Immortal Time-Bias-Corrected Survival of Highly Sensitized Patients and HLA-desensitized Kidney Transplant Recipients

Abstract

Introduction: In the setting of kidney transplantation (KT), we assessed the efficacy of desensitization and compared the survival of desensitized patients (HLA-incompatible KT) with similarly sensitized patients receiving HLA-compatible KT or sensitized patients still on a waiting list after adjusting for the usually unaccounted immortal time bias.

Methods: All patients in a French KT center on the waiting list between August 1994 and December 2019 with a high level of sensitization (panel-reactive antibodies [PRAs] ≥80%) were included. The primary outcome was all-cause mortality. A time-varying covariate Cox survival model was used to account for the immortal time bias. A landmark analysis was used as a sensitivity analysis.

Results: During the study period, 326 patients with high PRAs were followed, among which 147 (45%) remained on the waiting list at the time of last follow-up and 179 benefited from a KT. Thirty-six patients were desensitized, of which 30 received a kidney transplant, including eight deceased kidney donors. There were no differences in mortality rates between desensitized KT patients, nondesensitized KT patients, and waitlisted patients after adjusting for immortal time bias (hazard ratio [HR] = 0.48, P = 0.22). Death-censored graft survival was similar between desensitized and nondesensitized KT patients (HR = 0.92, P = 0.88 adjusting for donor age >65 years, donor status, and time on the waiting list). Mean estimated glomerular filtration rate at 1 year post-KT was similar for desensitized KT patients (53.3 ± 21 vs. 53.6 ± 21 ml/min per 1.73 m² for nondesensitized patients; P = 0.95).

Conclusions: HLA-desensitization was effective for highly sensitized patients and gave access to KT without detrimental effects on patient or graft survival rates.

Keywords: HLA-incompatible; desensitization; end-stage renal disease; kidney graft survival; kidney transplantation; patient survival.

Graphical abstract

Figure 1

Landmark survival analysis within a Cox's model of desensitized patients and comparable highly sensitized patients. A landmark at 36 months postregistration on the waiting list was set. Survival curve of desensitized patients in the setting of HLA-incompatible kidney transplantation (light blue) is compared to highly sensitized patients remaining on the kidney-transplant wait-list (WL) at follow-up (dark blue), to highly sensitized patients that received a transplant without desensitization (green) and to desensitized patients who did not receive a kidney graft (red).

Figure 2

Overall comparison of kidney graft survival (death censored) between desensitized patients and patients that received a kidney transplant without desensitization. Kaplan-Meier estimates of death-censored kidney graft survival of desensitized patients in the setting of HLA-incompatible living donors (LD des, light blue), or deceased-donor (DD des, red) kidney transplantation to highly sensitized patients that received a living donor kidney transplant (LD no des, green), or deceased donors (DD no des, dark blue) without desensitization.