Influence of renal function on long-term graft survival and patient survival in renal transplant recipients.

OBJECTIVES: Renal function post kidney transplantation is an outcome of interest for both clinicians and regulators evaluating immunosuppressive treatments post-transplantation. The current review sought to provide a synopsis of currently available literature examining the relationship between post-transplantation renal function and long-term graft survival and patient survival. METHODS: A systematic literature review was performed using the PubMed, EMBASE and Cochrane Library databases. The search strategy was designed based on high level Medical Subject Heading (MeSH) terms and designed to capture studies published in English to 2012 and identified a total of 2683 unique hits; for inclusion studies were required to have >100 patients. Following two rounds of screening, a total of 27 studies were included in the final review (26 of which were identified via the literature review and one study was identified via searches of the reference sections of included studies). RESULTS: The consensus among studies was that lower post-transplantation GFR, in particular 12 month GFR, was consistently and significantly associated with an increased risk for overall graft loss, death-censored graft loss and all-cause mortality in both univariate and multivariate analyses. The magnitude of the association between reduced GFR and outcomes was greater for death-censored graft loss versus overall graft loss and for graft loss in comparison with overall patient mortality. The predictive utility of GFR alone in predicting long-term outcomes was reported to be limited. CONCLUSIONS: Lower GFR and greater rates of decline in GFR post-transplantation are associated with an increased risk for graft loss (overall and death-censored) and all-cause mortality; however, the predictive utility of GFR alone in predicting long-term outcomes is limited.

An estimation of the long-term clinical and economic benefits of insulin lispro in Type 1 diabetes in the UK.

AIMS: To determine the long-term health economic benefits associated with lispro vs. regular human insulin (RHI) in UK Type 1 diabetic (T1DM) patients using the previously published and validated CORE Diabetes Model. METHODS: A literature review designed to capture clinical benefits associated with lispro and T1DM cohort characteristics specific to UK was undertaken. Clinical benefits were derived from a Cochrane meta-analysis. The estimated difference (weighted mean) in glycated haemoglobin (HbA(1c)) was -0.1% (95% confidence interval -0.2 to 0.0%) for lispro vs. RHI. Severe hypoglycaemia rates for lispro and RHI were 21.8 and 46.1 events per 100 patient years, respectively. Costs and disutilities were accounted for severe hypoglycaemia rates. All costs were accounted in 2007 poundUK from a National Health Service (NHS) perspective. Future costs and clinical benefits were discounted at 3.5% annually. RESULTS: In the base-case analysis, lispro was projected to be dominant compared with RHI. Lispro was associated with improvements in quality-adjusted life expectancy (QALE) of approximately 0.10 quality-adjusted life years (QALYs) vs. RHI (7.60 vs. 7.50 QALYs). Lifetime direct medical costs per patient were lower with lispro treatment, pound70 576 vs. pound72 529. Severe hypoglycaemia rates were the key driver in terms of differences in QALE and lifetime costs. Sensitivity analyses with assumptions around time horizon, discounting rates and benefits in terms of glycaemic control or hypoglycaemic event rates revealed that lispro remained dominant. CONCLUSIONS: Our findings suggest that lispro is likely to improve QALE, reduce frequency of diabetes-related complications and lifetime medical costs compared with RHI.