Dr. Hricik: So I think the answer to that question has become a moving target in the past 10 years or so, in part because the very term chronic allograft nephropathy, I think, is increasingly becoming obsolete—and the reason for that is we now recognize that there are various histologies that constitute that very broad definition. So we now know, for example, that some patients have so-called transplant glomerulopathy, which was once a component of chronic allograft nephropathy. Now we know that transplant glomerulopathy is probably a form of antibody-mediated rejection.1 There are some patients who have pure interstitial fibrosis and tubular atrophy, or IFTA, on their biopsies. Some of these patients may have true calcineurin inhibitor toxicity, which could warrant conversion to another agent.
But data have now convincingly shown that fibrosis alone is probably not as harmful to long-term graft survival as we once thought it was—if you have fibrosis associated with inflammation, that tends to be a harbinger for poor graft survival.2 So if anything, eliminating CNIs in patients who have transplant glomerulopathy or fibrosis with inflammation is probably not a good idea.
Narrator: In addition to glomerular filtration rates >40 mL/min, other parameters that are needed prior to the switch is made in order to have a benefit, as per this study, are protein excretion <800 mg/day and creatinine <2.5 mg/dL.
Dr. Hricik: Now, for patients with pure IFTA, there are some conversion regimens that can be considered. I think some patients benefit from conversion to an [m]TOR inhibitor [or mammalian target of rapamycin], but results of the CONVERT study showed us that most of the benefit occurs in patients who already have glomerular filtration rates >40 mL/min and who have minimal proteinuria.3 Otherwise, conversion to [m]TOR inhibitors is not very successful. And of course, the newest drug that some are considering is belatacept. But right now I would say the scientific evidence for converting patients with chronic renal dysfunction to belatacept is not robust,4,5 and further studies are needed.