Is delayed graft function causally associated with long-term outcomes after kidney transplantation? Instrumental variable analysis

Abstract

Background: Although some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. We investigated this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences.

Methods: We identified 80,690 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients between 1997 and 2010. We used cold ischemia time (CIT) as an instrument to test the hypothesis that DGF causes death-censored graft failure and mortality at 1 and 5 years after transplantation, controlling for an array of characteristics known to affect patient and graft survival. We compared our IVM results with a multivariable linear probability model.

Results: DGF occurred in 27% of our sample. Graft failure rates at 1 and 5 years were 6% and 22%, respectively, and 1-year and 5-year mortality rates were 5% and 20%, respectively. In the linear probability model, DGF was associated with increased risk of both graft failure and mortality at 1 and 5 years (P<0.001). In the IVM, we found evidence suggesting a causal relationship between DGF and death-censored graft failure at both 1 year (13.5% increase; P<0.001) and 5 years (16.2% increase; P<0.001) and between DGF and mortality at both 1 year (7.1% increase; P<0.001) and 5 years (11.0% increase; P<0.01). Results were robust to exclusion of lower quality as well as pumped kidneys and use of a creatinine-based definition for DGF.

Conclusion: Instrumental variables analysis supports a causal relationship between DGF and both graft failure and mortality.

Figure 1. Instrumental variables analysis

1. There must be a relevant association between the instrument and the exposure. This bold line indicates that the instrument is relevant.

2. There must not be a relationship between the instrument and the dependent variable either directly or through association with unobserved variables. The “X” through the thin dotted lines indicates that the instrument is exogenous. Any relationship between the instrument and the dependent variable may only exist through the independent variable.