Quantifying lead time bias when estimating patient survival in pre-emptive living kidney donor transplantation

Abstract

Pre-emptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants over 1998-2017. Patients were transplanted pre-emptively (n=1435) or after receiving up to 6 months of dialysis (n=712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated pre-dialysis) using left-truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9 mL/min/1.73m2 in the non pre-emptive, and 9.6 mL/min/1.73m2 in the pre-emptive group. In the matched cohort (n=1398) pre-emptive transplantation was not associated with a survival advantage ((hazard ratio (HR) for pre-emptive vs. non pre-emptive 1.12 (95% CI 0.79-1.61)). Accounting for lead time, moved the point estimates towards a survival disadvantage for pre-emptive transplantation (eg. HR assuming 4mL/min/1.732 /year eGFR decline, 1.21 (0.85,1.73)), but in all cases the 95% CIs crossed 1. The optimal timing of pre-emptive living donor kidney transplantation requires further study.