Graft function variability and slope and kidney transplantation outcomes

Abstract Background It is critical to identify kidney transplant recipients (KTRs) at higher risk of adverse outcomes to focus monitoring and interventions to improve outcomes. We examined the associations between graft function variability and long-term outcomes in KTRs in an observational study. Methods We identified 2919 KTRs in the Wisconsin Allograft Recipient Database (WisARD) who had a functioning allograft 2 years after transplantation and at least 3 outpatient measurements of estimated glomerular filtration rate (eGFR) from 1 to 2 years post-transplant. Graft function slope was calculated from a linear regression of eGFR and variability was defined as the coefficient of variation around this regression line. Associations of eGFR variability and slope with death, graft failure, cardiovascular events (CVE), and acute rejection were estimated. Results Compared to the lowest quartile, the highest quartile of eGFR variability was associated with a higher risk of death (adjusted hazard ratio [HR]: 1.85; 95% CI: 1.23-2.76), but not with a higher risk of graft failure (subHR: 1.16; 95% CI: 0.85-1.58), independent of eGFR and slope of eGFR. Greater eGFR variability was associated with higher risk of cardiovascular- and infection-related death and CVE but not malignancy-related death or allograft rejection. Including variability of eGFR significantly improved prediction of mortality but not prediction of graft failure. Conclusions Variability of eGFR is independently associated with risk of death, especially cardiovascular disease-related death and CVE, but not graft failure. Variability of eGFR may help identify KTRs at higher risk of death and CVE.