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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Clinical Investigator Award (CIA) (K08)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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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
Sharma, Pratima; Goodrich, Nathan P; Zhang, Min et al. (2013) Short-term pretransplant renal replacement therapy and renal nonrecovery after liver transplantation alone. Clin J Am Soc Nephrol 8:1135-42
Sharma, Pratima; Barman, Pranab (2013) Everolimus for liver transplant recipients: is it ready for prime time? Gastroenterology 144:459-61
Shreiner, Andrew; Dasika, Narasimham L; Sharma, Pratima (2013) Lower GI bleeding in a patient with cirrhosis and history of colorectal cancer. Peristomal varices secondary to portal hypertension. Gastroenterology 145:e3-4
Sharma, Pratima; Welch, Kathy; Hussain, Hero et al. (2012) Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era. Dig Dis Sci 57:806-12
Sharma, Pratima; Schaubel, Douglas E; Gong, Qi et al. (2012) End-stage liver disease candidates at the highest model for end-stage liver disease scores have higher wait-list mortality than status-1A candidates. Hepatology 55:192-8
Sharma, Pratima; Lok, Anna S (2011) Interferon-free treatment regimens for hepatitis C: are we there yet? Gastroenterology 141:1963-7
Sharma, P; Schaubel, D E; Guidinger, M K et al. (2011) Impact of MELD-based allocation on end-stage renal disease after liver transplantation. Am J Transplant 11:2372-8