Raccoon rabies virus variant transmission through solid organ transplantation.

IMPORTANCE: The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation. OBJECTIVES: To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor. DESIGN: Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons. MAIN OUTCOMES AND MEASURES: Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTS: In retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL). CONCLUSIONS AND RELEVANCE: Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.

The aluminum beverage tab and a soldier with chronic abdominal pain.

Since its introduction in the 1960s, the aluminum pull-tab has been an uncommon cause of aspiration and intestinal obstruction. In many cases, the inability to visualize aluminum on imaging studies delayed diagnosis and therapy or missed the foreign body altogether. Early reports of injury secondary to pull-tab ingestion or aspiration spurred the beverage industry to re-engineer the pop-tab in the 1980s. The new design meant to reduce injury by keeping the tab attached permanently to the can. Despite this innovation, the aluminum pop-tab continues to be a cause of injury. Here, we describe the inadvertent ingestion of an aluminum pop-tab by a 22-year-old patient that resulted in chronic intermittent abdominal distress due to recurrent bowel obstruction for 4 years. This case is unique in the length of delayed diagnosis and demonstrates the elusive nature of an aluminum foreign body.

Incidence, predictors and outcomes of transplant renal artery stenosis after kidney transplantation: analysis of USRDS.

OBJECTIVE: We analyzed the United States Renal Data System registry to study the risks, predictors, and outcomes of transplant renal artery stenosis (TRAS) in contemporary practice. METHODS: The study sampled comprised adults with Medicare primary insurance who received kidney transplants in 2000-2005. We examined associations of recipient, donor and transplant factors with time-to-TRAS by the Kaplan-Meier method and multivariate Cox regression. Survival analysis methods were employed to estimate graft survival after TRAS, and to model TRAS as a time-dependent outcome predictor. Kaplan-Meier analysis was used to estimate time to allograft loss in patients who did or did not have an angioplasty procedure for TRAS. RESULTS: There were 823 cases of TRAS among 41,867 transplant patients, with an incidence rate of 8.3 (95% CI 7.8-8.9) cases per 1,000 patient-years. Mean time to diagnosis of TRAS was 0.83 + or - 0.81 years after transplant. Factors associated with TRAS were older recipient and donor age, extended criteria donors, induction immunosuppression, delayed graft function, and ischemic heart disease. There was no association of TRAS with deceased donors, prolonged cold ischemia time, acute rejection or cytomegalovirus status. TRAS was associated with increased risk of graft loss (including death; adjusted hazard ratio 2.84, 95% CI 1.70-4.72). Among the 823 patients with TRAS, 145 (17.6%) underwent angioplasty. Graft survival after TRAS was not significantly different in patients treated with angioplasty compared to those without angioplasty. CONCLUSIONS: TRAS is an important complication that predicts adverse patient and graft outcomes. Treatment strategies for TRAS warrant prospective investigation in clinical trials.

Outcomes in African-Americans vs. Caucasians using thymoglobulin or interleukin-2 receptor inhibitor induction: analysis of USRDS database.

AIM: We used the USRDS database to test the hypothesis that graft survival was similar using either rabbit antithymocyte globulin (rATG) vs. interleukin-2 receptor inhibitor (IL2i) in the Prograf era. We further explored the variable of race in the two groups of patients. METHODS: We conducted a retrospective cohort study of kidney transplant patients in the USRDS from 2000 through 2005 to compare graft survival (including death) using rATG vs. IL2i with particular reference to outcomes between African-Americans vs. Caucasians. Kaplan-Meier analysis was performed to assess patient and graft survival after transplantation, stratified by recipient induction with rATG versus IL2i. Cox regression analysis was performed to assess adjusted survival after transplantation, assessing whether induction rATG (vs. IL2i) was significant as an interaction term (i.e. an effect modifier) with black race for graft survival. Propensity score analysis was used to address potential confounding by indication. RESULTS: In stratified Cox Regression analysis limited to IL2i, black race was significantly associated with graft loss (adjusted hazard ratio (AHR) 1.17, 95% CI, 1.09-1.26). In analysis limited to rATG induction, black race was not significant (AHR 1.00, 95% CI, 0.92-1.10). We detected a significant interaction between rATG and black race (in comparison with non-black race) for the development of graft loss (AHR, 0.86, 95% CI, 0.76-0.97). Analysis limited to black recipients showed that while use of rATG was not significantly different from IL2i (AHR 0.95, 95% CI 0.87-1.04), the direction of this association was in the opposite direction of non-blacks. CONCLUSIONS: Patient and graft survival were similar in African-American and Caucasian recipients of kidney transplantation using either rATG or IL2i. Limitations of the study are the retrospective nature of USRDS data, center-bias in using rATG vs. IL2i and lack of data on steroid dosage. Results of the present study call for a critical review of induction practices.

Influence of race on kidney transplantation in the Department of Defense healthcare system.

