Başkent Üniversitesi Makaleler

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    Impact of the Addition of Maintenance Steroids to a Rapid Steroid Discontinuation Immunosuppressive Protocol Following Acute Renal Transplant Rejection
    (Başkent Üniversitesi, 2009-12) Arora, Swati; Sureshkumar, Kalathil K.; Dikkala, Sudharani; Marcus, Richard J.
    Objectives: Rapid steroid discontinuation immuno­suppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. Materials and Methods: The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection × 1 and no maintenance steroids, (ii): acute rejection × 1 and started on maintenance steroids, (iii): acute rejection × 2 and no maintenance steroids (iv): acute rejection × 2 and started on maintenance steroids, and (v): no acute rejection Results: Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes—whether they were started on maintenance steroids (P = .003) or not (P = .006)—but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). Conclusions: More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.
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    Pretransplant Detection of Anti-Endothelial Cell Antibodies Could Predict Renal Allograft Outcome
    (Başkent Üniversitesi, 2009-06) Ismail, Amani M.; Mansour, Merveet A.; El-Agroudy, Amgad E.; Badawi, Rasha M.
    Objectives: Endothelial cells that line the vasculature are targets for immune-mediated assault through anti-endothelial cell antibodies. The aim of this work was to detect anti-endothelial cell antibodies and describe the association with kidney allograft rejection and graft survival. Materials and Methods: The study included 60 patients who had undergone live-donor kidney transplant. Inclusion criteria included first kidney transplant, panel reactive antibody titer less than 5%, cause of end-stage renal disease not including vasculitis or systemic lupus erythematosus, and age > 18 years. Patients were classified into 2 groups: 40 patients with anti-endothelial cell antibodies (referred to as the positive group) and 20 patients without anti-endothelial cell antibodies (referred to as the negative group). Results: Serum creatinine level was higher in the positive group at 1 month and 1 year (P = .04). The occurrence of acute rejection was not significantly different in the positive group (18 patients [45.0%]) compared with the negative group (5 patients [25.0%], P = .5). However, the number of acute rejection episodes was higher in the positive group (22 episodes) compared with the negative group (6 episodes, P = .04). In patients who experienced acute rejection, chronic nephropathy was more frequent in the positive group (6 of 18 patients, 33.3%) compared with the negative group (1 of 5 patients, 20.0%) (P = .03). One-year and 5-year graft survival was 91% and 79% in the positive group, and 100% and 91% in the negative group, respectively. The difference at 5 years was significant (P = .04). Conclusions: The presence of anti-endothelial cell antibodies was associated with a higher number of acute rejection episodes and lower long-term graft survival in kidney transplants. It could be an informative test to identify patients at high risk for immunological graft loss.
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    Serial Resistive Index and Pulsatility Index for Diagnosing Renal Complications in the Early Posttransplant Phase: Improving Diagnostic Efficacy by Considering Maximum Values
    (Başkent Üniversitesi, 2008-06) Radmehr, Ali; Shakiba, Madjid; Taheri, Amir Pejman Hashemi; Jandaghi, Ali Babaei
    Objectives: To present new approaches to using duplex Doppler scanning to detect kidney complications in the early posttransplant period. Materials and Methods: We assessed the resistive index and the pulsatility index in 127 renal transplant patients (73 men, mean age, 35.2 ± 14 years) who underwent duplex Doppler scanning on the first, third, and fifth days after transplant. Biopsies were performed in patients suspected of having graft dysfunction owing to clinical and laboratory findings. To differentiate complicated from healthy grafts, a receiver operating characteristic curve analysis was done, and an area under the curve was calculated for each variable. Results: In total, 47 grafts (37%) became complicated (40 rejections). The mean resistive index and mean pulsatility index were statistically significantly higher on the first, third, and fifth days after transplant in patients with complicated grafts than they were in patients with noncomplicated grafts (P < .0001). The mean resistive index and mean pulsatility index showed a significant rise from the first to the fifth day in patients with complicated grafts (P ≤ .014). The area under the curve of the receiver operating characteristic curve for resistive index and pulsatility index on successive days was statistically significant (P < .0001). The resistive index and the pulsatility index area under the curve were statistically significantly lower on the first day than they were on subsequent days. Considering the maximum value of a serially measured resistive index and pulsatility index (which were determined by comparing 3 measurements on the fifth day and selecting the highest one) as a new variable showed a better area under the curve compared with that calculated on the third day (P = .05 for resistive index; P = .012 for pulsatility index). Conclusions: The resistive index and the pulsatility index are effective means of diagnosing post­transplant renal complications. Including a serial assessment and considering the maximum values could improve the diagnostic efficacy on the fifth day after transplant.
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    Risk Factors for Delayed Graft Function Defined as Need for Dialysis or Failure of Creatinine to Fall by 10% in the First 24 Hours After Transplant
    (Başkent Üniversitesi, 2008-03) Stratopoulos, Charalabos; Friend, Peter J.; Sinha, Sanjay; Vaidya, Anil; Muthusamy, Anand; Zilvetti, Miguel; Brockmann, Jens; Roberts, Ian S. D.
