Outcomes of Kidney Transplant Recipients on Dual Antiplatelet Therapy

Research Article

Austin J Nephrol Hypertens. 2015;2(3): 1040.

Outcomes of Kidney Transplant Recipients on Dual Antiplatelet Therapy

Paul D Bailey¹*, Hirra Ali², Michelle Lubetzky¹ and Liise K Kayler²

¹Department of Medicine, Albert Einstein College of Medicine, USA

²Department of Surgery, Montefiore Medical Center, USA

*Corresponding author: Paul D. Bailey, Department of Medicine, Albert Einstein College of Medicine, USA

Received: April 15, 2015; Accepted: May 25, 2015; Published: May 30, 2015


Background: Kidney Transplant (KTX) recipients often have co morbidities requiring anti-platelet therapy with 1 or 2 agents. Whereas a few reports have examined outcomes with one agent, none have evaluated outcomes of KTX recipients on dual antiplatelet agents.

Methods: Consecutive adult kidney-only recipients from 10/11-9/14 taking aspirin alone (ASA, n=135), ASA and Plavix® (DUAL, n=23), or no Antiplatelet therapy (NONE, n=209) at the time of transplantation were assessed for several outcomes post-transplantation.

Results: Of 367 patients, the overall incidence of blood transfusion within 5 days of KTX was 34.6%. Compared to the NONE group, DUAL or ASA alone, were associated with perioperative blood transfusion (27.8%, 52.2%, 42.2%, p<0.01), but not reoperation for bleeding (1.0%, 0.0%, 1.5% p=0.79), delayed graft function (47.9%, 52.2%, 51.1% p=0.81), length of stay > 6 days (31.1%, 34.8%, 36.3% p=0.60), 30-day readmission (26.8%, 21.7%, 33.6% p=0.30), or overall graft failure (7.7%, 4.4%, 7.4% p=0.85), respectively. Despite univariate association, blood transfusion was not significantly associated with ASA (aOR: 1.42, CI: 0.86-2.34), or DUAL (aOR: 1.87, CI: 0.75-4.66) on multivariate analysis.

Conclusion: KTX with single or dual antiplatelet therapy may not carry an increased risk of blood transfusion or other adverse outcomes after other risk factors are accounted for.

Keywords: Bleeding; Renal Transplant; Antiplatelet; Plavix®; Aspirin; Complication; Kidney transplantation; Blood transfusion; Anticoagulation


Kidney Transplant (KTX) recipients often have co morbidities that require anti-platelet therapy with 1 or 2 agents most commonly Aspirin® and/or Plavix®. Patients with end-stage renal disease are already at a higher risk of bleeding due to platelet dysfunction and uremia [1]; and bleeding risk is thought to be potentiated with the use of Aspirin® and/or clopidogrel bisulfate (Plavix®) which inhibit platelet function, albeit via different mechanisms. Long term use of Aspirin® leads to a reduction in thromboxane A2 in platelets which inhibits platelet aggregation. Plavix® asserts its action by irreversibly binding to the P2Y12 ADP receptor on platelets, inhibiting platelet aggregation and fibrin cross-linking. Patients taking Aspirin® and Plavix® are at increased risk of bleeding because both platelet aggregation and activation pathways are inhibited.

Dual anti-platelet therapy is often considered a contraindication to KTX because of the potential risk of bleeding. Many programs will not transplant patients taking dual anti-platelet therapy until at least one of the anti-platelet agents has been discontinued. This may result in prolongation of waiting time and/or reduced access to transplantation [2]. Alternatively, other programs, will perform kidney transplantation in the setting of dual anti-platelet therapy as long as the anti-platelet agents can be temporarily withheld in the perioperative period despite the potential increased risk of bleeding transfusion [2,3]. Since blood transfusion, in and of itself, has not been shown to be a strong risk factor for adverse outcomes in the transplant population. Most analyses have shown no correlation of blood transfusion with graft survival [4,5], sensitization [4], acute rejection [4], or allograft nephropathy [4], although, one analysis suggested an increased risk of graft failure and patient death [6]. There are no reports of outcomes of KTX recipients on two antiplatelet agents at the time of surgery. The purpose of this study is to examine short-term outcomes of patients receiving single or dual agent antiplatelet therapy at the time of transplantation in terms of blood transfusion, reoperation, readmission and organ function.


A retrospective cohort study of consecutive adult living- and deceased-donor kidney-only recipients at Montefiore Medical Center between October 3, 2011 and September 3, 2014 was performed to evaluate outcomes between kidney transplant recipients receiving single-antiplatelet therapy with Acetylsalicylic Acid (ASA), dualantiplatelet therapy with ASA and Plavix® (Dual; clopidogrel bisulfate, Bristol Meyers Squibb, Princeton NJ) or no antiplatelet therapy (NONE) at the time of transplantation. Exclusions were patients with therapeutic levels of warfarin (n=19) or heparin (n=2) at the time of transplant, and those on Plavix® alone (n=7). Our protocol requires that patients on dual therapy who are able to temporarily hold both anti-platelet agents after kidney transplant to be eligible for transplantation. The ASA group was comprised of patients were taking in the majority Aspirin® (n=133; Bayer, Leverkusen, Germany), but also Micropirin® (n=1; Dexcel Pharma Ltd, Daventry UK) or Aggrenox® (n=1; Boehringer Ingelheim Pharmaceuticals, Ingelheim am Rhein, Rhineland-Palatinate)

The primary outcome was at least one blood transfusion during or within 5 days of transplantation. Secondary outcomes were (a) reoperation for bleeding (b) delayed graft function (DGF, defined as dialysis within 1 week post-transplantation)(c)length of stay (LOS)> 6 days (median value), (d) 30 day rehospitalization from day of transplant hospitalization discharge, and (e)overall graft failure following transplantation (defined as allograft nephrectomy, retransplantation, return to chronic dialysis, or death).

