compared to angiotensin II blockade (Chatziantoniou and Dussaule, 2005;Dussaule and Chatziantoniou, 2007). Interestingly these two groups of drugs demonstrated synergistic effects in the prevention of advanced structural changes such as tubulointerstitial fibrosis, podocyte loss in the kidney of rats with type 1 diabetes as demonstrated using a selective ETA blocker and ACE blocker (Gagliardini et al, 2009).…”

Mouse Mast Cell Protease-4 Deteriorates Renal Function by Contributing to Inflammation and Fibrosis in Immune Complex-Mediated Glomerulonephritis

“…To establish whether mMCP-4 interferes with the remodeling component of anti-GBM–induced GN, we examined the expression of Ang II, a peptide with multiple proinflammatory roles that promotes proliferation and fibrogenesis in the kidney (21, 44). The increase in local expression of interstitial Ang II observed in WT mice upon anti-GBM stimulation was not apparent in mMCP-4–deficient animals.…”

“…The murine counterpart of human mast cell chymase, mMCP-4, was shown to attract granulocytes and macrophages (17, 18), to regulate homeostatic intestinal epithelial migration and barrier function (19), and to convert Ang I into Ang II, a vasoactive peptide with potent inflammatory and fibrogenic properties (20, 21). These observations suggest that mMCP-4 may play an important role in tissue inflammation and remodeling in the kidney.…”

Alteration of connexin expression is an early signal for chronic kidney disease

“…These pathologies may affect any of the kidney structures including renal vessels, glomeruli, and the tubulointerstitial compartment. All these events are linked by their common ability to promote development of chronic inflammation leading to fibrosis and to progressive decline of renal function (7).…”