BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.     

Rodentizidresistenz und Konsequenzen

Resistance to anticoagulant rodenticides, such as warfarin was first described in 1958. Polymorphisms in the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene and respective substitutions of amino acids in the VKOR enzyme are the major cause for rodenticide resistance. Resistant Norway rats in Germany are characterized by the Tyr139Cys genotype, which is spread throughout the northwest of the country. Resistant house mice with the VKOR variants Tyr139Cys, Leu128Ser and Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu (spretus type) are distributed over a number of locations in Germany. Resistance can reduce management attempts with consequences for stored product protection, hygiene and animal health. Anticoagulants of the first generation (warfarin, chlorophacinone, coumatetralyl) as well as bromadiolone and difenacoum are not an option for the control of resistant Norway rats. The same applies for house mice whereby the tolerance to compounds can be different between local incidences. Due to the higher toxicity and tendency to persist, the most potent anticoagulant rodenticides brodifacoum, flocoumafen and difethialone should be applied but only where resistance is known. In other cases less toxic anticoagulants should be preferred for rodent management in order to mitigate environmental risks. Resistance effects of further VKOR polymorphisms and their combinations, the spread of resistant rats and conditions supporting and reducing resistance should be investigated in order to improve resistance management strategies.     

Gesundheitsschädlinge

Globally, infectious diseases pose the most important cause of death. Among known human pathogenic diseases, approximately 50?% are zoonoses. When considering emerging infectious diseases separately 73?% currently belong to the group of zoonoses. In Central Europe, hard ticks show by far the biggest potential as vectors of agents of human disease. Lyme borreliosis, showing an estimated annual incidence between 60,000 and 214,000 cases is by far the most frequent tick-borne disease in Germany. Continually, formerly unknown disease agents could be discovered in endemic vector species. Additionally, introduction of new arthropod vectors and/or agents of disease occur constantly. Recently, five mosquito species of the genus Aedes have been newly introduced to Europe where they are currently spreading in different regions. Uncommon autochthonous transmission of dengue and chikungunya fever viruses in Southern Europe could be directly linked to these vector species and of these Ae. albopictus and Ae. japonicus are currently reported to occur in Germany. The German Protection against Infection Act only covers the control of public health pests which are either active hematophagous vectors or mechanical transmitters of agents of diseases. Use of officially recommended biocidal products aiming to interrupt transmission cycles of vector-borne diseases, is confined to infested buildings only, including sewage systems in the case of Norway rat control. Outdoor vectors, such as hard ticks and mosquitoes, are currently not taken into consideration. Additionally, adjustments of national public health regulations, detailed arthropod vector and rodent reservoir mapping, including surveillance of vector-borne disease agents, are necessary in order to mitigate future disease risks.     

Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial dysfunction in septic rats

Introduction  

Increasing evidence indicates that epidural anesthesia improves postoperative pulmonary function. The underlying mechanisms, however, remain to be determined. Because pulmonary nitric oxide has been identified to play a critical role in pulmonary dysfunction in sepsis, we hypothesized that thoracic epidural anesthesia (TEA) modulates endothelial dysfunction via a nitric oxide-dependent pathway.     

Ischemic preconditioning improves rat kidney graft function after severe ischemia/reperfusion injury

Ischemic preconditioning (IP) has been shown to ameliorate renal ischemia reperfusion injury. Using a rat kidney transplantation model we determined if IP improves graft function after prolonged cold storage. MATERIALS AND METHODS: Syngeneic rat kidneys were divided into two groups. Prior to 42 hours of cold storage in UW and transplantation, one group (n = 10) received IP (15 minutes of warm ischemia/10 minutes of reperfusion), whereas another group (n = 10) received no treatment. Early graft function and 1-week recipient survival were assessed. RESULTS: Recipient survival was not significantly different between groups [70% (IP) vs 40% (non-IP); P = .28]. IP treatment led to a quicker recovery of renal function. On PODs 3 and 6, serum creatinine levels in the IP group were significantly lower compared with the untreated group. In conclusion, one cycle of IP (15/10) accelerates recovery of renal graft function after severe ischemia reperfusion injury. This simple treatment modality may improve outcomes of renal transplants with prolonged cold storage.     

Modulation of hypoxic pulmonary vasoconstriction is time and nitric oxide dependent in a peritonitis model of sepsis

Objective This study assessed modulation of hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs during sepsis induced by cecal ligation and perforation (CLP) at different times and its relationship to nitric oxide synthases (NOS).Design and setting Prospective controlled trial in a university research laboratory.Subjects 102 male Sprague-Dawley rats.Interventions Groups 1–3 received sham laparotomy 6 h before lung isolation: group 1, only laparotomy; group 2, concurrently l-N ⁶-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg); group 3, concurrently N -nitro-l-arginine methylester (L-NAME, 5 mg/kg). Groups 4–6 received CLP 6 h before lung isolation: group 4, only CLP; group 5, concurrently L-NIL; group 6, concurrently L-NAME. The same experiments were carried out with sham and CLP treatment for 24 h (groups 7–12). Exhaled NO from rats lungs was measured after anesthesia and tracheostomy. After the pulmonary circuit was isolated and perfused, angiotensin II (0.1 µg) was injected into the inflow tract. The lungs were ventilated with the hypoxic mixture (HPV, 3% O₂) for 10 min and then again with the normoxic mixture (21% O₂) for an equal period. Changes in perfusion pressure were measured. Endothelial (eNOS) and inducible NOS (iNOS) expression of the lungs was determined.Measurements and results Treatment with L-NAME but not L-NIL increased HPV in sham lungs. HPV was unaltered after CLP 6 h and decreased after CLP 24 h compared to sham. In CLP animals eNOS protein expression was reduced whereas iNOS expression was increased compared to sham animals. Exhaled NO, reflecting NOS activity was twice as high in the CLP 24 h group than in the CLP 6 h group.Conclusions In the CLP sepsis model modulation of HPV was time-dependent. In addition, vasoconstriction to hypoxic stimuli was dependent on NOS activity.L.G. F. is supported by Innovative Medizinische Forschung Münster, Germany (Fi-1-2000-4)     

Outcomes of surgical repair of bile leaks and strictures after adult‐to‐adult living donor liver transplant

Melcher ML, Freise CE, Ascher NL, Roberts JP. Outcomes of surgical repair of bile leaks and strictures after adult‐to‐adult living donor liver transplant.
Clin Transplant 2010: 24: E230–E235. © 2010 John Wiley & Sons A/S. Abstract: We sought to determine factors that predict the successful surgical repair of biliary complications after adult living donor liver transplantation (ALDLT). Methods: Records of 82 consecutive ALDLT right lobe recipients were reviewed. Operations were performed on 19 recipients for biliary complications. Post‐operative biliary complications were analyzed. Fisher’s exact test was used to identify variables that correlated with successful surgical repair. Results: A total of 29 recipients had biliary complications, of which 19 had a surgical repair. The five recipients, operated on for a stricture without history of leaks, did not develop further complications. However, nine of 14 with a history of a leak developed further complications after surgical repair (p‐value = 0.044). All five who presented with a biliary complication more than 100 d after transplant had successful surgical repair; however, nine out of 13 who presented within 57 d had additional complications after repair. Conclusions: Operations for strictures after ALDLT are more successful than operations for leaks. Recipients with isolated biliary strictures after ALDLT can be managed surgically; however, recipients with history of a leak often require additional interventions after surgical repair.