Discussion
ABMR, ESKD, infections, fungal infections, impaired immunity
INFECTIONS, FUNGAL INFECTIONS, KIDNEY DISEASE, COMPLICATIONS
Management of highly sensitized ESKD patients represent a conundrum for KT teams. It is well recognized that patients who are denied a KT have an increased mortality compared to recipients of an HLA incompatible KT, and this holds true in the presence of a historic positive cytotoxic crossmatch [Several strategies aimed at reducing anti-HLA antibody levels and enhancing the chances of HS patients being offered a KT have been elaborated. Early protocols utilizing exclusively IVIg [With regards to apheresis techniques, IADS has been shown to be more efficient than plasma exchange for lowering anti-HLA antibody titers [Only few experiences with IADS-based desensitization have been reported so far. Using a protocol akin to ours, Noble et al reported on 36 patients including 8 living donors. In six cases (16.7%) the IADS protocol was aborted due to failure to clear DSA or complications. With a different approach [However, the shortcomings of desensitization protocols should be recognized. While these have been instrumental in offering a therapeutic opportunity for HS patients, post-KT DSA rebound significantly increases the risk of ABMR as shown in the We observed significant infectious complications in our cohort. This is unsurprising for a number of reasons. HS ESKD patients may have impaired immunity due to previous immunosuppression for native kidney disease, previous KT and on top of the burden of dialysis and ESKD itself. The multi-targeted immune desensitization protocol used here would have further enhanced the infectious risk. The high rate of invasive fungal infections (We recognize the limitations of the current study. Our data are observational and from a single center with a modest number of patients. However, these types of patients, that is those who are HS and who have been waitlisted for a significant amount of time, are uncommon. Nevertheless, as the fraction of HS patients is expected to grow over the coming years there is a dire need to devise strategies to raise the prospects of KT. Currently, there is no consensus on how to manage this very high-risk group resulting in divergent strategies around the world. Unfortunately, outcomes for these patients are dismal and so transplantation remains their only hope, albeit with the risks described here.When contemplating IADS-based desensitization KT the risks entailed by remaining on the waiting list should be carefully weighed against the hazards of a potentially short-lived graft function, the high likelihood of ABMR and severe infections. Importantly, immunoadsorption strategy is not associated with an improved probability of being alive with a functioning graft at the end of the follow-up compared to those receiving no immunoadsorption. Indeed, those who received immunoadsorption had poorer graft outcomes following transplantation.In our experience, the exceedingly high risk of ABMR and lethal infections outweighed the potential benefits of KT, precluding the universalization of our IADS-based desensitization strategy in its current scheme. However, there may be select groups of patients that might benefit from immunoadsorption and these should be defined in future studies. Single IADS, or better yet imlifidase, may represent less cumbersome options. Regardless of the adopted strategy, clinicians should be wary of the high rate of ABMR and candidates should be selected and informed accordingly.