Modeling Long-Term Graft Survival With Time-Varying Covariate Effects: An Application to a Single Kidney Transplant Centre in Johannesburg, South Africa.

Patients' characteristics that could influence graft survival may also exhibit non-constant effects over time; therefore, violating the important assumption of the Cox proportional hazard (PH) model. We describe the effects of covariates on the hazard of graft failure in the presence of long follow-ups. We studied 915 adult patients that received kidney transplant between 1984 and 2000, using Cox PH, a variation of the Aalen additive hazard and Accelerated failure time (AFT) models. Selection of important predictors was based on the purposeful method of variable selection. Out of 915 patients under study, 43% had graft failure by the end of the study. The graft survival rate is 81, 66, and 50% at 1, 5, and 10 years, respectively. Our models indicate that donor type, recipient age, donor-recipient gender match, delayed graft function, diabetes and recipient ethnicity are significant predictors of graft survival. However, only the recipient age and donor-recipient gender match exhibit constant effects in the models. Conclusion made about predictors of graft survival in the Cox PH model without adequate assessment of the model fit could over-estimate significant effects. The additive hazard and AFT models offer more flexibility in understanding covariates with non-constant effects on graft survival. Our results suggest that the period of follow-up in this study is long to support the proportionality assumption. Modeling graft survival at different time points may restrain the possibility of important covariates showing time-variant effects in the Cox PH model.