BACKGROUND: We report the influence of race on transplant outcomes in the Department of Defense (DOD) system. METHODS: Retrospective cohort analysis of all kidney transplants performed at WRAMC from 1996 to 2005. Kaplan-Meier analysis was used to assess for differences in graft survival, and Cox regression was used to calculate adjusted hazard ratios for graft loss. For our analyses, we used the cutoff of 6 years (year 2000) when we introduced thymoglobulin induction; maintenance immunosuppression consisted of mycophenolate mofetil and tacrolimus, and rapid steroid taper (completed withdrawal at 6 weeks) was used for all patients. RESULTS: There were 220 transplants (91 Blacks, 107 Caucasians and 22 Asians). Because the curve for graft survival for Blacks over time violated the proportional hazards assumption (at 6 years post-transplant), analysis was segregated into two segments. Through 6 years of follow-up, graft survival was 77% for Blacks and 81% for non-Blacks (p = 0.74 by log rank). Through 9 potential years of follow-up, graft survival for Blacks was 56% and 78% for Whites (p = 0.005). In Cox regression analysis, Black race, compared with non-Black race, was not significantly associated with graft loss at 6 years, but was significantly associated with graft loss occurring after 6 years. CONCLUSIONS: In the DOD health system, no significant differences were seen in graft survival among recipients of different races at 6 years. Black recipients who received a kidney transplant before the year 2000 showed decreased graft survival compared to non-Blacks. This was consistent with change in immunosuppressive regimen in our institution with the introduction of thymoglobulin induction and maintenance therapy with tacrolimus, mycophenolate mofetil and withdrawal of prednisone at 6 weeks.

Complete heart block following penetrating chest trauma in operation Iraqi freedom.

We present a 30-year-old US army soldier who had penetrating chest trauma from a road side explosive with focal cardiac injury. The soldier had penetration of his right atrium and subsequent traumatic membranous ventricular septal defect and complete heart block. He was brought to a Combat Support Hospital where fortuitously the assigned trauma surgeon on-call was a cardiothoracic surgeon, and the assigned trauma intensivist on-call was a cardiac electrophysiologist. Of course, the only source they knew of a pacemaker was halfway around the world. We discuss the management of this injury in an austere combat environment.

Report of the first peritoneal dialysis program in Guyana, South America.

INTRODUCTION: In 2008, we initiated the first Guyanese comprehensive kidney replacement program, comprising hemodialysis (HD), peritoneal dialysis (PD), vascular access procedures, and living-donor kidney transplantation. The government of Guyana, US-based philanthropists, US-based physicians, and Guyanese caregivers teamed up to form a public-private partnership. This pilot program was free of cost to the patients. METHODS: From July 2010 to the time of writing, we placed 17 patients with end-stage kidney disease on PD, which was used as a bridge to living-donor kidney transplantation. During the same period, we placed 12 primary arteriovenous fistulae. RESULTS: The 17 patients who received a PD catheter had a mean age of 43.6 years and a mean follow-up of 5.3 months. In that group, 2 deaths occurred (from multi-organ failure) within 2 weeks of catheter placement, and 2 patients were switched to HD because of inadequate clearance. Technical issues were noted in 2 patients, and 3 patients developed peritonitis (treated with intravenous antibiotics). An exit-site abscess in 1 patient was drained under local anesthesia. The peritonitis rate was 0.36 episodes per patient-year. Of the 17 patients who received PD, 4 underwent living-donor kidney transplantation. CONCLUSIONS: In Guyana, PD is a safe and cost-effective option; it may be equally suitable for similar developing countries. In Guyana, PD was used as a bridge to living-donor kidney transplantation. We have been able to sustain this program since 2008 by making incremental gains and nurturing the ongoing public-private partnership.

Transplantation of A2 kidneys into B and O recipients leads to reduction in waiting time: USRDS experience.

INTRODUCTION: Strategy of transplanting kidneys from A2 donors into patients with blood group B and O recipients has been used to alleviate the long waiting times. MATERIALS AND METHODS: We used an inception cohort of US Renal Data System data base with patients older than 18 years who underwent renal transplantation between January 1995 and July 2006. The primary outcome variable was allograft loss (including death). Bivariate analysis of factors associated with receiving A2 or A2B kidneys was performed with chi-square testing for categorical variables (Fisher's exact test used for violations of Cochran's assumptions) and Student's t test for continuous variables (Mann-Whitney U test used for nonnormally distributed variables). RESULTS: There were 150,118 first kidney transplants of whom 113 received kidney transplant from A2 to O, and 125 patients received A2 to B kidney transplant. Compared with other recipients from the same blood group, recipients of A2 kidneys had significantly shorter wait times. O recipients had a median wait time of 1.63 years (range 0.00-17.21 years), whereas O recipients who received A2 kidneys had a median wait time of 0.70 years (range 0.02-1.47 years; P<0.001). B recipients had a median wait time of 1.90 years (range 0.00-17.52 years), whereas B recipients who received A2 kidneys had a median wait time of 0.74 years (range 0.10-5.21 years; P<0.001). There was no significant difference in graft loss or death between A2 to O and B versus all other recipients. CONCLUSIONS: The results showed that comparatively few patients received A2 to B or O kidney transplant.

