Fatal transplant-associated west nile virus encephalitis and public health investigation-california, 2010.

BACKGROUND: In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. METHODS: A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. RESULTS: Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor's serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. CONCLUSIONS: Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients.

Laryngotracheal transplantation: technical modifications and functional outcomes.

OBJECTIVES/HYPOTHESIS: Laryngeal transplantation offers the potential for patients without a larynx to recover their voice, which is critical in our communication age. We report clinical and functional outcomes from a laryngotracheal transplant. Widespread adoption of this technique has been slowed due to the ethical concerns of life-long immunosuppression after a nonvital organ transplant. Our patient was already on immunosuppressive medication from prior kidney-pancreas transplantation, and therefore was not exposed to added long-term risk. We describe the unique technical advances, clinical course, and rehabilitation of this patient and the implications for future laryngeal transplantation. STUDY DESIGN: Case report. METHODS: A laryngotracheal transplantation was performed in a 51-year-old prior kidney-pancreas transplant recipient presenting with complete laryngotracheal stenosis. Surgical modifications were made in the previously described technique related to retrieval, vascular supply, and reinnervation. This resulted in a robustly vascularized organ with well-perfused long-segment tracheal transplant and early return of motor reinnervation. RESULTS: A multidisciplinary approach resulted in a successful transplant without evidence of rejection to date. Postoperatively, the patient continues to rely on a tracheotomy but has had the return of an oral and nasal airway, vocalization, smell, and taste, all experienced for the first time in 11 years. CONCLUSIONS: We have demonstrated that our methods may result in a successful laryngotracheal transplant. We describe the preparation, surgical technique, rehabilitation, and interventions employed in achieving optimal outcomes. This report contributes valuable information on this rarely performed composite transplant.

Acute humoral rejection in pediatric renal transplant recipients receiving steroid minimization immunosuppression.

SM protocols have increasingly gained acceptance owing to their favorable side effect profile with comparable cellular rejection rates. After encountering SM patients with AHR, we performed a case-control study to identify predictors associated with AHR in this cohort. Patients with (n = 4) and without (n = 19) biopsy proven AHR on a SM regimen were compared using the Student's t-tests. The median age at transplant was 13.8 yr. Compared to controls, the AHR cohort was older (15.9 vs. 12.1 yr, p = 0.01). Children with AHR had a lower mean tacrolimus trough level and were more likely to have a sub-therapeutic trough at six months (3.5 vs. 5.5 ng/mL, p = 0.05); mean MMF doses were lower at all times points except three months in the AHR group (not statistically significant). This occurred in spite of higher MPA trough levels at all study points in the AHR group (significant at 3 [p = 0.019] and 6 [p = 0.03] months). Children receiving a SM regimen have a lower safety net and may benefit from more intensive monitoring of tacrolimus exposure. MMF dose modifications based on MPA trough determinations should be resisted in the setting of SM.

Success of a steroid-minimization immunosuppression protocol for renal transplantation in the presence of donor-specific antibodies.

Steroid-minimization regimens have gained tremendous popularity for renal Tx in the recent past since they are associated with lower metabolic complications and other adverse effects related to long-term steroid exposure. Most such protocols have been restricted to low-risk recipients due to the concern for acute rejection with steroid-minimization. Herein, we report our experience in managing a child who received a positive flow cytometry cross-match living donor kidney transplant with low titer DSA and was successfully managed using a steroid-minimization drug regimen. The purpose of our report is to make pediatric transplant care providers aware of the feasibility of using a steroid-minimization immunosuppression regimen even in children who have traditionally been perceived to be at higher risk for immunologic complications, allowing successful avoidance of steroid toxicity.

Acute renal transplant injury and interaction between antithymocyte globulin and pooled human immunoglobulin.

The increasing number of highly sensitized patients awaiting renal transplantation has prompted the use of induction immunosuppression regimens including pooled human intravenous immunoglobulin (IVIG) combined with polyclonal anti-lymphocyte sera. We report a case of a patient who received a live donor transplant after abrogation of donor-specific positive cytotoxic crossmatch by IVIG. She developed early acute tubular injury associated with IVIG, mannitol, and hypertonic saline infusion. Furthermore, a possible interaction between IVIG and rabbit antithymocyte globulin (ATG) occurred, suggested by an increased number of peripheral CD3(+) lymphocytes after initial rapid lymphodepletion. We suggest that IVIG-associated nephrotoxicity should be considered in the differential diagnosis of early allograft dysfunction, and furthermore, that IVIG may interact with polyclonal antilymphocyte serum to affect the amount of lymphodepletion achieved.

Disseminated microsporidiosis in a pancreas/kidney transplant recipient.

Human microsporidiosis has been described most commonly in patients with acquired immunodeficiency syndrome and only rarely in those with other forms of immunosuppression. Only 11 cases of microsporidiosis have been reported previously in solid transplant recipients. To our knowledge, this is the first report to describe a case of microsporidiosis in a pancreas/kidney transplant recipient in whom multi-organ system dissemination was observed. This infection was not detected until postmortem examination of stained tissue sections revealed microsporidian spores that were identified as Encephalitozoon species by transmission electron microscopy. It is suspected that leakage from the duodenal anastomosis to the bladder may have contributed to the dissemination of this infection.

Pretransplantation soluble adhesion molecule expression predicts outcome after living donor renal transplantation.

HYPOTHESIS: Occult pretransplantation systemic inflammation will identify patients at risk for poor outcomes after renal transplantation. DESIGN: Retrospective cohort study. Adhesion molecule levels were measured in pretransplantation serum samples from 86 recipients. Univariate and multivariate analyses were conducted to assess a possible correlation between serum adhesion molecule level and outcome. SETTING: University referral center. MAIN OUTCOME MEASURES: Allograft rejection and survival. RESULTS: Patients with low levels of vascular cell adhesion molecule 1 had less graft rejection (P=.007). Low levels of vascular cell adhesion molecule 1 independently predicted decreased rejection (relative risk, 0.17; P=.01), and high levels of vascular cell adhesion molecule 1 independently predicted graft loss (relative risk, 3.83; P=.02). Similar correlations were observed for intercellular adhesion molecule 1. CONCLUSIONS: Decreased pretransplantation adhesion molecule expression correlates with less rejection, and increased levels correlate with graft loss. Assessment of pretransplantation inflammatory status may be useful in optimizing immunosuppression therapy.

Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: a matched-pair pilot study.

Sirolimus, a potent new immunosuppressant, has been anecdotally associated with surgical wound complications. We studied postoperative surgical wound complications in 15 kidney recipients receiving sirolimus, prednisone, and tacrolimus or cyclosporine (study group) compared with 15 recipients receiving tacrolimus, prednisone, and mycophenolate mofetil who were pair-matched for surgical wound complication risk factors. Surgical wound complications were defined as any complication related to the surgical transplant wound requiring reintervention. Fifty-three percent of the study group and 7% of the control group experienced more than one surgical wound complication (P=0.014), and the relaparotomy incidence was 33% and 7%, respectively. Four graft losses have occurred since the beginning of the study: one chronic rejection and two deaths with function in the study group, and one death with function in the control group. At 1 year, graft survival for study recipients compared with control recipients was 87% and 93%, respectively; patient survival was 93% in both groups. Recipients receiving sirolimus demonstrated a significantly higher surgical wound complication rate, but graft and patient survival were not affected. Peritransplant immunosuppression with sirolimus and steroids warrants careful consideration, particularly in recipients with surgical complication risk factors.