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Kidney Donor Profile Index (KDPI) and cold ischemic time (CIT) independently influence recipient outcomes after kidney transplantation; however, the compound effect of these variables on posttransplant outcomes is unknown.The Scientific Registry of Transplant Recipients database of deceased-donor kidney transplant recipients between January 2012 and December 2016 was reviewed. Recipients were stratified based on their KDPI (0%-20%, 21%-85%, 86%-100%) and then based on CIT (0-12, 13-24, 25-30, 31-36, ≥ 37 hours). The primary outcome is 1-year allograft loss. Secondary outcomes include primary nonfunction, delayed graft function, biopsy-proven rejection, and 1-year recipient mortality.Allograft loss was not affected by CIT for KDPI 0% to 20% (P = .898) or KDPI 86% to 100% (P = .731), but was significantly different for KDPI 21% to 85% (P .001). The KDPI 21% to 85% group was the only group with a significant difference in primary nonfunction, demonstrating a linear rise with increasing CIT (P .001). CIT did not affect recipient mortality for any KDPI group (KDPI 0%-20%, P = .306; KDPI 21%-85%, P = .098; KDPI 86%-100%, P = .774). Incidence of delayed graft function was greater for each KDPI group (P .001) with increased CIT. Biopsy-proven rejection was not affected by CIT for KDPI 21% to 85% (P = .244) or KDPI 86% to 100% (P = .946). For KDPI 0% to 20%, there was a significant difference (P = .024); however, the incidence was not linear with increasing CIT. For the KDPI 86% to 100% group, incidence of mortality, allograft loss, primary nonfunction, and biopsy-proven rejection did not differ between CIT groups.Extended CIT alone should not hinder utilization of higher KDPI organs.

Background Historically, there is perceived pressure to achieve therapeutic levels of tacrolimus quickly after heart transplant (HT). We evaluated the association between time within therapeutic tacrolimus range and time to therapeutic trough and rejection in the 30 days following HT. Methods This is a single-center retrospective cohort study of consecutive adult HT patients receiving immunosuppression. Goal trough tacrolimus levels were 10-15 ng/ml. Surveillance endomyocardial biopsies were performed weekly for 4 weeks. Outcomes included the effect of time to and time-in-therapeutic tacrolimus range (Rosendaal method) on 30-day clinical rejection, 1R/1B, and 2R or higher histologic occurrences. Results We reviewed 67 HT patients (median age 58.8 yrs). For clinical rejection versus no-rejection groups, the median (25th, 75th percentile) time to therapeutic tacrolimus levels was 9.5 (8, 12.3) days versus 9.0 (7, 13) days (p=0.623). The median time-in-therapeutic tacrolimus range was 34.1% (23.2, 42.2) versus 36.2% (19.9, 51.2), respectively (p=0.512). Similarly, we observed no significant differences in time to and time-in-therapeutic tacrolimus range in patients who developed grade 1R/1B (p=0.650 and p=0.725) or grade 2R or higher histology (p=0.632 and p=0.933). Conclusions Our small single-center analysis suggests that neither time to nor time in therapeutic tacrolimus range predicted acute rejection within 30 days of HT.

Background: National practice guidelines do not provide clear recommendations on combination pharmacological regimens to reduce cardiothoracic surgery (CTS) postoperative atrial fibrillation (POAF). Objective: This study examines if there is a reduction in POAF rates after implementing a perioperative prophylaxis guideline that includes amiodarone, β-blockers, and high-intensity statins. Methods: Data were retrospectively collected on 400 adults (200 patients pre–guideline implementation and 200 patients post–guideline implementation) with a CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus, and Vascular Disease) score of at least 3 points after CTS. Data were collected on the incidence of POAF lasting more than 5 minutes and secondary outcomes, including the length of hospitalization, guideline adherence rate, adverse events, and timeliness of POAF treatment. Results: Guideline implementation increased prophylactic amiodarone ( P < 0.0001), statin ( P = 0.029), and high-intensity statin ( P = 0.002) use without changing β-blocker use (64.5% vs 67.0%, P = 0.673) and reduced POAF (39.5% vs 52.0%, P = 0.016) and ventricular tachycardia (15.5% vs 24.5%, P = 0.034) compared with preguideline rates. Length of hospitalization and other postoperative adverse events, including stroke and mortality, were not statistically different. Subgroup analyses of patients who were adherent to both the amiodarone and β-blocker recommendations (28% of the total) or to all 3 recommended therapies (24% of the total) had significant decreases in POAF ( P = 0.001; P < 0.001), length of hospitalization ( P = 0.023; P = 0.049), length of intensive care unit stay ( P = 0.045; P = 0.040), and ventricular tachycardia ( P = 0.008; P = 0.017) compared with preguideline patients, respectively. Conclusions: A perioperative guideline of amiodarone, β-blockers, and high-intensity statins reduced POAF, but better benefits may result from enhanced adherence.

