Belatacept-based regimens are associated with improved cardiovascular and metabolic risk factors compared with cyclosporine in kidney transplant recipients (BENEFIT and BENEFIT-EXT studies).
ABSTRACT Cardiovascular disease, the most common cause of death with a functioning graft among kidney transplant recipients, can be exacerbated by immunosuppressive drugs, particularly the calcineurin inhibitors. Belatacept, a selective co-stimulation blocker, may provide a better cardiovascular/metabolic risk profile than current immunosuppressants.
Cardiovascular and metabolic endpoints from two Phase III studies (BENEFIT and BENEFIT-EXT) of belatacept-based regimens in kidney transplant recipients were assessed at month 12. Each study assessed belatacept in more intensive (MI) and less intensive (LI) regimens versus cyclosporine A (CsA). These secondary endpoints included changes in blood pressure, changes in serum lipids, and the incidence of new-onset diabetes after transplant (NODAT).
A total of 1209 patients were randomized and transplanted across the two studies. Mean systolic blood pressure was 6 to 9 mm Hg lower and mean diastolic blood pressure was 3 to 4 mm Hg lower in the MI and LI groups versus CsA (P ≤ 0.002) across both studies at month 12. Non-HDL cholesterol was lower in the belatacept groups versus CsA (P<0.01 MI or LI vs. CsA in each study). Serum triglycerides were lower in the belatacept groups versus CsA (P<0.02 MI or LI vs. CsA in each study). NODAT occurred less often in the belatacept groups versus CsA in a prespecified pooled analysis (P<0.05 MI or LI vs. CsA).
At month 12, belatacept regimens were associated with better cardiovascular and metabolic risk profiles, with lower blood pressure and serum lipids and less NODAT versus CsA. The overall profile of belatacept will continue to be assessed over the 3-year trials.
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ABSTRACT: OBJECTIVE Identification of patients at high risk for new-onset diabetes after kidney transplantation (NODAT) will facilitate clinical trials for its prevention.RESEARCH DESIGN AND METHODS We previously described a pretransplant predictive risk model for NODAT using seven pretransplant variables (age, planned use of maintenance corticosteroids, prescription for gout medicine, BMI, fasting glucose, fasting triglycerides, and family history of diabetes). We have now applied the initial model to a cohort of 474 transplant recipients from another center for validation. We performed two analyses in the validation cohort. The first was a standard model with variables derived from the original study. The second was a summary score model, in which the sum of dichotomized variables (all the variables dichotomized at clinically relevant cut points) was used to categorize, individuals into low (0-1), intermediate (2, 3), or high (4-7) risk groups. We also conducted a combined database analyses, merging the initial and validation cohorts (n = 792) to obtain better estimates for a prediction equation.RESULTSAlthough the frequency of several risk factors differed significantly between the two cohorts, the models performed similarly in each cohort. Using the summary score model, incidences of NODAT in low-risk, medium-risk, and high-risk groups in the initial cohort were 12, 29, and 56%, and in the validation cohort incidences were 11, 29, and 51%.CONCLUSIONSA pretransplant model for NODAT, including many type 2 diabetes risk factors, predicted NODAT in the validation cohort.Diabetes care 09/2013; · 7.74 Impact Factor
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ABSTRACT: Although advances in immunosuppression, tissue typing, surgery, and medical management have made transplantation a routine and preferred treatment for patients with irreversible renal failure, successful transplant recipients have a greatly increased risk of premature mortality because of cardiovascular disease and malignancy compared with the general population. Conventional cardiovascular risk factors such as hyperlipidaemia, hypertension, and diabetes are common in transplant recipients, partly because of the effects of immunosuppressive drugs, and are associated with adverse outcomes. However, the natural history of cardiovascular disease in such recipients differs from that in the general population, and only statin therapy has been studied in a large-scale interventional trial. Thus, the management of this disease and the balance between management of conventional risk factors and modification of immunosuppression is complex.The Lancet 10/2011; 378(9800):1419-27. · 39.21 Impact Factor
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ABSTRACT: New onset diabetes after kidney transplantation (NODAT) remains a common complication after transplantation and is associated with significant morbidity and mortality. The review will examine recent advances in our knowledge of this metabolic disorder and speculate upon future development. Research continues to broaden the horizon of existing and emerging risk factors that contribute to development of NODAT. Attempts to use this knowledge to develop quantitative risk scoring composites have been made, utilizing either pretransplant or 1-year posttransplantation variables, with variable success. Reassuringly a number of clinical trials have been published, or are currently in progress, that utilize pharmacological intervention for both prevention and management of NODAT. These are both in the form of differential immunosuppressant regimens or use of antiglycemic agents. Upcoming results will prove crucial in developing a genuine evidence-base for NODAT management. Rather than simple translation of data from the general to kidney transplant population, clinicians must appreciate that NODAT constitutes a distinct metabolic entity with unique pathophysiology. As such targeted strategies to prevent and manage NODAT require focused investigation to deal with this common complication.Current opinion in nephrology and hypertension 11/2012; 21(6):574-9. · 3.96 Impact Factor