Quantifying the risk of incompatible kidney transplantation: a multicenter study

Area of Science:

• Nephrology
• Transplantation Immunology
• Health Policy

Background:

• Incompatible live donor kidney transplantation (ILDKT) improves survival for patients with anti-HLA donor-specific antibodies (DSA).
• Current Program-Specific Reports (PSRs) do not account for ILDKT, creating regulatory vulnerabilities for transplant centers.
• DSA can be categorized by crossmatch results: positive Luminex, negative flow (PLNF); positive flow, negative cytotoxic (PFNC); and positive cytotoxic (PCC).

Purpose of the Study:

• To analyze the association between different categories of DSA and outcomes (graft loss, mortality) after ILDKT.
• To evaluate the impact of ILDKT on the risk of transplant centers being flagged by the Centers for Medicare & Medicaid Services (CMS).

Main Methods:

• Retrospective analysis of DSA data from 22 centers, categorizing patients into PLNF, PFNC, and PCC groups.
• Statistical adjustment for PSR model factors, comparing outcomes against 9669 compatible kidney transplant recipients.
• Simulation of CMS flagging criteria to assess the effect of varying ILDKT rates on center risk.

Main Results:

• While PLNF patients showed similar graft loss and mortality to controls, PFNC and PCC groups experienced significantly increased graft loss and mortality within the first year post-transplant.
• PFNC was associated with a 1.64-fold increased risk of graft loss and 2.04-fold increased mortality.
• PCC was associated with a 5.01-fold increased risk of graft loss and 4.59-fold increased mortality.
• Centers performing higher rates of ILDKT (especially PCC) faced substantially higher odds of being flagged by CMS.

Conclusions:

• ILDKT, particularly with higher levels of DSA (PFNC and PCC), is associated with increased short-term graft loss and mortality.
• The current PSR system's failure to account for ILDKT places centers performing this life-saving procedure at significant regulatory risk.
• Revisions to PSRs are needed to accurately reflect the outcomes of ILDKT and prevent undue regulatory scrutiny of centers providing this critical treatment.