In high-risk patients, candiduria may be associated with the development of urinary tract infections (UTI) and invasive candidiasis. The triazole antifungals achieve good urine concentrations, but their use is limited by the emergence of non-albicans Candida spp. with low-triazole susceptibility. The echinocandins remain fungicidal against many azole-resistant Candida spp., but low urine concentrations limit their use. We examined the rates of candiduria elimination in micafungin-treated patients.This retrospective analysis evaluated consecutive patients with candiduria (1/2008-4/2011) who were treated with micafungin (100 mg/day) and had post-micafungin urine cultures. Patients were deemed to have either candiduria or UTI and were assessed for short-term (within 2 weeks post-micafungin) and long-term (1 month post-micafungin) urine sterilization.Thirty-three patients meeting our inclusion criteria were identified. Of these, 16 (48 %) were diagnosed with a Candida UTI. A total of 25 patients (76 %) had Foley catheters, which were replaced in 11 (44 %) cases. The majority of patients had Candida albicans (39 %), but Candida krusei and Candida glabrata (33 %) were also isolated. Eight patients (24 %) were immunocompromised, and 29 (88 %) received broad-spectrum antibiotics. Rates of urine sterilization during micafungin treatment, 2 weeks after micafungin, and 1 month after micafungin were 81, 78, and 75 %, respectively.Among hospitalized patients with candiduria, micafungin administration was frequently associated with both short- and long-term urine sterilization. This was observed among patients with or without Foley removal and among those with Candida albicans, as well as non-albicans Candida spp.

Pregnancy in solid organ transplant recipients carries numerous risks to the mother such as increased risk of rejection, gestational diabetes mellitus, and preeclampsia. The developing fetus is subjected to risks such as birth defects, preterm delivery, and low birth weight. Typically, these risks can be managed through intensive, multidisciplinary prenatal care and a proper immunosuppressive regimen. In the setting of rejection, however, little data are available to suggest safe and effective treatment of acute cellular rejection, antibody-mediated rejection, or mixed rejection episodes in the pregnant solid organ transplant recipient. We describe the first case, to our knowledge, in which antithymocyte globulin (rabbit) was used to successfully treat a pregnant renal transplant recipient who experienced a mixed rejection episode. A 22-year-old, African American woman with stage 6 chronic kidney disease received a deceased donor renal transplant after undergoing hemodialysis for 3 years. Her maintenance immunosuppressive regimen at the time of transplantation consisted of tacrolimus, prednisone, and mycophenolate mofetil. Despite counseling efforts on the importance of having a planned pregnancy after kidney transplantation so that her immunosuppressive medications could be optimized, the patient became pregnant 12 months later; her mycophenolate mofetil was changed to azathioprine to reduce the risk of fetal deformities or death. Three months later, the patient was admitted for biopsy of her transplanted kidney and was evaluated for possible kidney rejection. After confirmation of a mixed 1B acute cellular rejection and antibody-mediated rejection episode, the patient decided to pursue resolution of her rejection episode and continue the pregnancy despite the potential risks to the fetus. She was treated with high-dose corticosteroids, intravenous immunoglobulin, plasmapheresis, and antithymocyte globulin (rabbit). Twenty-nine months after transplantation, the patient was induced and gave birth to a healthy baby boy. Our patient's case offers unique insight into the potential management of a rejection episode requiring aggressive immunosuppressive therapy. Although potent immunosuppressive therapies were successfully used in our patient, further studies are needed to make definitive recommendations regarding the use of such therapies for treatment of rejection episodes in pregnant solid organ transplant recipients. The risks and uncertainties of treating rejection episodes should always be discussed with and understood by the patient before an informed decision is made.

