Glomerular scarring: Can we delay or even reverse glomerulosclerosis by RAAS inhibition?

Abstract

In a recent publication, Macconi et al. show that reversal of focal and segmental glomerulosclerosis (FSGS) lesions in aged Munich Wistar Frömter (MWF) rats treated with high-dose angiotensin-converting enzyme inhibitors (ACE) inhibitors is associated with a reconstitution of the number of podocytes [1]. Aged MWF rats spontaneously develop hypertension, proteinuria, and focal and segmental glomerulosclerosis due to an unknown genetic defect. In 2006, the Remuzzi group has shown that treatment of aged MWF rats with very high doses of the ACE inhibitor lisinopril (>10 mg/kg/day) could revert proteinuria, and additional loss of renal function could be prevented effectively [2]. A detailed histological analysis showed that glomerular scarring was effectively reduced by this treatment suggesting that regression of glomerular scars could be achieved in these animals. In a recent paper, Macconi et al. followed up on this important finding and investigated changes in resident glomerular cells. They showed th the absolute podocyte number was decreased from 159 to 109 podocytes per glomerulus in aged MWF rats and that lisinopril treatment could restore the podocyte number to 144 (P > 0.01). As a mechanism for this cell renewal, the authors show that ∼10% of podocytes co-expressed the proliferation marker Ki-67 in the treated rats suggesting that podocytes could undergo cell divisions in situ or that these cells could be regenerated from parietal cells. To support the latter notion, the authors show that a significantly higher proportion of parietal podocytes were present in the treated animals. This raises the interesting possibility for the existence of a glomerular regenerative mechanism. © The Author 2010.