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

Neel M. Butala, Peter P. Reese, Mona D. Doshi, Chirag Parikh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1008-1014
Number of pages7
JournalTransplantation
Volume95
Issue number8
DOIs
StatePublished - Apr 27 2013

Fingerprint

Delayed Graft Function
Kidney Transplantation
Transplants
Mortality
Linear Models
Kidney
Cold Ischemia
Graft Survival
Random Allocation
Registries
Cause of Death
Creatinine
Transplantation
Tissue Donors

Keywords

  • Allograft failure
  • Cold ischemia time
  • Delayed graft function
  • Kidney transplantation
  • Outcomes

ASJC Scopus subject areas

  • Transplantation

Cite this

Is delayed graft function causally associated with long-term outcomes after kidney transplantation? Instrumental variable analysis. / Butala, Neel M.; Reese, Peter P.; Doshi, Mona D.; Parikh, Chirag.

In: Transplantation, Vol. 95, No. 8, 27.04.2013, p. 1008-1014.

Research output: Contribution to journalArticle

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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.",
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AU - Reese, Peter P.

AU - Doshi, Mona D.

AU - Parikh, Chirag

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N2 - 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.

AB - 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.

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