Background— Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection seen in immunosuppressed patients, including solid-organ transplant recipients. Sulfamethoxazole/trimethoprim (SMX/TMP) has long been considered first-line therapy for PCP prophylaxis. Optimal dosing regimens in solid-organ transplant recipients have not been fully defined. Objective— To examine the tolerability of a 1-year, 3-times weekly, prophylactic regimen of a single-strength SMX/TMP tablet. Study Design— Single-center, retrospective cohort study. Setting— A tertiary-care medical center, including inpatient hospitalizations and outpatient transplant clinic visits. Patients— Adult patients who received a kidney transplant between December 1, 2010, and November 30, 2012, at Hartford Hospital. Patients receiving a concurrent extrarenal transplant were excluded. Patients' charts were reviewed for up to 1 year after transplant. Results— A total of 88 patients were included in the analysis. Sixty-seven patients finished a full year of SMX/TMP after transplant, 10 patients discontinued SMX/TMP less than 1 year after transplant, and 11 patients started taking atovaquone instead of SMX/TMP after transplant. Documented reasons for discontinuation included hyperkalemia, leukopenia, diarrhea, and simplification of medication regimen. Patients without a documented reason for discontinuation did not have any obvious anomalies in laboratory values that would account for the discontinuation. Patients who received atovaquone for PCP prophylaxis had higher rates of recurrent urinary tract infections than did patients who received SMX/TMP for prophylaxis (33% vs 7%, P = .02). A longer postoperative stay (median [interquartile range, IQR] 13 [8.25–26] days vs 7 [6-9.5] days, P = .02), higher rates of delayed graft function (50% vs 10%, P = .004), as well as higher serum creatinine levels on postoperative day 7 (6.25 [2.4–10.1] mg/dL vs 1.8 [1.2–4.2] mg/dL, P = .01), postoperative month 1 (1.9 [0.8] mg/dL vs 1.4 [0.5] mg/dL, P = .002), and postoperative month 12 (1.6 [0.5] mg/dL vs 1.3 [0.3] mg/dL, P = .04) were associated with early SMX/TMP discontinuation. Conclusion— A low-dose prophylactic SMX/TMP regimen of 1 single-strength tablet 3 times weekly is well tolerated. Discontinuation rates were lower than other rates reported for higher-dose regimens.

Clostridium difficile is a bacterial enteric pathogen, which causes clinical disease among solid organ transplant (SOT) recipients. This large, single-center, retrospective study describes incidence, demographics, and impact of C . difficile infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver (n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in our population during the 40-month period of study was 4%. CDI incidence among cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and 3.2%, respectively ( P =0.03 between organ-types). Median time from transplant to CDI for all was 51 (14–249) days, with liver recipients having the shortest time to infection, median 36 (15–101) days, and lung recipients having a longer time to infection, median 136 (29–611) days. Antibiotic exposure within 3months of CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%, 58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant recipients, respectively. Most patients (83%) were hospitalized within the 3months preceding CDI. Recipients were followed for a median time of 23 (16–31) months; at the time of last follow-up, 83% of allografts were functioning, and 86% of patients were alive. One death and 1 graft failure were causally related to CDI. CDI had an overall incidence of 4%; clinicians should have heightened awareness for CDI, especially among patients receiving antibiotics, with increased monitoring and aggressive management of CDI.

Context Cytomegalovirus (CMV) is an opportunistic infection that causes profound morbidity and mortality after orthotopic liver transplant (OLT). The CMV immunoglobulin G serostatuses of donors and recipients are the main factors influencing risk for development of CMV infection after transplant. Objective To compare acyclovir and valganciclovir for preventing CMV infection after OLT. Design, Setting, and Patients Retrospective assessment of adult OLT recipients at intermediate risk for CMV infection at New York Presbyterian Hospital. Intervention All patients received ganciclovir 5 mg/kg intravenously every 12 hours or valganciclovir 900 mg orally every 12 hours for 7 days after transplant. On postoperative day 8, patients received antiviral prophylaxis according to risk stratification: acyclovir 800 mg orally 3 times daily in donor seronegative/recipient seropositive (D-/R+) patients or valganciclovir 900 mg orally once daily in donor seropositive/recipient seropositive (D+/R+) patients. Main Outcome Measure Composite incidence of CMV infection, syndrome, or tissue-invasive disease. Results Of 275 OLT recipients, 89 were at intermediate risk for CMV infection (29 D−/R+, 60 D+/R+). CMV infection, syndrome, or tissue-invasive disease occurred in 1 patient (3%) in the D−/R+ group and 5 patients (8%) in the D+/R+ group ( P=.66). One patient (3%) in the D−/R+ group had a CMV infection develop. Five D+/R+ recipients (8%) had CMV infection; 3 of them had CMV syndrome (5%), 1 had CMV hepatitis (1.6%), and the other had CMV esophagitis (1.6%); all events occurred after prophylaxis was discontinued. The rates of CMV infection were similar in D−/R+ patients treated with acyclovir and D+/R+ patients receiving valganciclovir. This risk-stratified approach to viral prophylaxis after OLT resulted in an acceptable rate of CMV infection in D−/R+ recipients and may avoid the costs and adverse effects associated with valganciclovir therapy.

