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Kidney Transplant Patients (kidney + transplant_patient)
Selected AbstractsExogenous Interferon-, Immunotherapy for Invasive Fungal Infections in Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010D. Armstrong-James The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-, (IFN-,) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-, injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-, immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-, immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group. [source] Is Rituximab Safe to Use in Kidney Transplant Patients?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010G. Tydén No abstract is available for this article. [source] Is Rituximab Safe to Use in Kidney Transplant Patients?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010S. C. Jordan Rituximab is an emerging therapeutic agent in transplantation, but concerns remain over proof of efficacy, safety and dosing. See article by Kamar et al on page 89. [source] Subclinical Rejection in Stable Positive Crossmatch Kidney Transplant Patients: Incidence and CorrelationsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009E. S. Kraus We reviewed 116 surveillance biopsies obtained approximately 1, 3, 6 and 12 months posttransplantation from 50 +XM live donor kidney transplant recipients to determine the frequency of subclinical cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). Subclinical CMR was present in 39.7% of the biopsies at 1 month and >20% at all other time points. The presence of diffuse C4d on biopsies obtained at each time interval ranged from 20 to 30%. In every case, where histological and immunohistological findings were diagnostic for AMR, donor-specific antibody was found in the blood, challenging the long-held belief that low-level antibody could evade detection due to absorption on the graft. Among clinical factors, only recipient age was associated with subclinical CMR. Clinical factors associated with subclinical AMR were recipient age, positive cytotoxic crossmatch prior to desensitization and two mismatches of HLA DR 51, 52 and 53 alleles. Surveillance biopsies during the first year post-transplantation for these high-risk patients uncover clinically occult processes and phenotypes, which without intervention diminish allograft survival and function. [source] Case Mix, Quality and High-Cost Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Englesbe A better understanding of high-cost kidney transplant patients would be useful for informing value-based purchasing strategies by payers. This retrospective cohort study was based on the Medicare Provider Analysis and Review (MEDPAR) files from 2003 to 2006. The focus of this analysis was high-cost kidney transplant patients (patients that qualified for Medicare outlier payments and 30-day readmission payments). Using regression techniques, we explored relationships between high-cost kidney transplant patients, center-specific case mix, and center quality. Among 43 393 kidney transplants in Medicare recipients, 35.2% were categorized as high-cost patients. These payments represented 20% of total Medicare payments for kidney transplantation and exceeded $200 million over the study period. Case mix was associated with these payments and was an important factor underlying variation in hospital payments high-cost patients. Hospital quality was also a strong determinant of future Medicare payments for high-cost patients. Compared to high-quality centers, low-quality centers cost Medicare an additional $1185 per kidney transplant. Payments for high-cost patients represent a significant proportion of the total costs of kidney transplant surgical care. Quality improvement may be an important strategy for reducing the costs of kidney transplantation. [source] CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008D. D. Bloom Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo. [source] Posttransplant Prophylactic Intravenous Immunoglobulin in Kidney Transplant Patients at High Immunological Risk: A Pilot StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007D. Anglicheau The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n = 30), and/or donor-specific anti-HLA antibodies (n = 14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p < 0.0001). GFR was 50 ± 17 mL/min/1.73 m2 and 48 ± 17 mL/min/1.73 m2 at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 ± 27% to 5 ± 12%, p < 0.01; class II: from 25 ± 30% to 7 ± 16%, p < 0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy. [source] Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte DepletionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007L. K. Kayler Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5,90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 ± 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup. [source] Dendritic Cell Deficiency in the Blood of Kidney Transplant Patients on Long-Term Immunosuppression: Results of a Prospective Matched-Cohort StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005Holger Hackstein Evidence from in vitro studies suggests that immunosuppressive drugs interfere with key functions of dendritic cells (DCs), but the in vivo relevance of these findings is elusive. We prospectively analyzed the major DC precursor subsets in the blood of kidney transplant recipients on long-term immunosuppression (,1 year). A total of 87 patients were compared to 87 age- and sex-matched controls. Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2 DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow cytometry. Long-term immunosuppression was associated with significant reduction of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p < 0.0001; two-tailed Mann-Whitney U -test) with the strongest negative impact on pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly affected. Analysis of the relative impact of different agents revealed a significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The functional relevance of pDC deficiency was confirmed independently by Interferon-alpha analysis after Toll-like receptor 7 (p , 0.001) and 9 (p < 0.05) stimulation. These results indicate for the first time a profound negative impact of long-term immunosuppression on major DC subsets in kidney transplant recipients. DC deficiency may have important implications with respect to viral infections and tumor development. [source] Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft LossAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Everly The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 ± 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy. [source] Chagas' disease reactivation with skin symptoms in a patient with kidney transplantINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2007Verónica Gallerano MD Immunodepressed patients in the intermediate phase of Chagas' disease may undergo reactivation of the disease together with atypical symptoms. The case of an immunodepressed kidney transplant patient with reactivation of Chagas' disease with skin symptoms is reported. A 65-year-old man presented with infiltrated erythematous lesions on the anterior aspect of the right thigh of 2 weeks' duration. The lesions later extended to the abdomen, thorax, and lower limbs. In the histologic skin examination, amastigotes and Trypanosoma cruzi trypoamastigotes were observed. A fresh smear showed positive parasitemia. Using the Strout hemoconcentration method, multiple Trypanosoma cruzi trypoamastigotes with motility could be seen. Polymerase chain reaction was positive for Trypanosoma cruzi. An immunofluorescence test was positive (1 : 64) and there was hemoagglutination (1 : 32). Treatment was started with benznidazole, 7 mg/kg/day. The patient did not evolve favorably and died 20 days after hospitalization. Skin lesions may be a manifestation of the reactivation of Chagas' disease in immunosuppressed patients. All patients with positive Chagas' serology who require immunosuppressant drugs should receive specific treatment for Chagas' disease. [source] Rapid progression of small cell carcinoma in a renal transplant recipientINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2006ANTTI RANNIKKO Abstract, Immunosuppression is thought to be responsible for the increased incidence of tumor development after organ transplantation. Natural history of these tumors may be more aggressive than would be expected for a similar tumor in a patient without transplant. We describe the fulminant course of small cell carcinoma, likely of prostatic origin, in a kidney transplant patient. Small cell carcinoma (SCC) and especially SCC of the prostate is an aggressive and rare type of tumor. Due to its rarity, only case reports have been published. To our knowledge, this is the first case of SCC, likely of prostatic origin, in an organ transplant recipient (OTR). The case illustrates the aggressiveness of the disease as reflected by its fulminant progression, which may have been further accentuated by the immunosuppression. [source] Cat-scratch disease relapse in a kidney transplant recipientPEDIATRIC TRANSPLANTATION, Issue 1 2007Michelle N. Rheault Abstract:, Cat-scratch disease, an infectious illness infrequently reported in kidney transplant patients, is caused by the organism Bartonella henselae and is transmitted through contact with cats or kittens. It is a self-limited disorder in the general pediatric population. Here we present a case of unsuspected cat-scratch disease in a pediatric kidney transplant patient who presented with fever and lymphadenopathy. Eight months after treatment with a short course of azithromycin, the patient developed a recurrence of cat-scratch disease. We emphasize that the evaluation of a young immunocompromised kidney transplant patient presenting with fever and lymphadenopathy should include unusual infections such as cat-scratch disease. We review the diagnosis and treatment of this uncommon infection in the organ transplant population. [source] Giant warts in a kidney transplant patient: regression with sirolimusBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2010M. Kostaki No abstract is available for this article. [source] Disability following kidney transplantation: the link to medication coverageCLINICAL TRANSPLANTATION, Issue 2 2007D.P. Slakey Abstract:, There is no uniformity regarding patient disability following kidney transplantation. Given improved results of patient and graft survival, and the link between insurance, medication coverage and disability, efforts must be made to define disability after a successful transplant. We conducted an individual questioner study of kidney transplant patients to determine factors relating to patient-perceived disability. Seventy patients participated in the study. Patient perception of disability did not correlate with education or ethnicity. Most patients believed they were disabled on dialysis and this did not change following transplantation. While 42 (60%) of the patients felt that they could work, either full-time or part-time, only 20 (28%) were actually working or in school. Most patients believe that working will eliminate disability status and, therefore, insurance and medication coverage. Patients considered disability more related to their status as a kidney transplant patient than any specific physical limitations. The link, whether real or perceived, between ,disability' and immunosuppressive medication coverage is a significant barrier for many patients. The transplant community must reach some degree of consensus regarding post-transplant activity restrictions. The transplant community needs to find a way to take an active role in post-transplant education and employment. [source] Our experience with third renal transplantation: Results, surgical techniques and complicationsINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2007Mohammad Hossein Nourbala Background: Despite the popularity of kidney transplantation in the current era, second and third kidney transplantation are not yet widely accepted and practiced. Each center