Lyndsey J. Bowman

The role of tacrolimus in renal transplantation

Tacrolimus gained FDA approval for use in liver transplantation in 1994 and, approximately 3 years later, was approved for the prevention of acute rejection in kidney transplantation. Over the last decade tacrolimus has become the calcineurin inhibitor of choice for the prevention of rejection in renal transplantation. The objective of this study was to provide a review and update of the literature on the use of tacrolimus in renal transplantation. Numerous clinical trials have shown tacrolimus to be superior to cyclosporine in the prevention of acute rejection and recent trials have demonstrated superiority of tacrolimus over cyclosporine in terms of allograft survival. Post-transplant diabetes remains more common with tacrolimus than cyclosporine, despite lower doses of both tacrolimus and corticosteroids. A novel once-daily dosage form of tacrolimus has recently been developed and is approved for use in Europe. Tacrolimus remains an important immunosuppressant for the prevention of acute rejection. The prolonged-release formulation may improve compliance and possibly long-term outcomes.

Impact of prophylactic versus preemptive valganciclovir on long-term renal allograft outcomes.

Background. Both prophylactic and preemptive oral valganciclovir therapy are effective for the management of cytomegalovirus (CMV) postrenal transplantation in the short term. The long-term effect of either strategy is less well defined. Methods. We analyzed the data on 115 adult recipients previously enrolled in a prospective randomized controlled trial of prophylaxis versus preemptive therapy for CMV. The primary outcome was a composite of freedom from acute rejection, graft loss, or death. Secondary outcomes included individual primary outcomes, posttransplant cardiovascular events, new-onset diabetes mellitus after transplantation, achievement of goal blood pressure, change in body mass index, interstitial fibrosis/tubular atrophy, and change in renal function. The analysis period was a minimum of 48-month posttransplant or a date of death or graft loss, whichever was earlier. Results. The primary outcome was similar between groups (83% prophylactic vs. 81% preemptive, P=0.754). The secondary outcomes showed similarities between the prophylactic and preemptive groups. Four patients in the prophylactic group (8%) compared with none in the preemptive group (0%) died with a functioning graft, P=0.043. Conclusions. Within the limitations of sample size, our data suggest that either strategy for the management of CMV immediately after transplantation seems effective for patient and graft survival in the long term. CMV management is one of the many therapeutic strategies incorporated into a renal transplantation protocol, which often differs among institutions, and the decision as to which approach to use remains center- and resource-specific. The increased incidence of death in the prophylactic group requires further investigation.

Topical recombinant human thrombin in surgical hemostasis.

The achievement of hemostasis is paramount, and good operative practice is crucial to all surgical procedures. Intraoperative hemostasis is usually achieved through suture ligation for larger vessels and electrocautery of smaller vessels; certain cases, however, are not amenable to these techniques, especially when there is diffuse raw surface bleeding. When operative hemorrhage exists despite appropriate preventive actions and good surgical technique, additional methods for controlling intra- and perioperative hemorrhage should be considered, and may include the use of topical thrombin. Recombinant human thrombin (rhThrombin) was approved by the Food and Drug Administration in 2008, with the expectation of overcoming the disadvantages of previously available topical thrombin preparations. The efficacy of rhThrombin has been demonstrated in three randomized controlled trials and found to be effective for achieving hemostasis within 10 minutes of administration for mild to moderate diffuse raw surface bleeding. rhThrombin is equally as effective as bovine thrombin, with a significantly lower risk of immunogenicity. Similar economic parameters, efficacy, and safety profiles between rhThrombin and other available thrombin preparations may support its use over other bovine- and plasma-derived human thrombin products and carry limited to no risk of viral transmission or development of antithrombin antibodies.

Topical use of recombinant human thrombin for operative hemostasis.

Background: The topical use of thrombin has a long history in surgery as an adjunct for achieving operative hemostasis. Until recently the majority of thrombin used topically was derived from bovine plasma. This preparation has been proven to be immunogenic and has led to safety concerns in recent years. Recombinant human thrombin (rhThrombin) has recently been developed as an alternative for topical use for surgical hemostasis. Objective: To review the clinical safety and efficacy data relating to rhThrombin using bovine-derived thrombin as a comparative standard. Methods: This review summaries recent literature regarding topical use of rhThrombin using bovine thrombin as the ‘gold standard’ for topical surgical hemostasis. Conclusions: The data indicates that topical rhThrombin is as effective as bovine thrombin for hemostasis and significantly less immunogenic.

Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant

The use of potent immunosuppression increases the risk of infectious complications following kidney transplantation. Sulfamethoxazole‐trimethoprim (SMX/TMP) is an inexpensive broad‐spectrum antimicrobial agent used in our center as lifelong prophylaxis against Pneumocystis jirovecii, unless contraindicated. This study evaluated the clinical impact of SMX/TMP prophylaxis compared with no prophylaxis with SMX/TMP (NoPPx), but with alternative agents.

Tacrolimus‐Induced Cardiomyopathy in an Adult Renal Transplant Recipient

Tacrolimus‐induced cardiomyopathy (TICM) is a rare but serious adverse effect of tacrolimus, which has been described primarily in pediatric non‐renal transplant recipients. We describe a case of TICM in an adult renal transplant recipient that resulted in allograft dysfunction and multiple hospital admissions for heart failure exacerbation. Prompt and complete reversal of TICM occurred after tacrolimus discontinuation. Although tacrolimus‐induced cardiomyopathy is reversible, availability of alternative immunosuppressants is limited, particularly in the setting of renal dysfunction. Available studies and patient‐specific factors must be considered when determining an alternative maintenance immunosuppression regimen. We chose to use belatacept as alternative immunosuppression in this patient with TICM. Over the next 3 years, the patient remained free of hospital admissions and acute rejection, and demonstrated superior renal allograft function than was observed before her first heart failure admission. We believe that belatacept is an acceptable alternative to tacrolimus therapy for resolution of TICM.

Once weekly fluconazole for antifungal prophylaxis post-liver transplantation.

BACKGROUND Invasive fungal infections (IFI) remain a significant cause of morbidity and mortality in orthotopic liver transplantation (OLT) recipients. In this retrospective study, the outcomes of a protocol using once weekly fluconazole for 3 months after OLT in low- and high-risk patients were reviewed. METHODS In total, 221 OLTs were evaluated in the 3-year period after institution of the new protocol to determine the incidence of IFI within 6 months post-OLT. RESULTS In this cohort, 11 IFIs developed during the 6-month post-transplant period, with the majority being non-albicans Candida. High-risk patients had a greater rate of IFI (16.7% versus 3.4%, P = 0.038) and a significantly longer intensive unit care (ICU) and hospital lengths of stay compared with low-risk patients. Patient and graft survival were similar between the groups. Our patient population appeared to be at low risk for IFI, with 92% of the entire cohort considered low risk. DISCUSSION Given the low incidence of IFI in the low-risk group and the possibility of such protocol selecting out for fluconazole-resistant fungi, the use of weekly fluconazole for 3 months may not be justifiable in low-risk OLT recipients. Given the increased resource utilization observed with IFI, further examination of a more intensive prophylactic strategy in high-risk patients may be warranted.