    Objectives: Delayed graft function after deceased-donor transplant remains a significant clinical problem. The conventional definition of delayed graft function is the requirement of dialysis within the first week after transplant, but this criterion has many problems that have led to many controversies including those of incidence and significance. Therefore, we sought to identify the possible risk factors of delayed graft function and to investigate their effect on short-term graft survival, according to a composite criterion. Materials and Methods: We reviewed the records of 94 renal transplants obtained from heart-beating deceased donors done at our center during a 2-year period. Variables related to the donor, recipient, and graft were retrospectively collected. Follow-up was 12 months. Delayed graft function was defined as the need for dialysis or the failure of the creatinine level to fall by 10% during the first 24 hours after transplant. To confirm suspected rejection, protocol biopsies were done, irrespective of graft function, on the seventh and 28th days after transplant, or when indicated to confirm suspected rejection. Results: The overall incidence of delayed graft function was 31.9%. Multivariate analysis showed donor age as a significant independent predictor of delayed graft function (OR=1.05, P = .03, 95% CI: 1.01-1.09), whereas donor hypotension was the only independent risk factor associated with a worse 1-year graft survival rate (OR=4.6, P = .021, 95% CI: 1.3-16.5). No association could be established between delayed graft function, acute rejection, and graft survival. Conclusions: Advanced donor age is a predictor of delayed graft function defined as the need for dialysis or the failure of creatinine to fall by 10% during the first 24 hours after transplant. Preventing hemodynamic instability should be an important aspect of donor care.
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    Steroid Avoidance in Renal Transplant Patients Maintained on a Cyclosporine-based Protocol
    (2007-12) Ko, Tina Y; Julie A Haddy,; Sureshkumar, Kalathil K.; Breckenridge, Molly; Patel, Satish; Marcus, Richard J.; Sandroni, Stephen E.; McGill, Rita L.; Carpenter, Barbara J.; Nghiem, Dai D.
    Objective: The aim of this study was to analyze the effect of steroid avoidance, as compared with our pre-existing protocol that contained steroids, on renal allograft and patient survival. Secondary outcomes included body weight, diabetes, hyperlipidemia, and infection. Materials and Methods: This retrospective chart review of the results of steroid avoidance was performed in 169 patients who had undergone renal transplant between January 2000 and March 2002 and had received an immunosuppression regimen of cyclosporine, mycophenolate mofetil, and pred­nisone; and 148 patients who had undergone transplant between November 2002 and November 2004 who had received induction immuno­suppression with a steroid taper by postoperative day 4 and were maintained on cyclosporine and mycophenolate mofetil. Results: One-year allograft survival rates, rejection-free graft survival rates, and patient survival rates were 88%, 76%, and 97%, respectively, in the steroid-maintenance group compared with 90%, 74%, and 96%, respectively, in the steroid-avoidance group (P = NS). No differences were detected in multiple secondary variables related to the metabolic effects of steroid therapy. Conclusions: These data suggest that steroid avoidance can be performed safely and effectively in patients on a cyclosporine-based protocol of immuno­suppression. Longer follow-ups are suggested to determine the effects of limited steroid exposure on the metabolic profiles of patients.
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    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.
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    Can Renal Scan Findings Predict Biopsy-Proven Allograft Rejection?
    (Başkent Üniversitesi, 2005-06) Qureshi, JI; Al-Saeedy, AR; Barret, J.; Al-Ghamdi, G.; Al-Flaiw, A.; Hejaili, F.; Taher, S.; Raza, H.; Jumani, A.; Ghalib, M.; Al-Khader, A.
    Objectives: To assess the usefulness of isotopic renogram in diagnosing acute renal graft rejection. Materials and Methods: Degree of perfusion and allograft uptake of tracer were correlated with the clinical and biopsy diagnoses in 15 postrenal transplant patients with varying degrees of renal impairment. Renographic findings and perfusion calculations were done by a blinded observer. Results: A strong correlation was found between renal histology and renal scan findings in 13 of 15 patients. Sensitivity and specificity of renal scanning in diagnosing acute rejection were 85% and 50% respectively (using renal biopsy findings as the gold standard). Conclusion: Our results demonstrate a strong correlation between blinded perfusion assessment and biopsy-proven acute rejection. We conclude, therefore, that single renal flow scan with DTPA (noninvasive/nonnephrotoxic) allows a physician to tailor therapy for acute renal graft dysfunction. We suggest that in cases with a renographic diagnosis of AR, the patient should receive standard antirejection therapy. Renal biopsy should be reserved for those instances when the renographic findings are not definitive and those when the patient fails to respond to a standard methylprednisolone therapy.
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    Infection Related Renal Impairment: A Major Cause of Acute Allograft Dysfunction
    (Başkent Üniversitesi, 2003-06) Nampoory, Mangalathillam R.N.; Johny, Kaivilayil V.; Costandy, Jamal N.; Nair, Madhavan P.; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, Mustafa
    We prospectively analyzed the impact of post transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40 + 14 years). During the follow-up period, 52 patients expired and 64 lost on follow-up. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100 + 90.2) than that of acute rejection (166 + 127.1), but was more than that in cyclosporine toxicity (50 + 42.2) . Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=<0.01). Ecoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR.