Renal Function Variability: An Independent Risk Factor for Graft Loss and Death following Kidney Transplantation

Abstract

Background: Several studies have been performed to evaluate surrogate markers of long-term allograft function in renal transplant recipients. These include serum creatinine, estimated glomerular filtration rate (eGFR), slope of eGFR, and more recently eGFR variability. The aim of this study was to measure eGFR slope while assessing the variability of this slope and if high variability occurring at any time post-transplant was predictive of poorer long-term outcomes in a large cohort of kidney transplant recipients. Methods: Adult solitary kidney transplant recipients transplanted between July 1, 2005 and July 31, 2015 were included. The primary outcome was time to graft loss, defined as return to chronic dialysis, retransplant, or death. Secondary outcomes were death-censored graft loss and acute allograft rejection. Cox regression was utilized for primary and secondary outcomes. Multivariate logistic regression was used to determine baseline factors predictive of high eGFR variability. Results: A total of 1,543 patients were included in the analysis. The percentage of patients who experienced an eGFR coefficient of variation of <30% was 79.6% (1,229/1,543), while 20.4% (314/1,543) patients had high eGFR variability (≥30%). Patients with high eGFR variability tended to be younger, African-American and female. Those with higher eGFR variability, accounting for confounding and other eGFR measures (peak and slope), had significantly lower overall patient and graft survival. Conclusion: This study provides a novel analysis of the utility of eGFR variability in a large cohort. The clinical use of the slope of eGFR and eGFR variability may aid in predicting long-term graft outcomes and facilitate early patient discussions to change the trajectory of allograft function.

Relationship of Serum Bicarbonate Levels with 1-Year Graft Function in Kidney Transplant Recipients in Switzerland

“…Interestingly, in our cohort, the individual course of eGFR varied strongly between the 90 study participants. This strong variability has been previously reported [24, 25] and is not surprising, as many factors such as medication, donor characteristics, and general health status differ strongly not only between patients but also for the individual patient, and for medication. However, high variability of kidney function after KTx has been described as an independent risk factor for graft loss and death [24-26].…”

“…This strong variability has been previously reported [24, 25] and is not surprising, as many factors such as medication, donor characteristics, and general health status differ strongly not only between patients but also for the individual patient, and for medication. However, high variability of kidney function after KTx has been described as an independent risk factor for graft loss and death [24-26]. Thus, we used a mixed linear model including all available eGFR and bicarbonate values over the first year after KTx.…”

Graft Function Variability and Slope and Kidney Transplantation Outcomes

“…Few studies have assessed the association between graft function variability and outcomes among KTRs. 5 , 8 These studies were not able to incorporate graft function slope appropriately and failed to differentiate the association of graft function variability with death from those with graft failure, which are competing risk events posttransplantation. These studies also did not assess whether variability provides additional prognostic information for transplantation outcomes.…”

Pretransplant dialysis modality and long‐term patient and kidney allograft outcome: a 15‐year retrospective single‐centre cohort study

“…Furthermore, changes in graft function over time as estimated by eGFR slope have been shown to be highly correlated with measured iothalamate GFR slopes in allograft recipients, thus providing valuable information for the trajectory of functional decline . In addition, it has been shown that eGFR slope is a strong predictor of long‐term kidney allograft outcome and may facilitate its prediction . While the overwhelming number of studies analysing pretransplant RRT modality did not incorporate data on actual allograft function, there are only two reports taking into account creatinine or eGFR, both failing to demonstrate graft function differences in recipients with pretransplant HD versus PD regimens.…”