Liver transplantation (LTx) is now well-established as a means of restoring health in patients with end-stage liver disease (ESLD), the 10th leading cause of death in the US. With a long-term goal of optimizing the outcome of patients undergoing LTx, we have developed state-of-the-art statistical models applicable to daily care of LTx patients. One such example is the model for end stage liver disease (MELD), which has been adopted as an indicator of disease serverity with which to determine organ allocation priority for LTx in US. The focus of investigation in this application is renal insufficiency (Rl), a common and important problem in the setting of LTx. Rl prior to LTx is an important predictor of death;in some patients, it also necessitates combined liver-kidney transplantation. After LTx, some recovery of renal function occurs, but in more than a third of patients, Rl fails to resolve. Immunosuppressive drugs after LTx tend to be nephrotoxic, further decreasing the renal function of our patients. In this application, we address these issues by accomplishing the following aims.
Aim1 : We will investigate the best ways to estimate renal function in patients waiting for LTx and determine whether incorporating measures of renal function enhances the accuracy of survival prediction by MELD.
Aim 2 : We will identify predictors of reversibility of renal damage in patients with ESLD to inform the decision whether to perform combined liver-kidney transplantation. Predictive factors to be studied include renal histology (from biopsies obtained at the time of LTx surgery), a profile of serial GFR estimates, and urinary protein markers (microalbumin, a1-microglobulin and retinol-binding protein) prior to LTx.
Aim 3 : We will determine whether single nucleotide polymorphisms on the endothelial nitric oxide synthase gene determinine susceptibility to Rl before and after LTx. The results of Aim 1 will help allocate livers to patients at the highest risk of mortality.
Aim 2 will yield information with which to reduce morbidity and mortality from Rl among LTx patients. The results of Aim 3 will help clinicians better assess patients at risk of Rl in order to optimize pre- and post-LTx management. Taken altogether, our projects will advance knowledge about the renal insufficiency that occurs in patients undergoing liver transplantation and will help achieve optimal outcomes by providing clinical tools with which to identify for patients at risk of poor outcome and to facilitate timely interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK034238-25
Application #
8099045
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Everhart, James
Project Start
1986-01-15
Project End
2012-12-30
Budget Start
2011-07-01
Budget End
2012-12-30
Support Year
25
Fiscal Year
2011
Total Cost
$494,386
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Laskey, Heather L; Schomaker, Nathan; Hung, Kenneth W et al. (2016) Predicting renal recovery after liver transplant with severe pretransplant subacute kidney injury: The impact of warm ischemia time. Liver Transpl 22:1085-91
Udompap, Prowpanga; Mannalithara, Ajitha; Heo, Nae-Yun et al. (2016) Increasing prevalence of cirrhosis among U.S. adults aware or unaware of their chronic hepatitis C virus infection. J Hepatol 64:1027-1032
Allen, Alina M; Kim, W Ray (2016) Epidemiology and Healthcare Burden of Acute-on-Chronic Liver Failure. Semin Liver Dis 36:123-6
Angeli, Paolo; Ginès, Pere; Wong, Florence et al. (2015) Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol 62:968-74

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