Induction therapy with interleukin-2 receptor antagonists has been established as an effective immunosuppressive strategy in the management of heart transplant (HTx) recipients. We compared outcomes following HTx in patients receiving basiliximab, daclizumab, or no induction therapy.We investigated post-transplant prognosis of patients receiving basiliximab (n=67), daclizumab (n=98) or no induction therapy (n=70). Patients treated with daclizumab (50.3 ± 14.7 years) were younger than those receiving basiliximab (55.8 ± 11.2 years) or no induction therapy (54.9 ± 14.1 years; both P0.05). Patients receiving either induction therapy showed better survival 1 year after HTx (95%) than those without induction therapy (82%; P0.001). Survival was similar between patients receiving basiliximab and daclizumab. The incidence of acute cellular or antibody-mediated rejections did not differ among the groups. The main reason that patients did not receive induction therapy was ongoing infection (65.7%), which was more common in patients on ventricular assist device (VAD) support than those without VAD (76.1% vs. 45.8%; P=0.004). The VAD-related infection rate in the entire study cohort was 29.7% (35/118 VAD recipients).Survival following HTx was worse in patients not receiving induction therapy. No differences were noted in survival or the incidence of rejection between the daclizumab- and basiliximab-treated groups. Induction therapy was less used in patients with infection, which was related to prior VAD support.

Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients.

Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population.

Risk evaluation and mitigation strategies (REMS) required by the Food and Drug Administration are implemented to manage known or potential risks associated with medications and to ensure ongoing safe use throughout the life of a pharmaceutical agent. Healthcare organizations have begun to adopt information technologies with clinical decision support (CDS) to ensure safe use of medications. Systems have been expanded and customized to also ensure compliance with regulatory standards. End users who are unfamiliar with particular medication use provisions are at risk of unknowingly inappropriately fulfilling specific components. Institution-specific customization of vendor-provided CDS is useful to enhance provider awareness and ensure compliance with standards. Integration of health information technology systems to fulfill REMS requirements is novel and important to ensure consistency as healthcare standards evolve.

Purpose Published evidence on a rare but serious malignancy associated with use of the first biological agent approved for long-term maintenance immunosuppression in renal transplant recipients is reviewed. Summary Belatacept (Nulojix, Bristol-Myers Squibb) is approved by the Food and Drug Administration for use in combination therapy to prevent renal graft rejection in patients who are Epstein-Barr virus seropositive. Belatacept appears to offer some advantages over calcineurin inhibitor-based regimens (e.g., no need for therapeutic drug monitoring), but its use poses a risk of posttransplant lymphoproliferative disorder (PTLD), a rapidly progressing and often lethal malignancy. The efficacy and safety of more-intensive and less-intensive belatacept regimens were established in two Phase III clinical trials, which found that rates of patient and graft survival were comparable to those in cyclosporine users; belatacept was shown to be superior in preserving renal function. The occurrence of PTLD, particularly PTLD involving the central nervous system, in 0–4% of belatacept-treated patients in clinical trials prompted postmarketing initiatives: (1) implementation of a risk evaluation and mitigation strategy (REMS) program to help ensure the safe and proper use of belatacept, (2) longitudinal studies to better define the risks and outcomes of belatacept therapy, and (3) a manufacturer-created patient registry to track belatacept use and encourage voluntary reporting of associated adverse events. Conclusion Appropriate patient selection and adherence to REMS requirements, including patient counseling and facilitation of registry enrollment, are essential in mitigating the increased risk of PTLD associated with belatacept therapy.

Background A correlation exists between polyomavirus BK (BKV) viremia in renal transplant recipients (RTR) and the degree of immunosuppression. However, the impact of pre-transplant desensitization on the incidence of BKV viremia is unknown. Methods This retrospective study evaluated living-donor RTR between January 2004 and December 2008 receiving routine BKV viral load monitoring. Patients were divided into those who underwent pre-transplant desensitization (n = 20) and those who did not (n = 71). The primary endpoint was the incidence of BKV viremia at 1 year post transplant. Results All demographic data were similar, except for more female patients (65% vs. 36.6%; P = 0.0392) in the desensitized group. More desensitized patients had a previous transplant (75% vs. 12.7%; P

Ischemia reperfusion injury (IRI) is an early, non-specific inflammatory response that follows perfusion of warm blood into a cold asanguinous organ following transplantation. The occurrence of IRI may have a pivotal impact on acute and long-term renal allograft function. Initially, IRI contributes to delayed graft function (DGF), a term typically defined as the need for dialysis within one wk after renal transplantation. DGF frequently leads to prolonged hospital stay, increased healthcare costs, and potentially worse prognosis. Strategies to prevent IRI have so far been fairly limited, poorly defined, inadequately studied, and mostly anecdotal. The purpose of this review is to summarize the existing and novel therapies, which may mitigate IRI in renal transplantation. Agents currently in the pipeline include: Diannexin, which reduces endothelial cell injury by shielding phosphatidylserine; YSPSL, which mimics the binding portion of P-selectin glycoprotein ligand-1 to competitively inhibit translocation of P-selectin and recruitment of polymorphonuclear leukocytes to the surface of endothelial cells; and I5NP, a synthetic small interfering ribonucleic acid that results in the inhibition of p53 expression. These agents represent an exciting frontier in transplant pharmacotherapy; they are in various phases of investigation and may have broader benefits in reducing complications of DGF.