has its own regulations and experiences and there is no accepted protocol for third kidney transplantation. We report here our 15 years of experience with third kidney transplantation. Methods: This is a report of all the third kidney transplantations performed in Baqiyatallah Hospital, Tehran, Iran, between 1991 and 2006. Demographic data, surgical techniques, complications and outcomes are reported. Results: Of the nine third kidney transplant patients, six were male. The median age was 43 years (32,52). All of the patients received kidney from living donors. All operations were performed by a midline incision and the grafts were placed at the midline, in the intraperitoneal space. For arterial anastomosis, we used internal iliac, right common iliac and both the right external iliac and inferior mesenteric artery in 4, 4 and 1 case(s), respectively. For venous anastomosis, we used vena cava, common iliac and external iliac veins in 3, 5 and 1 case(s), respectively. During the follow up period (38 months), 6 grafts (66.6%) were functioning. None of the graft rejections were due to surgical complications. Wound dehiscence occurred in two patients. No other surgical complications including infection, lymphocele or hemorrhage were observed. Conclusion: Third kidney transplantation is a field that has not been fully explored. The rate of complications seems to be not much higher than the first transplantation. Defining a standard protocol seems necessary. [source] Matrix metalloproteinase-3 gene polymorphism in renal transplant patients with gingival overgrowthJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2010A. Drozdzik Drozdzik A, Kurzawski M, Lener A, Kozak M, Banach J, Drozdzik M. Matrix metalloproteinase-3 gene polymorphism in renal transplant patients with gingival overgrowth. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01221.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:, Gingival enlargement frequently occurs in transplant patients receiving immunosuppressive drugs. It was hypothesized that gingival enlargement associated with cyclosporine use results from reduced degradation of extracellular matrix in the gingiva. Matrix metalloproteinase-3 (MMP-3) is involved in biodegradation of the extracellular matrix, and its inhibition may contribute to an abnormal accumulation of fibronectin and proteoglycans, which are MMP-3 substrates. The aim of this study was to investigate whether an association exists between MMP-3 genotypes and gingival enlargement in kidney transplant patients medicated with cyclosporine A. Material and Methods:, Sixty-four unrelated kidney transplant patients suffering from gingival overgrowth, as well as 111 control transplant patients without gingival overgrowth, were enrolled in the study. Gingival overgrowth was assessed 6 mo after transplantation. During the post-transplant period all patients were given cyclosporine A as a principal immunosuppressive agent. MMP-3 polymorphism was determined using a PCR restriction fragment length polymorphism assay. Results:, In kidney transplant patients suffering from gingival overgrowth the mean gingival overgrowth score was 1.35 ± 0.57, whereas in control subjects the mean gingival overgrowth score was 0.0. The distribution of MMP-3 -1178A/*dupA alleles among all kidney transplant patients, as well as in the two study subgroups, did not differ significantly from Hardy,Weinberg equilibrium. The frequency of the MMP-3-1171*A/*A genotype (28.1% for gingival overgrowth vs. 26.1% for controls) and of the MMP-3-1171*dupA/*dupA genotype (32.8% for gingival overgrowth vs. 22.5% for controls) was similar for both study groups. The risk of gingival overgrowth was lowest among patients carrying the MMP-3-1171*A/*dupA genotype (odds ratio 0.52), but this did not differ markedly from the other genotypes. Conclusion:, No association between MMP-3 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered cyclosporine A. [source] Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX-3 indexJOURNAL OF VIRAL HEPATITIS, Issue 6 2010L. L. Schiavon Summary., HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR , F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ,4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients. [source] Peripheral blood lymphocytes P-glycoprotein (P-gp, gp-170) expression in allogeneic kidney transplant patientsNEPHROLOGY, Issue 3 2006KATARZYNA KOTRYCH SUMMARY: Aim and Methods: P-glycoprotein (gp-170, P-gp) is a transmembrane transporter involved in drug, for example cyclosporine A, efflux from the cells thus limiting their intracellular concentration. Expression of the transporter on the surface of immune competent cells may be associated with poor prognosis in kidney transplant patients. The aim of the present study was to evaluate P-gp expression on the surface of CD4+, CD8+, CD19+ and CD56+ cells in kidney transplant patients treated with cyclosporine A as a main immunosuppressant, using flow cytometry. Results: It was found that P-gp expression in kidney transplant patients with acute rejection did not differ significantly from transplanted patients without rejection studied in the same period after transplantation, as well as from the healthy controls. Administration of 3-day course of 1000 mg/24 h methylprednisolone did not affect the expression of P-gp in the studied cells, except for significant elevation in CD56+ cells, which disappeared at 2 weeks after cessation of steroid administration. Conclusion: Based on the results from the present study it can be concluded that P-gp expression is not a prognostic factor of acute kidney graft rejection. [source] Cat-scratch disease relapse in a kidney transplant recipientPEDIATRIC TRANSPLANTATION, Issue 1 2007Michelle N. Rheault Abstract:, Cat-scratch disease, an infectious illness infrequently reported in kidney transplant patients, is caused by the organism Bartonella henselae and is transmitted through contact with cats or kittens. It is a self-limited disorder in the general pediatric population. Here we present a case of unsuspected cat-scratch disease in a pediatric kidney transplant patient who presented with fever and lymphadenopathy. Eight months after treatment with a short course of azithromycin, the patient developed a recurrence of cat-scratch disease. We emphasize that the evaluation of a young immunocompromised kidney transplant patient presenting with fever and lymphadenopathy should include unusual infections such as cat-scratch disease. We review the diagnosis and treatment of this uncommon infection in the organ transplant population. [source] Immunotherapy for Invasive Fungal Infections in Transplant Patients: Back to the Future?