ESTIMATING THE BENEFITS OF EARLY PANCREAS ONLY TRANSPLANTATION IN IDDM: A THEORETICAL ANALYSIS

Abstract

865 Some patients with type 1 diabetes mellitus and early retinopathy and nephropathy (proteinuria but preserved function) seek a pancreas transplant alone (PTA) to prevent blindness and end stage renal failure (ESRD). The need to take nephrotoxic immunosuppressive therapy has tempered the enthusiasm of providers. This analysis determines how effective PTA should be to warrant transplantation before irreversible end organ disease develops. The model assumes that diabetic patient mortality increases with age and level of renal impairment. Development of blindness and rate of deterioration in renal function were taken from the DCCT model (JAMA 1996). The model also assumes a 3-4% peri-operative surgical mortality, an increase risk of death with immunosuppressive therapy (infection and cancer), forestalls blindness and ESRD only with normal pancreas function, did not alter cardiovascular disease, and may induce ESRD from nephrotoxic therapy. The model predicts that with an overall pancreas graft life expectancy of 10 years, a 3.2 year patient survival advantage could accrue to IDDM patients, despite the up front mortality from surgery and a 20% higher annual mortality from immunosuppressive therapy. This strategy could result in a 50% reduction in blindness and 27% reduction in ESRD. In a sensitivity analysis, a 1% annual incidence of ESRD from nephrotoxicity would limit the gain in patient survival to 1.9 years and a 2.7% annual incidence of ESRD from nephrotoxicity would negate any survival benefit from PTA. Shorter PTA graft expectancy, transplanting at earlier stages of disease, transplanting in patients with slower transitions from proteinuria to ESRD, or assuming PTA has less of an impact on preventing blindness would also reduce benefit. Incorporating reasonable costs, utilities and discount rates, the calculated cost/quality life year gained for PTA could be as low as $46,000/quality adjusted life year. PTA increased to $78,500/quality adjusted life year with a 1% annual incidence of ESRD from drug toxicity. This model suggests that PTA may be a reasonable option in more patients than is currently recognized. Criteria for patient selection should include risk for progression to blindness and ESRD, improvement in quality of life with pancreas function and expected reduction in quality of life with blindness and ESRD. The use of non-nephrotoxic agents (rapamycin, IL-2 receptor antibodies and MMF) along with calcineurin inhibitor sparing protocols, should have an important impact on implementing studies of this option.