Background A recent randomized trial demonstrated that 1 year of antiviral prophylaxis for cytomegalovirus (CMV) after lung transplantation is superior to 3 months of treatment for prevention of CMV disease. However, it is uncertain if a shorter duration of prophylaxis might result in a similar rate of CMV disease among select lung transplant (LT) recipients who are at lower risk for CMV disease, based on baseline donor (D) and recipient (R) CMV serologies. Methods We retrospectively assessed incidence, cumulative probability, and predictors of CMV disease and viremia in LT recipients transplanted between July 2004 and December 2009 at our center, where antiviral CMV prophylaxis for 6–12 months is standard. Results Of 129 LT recipients, 94 were at risk for CMV infection based on donor CMV seropositivity (D+) or recipient seropositivity (R+); 14 developed CMV disease (14.9%): 11 with CMV syndrome, 2 with pneumonitis, and 1 with gastrointestinal disease by the end of follow-up (October 2010); 17 developed asymptomatic CMV viremia (18.1%). The cumulative probability of CMV disease was 17.4% 18 months after transplantation. CMV D+/R− recipients who routinely received 1 year of prophylaxis were more likely to develop CMV disease compared with D+/R+ or D−/R+ recipients, who routinely received 6 months of prophylaxis (12/45 vs. 2/25 vs. 0/24, P = 0.005). Recipients who stopped CMV prophylaxis before 12 months (in D+/R− recipients) and 6 months (in R+ recipients) tended to develop CMV disease more than those who did not (9/39 vs. 3/41, P = 0.06). Conclusions On a 6-month CMV prophylaxis protocol, few R+ recipients developed CMV disease in this cohort. In contrast, despite a 12-month prophylaxis protocol, D+/R− LT recipients remained at highest risk for CMV disease.

Background: Postoperative pain is a common complication of laparoscopic living-donor nephrectomies (LLDNs). Objective: To determine whether intravenous (IV) acetaminophen administration post-LLDN influenced length of stay (LOS) when used for pain management. Methods: This single-center, retrospective study compared patients undergoing LLDN who had received IV acetaminophen for pain control versus those who did not between June 1, 2011, and November 30, 2015. Patient LOS, 30-day readmissions, frequency of pain assessments, patient-reported pain scores, and opioid administration were assessed. Results: A total of 90 patients were included in the analysis (IV acetaminophen, n = 48; non-IV acetaminophen, n = 42). Patients who did not receive IV acetaminophen were more often older (48.8 ± 12.1 vs 39.3 ± 12.1 years; P = 0.012) and female (71.4% vs 47.9%; P < 0.001). The average LOS was similar between the 2 groups (median = 3.0; interquartile range = [3, 4] vs 3.5 [3, 4]; P = 0.737). The 30-day readmissions were higher in the IV acetaminophen group (16.7%) compared with the group not receiving IV acetaminophen (2.4%; P = 0.033). After the first postoperative day, the frequencies of pain assessments performed were similar among the 2 groups. There was no difference in average pain scores between the groups at any time after LLDN. Conclusions: Patients receiving IV acetaminophen were found to have no improvements in hospital LOS, average pain score, or opioid requirements compared with patients not receiving IV acetaminophen. Patients who received IV acetaminophen were also found to have a higher 30-day readmission rate.

Background: Impaired glucose regulation posttransplantation can affect allograft survival and may lead to the development of posttransplant diabetes mellitus (PTDM). Objectives: The primary purpose of this study is to assess the difference in insulin burden between liver transplant patients who develop PTDM and patients who do not. Methods: This was a single-center, retrospective study. Adult liver transplant recipients transplanted between January 1, 2005, and August 1, 2013, were included. PTDM was defined as: (1) use of an oral antihyperglycemic agent for ≥30 consecutive days after transplant, (2) use of insulin ≥30 consecutive days after transplant, or (3) hemoglobin A1C ≥6.5 any time after transplant. Results: Of the 114 patients included, 48 (42%) developed PTDM. The average 24-hour insulin requirement on the medical floors was 17.2 ± 14.5 units in the PTDM group and 11.3 ± 12.2 units in the PTDM-free group; P = 0.02. The average blood glucose level on the medical floor was 184.7 ± 31.5 mg/dL in the PTDM group and 169.3 ± 31.4 mg/dL in the PTDM-free group; P = 0.013. Multivariate analysis revealed that experiencing rejection was positively associated with the development of PTDM: adjusted odds ratio (AOR) = 3.237; 95% CI = 1.214-8.633. Basiliximab was negatively associated with the development of PTDM: AOR = 0.182; 95% CI = 0.040-0.836. Conclusion: Univariate analyses suggest that insulin burden is a positive risk factor for the development of PTDM; this association is lost in multivariate analyses. Rejection was a positive predictor, and use of basiliximab was a negative predictor for the development of PTDM.

