Quantifying the Risk of Incompatible Kidney Transplantation: A Multicenter Study

Abstract

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti‐HLA donor‐specific antibody (DSA). Program‐specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15–2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71–6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28–3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98–7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal‐quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19‐, 1.33‐ and 1.73‐fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22‐, 4.09‐ and 10.72‐fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life‐saving treatment in jeopardy of regulatory intervention.

Functional Outcomes of Face Transplantation

“…(73). In a recent study of Orandi et al (74), mortality after kidney transplantation 5-year unadjusted mortality ranged between 9.3% and 19.1% depending on antibody-related graft compatibility.…”

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

“…Other studies have shown that DSA assessments using MFI alone may not be sufficient for assessing the potential risk for graft damage and decreased survival. Multiple assays are used, such as Flow‐XM,21, 27 C1q‐SAB assays,17 C3d‐SAB assays,28 or IgG‐subclass analysis 29. Our cohort includes 63 patients participating in the Eurotransplant Acceptable Mismatch program with an HLA antibody profile based on CDC, in some cases supplemented with solid phase assays 30.…”

“…As far as we could find, there were no large cohorts describing the effect of pretransplant DSAs with negative CDC‐XM in exclusively living donor kidney transplants without desensitization treatment. Orandi et al21 studied the outcomes of incompatible living donor kidney transplants based on the risk determined by using the SAB assay, flow cytometry crossmatch (FCXM), or CDC‐XM and found that patients with a positive SAB assay and a negative FCXM (n = 185) who were desensitized had similar graft survival as a large group of compatible patients (n = 9669), while patients with a positive FCXM (n = 536) or a positive CDC‐XM (n = 304) experienced an increased risk of graft loss. Another study about living donor transplants performed after a positive FCXM (n = 41) reported that the long‐term survival was worse in desensitized recipients compared with matched recipients with a negative FCXM (n = 41) 22…”

Being Thoughtful about Desensitization

“…This manuscript follows a similar pattern as others reporting the results of recent desensitization trials (2). That is, it fails to acknowledge that, since December 4, 2014, the kidney allocation system (KAS) prioritizes highly sensitized patients and hence, has dramatically reduced the mean waiting time for an organ offer (3).…”