P1638EARLY RENAL FUNCTION TRAJECTORIES, CYTOMEGALOVIRUS SEROSTATUS AND LONG-TERM GRAFT OUTCOMES IN KIDNEY TRANSPLANT RECIPIENTS: A BAYESIAN ANALYSIS STUDY
Authors: Law Jonathan , Borrows Richard , McNulty David , Sharif Adnan , Ferro Charles 
Published: June 2020

Abstract

Background and Aims
Despite significant improvements in short-term kidney transplant survival, long-term graft survival has not improved to the same degree with transplant failure being a top four cause of end-stage renal disease. We previously showed in a prevalent kidney transplant population that most patients do not experience linear renal function trajectories1. Many, instead, have periods of stability whilst others experience rapid progression. We also showed that episodes of rapid progression are associated with graft loss. Understanding trajectories of kidney allograft function is, therefore, key to defining the mechanisms underpinning allograft dysfunction. In this study, we evaluated the allograft function trajectories and associated factors, in an unselected, incident population of kidney allograft recipients in the early period post-transplantation. We also investigate whether episodes of rapid progression or non-progression are associated with graft loss in an extended follow-up period

Method
Demographic and clinical data were obtained from electronic health records. We used Bayesian smoothing techniques1 to create 10,000 Monte Carlo sample curves for 310 kidney transplant recipients for estimated glomerular filtration rates from 3-27 months after transplantation. This technique produces a smooth curve for each patient that reflects the gradual, longer term changes in eGFR values, rather than the rapid, short-term changes because of clinical and biologic variation as well as other interference including measurement error. The estimated trajectory is a smooth curve, allowing its slope to be calculated month by month. The probability of having an episode of rapid progression (decline greater than 5 ml/min/1.73m2/year in any 1-month period) and non-progression (decline no greater than -1ml/min/1.73m2/year) were calculated. Overall follow-up period was 8 years. Factors associated with having an episode of rapid progression, non-progression, and associations with long-term graft loss were explored.

Results
A median of 54 eGFR measurements per patient were available from 3-27 months for analysis. 65 patients (21%) had a probability of rapid progression greater than 0.8. During the follow-up period, 34 patients (11%) lost their graft. In multivariable Cox Proportional Hazard analysis, a probability greater than 0.8 of rapid progression was associated with long-term death-censored graft loss (Hazard ratio, 2.17; 95% CI, 1.04-4.55). In separate multivariable logistic regression models, cytomegalovirus serostatus donor positive to recipient positive (Odds ratio [OR], 3.82; 95% CI 1.63-8.97), CMV donor positive (OR 2.06; 95% CI 1.15-3.68), and CMV recipient positive (OR 2.03; 95% CI 1.14-3.60) were associated with having a greater than 0.8 probability of an episode of rapid progression. Having a probability greater than 0.8 of non-progression was not associated graft loss.

Conclusion
Early episodes of rapid progression are associated with long-term death-censored graft loss and are associated with cytomegalovirus seropositivity. Possible mechanisms include adverse cytomegalovirus-related immunomodulatory effects resulting in increased infections, glomerular injury and allograft vasculopathy. Further investigation into these factors may yield potentially modifiable risk factors and improve graft survival.