Date of Award
Medical Doctor (MD)
Chirag R. Parikh
Medicine, Sociology, Economics
This thesis details 2 studies using novel approaches to understand kidney transplant outcomes: instrumental variables and social network analysis. Together, these studies demonstrate the value of interdisciplinary approaches to advance the field of kidney transplantation.
While some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. In our first study, we investigate this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences. We identified 73,714 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients (SRTR) between 1997 and 2010. We used cold ischemia time (CIT) as an instrument to test the hypothesis that DGF causes death-censored graft loss and mortality at 1 and 5 years post-transplant, controlling for an array of characteristics known to affect patient and graft survival. We compared our IVM results to a multivariable linear probability model (LPM). DGF occurred in 27% of our sample. Graft loss 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 LPM, DGF was associated with increased risk of both graft loss 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 loss at both 1 year (13.6% 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). We conclude that instrumental variables analysis supports a causal relationship between DGF and both graft loss and mortality.
Given growth in kidney transplant waiting lists and discard rates, donor kidney acceptance is an important problem. In our second study, we apply tools of social network analysis to examine whether Organ Procurement Organization (OPO) network centrality affects discard rates and recipient outcomes. We identified 96,364 kidneys recovered for transplant from deceased donors in SRTR between 2000 and 2010 and transplanted to adults without previous transplant or 0 HLA mismatches. We constructed the kidney transplant network for each year with each OPO representing a node and each kidney sharing relationship between OPOs representing a directed tie between nodes. The primary exposures were OPO out-degree centrality and in-degree centrality. The primary outcomes were kidney discard, DGF, and 1-year graft loss. We constructed logistic regression models, restricting analysis to observations from the 50% of OPOs with highest discard rate and stratifying remaining OPOs into 2 groups by kidney volume. Models controlled for kidney donor risk index, mean waiting list time, and procurement year and region dummies. Among high-volume OPOs, an increase in one additional OPO to which a kidney was given by a procuring OPO in the procurement year was significantly associated with a 1.8% lower likelihood of discard for a given kidney (OR: 0.982, CI: 0.97, 0.995), but had no association with 1-year graft loss. We conclude that interventions to promote broader inter-OPO sharing should be developed to reduce discard rates.
Butala, Neel, "Novel Interdisciplinary Approaches To Understanding Kidney Transplantation Outcomes" (2014). Yale Medicine Thesis Digital Library. 1863.