Kidney Transplantation. Arrival of the Next Frontier. Part II

As featured in the July edition of Kidney News, this issue again highlights advances in kidney transplantation. The July issue included articles on the new kidney transplant allocation system, updates from the apolipoprotein L1 (APOL1) Long-term Kidney Transplantation Outcomes (APOLLO) study, recent groundbreaking advances in xenotransplantation, racial inequities and measures to address them, and a review of the increasingly encountered challenge of oxalosis in kidney transplantation. We now turn our attention to genomics, biomarkers, new insights into thrombotic microangiopathy (TMA), focal segmental glomerulosclerosis recurrence in transplantation, and finally, updates on the use of belatacept.

Since the first successful kidney transplant in 1954, genetic mismatch has been recognized as an important factor in determining graft outcomes. In this issue, Dr. Elhassan and colleagues track the arc of genomics in kidney transplantation over the last six decades. We now recognize that genomics in kidney transplantation goes beyond the human leukocyte antigen system. Genome-wide association studies have identified genetic signals that can be associated with 5-year graft outcomes and development of skin cancer (1). In addition to discussing genetic determinants affecting the metabolism of immunosuppression, the authors delve into the novel concept of “genomic collision,” defined as a phenomenon in which kidney donor cells express proteins on their surface that are not present in the recipient and elicit an immunologic response, which ultimately results in measurable donor-specific antibodies and poorer graft outcomes (2).

Reliable biomarkers continue to elude the field of kidney transplantation, and a large number of kidneys may be discarded because of unfavorable “donor characteristics,” despite the lack of association between severe donor kidney injury and adverse recipient outcomes (3). Drs. Wen and Parikh discuss emerging kidney repair biomarkers that could be used to predict the likelihood of delayed graft function and therefore, reduce organ discards.

Dr. Java provides new insights into the pathogenesis of TMA in transplantation, which can be a diagnostic conundrum. She describes different presentations of TMA, an algorithmic approach in the setting of suspected disease, and guidelines for the duration of eculizumab treatment.

Focal segmental glomerulosclerosis (FSGS) continues to be a therapeutic quandary for both general and transplant nephrologists. Drs. Hullekes and Verhoeff and co-authors provide a background to this disease in kidney transplantation, along with updates to our understanding of the pathogenesis. Anti-nephrin antibodies have been increasingly implicated in FSGS, with the authors proposing their use as a potential biomarker before transplantation in a subset of patients (4, 5). In addition, they discuss the importance of genetic testing in FSGS to further clarify risk of recurrence post-transplantation.

Belatacept is increasingly being used as part of the immunosuppression regimen in the United States. Dr. Kott and colleagues discuss recent studies involving belatacept and various settings in which it may be considered an alternative to calcineurin inhibitors.

The content covered in these editions of Kidney News has shown that kidney transplantation has progressed on multiple fronts. There continue to be multiple challenges and uncertainties that will require a concerted, patient-centered effort to solve.