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: The initial aim of this study was to evaluate the possibility of influencing atherosclerosis in hyperlipidaemic renal transplant patients by lowering blood lipids with gemfibrozil treatment. Although this double-blind, randomized trial was stopped after 6 months owing to the suspicion of drug interference, we report here on the results of baseline ultrasonographic examinations. The outpatient clinic at the Department of Transplantation Surgery, Huddinge University Hospital, Huddinge, Sweden. The carotid arteries were examined in 16 out of the 19 kidney transplant patients included in the study using an ultrasonographic duplex scanner. Plaque occurrence and the common carotid intima-media thickness of the renal transplant recipients were compared to the same parameters in a normotensive control group of approximately the same age from a previous study. An increased prevalence of plaque (75% of the patients having plaque on one or both sides) was seen in the hyperlipidaemic renal transplant patients in comparison with the control group (16%; P < 0.001). The common carotid intima-media complex was thicker (P < 0.05), and the lumen diameter and the calculated cross-sectional intima-media area were greater (P < 0.01-0.001) in the transplant recipients. Markedly increased atherosclerotic wall changes are seen in the carotid arteries of patients with hyperlipidaemia after renal transplantation.Journal of Internal Medicine 03/1996; 239(2):177-80. · 6.46 Impact Factor
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ABSTRACT: Immunological rejection is the most important cause of kidney transplant failure. Recently, nonimmunological causes of long-term allograft failure have become more widely appreciated. In primary chronic renal disease, blood pressure is of overriding importance for long-term renal function. The role of blood pressure in determining long-term transplant outcome has not yet been established. We studied the influence of blood pressure post-transplantation on long-term kidney graft outcome in 29,751 patients. Outpatient blood pressure measurements were recorded and reported to the Collaborative Transplant Study. Graft and patient survival rates were analyzed over seven years in relation to blood pressure. Increased levels of systolic and diastolic blood pressure post-transplantation were associated with a graded increase of subsequent graft failure (P < 0.0001). Chronic graft failure was significantly associated with blood pressure even when patient death was censored (P < 0.0001). Cox regression analysis established increased blood pressure as an independent risk factor for graft failure. We conclude that post-transplant blood pressure is a highly significant predictor of long-term kidney graft outcome. Whether aggressive lowering of blood pressure improves long-term transplant outcome will have to be studied prospectively.Kidney International 01/1998; 53(1):217-22. · 7.92 Impact Factor
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ABSTRACT: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.Transplantation 09/1997; 64(3):436-43. · 3.78 Impact Factor