Post-liver transplant chronic renal failure (CRF), defined as estimated glomerular filtration rate (eGFR) <30 ml/min or end-stage renal disease (ESRD), is one of the major post-transplant co-morbidities among non-renal solid organ transplant recipients associated with increased mortality and high costs. Among all non-renal solid organ transplant recipients, liver transplant (LT) recipients have the second highest incidence of post-LT CRF despite the lower level of immunosuppression by calcineurin inhibitors, compared to heart and lung transplant recipients. The spectrum of renal dysfunction in the end-stage liver disease candidates varies from slight elevation in serum creatinine from pre-existing renal disease to full blown renal failure from hepatorenal syndrome requiring renal replacement therapy (RRT). Although candidates with hepatorenal syndrome usually recover their renal function after LT, the timing of renal recovery is variable. Moreover, the factors associated with renal recovery are not very well elucidated. On the other hand, candidates with pre-existing kidney disease are unlikely to recover their renal function after LT and may demonstrate stable renal function or progression to post-LT CRF. The overarching goal of this proposal is to understand the epidemiology of post- LT CRF among LT recipients. The main hypothesis is that there are other recipient, donor and transplant factors besides serum creatinine that contribute to the burden of post-LT CRF. To test this hypothesis, I have three aims:
Aim 1 : To develop and validate a model to predict the risk of post-LT CRF among candidates with eGFR e 30ml/min at LT;
Aim 1 b: To evaluate the contribution of post-LT CRF reflected in post-LT hospitalization rates;
Aim 2 : To examine the factors predicting renal recovery after LT among candidates with eGFR <30 ml/min or on RRT;
Aim 3 : To estimate the predicted a) post-LT CRF rates b) renal recovery rates after LT and c) hospitalization rates under the Model for end-stage Liver Disease (MELD), a measure of waitlist mortality and current allocation tool for LT, and alternative waitlist mortality models. I will use national data from the Scientific Registry of Transplant Recipients (SRTR) and the Centers for Medicare and Medicaid Services (CMS) ESRD Program to conduct these studies. The conducive environment at the University of Michigan, didactic coursework from the highly rated School of Public Health, combined with excellent mentoring from experiential mentors, and access to large national clinical (SRTR) and administrative (CMS) databases will provide me with a strong foundation and aid me in achieving my long term career goal to become an independent, interdisciplinary, clinical investigator and leader in the field of organ transplantation.

Public Health Relevance

Post-transplant chronic renal failure is one of the major public health problems among non-renal solid organ transplant recipients. The proposed studies would provide a better understanding of the epidemiology of post-LT CRF and improve post-transplant outcomes. These results may have implications in prevention and management during pre-, peri- and post-LT period including individualized tailoring of immunosuppression.

Agency
National Institute of Health (NIH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK088946-04
Application #
8661169
Study Section
Digestive Diseases and Nutrition C Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Sharma, Pratima; Shu, Xu; Schaubel, Douglas E et al. (2016) Propensity score-based survival benefit of simultaneous liver-kidney transplant over liver transplant alone for recipients with pretransplant renal dysfunction. Liver Transpl 22:71-9
Levitsky, J; O'Leary, J G; Asrani, S et al. (2016) Protecting the Kidney in Liver Transplant Recipients: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice. Am J Transplant 16:2532-44
Sharma, Pratima; Parikh, Neehar D; Yu, Jessica et al. (2016) Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients. Liver Transpl 22:1092-8
Goodrich, Nathan P; Schaubel, Douglas E; Smith, Abigail R et al. (2016) National Assessment of Hospitalization Rates for Incident End-Stage Renal Disease After Liver Transplantation. Transplantation 100:2115-21
Bari, Khurram; Sharma, Pratima (2015) Impact of body mass index on posttransplant outcomes reexamined. Liver Transpl 21:1238-40
Sharma, Pratima; Bari, Khurram (2015) Chronic Kidney Disease and Related Long-Term Complications After Liver Transplantation. Adv Chronic Kidney Dis 22:404-11
Yu, Jessica; Hosmer, Amy; Parks, Tamara et al. (2015) Predictors of Early Hospitalization After Deceased Donor Liver Transplantation. Dig Dis Sci 60:3242-7
Sharma, Pratima; Schaubel, Douglas E; Goodrich, Nathan P et al. (2015) Serum sodium and survival benefit of liver transplantation. Liver Transpl 21:308-13
Salgia, Reena J; Goodrich, Nathan P; Simpson, Heather et al. (2014) Outcomes of liver transplantation for porto-pulmonary hypertension in model for end-stage liver disease era. Dig Dis Sci 59:1976-82
Barman, Pranab M; Sharma, Pratima; Krishnamurthy, Venkat et al. (2014) Predictors of mortality in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Dig Dis Sci 59:2821-5

Showing the most recent 10 out of 21 publications