Browsing by Author "Cockwell, Paul"

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Cyclophosphamide Exposure Pretransplant Is Associated With Complications in the First Year After Kidney Transplant
(Başkent Üniversitesi, 2011-08) Sharif, Adnan; Cockwell, Paul; Borrows, Richard; Markarian, Nina; Smith, Samuel; Krishnan, Hari; Chand, Sourabh
Objectives: Some patients needing a kidney transplant have used cyclophosphamide before the transplant. Long-term bone marrow damage associated with cyclophosphamide could manifest with myelotoxic complications after transplant in the context of the immunosuppressant, but evidence for this has not been published. Materials and Methods: We performed a retrospective, single-center analysis of renal transplant recipients with prior cyclophosphamide exposure and compared posttransplant short-term outcomes to a random control group (clinical outcomes identified by searching automated electronic databases). Results: Sixteen recipients had taken cyclophosphamide before the transplant and were compared with a control group of 32 patients. Hospitalization rates were equal, and although there were 3 times more hospitalizations secondary to an infective course in the cyclophosphamide group, this did not achieve significance (0.63 vs 0.22; P = .147). There was no difference in rates of bacteriuria, cytomegalovirus, or Polyomavirus. The cyclophosphamide group was at significantly greater risk of needing a blood transfusion immediately after the transplant (average number of units of blood per patient, 0.44 vs 0.19; P = .038). Also, they were 3 times more likely to require anemia treatments 1 year after the transplant (average number of anemia treatment medications, 0.75 vs 0.25; P = .014). Full blood count parameters, graft function, and graft and patient survival at 1 year posttransplant were equal. Conclusions: Evidence suggests that pretransplant administration of cyclophosphamide is associated with adverse short-term outcomes posttransplant. Further analyses are warranted to investigate these preliminary findings to determine whether myelosuppressive immunosuppressant should be modified in the context of prior cyclophosphamide exposure.
Mortality Prediction After Kidney Transplantation: Comparative Clinical Use of 7 Comorbidity Indices
(Başkent Üniversitesi, 2011-02) Shabir, Shazia; Borrows, Richard; Moore, Jason; He, Xiang; Liu, Xiang; Johnston, Atholl; Little, Mark A.; Inston, Nicholas; Cockwell, Paul; Ball, Simon
Objectives: Despite comorbidity associated with chronic kidney disease, little data exist applying comorbidity scoring systems to renal transplant recipients. This study compared the performance of 7 established comorbidity scores in predicting mortality after kidney transplantation. Materials and Methods: We retrospectively analyzed prospectively collected data from 2033 incident renal transplant recipients. Comorbidity was assessed at baseline, and the following scores were derived: Recipient Risk Score, Charlson Comorbidity Index, Age-adjusted Charlson Comorbidity Index, Modified End-Stage Renal Disease Charlson Comorbidity Index, Foley Score, Wright-Khan Index, and Davies Index. Cox models investigated the association of each comorbidity score with mortality; performance characteristics were tested using receiver operating characteristic curve analysis. Results: Age-stratified Cox analyses showed the Recipient Risk Score-based model displayed the best fit, and receiver operating characteristic curve analysis showed the Recipient Risk Score demonstrated greatest predictive use (5-year mortality c-statistic: 0.787). The independent effect of age on mortality was demonstrated after analysis of scores not containing age as a component (the Charlson Comorbidity Index, the Modified End-Stage Renal Disease Charlson Comorbidity Index, the Davies Index); addition of age to these scores improved fit. Conclusions: Of the currently available comorbidity scores, the Recipient Risk Score demonstrated greatest use. This has implications for deceased-donor allocation algorithms, assessment of confounders in clinical research, and potentially, individual patient management.
Serial Changes in the Expression of CXCR3 and CCR5 on Peripheral Blood Lymphocytes Following Human Renal Transplantation
(Başkent Üniversitesi, 2007-12) Inston, Nicholas; Drayson, Mark; Ready, Andrew; Cockwell, Paul
Objectives: In animal models of transplantation, chemokine receptors have been shown to direct the infiltration of T cells in immune responses and inflammation and to be critical in cellular recruitment. Although the chemokine receptors CXCR3 and CCR5 and their ligands have been found during acute rejection in transplanted human kidneys, the kinetics of expression on peripheral blood lymphocytes is unknown. Materials and Methods: Using a whole-blood red-cell lysis fluorescence-activated cell sorter, serial expressions of CXCR3 and CCR5 on T-cell subsets were analyzed in 19 human renal transplant recipients following transplant. Results: In patients developing allograft rejection (n=6), increased expression of CXCR3 occurred on the surface of CD4+ T cells by the third day after transplant. In patients remaining rejection free (n=13), decreased expression was seen. In patients experiencing allograft rejection and in those remaining rejection free, levels of CXCR3 on CD8+ T cells and CCR5 on CD4+ and CD8+ cells remained stable throughout the study. Conclusions: During allograft rejection, expression of CXCR3, but not CCR5, increases on peripheral CD4+ T cells prior to clinical evidence of allograft rejection and remains elevated for more than 2 weeks following transplantation. This may represent a specific molecular target for identifying and preventing allograft rejection.