Pneumocystis pneumonia (PCP) is associated with significant morbidity and mortality in renal transplant recipients (RTR). Trimethoprim-sulfamethoxazole (TMP-SMZ) is considered the prophylactic agent-of-choice. Some patients require an alternative owing to TMP-SMZ intolerance. This is the first evaluation of full-dose atovaquone vs. TMP-SMZ for PCP prevention in RTR. One hundred and eighty-five RTR were evaluated in this single-center, retrospective analysis. Patients received either single-strength TMP-SMZ daily (group I; n = 160) or 1500 mg/d of atovaquone and of a fluoroquinolone for one month (group II; n = 25). The primary endpoint was the incidence of PCP at 12 months post-transplant. There were no cases of PCP in either group. There were comparable rates of infections from bacterial pathogens and cytomegalovirus, but rates of BK viremia were significantly higher in group I (22.5%) vs. group II (4%; p = 0.03). The incidence of leukopenia was similar in both groups. Higher mean potassium levels were seen in group I at three months post-transplant but were comparable at all other time points. The need for dose reduction and/or premature discontinuation of therapy secondary to adverse events was more prevalent in TMP-SMZ-treated patients. In our experience, atovaquone appears to be effective in preventing PCP post-renal transplant and also demonstrates good tolerability.

To review available data describing the epidemiology, outcomes, prevention, and treatment of influenza virus in the solid organ transplant population and to evaluate the strengths and limitations of the current literature, with a focus on literature reviewing annual influenza strains and the recent pandemic novel influenza A/H1N1 strain.A systematic literature search (July 1980-June 2011) was performed via PubMed using the following key words: influenza, human; influenza; novel influenza A H1/N1; transplantation; solid organ transplantation; kidney transplant; renal transplant; lung transplant; heart transplant; and liver transplant.Papers were excluded if they were not written in English or were animal studies or in vitro studies. Data from fully published studies and recent reports from international conferences were included.The influenza virus presents a constant challenge to immunocompromised patients and their health care providers. The annual influenza strain introduces a highly infectious and pathogenic risk to solid organ transplant recipients. In 2009, the World Health Organization declared a pandemic as a result of a novel influenza A/H1N1 strain. The pandemic introduced an additional viral threat to solid organ transplant patients at increased risk for infectious complications. The mainstay for prevention of influenza infection in all at-risk populations is appropriate vaccination. Antiviral therapies against influenza for chemoprophylaxis and treatment of infection are available; however, dosing strategies in the solid organ transplant population are not well defined.The solid organ transplant population is at an increased risk of severe complications from influenza infection. Identifying risks, preventing illness, and appropriately treating active infection is essential in this patient population.

Study Objective. To compare the safety and efficacy of rabbit antithymocyte globulin (r-ATG) with basiliximab in renal transplant recipients for whom an early steroid withdrawal (ESW) regimen was planned. Design. Single-center, retrospective, cohort study. Setting. Tertiary care medical center, including inpatient hospital stays and outpatient nephrology clinics. Patients. Ninety-nine consecutive adult recipients of living- or deceased-donor renal transplants between January 1, 2004, and December 31, 2007, in whom ESW was planned and who received either r-ATG or basiliximab; patients receiving an extended-criteria kidney donation or a donation after cardiac death were excluded. Measurements and Main Results. All patients received mycophenolate mofetil and tacrolimus as maintenance therapy with planned ESW. Induction therapy was either r-ATG 1.5 mg/kg/day for 4 days (68 patients) or basiliximab 20 mg on postoperative days 0 and 4 (31 patients). The primary composite end point of biopsy-proven acute rejection (BPAR), graft loss, and death occurred in 6 patients (9%) and 9 patients (29%) in the r-ATG and basiliximab groups at 1 year after transplantation, respectively (p=0.01), with rates of 7% (5/68 patients) and 26% (8/31 patients) for BPAR (p=0.02), 0% and 3% (1/31 patients) for graft loss (p=0.31), and 2% (1/68 patients) and 0% for patient death (p>0.99). Average time to first BPAR was significantly longer in the r-ATG group (mean ± SD 151.4 ± 82.9 vs 53.6 ± 68.4 days, p

Objective To describe the pharmacology and safety of oral over-the-counter cough suppressants and expectorants and to present recommendations for the use of these agents in solid-organ transplant recipients based on the potential for adverse drug reactions or drug-disease interactions. Data Sources and Extraction Data from journal articles and other sources describing the pharmacology and safety of over-the-counter cough suppressants and expectorants, drug-drug interactions with immunosuppressive agents, and drug-disease state interactions are reviewed. Data Synthesis Potential and documented drug-drug interactions between immunosuppressive agents and over-the-counter cough medications guaifenesin, dextromethorphan, diphenhydramine, and codeine were evaluated on the basis of pharmacokinetic and pharmacodynamic principles. Interactions between these cough medications and the physiological changes in the body following transplantation also were examined. Conclusion Diphenhydramine requires additional monitoring when used to treat cough in transplant recipients owing to its anticholinergic properties and the potential for interactions with cyclosporine. Dextromethorphan can be used in most transplant recipients, although greater caution should be exercised if the patient has undergone liver transplant or has liver impairment. Guaifenesin can be used in transplant recipients but should be used with caution in patients receiving kidney or lung transplants and in patients with renal impairment. Codeine combined with guaifenesin is another option for cough and can be used in most transplant patients although those with reduced renal function should be monitored carefully for adverse events.

INTRODUCTION BK polyomavirus (BKPyV) continues to impact renal transplant recipients (RTR). The New England BK Consortium aims to jointly optimize screening and management of BKPyV. METHODS Our first project was to survey centers' BKPyV screening protocols and compare them to consensus guidelines. RESULTS Thirteen of 15 centers (86.7%) returned the survey. Only two center reported using monitoring parameters that were in line with consensus guidelines for BKPyV screening, while the majority of centers reported less intensive methods and shorter duration. One center reported performing renal biopsies in all patients with plasma viral loads >10 000 copies/mL, while all other centers only perform for-cause biopsies. For presumptive nephropathy, 11 centers recommend a biopsy for confirmation. For management of documented BKPyV-associated nephropathy, 12 centers propose further immunosuppression reduction. Nine centers report CNI dose reduction as their primary treatment. More than half of centers surveyed reported use of leflunomide, cidofovir or intravenous immunoglobulin. CONCLUSIONS There was a large variance in BKPyV screening and management strategies among centers. Due to these results, all participating centers agreed to implement uniform screening and aim to optimize management protocols.

Background and objectives: Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. Design, setting, participants, & measurements: This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. Results: A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. Conclusions: This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

For more than 60 years, warfarin was the only oral anticoagulation agent available for use in the United States. In many recent clinical trials, several direct oral anticoagulants (DOACs) demonstrated similar efficacy with an equal or superior safety profile, with some other notable benefits. The DOACs have lower inter- and intrapatient variability, much shorter half-lives, and less known drug-drug and drug-food interactions as compared to warfarin. Despite these demonstrated benefits, the use of DOACs has not gained uniform acceptance because of lack of supportive data in special patient populations, including recipients of solid organ transplants maintained on immunosuppression. This review describes the properties of several novel DOACs including their pharmacology and mechanisms of action as they relate to use among solid organ transplant recipients. We have particularly focused on (i) dosing in patients with impaired renal and hepatic function; (ii) considerations for drug-drug interactions with immunosuppressive medications; and (iii) management of the anticoagulated patients at the time of unplanned surgery. The risks and benefits of the use of DOACs in solid organ transplant recipients should be carefully evaluated prior to the introduction of these agents in this highly distinct patient population.

Background Clostridium difficile infection (CDI) is a common cause of nosocomial antibiotic-associated diarrhea with an increased incidence reported in solid organ transplant recipients. We sought to determine if kidney and/or pancreas transplant recipients possess unique risk factors for CDI. Methods Between January 2009 and February 2011, 942 kidney and 56 pancreas transplants were performed at the 2 centers. Of these, 28 recipients (kidney, n = 24; pancreas, n = 4) developed CDI. Cases were matched to controls (n = 56) in a 1:2 ratio. Results Those with CDI were mostly male patients (82% vs. 48%, P = 0.003), deceased-donor organ recipients (86% vs. 64%, P = 0.045), more likely to have leukopenia (18% vs. 4%, P = 0.038), and had undergone a gastrointestinal procedure within 3 months preceding CDI diagnosis (18% vs. 4%, P = 0.038). Cases had higher cumulative and restricted antimicrobial exposure in days (37 ± 79 vs. 8 ± 12, P = 0.009 and 27 ± 69 vs. 7 ± 10, P = 0.032). Cephalosporin use was more common among cases (43% vs. 16%, P = 0.008). Conclusion Careful antimicrobial selection and assurance of optimal treatment duration in the kidney and pancreas transplant population is prudent. Clinicians should have a heightened awareness of CDI risk particularly during periods of leukopenia and in the setting of gastrointestinal procedures.

