PirfenidoneIsRenoprotectiveinDiabeticKidneyDisease.ppt

Discussion These data are important in interpreting clinical data from antifibrotic approaches. It is clearly conceptually possible to have effects to reduce mesangial matrix expansion and by inference protect the GFR, without necessarily reducing albuminuria. Another important factor that seems to be refractive to PFD treatment is the BP. A BP-lowering effect as a result of PFD treatment cannot be ruled out in our studies; however, PFD was not found to lower BP in previous animal or human studies when BP was measured Discussion Angiotensin receptor antagonists have been used in the db/db mouse model and generally show DN to be delayed by the use of ACEIs Although we have not performed comparative studies with blockers of renin-angiotensin system (RAS), we speculate that treatment with PFD will be additive to that of ACEIs and angiotensin antagonists. As PFD has no reported effect on BP or blocking of the RAS, the mechanism of renoprotection by PFD is likely distinct to blockers of the RAS. Of note, one clinical study with PFD in patients with FSGS did not find any reduction of BP Discussion Thus far, the only clinical study reported to date for PFD in kidney disease is an open-label study of patients with advanced FSGS This study demonstrated that patients with refractory FSGS, whose disease did not respond to steroids, may have a slower decline in the renal function with PFD. Interestingly, PFD was found to have a significant reduction in slowing the rate of progression without affecting albuminuria Discussion However, the lack of effect on proteinuria raises the question of how to monitor patients with antifibrotic therapies to determine whether such an approach provides benefit in our animal study. It is also possible that the lack of rapid weight gain could potentially play a role in reducing the degree of progressive kidney disease; however, it is unlikely that this would be the major reason for the PFD-induced improvement, because the mice did continue to gai