Ticlopidine and clopidogrel, sometimes combined with aspirin, only minimally increase the surgical risk in renal transplantation: a case-control study.

BACKGROUND: Patients undergoing kidney transplantation are sometimes being treated with antiplatelet agents such as ticlopidine or clopidogrel. Some teams refuse to wait-list these patients for fear of bleeding during transplant surgery. METHODS: We retrospectively reviewed the records of 702 adult patients with a kidney transplant alone between 2000 and 2010. Nineteen (2.7%) patients were taking clopidogrel or ticlopidine when called in for transplantation. Furthermore, 10 of these 19 patients were also taking low-dose aspirin (ASA). We compared the risk of bleeding peri- and postoperatively, and the occurrence of cardiovascular complications within 30 days after renal transplantation between 19 cases and 39 controls randomly selected within the cohort. RESULTS: Platelets were administered to 7 cases (37%) versus 0 controls (P<0.001). A single case (5.3%) presented with significant bleeding during surgery following an implantation biopsy, and required 4 red bood cell (RBC) units. During the first day, 3 of the 19 cases (16%) and 1 of the 39 controls required RBC (P=0.1). No reoperation was performed for bleeding. After the transplant, clopidogrel or ticlopidine was resumed in only two patients. The platelet count and haemoglobin were similar between cases and controls at Day 30. No cardiovascular event occurred in cases or controls during the first month post-transplantation. At 5 years, graft and patient survival was similar in cases and controls. CONCLUSIONS: Clopidogrel and ticlopidine, sometimes in combination with ASA, are associated with a low risk of bleeding during renal transplantation and does not seem to be a contraindication for renal transplant surgery.

Efficacy and cardiovascular safety of daclizumab, mycophenolate mofetil, tacrolimus, and early steroid withdrawal in renal transplant recipients: a multicenter, prospective, pilot trial.

This single-arm, open-label, pilot study was designed to assess the efficacy and cardiovascular safety profile of daclizumab, a humanized monoclonal interleukin (IL)-2Ralpha antibody, in combination with mycophenolate mofetil (MMF), tacrolimus, and early corticosteroid withdrawal in renal transplant recipients. Seventy-nine renal allograft recipients were treated with daclizumab (1 mg/kg; five doses starting on the day before transplant and then every two weeks), MMF (1 g b.i.d.), tacrolimus (0.2 mg/kg/d), and low-dose prednisolone, which was withdrawn at day 150 after transplant. The rate of acute rejection was determined at 12 months. Lipid profile, oral glucose tolerance, and adverse events were monitored. Of the 76 patients eligible for analysis, eight (10.5%) developed biopsy-proven acute rejection (BPAR). Ten (13.2%) experienced clinical and/or BPAR. Corticosteroids were withdrawn completely in 91% of patients at 12 months. Graft and patient survival were 97.5% and 98.7% respectively. Mean total cholesterol and triglycerides were significantly lower at 12 months post-transplant than at baseline (201 +/- 47.5 vs. 190.8 +/- 43.6 mg/dL, p = 0.005 and 196.2 +/- 133.2 vs. 144.5 +/- 76.8 mg/dL, p < 0.001, respectively). Mean hemoglobin A1c levels did not differ between baseline (5.54%) and 12 months (5.48%). New-onset post-transplant diabetes mellitus occurred in 6.6% of the non-diabetic transplanted patients. The proportion of patients with abnormal oral glucose tolerance test (OGTT) was 47% at 3 months and 39% at 12 months (p = NS). Daclizumab induction in combination with MMF, tacrolimus, and low-dose (followed by withdrawal) prednisolone appears to be effective and safe in patients receiving renal allografts. The regimen appears to be associated with a favorable cardiovascular profile.

Guidelines for the treatment and management of new-onset diabetes after transplantation.

Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new-onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss. In 2003, International Consensus Guidelines on New-onset Diabetes after Transplantation were published, which aimed to establish a precise definition and diagnosis of the condition and recommend management strategies to reduce its occurrence and impact. These updated 2004 guidelines, developed in consultation with the International Diabetes Federation (IDF), extend the recommendations of the previous guidelines and encompass new-onset diabetes after kidney, liver and heart transplantation. It is hoped that adoption of these management approaches pre- and post-transplant will reduce individuals' risk of developing new-onset diabetes after transplantation as well as ameliorating the long-term impact of this serious complication.

Acute arterio-venous fistula occlusion decreases sympathetic activity and improves baroreflex control in kidney transplanted patients.

BACKGROUND: The acute bradycardia induced by the occlusion of an arteriovenous fistula (AVF), known as the Nicoladoni-Branham sign, is considerably larger than that which occurs during carotid sinus massage. This suggests increased arterial baroreflex sensitivity during acute AVF occlusion. Moreover, the influence of acute AVF occlusion on muscle sympathetic nerve traffic (MSNA, by microneurography) is unknown. We therefore assessed the effects of acute AVF occlusion on baroreflex sensitivity and on MSNA in patients with stable functional kidney grafts and patent AVF. METHODS: We measured blood pressure (BP), MSNA (n = 11), heart rate (HR), cardiac output (CO) and arterial baroreflex sensitivity (n = 18) at baseline and during acute, 30-s pneumatic AVF occlusions in 23 renal transplanted recipients. RESULTS: During the first 5 s of the AVF occlusion, mean BP increased from 98+/-4 to 112+/-4 mmHg (P<0.0001) while MSNA decreased to 28+/-5% of baseline values (P<0.0001) and HR decreased from 71+/-3 to 61+/-3 b.p.m. (P<0.0001). The largest increases in BP were accompanied by the most marked decreases in MSNA (r = -0.79, P = 0.003) and HR (r = -0.49; P = 0.01) during the first 5 s of the AVF occlusion. During AVF occlusion baseline CO of 6.9+/-0.3 decreased to 5.6+/-0.3 l/min (P<0.0001) while baroreflex sensitivity increased from 10+/-1 to 17+/-2 ms/mm Hg (P<0.001). CONCLUSIONS: Arterial baroreceptor activation and increased arterial baroreflex sensitivity decrease heart rate during AVF occlusion. In addition, our study is the first to demonstrate that arterial baroreflex activation decreases sympathetic nerve traffic during the Nicoladoni-Branham sign.