Outcomes of Clostridium difficile infection in recipients of solid abdominal organ transplants

Knowledge of outcomes of Clostridium difficile infection (CDI) in solid organ transplant (SOT) recipients is limited. To evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with CDI at a single center over 14 yr. Data pertaining to all episodes of CDI were collected. Multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. Overall, 170 patients developed 215 episodes of CDI. Among these patients, 162 episodes (75%) were cured, and in 103 episodes (48%), patients were cured within 14 d. In a multivariate analysis, lack of clinical cure at 14 d was predicted by recurrent episode (0.21, 95% CI 0.06–0.72, p = 0.0128), treatment with vancomycin (OR 0.27, 95% CI 0.1–0.74, p = 0.011), vasopressor support (OR 0.23, 95% CI 0.07–0.76, p = 0.0161), and CDI before the year 2004 (OR 0.44, 95% CI 0.2–0.98, p = 0.0446). The latter three factors are likely markers for severity of illness. In this cohort, 13 patients (8%) died during hospitalization, and 49 patients (29%) died within one yr. No deaths were attributed to CDI. Recurrent episode was a major predictor of treatment failure, suggesting that research into development of therapeutic options for recurrent disease is needed.     

Posttransplant anemia in solid organ recipients

Posttransplantation anemia (PTA) is a prevalent sequela of solid organ transplantation and a potential independent risk factor for cardiovascular morbidity and mortality in kidney transplant recipients. There are multiple causes of PTA, some of which are associated with early phase anemia (<6 months), whereas others more often induce anemia in the late posttransplant phase (>6 months). Although impaired kidney function contributes to PTA, it is only one of many factors that result in anemia in transplant recipients. Other causes include iron deficiency, medications, infections, acute rejection, inflammation, and erythropoietin deficiency. Unlike in the predialysis chronic kidney disease population, the impact of anemia after kidney transplantation outcomes is unknown. This is in large part due to the absence of controlled trials that address whether correction of anemia improves allograft function or patient morbidity and mortality. Current guidelines recommend evaluation for hemoglobin level of less than 12 g/dL and treatment when the value falls less than 11 g/dL and a target of 11 to 12 g/dL. Additional treatments may entail removing the cause of the anemia, nutritional supplementation, and/or an erythrocyte stimulating agent.     

Hypertension in solid organ transplant recipients

Hypertension (HT) is one of the most frequent complications of solid organ transplantation; about 70-90% of this population have high blood pressure or require antihypertensive therapy. Abnormal blood pressure is a potent non-immunological risk factor directly related to patient and graft survival. The etiology of hypertension after orthotopic heart transplantation is multifactorial and varies depending on the time following transplantation. In the early period after transplantation, hypertension is generally related to intravascular volume expansion and persistently increased systemic vascular resistance. Other factors predominant in kidney allograft recipients include: donor age, donor familial history of hypertension, transplant renal artery stenosis, graft function, the recurrence or de novo appearance of glomerulonephritis in transplanted kidney, and post-biopsy arteriovenous fistula. In liver and heart transplantation, hypertension is mainly due to impaired kidney function, with all its consequences. Another contributing factor is immunosuppressive regimen based on calcineurin inhibitors and steroids. The management of post-transplant hypertension usually requests non-pharmacological and pharmacological treatment. In this review, the pathogenesis and treatment of post-transplant hypertension in solid organ transplantation is presented.     

Genitourinary malignancies in solid organ transplant recipients

Malignancy is a recognized complication of transplantation. Genitourinary cancers are the second most common tumors in transplant recipients with prostate cancer and renal cell carcinoma the most common. Unlike the more common skin malignancies, genitourinary tumors have a significant impact on both graft and patient survival. Surgical and radiation treatments need to consider the location of heterotopic transplants and administration of chemotherapy may need alteration in light of immunosuppression being used. The major genitourinary malignancies and their management will be reviewed in this article with emphasis on the concerns that arise in a transplant recipient.     

Safety of anidulafungin in solid organ transplant recipients

The aim of this study was the evaluation of the safety of anidulafungin in adult solid organ transplantation (SOT) recipients. During the study period (14 months), we included all consecutive SOT recipients from 14 centers who received anidulafungin for at least 48 hours for the treatment of invasive fungal infections (IFIs) or as prophylaxis. Relevant clinical and analytical information on clinical charts was reviewed. Clinical side effects, liver function tests, and serum creatinine levels were assessed at least weekly. The need for the modification of immunosuppressive drugs was also recorded by the investigators. All patients were followed for at least 1 week after the end of treatment (EOT) or until death. Eighty-six SOT recipients were evaluated (56 transplant recipients, 20 lung transplant recipients, 8 kidney transplant recipients, and 2 heart transplant recipients). Sixty-two patients (72%) received anidulafungin for prophylaxis, and 24 (28%) received anidulafungin for the treatment of IFIs [candidemia/invasive candidiasis (16) or invasive aspergillosis (8)]. At the baseline, only 5% of the patients were neutropenic (<500 neutrophils/mL). There was no need for the modification of immunosuppressive drug doses because of anidulafungin therapy. No patient discontinued anidulafungin because of severe adverse effects. While receiving anidulafungin, 1 patient developed mild liver toxicity, but the liver function normalized without the discontinuation of anidulafungin. At EOT, the median serum creatinine, aspartate aminotransferase, and alanine aminotransferase levels were significantly lower than the baseline levels, even in liver transplant recipients and patients who had higher baseline levels of serum creatinine. In conclusion, these results show that anidulafungin is a well-tolerated drug in SOT recipients.     

Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients

Sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart-lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. Sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving.     

Dermatopathology of skin cancer in solid organ transplant recipients

Skin cancers occur more frequently in solid organ transplant recipients relative to the general population. Transplant recipients are at particularly high risk of squamous cell carcinoma, with up to a 100-fold increase in the relative risk when compared to the nontransplanted population. This compares with a 10- to 16-fold increase in basal cell carcinoma for renal transplant recipients. An increased incidence of melanoma in transplant patients has also been reported. Other types of skin cancer associated with immunosuppression in transplant patients include Kaposi sarcoma, Merkel cell carcinoma, and posttransplant lymphoproliferative disorder. This review discusses the epidemiology and pertinent pathologic features of each of these tumors. A brief clinical management strategy is outlined. In addition, the contribution of viral induced carcinogenesis with respect to Kaposi sarcoma, Merkel cell carcinoma, and posttransplant lymphoproliferative disorder is discussed.     

Autopsy-determined causes of death in solid organ transplant recipients

The aim of this study was to review the main causes of death as determined by autopsy of deceased solid organ transplant recipients. We reviewed 156 autopsies including 76 heart, 32 liver, 29 kidney, and 19 lung transplant recipients. The mean survival period varied depending on the transplanted organ: namely heart, 497 days; liver, 189 days; kidney, 1124 days; and lung, 252 days. Infections were the most common cause of death in all groups, varying from 21% in heart to 63% in lung recipients. Acute rejection, chronic rejection, and malignancies only appeared as the cause of death in heart recipients (14.5%, 9.2%, and 4%, respectively). Primary graft failure was present in heart (15.7%), kidney (3.4%), and lung (5.3%) recipients. The highest rate of surgical complications as a cause of death was observed in heart transplant recipients. In all groups there was a significant percentage (about 30%) of other pathologies that were responsible for death, such as pulmonary embolism, central nervous system pathology, acute pancreatitis, digestive hemorrhage, and acute myocardial infarction. Our results emphasize that infections are the main cause of death within the first year posttransplant, independent of the organ transplanted.