Incidence, predictors, costs, and outcome of renal cell carcinoma after kidney transplantation: USRDS experience.

INTRODUCTION: We carried out an analysis of the United States Renal Data System to determine the incidence, risk factors, prognosis, and costs associated with the diagnosis of renal cell carcinoma (RCC) after kidney transplantation. METHODS: This is a retrospective cohort of 40,821 Medicare primary renal transplant recipients transplanted from January 1, 2000, to July 1, 2005, and followed up till December 31, 2005, excluding those with prior RCC or nephrectomy. Kaplan-Meier analysis was performed to determine the time of occurrence of RCC, and Cox regression was used to determine factors associated with RCC. RESULTS: Three hundred sixty-eight patients were diagnosed with RCC within 3 years after transplant (incidence of 3.16 per 1000 person years). The 3-year incidence of RCC posttransplant was 9.29 per 1000 person years (2.3%) for those with pretransplant cysts and 3.08 per 1000 person years (0.7%) without pretransplant cysts. RCC was diagnosed disproportionately early posttransplant in patients with cysts. Cysts were independently associated with increased risk of RCC, as was male gender, older recipient, donor age, African American recipient, increased time on dialysis and acute rejection within first year posttransplant. RCC was associated with increased risk of mortality with a higher risk with pretransplant cysts. Patients who developed RCC had higher cumulative median costs ($55,456 at 2 years) than those who did not develop RCC ($40,369). There was no "clustering" of RCC in individual states or centers more than would be expected by chance. CONCLUSION: RCC was diagnosed disproportionately early in patients with pretransplant renal cysts and was associated with a worse prognosis and increased costs.

Incidence, predictors, and associated outcomes of prostatism after kidney transplantation.

BACKGROUND AND OBJECTIVES: Renal transplantation is increasingly performed in elderly patients, and the incidence of benign prostatic hyperplasia (BPH) increases with age. Anuric males on dialysis may have occult BPH and not develop obstructive symptoms until urine flow is restored after transplantation. If left untreated, BPH poses a risk for numerous complications, including acute urinary retention (AUR), recurrent urinary tract infections (UTI), and renal failure. The authors hypothesized that incident BPH after renal transplantation would adversely affect allograft survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medicare claims for BPH, AUR, UTI, and prostate resection procedures (transurethral resection of the prostate; TURP) were assessed in a retrospective cohort of 23,622 adult male Medicare primary renal transplant recipients in the United States Renal Data System database who received transplants from 1 January 2000 to 31 July 2005 and followed through 31 December 2005. RESULTS: The 3-yr incidence of BPH post-transplant was 9.7%. The incidences of AUR, UTI, and TURP after BPH diagnosis (up to 3 yr posttransplant) were 10.3%, 6.5%, and 7.3% respectively, and each was significantly associated with BPH. Cox regression analysis showed that recipient age per year, later year of transplant, and dialysis vintage were associated with incident BPH. Using Cox nonproportional hazards regression, BPH was significantly associated with renal allograft loss (including death). CONCLUSIONS: BPH is common in males after renal transplant and is independently associated with AUR, UTI, and graft loss. It is unknown whether treatment of BPH, either medical or surgical, attenuates these risks.

Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation.

Mycophenolate mofetil (MMF) use may be associated with progressive multifocal leukoencephalopathy (PML). We conducted a retrospective cohort study of 32,757 renal transplant recipients using the United States Renal Data System kidney transplant files for the incidence, prognosis, and clinical features associated with PML occurring after kidney transplant. Subjects were transplanted from January 1, 2000 to July 31, 2004 and followed through December 31, 2004. The incidence density of PML in MMF users was 14.4 cases/100,000 person-years at risk versus 0 for non-MMF users (P=0.11) by log rank test. Factors significantly associated with PML were BK virus infection (22.2% vs. 1.1%), pretransplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%), and use of antirejection medications in the first year (33% vs. 9.2%), all P less than 0.05. PML is rare in the renal transplant population. There was no significant association between PML and MMF, but MMF use in this cohort is too high to accurately assess an association.

Steroid-free immunosuppression in organ transplantation.

Although steroids have been the cornerstone of immunosuppressive regimens to treat and prevent rejection in organ transplantation, the past decade has seen many successful attempts to minimize or eliminate steroid use. This has been undertaken to decrease the diverse side effects seen with chronic steroid treatment. These efforts have focused on both steroid avoidance and complete elimination, and have been successful across broad patient groups. The key to these efforts has been the adoption of induction protocols with either lymphocyte-depleting agents or anti-interleukin-2 strategies, coupled with the use of the newer maintenance immunosuppressants. In this review, we address the feasibility and benefits of steroid-free and steroid avoidance protocols in kidney, pancreas, liver, and heart transplantation.