Surgery and Immunosuppression

Through a Gibson incision, allograft renal arteries and veins were generally anastomosed to the external iliac vessels using an end-to-side technique. Right renal veins were typically extended with the donor inferior vena cava by staple or suture closure of the suprarenal cava and left renal vein orifice (renal vein extension). Ureterovesical implantation was performed using an extra vesical technique with or without stent placement depending on surgeon preference. Patients received anti-thymocyte globulin (ATG, 1.5 mg/ kg/day for 3 days) or basiliximab (20 mg on the day of surgery and post-transplant day#3) induction treatment, along with tacrolimus, mycophenolate mofetil, and a corticosteroid taper. Corticosteroids were initiated intraoperatively at 500 mg of methylprednisolone, followed by an oral prednisone taper to 5 mg/day by 3 months. Intravenous immunoglobulin (500 mg/kg during transplant surgery and post-operative days 1 and 2) was also administered if positive flow-cytometry cross-match and/or donor-specific antibody. ATG was administered peripherally with 1000 U of heparin included in the formulation. At the discretion of the surgeon, a subgroup of patients received a single dose of 1000 – 3000 U IV heparin during the procedure. Venous thromboembolism prophylaxis was with sequential compression devices only. Desmopressin was not administered to patients on antiplatelet agents.


The following recipient covariates were evaluated for inclusion in the multivariable models; recipient age (continuous), sex, race (African-American vs. other), history of diabetes mellitus, induction (basiliximab vs. ATG), panel-reactive antibody (PRA) level > 0%, HLA- A, B, and DR mismatch> 3, body mass index (continuous), preoperative hemoglobin level > 10g/dL (median), cardiovascular disease (defined as any of prior myocardial infarction, coronary artery bypass graft, coronary angioplasty or stent), prior solid organ transplant, pre-emptive transplant, and renal vein extension. Donor covariates evaluated were age (continuous), sex, race (African-American vs. other) and type [living-donor, Expanded-Criteria Donor (ECD), Standard-Criteria Donor (SCD)]. The appropriate functional form of model covariates was determined by exploratory data analysis in unadjusted models and perceived impact on clinical meaningfulness. ECD was defined as donor age = 60 years or donor age 50-59 with two of the following: history of hypertension, terminal serumcreatinine = 1.5 mg/dl, or death from cerebrovascular accident. SCD was defined as deceased-donor not meeting ECD criteria.

Statistical Analysis

Univariate associations between exposure groups were examined using the Chi-Square tests for categorical variables and t-tests for continuous variables whose distributions approximated normality. The survival distribution for overall graft failure was examined with Kaplan-Meier curves and compared using the log-rank test. Logistic rejection models were fit to estimate the Odds Ratios (OR) and 95% confidence intervals (95%CI) for exposure groups for perioperative blood-transfusion with variables included in the model if associated with the outcome at an a level of 0.05. Time to outcome was defined as time from the date of transplant until date of outcome, censored for loss to follow-up and end of study period (10/31/14).

All statistical analysis was conducted using the SAS system version 9.2 (SAS Institute, Inc., Cary, N.C.). Statistical significance was identified by a p-value of less than 0.05 and all confidence intervals also used a 95% threshold. All p-values are two-sided. The study was approved by the Albert Einstein Institutional Review Board.


Of 367 patients, 209 (57%) were not receiving antiplatelet therapy at the time of transplantation, 135 (36.8%) were receiving ASA only, and 23 (6.3%) were receiving DUAL therapy. The overall incidence of blood transfusion was 34.6% within 5 days of kidney transplantation. Of those who received a blood transfusion 44.5% were given 1 unit, 31.9% received 2 units, 16.0% received 3 units, and 7.6% received 4 or more units.

Compared to the NONE group, the DUAL and ASA recipients were significantly older (50.5 ±14.8, 62.9 ± 6.6, 58.8 ± 9.4, years p < 0.01),more likely to be male (51.2%, 67.4%, 78.3% p < 0.01), diabetic (28.9%, 69.6%, 61.5% p < 0.01), or have cardiovascular disease (12.4%, 100%, 38.5%, p < 0.01),and less likely to have received a previous solid organ transplant (12.9%, 4.4%, 3.7%, p = 0.02), or receive ATG induction therapy (56.5%, 34.8%, 34.1%, p < 0.01), respectively (Table 1). Also, relative to NONE the DUAL and ASA groups were more likely to receive a kidney from an older donor (41.5 ± 15.6, 47.7 ± 17.3, 47.9 ± 16.7 p <0.01) and somewhat less likely to receive a living donor kidney (18.7%, 8.7%, 14.8% p = 0.07). Other baseline characteristics were similar between the groups (Table 1).