In the past decade, the availability of new immunosuppressive maintenance therapies for use in solid organ transplantation has remained limited. Patients and clinicians have relied on immunosuppressive drugs that require a significant amount of therapeutic monitoring and are associated with a variety of adverse effects that affect both quality of life and allograft function. Belatacept is an investigational intravenous biologic agent for long-term use in renal transplant recipients. The costimulatory pathway (signal 2) of T-cell activation and proliferation is produced by stimulation of the T-cell surface marker, CD28, and is essential to the immune system's cellular response and ability to recognize an allograft as foreign. Belatacept is a potent antagonist of B7-1 (CD80) and B7-2 (CD86) ligands present on antigen-presenting cells that are responsible for activation of CD28. Recent phase III trials describe various dosing strategies of belatacept versus a standard cyclosporine protocol in recipients of both living- and deceased-donor renal transplants, as well as in patients receiving kidneys transplanted from extended-criteria donors. Compared with cyclosporine, belatacept has been shown to be noninferior in both patient and allograft survival rates. However, the rate of biopsy-proven acute cellular rejection occurred more frequently in the belatacept groups. Also, compared with standard calcineurin-based regimens, the risk of posttransplant lymphoproliferative disorder is increased in patients receiving belatacept, with the greatest risk in transplant recipients who are Epstein-Barr virus seronegative before transplantation. However, this investigational immunosuppressive agent may avert common adverse effects experienced with standard immunosuppressive protocols including renal dysfunction, metabolic disorders, neurotoxicities, glucose abnormalities, and cosmetic effects. More data on the long-term risks of belatacept are needed to better define its role as immunosuppressive maintenance therapy. Aside from an increased risk of malignancy, belatacept's limited adverse-effect profile and convenient dosing strategy may make it an attractive option for immuno-suppressive maintenance for both the patient and clinician.

To report what we believe to be the first 2 cases of long-term (24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events.The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2RAs have been used for24 months as maintenance immunosuppression in patients intolerant of CNIs or sirolimus.To the best of our knowledge, these 2 cases are the first to demonstrate that IL-2RAs can be used as an alternative to a CNI in a de novo immunosuppressive regimen. Also, this is the first report to illustrate successful long-term use of IL-2RAs in renal transplant recipients. This alternative approach was well tolerated by our patients, with no apparent adverse events. Although the efficacy of such regimens cannot be determined with 2 case reports, the fact that intermittent intravenous IL-2RA administration was successfully accomplished in these patients provides impetus to evaluate this treatment modality in prospective studies.

Belatacept (LEA29Y) is an intravenous biologic for long-term maintenance immunosuppressive therapy in renal transplant recipients. It is currently being reviewed by the United States Food and Drug Administration (FDA) as a prophylactic therapy against acute cellular rejection (ACR) in de novo renal transplant recipients. To provide an in-depth review of the pharmacology, clinical efficacy, safety, and applications of belatacept, a MEDLINE database search was performed for all English-language articles evaluating the pharmacology and efficacy of belatacept, as well as abstracts from recent scientific meetings. Belatacept is a potent inhibitor of B7 binding to CD28, a potent T-cell co-stimulatory signal. The B7 ligands are found on the surface of antigen-presenting cells, specifically B7-1 (CD80) and B7-2 (CD86). CD80 and CD86 are essential ligands for CD28, a critical component of costimulation in the three-signal transplant model of T-cell activation. Belatacept has proven noninferiority compared with calcineurin-inhibitor (CNI)-based regimens in the incidence of patient and allograft survival. However, the incidence and severity of ACR has been shown to be increased in patients receiving belatacept therapy. Although rates of ACR are increased in patients receiving belata- cept, an overall improvement in allograft function has been described with average improve- ments in glomerular filtration rates of up to 12-15 mL/min higher than CNI-based regimens. The side-effect profile of belatacept has been shown to be similar or improved compared with CNI therapy; however, the risk of malignancy, specifically post-transplant lymphoproliferative disorder is notably higher. Because of the marked increase in the risk of malignancy and ACR, approval of belatacept by the FDA will rely on more robust data from long-term follow-up of currently available data.