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010Hans H. Hirsch For kidney transplant patients with life-threatening disseminated fungal infections and failure of modern antifungal therapies, exogenous interferon-gamma might represent an adjunct salvage therapy, but the risk-benefit ratio is not yet established. See Article by Armstrong-James et al on page 1796. [source] Predicting Coronary Heart Disease after Kidney Transplantation: Patient Outcomes in Renal Transplantation (PORT) StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010A. K. Israni Traditional risk factors do not adequately explain coronary heart disease (CHD) risk after kidney transplantation. We used a large, multicenter database to compare traditional and nontraditional CHD risk factors, and to develop risk-prediction equations for kidney transplant patients in standard clinical practice. We retrospectively assessed risk factors for CHD (acute myocardial infarction, coronary artery revascularization or sudden death) in 23 575 adult kidney transplant patients from 14 transplant centers worldwide. The CHD cumulative incidence was 3.1%, 5.2% and 7.6%, at 1, 3 and 5 years posttransplant, respectively. In separate Cox proportional hazards analyses of CHD in the first posttransplant year (predicted at time of transplant), and predicted within 3 years after a clinic visit occurring in posttransplant years 1,5, important risk factors included pretransplant diabetes, new onset posttransplant diabetes, prior pre- and posttransplant cardiovascular disease events, estimated glomerular filtration rate, delayed graft function, acute rejection, age, sex, race and duration of pretransplant end-stage kidney disease. The risk-prediction equations performed well, with the time-dependent c-statistic greater than 0.75. Traditional risk factors (e.g. hypertension, dyslipidemia and cigarette smoking) added little additional predictive value. Thus, transplant-related risk factors, particularly those linked to graft function, explain much of the variation in CHD after kidney transplantation. [source] Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Formulations in De Novo Kidney Transplantation: A Randomized, Open-Label TrialAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009Z. Wlodarczyk Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC0,24 of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC0,24 and Cmin for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID. [source] Interstitial Fibrosis Quantification in Renal Transplant Recipients Randomized to Continue Cyclosporine or Convert to SirolimusAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009A. Servais Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function. The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients taking part in the CONCEPT trial. This multicenter, prospective, trial included 193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to continue CsA, with mycophenolate mofetil. Routine biopsy with automated, quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients. At 1 year, renal function was significantly improved in the conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy results, however, showed no between-group difference in percentage of IF. Calculated GFR at 1 year was significantly associated with the percentage of IF (p = 0.004, R2= 0.07). By multivariate analysis diabetic patients had more fibrosis than non-diabetic patients. In conclusion, although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function, we found no difference of IF on 1-year biopsies. [source] Incidence, Risk Factors and Clinical Consequences of Neutropenia Following Kidney Transplantation: A Retrospective StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Zafrani Neutropenic episodes in kidney transplant patients are poorly characterized. In this retrospective study, neutropenia was experienced by 112/395 patients (28%) during the first year posttransplant. The only factor found to be significantly associated with the occurrence of neutropenia was combined tacrolimus-mycophenolate therapy (p < 0.001). Neutropenic patients experienced more bacterial infections (43% vs. 32%, p = 0.04). Grade of neutropenia correlated with the global risk of infection. Discontinuation of mycophenolic acid (MPA) due to neutropenia was associated with an increased incidence of acute rejection (odds ratios per day 1.11, 95% confidence intervals 1.02,1.22) but not with reduced renal function at 1 year. The time from onset of neutropenia to MPA discontinuation correlated with the duration of neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was safe and effective in severely neutropenic kidney graft recipients, with absolute neutrophil count >1000/,L achieved in a mean of 1.5±0.5 days. Neutropenia is an important and frequent laboratory finding that may exert a significant influence on outcomes in kidney transplantation. As well as leading to an increased incidence of infection, it is associated with a higher rate of allograft rejection if MPA is discontinued for >6 days (p = 0.02). G-CSF accelerates recovery of neutropenia and may be a good therapeutic alternative for severely neutropenic patients. [source] Case Mix, Quality and High-Cost Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Englesbe A better understanding of high-cost kidney transplant patients would be useful for informing value-based purchasing strategies by payers. This retrospective cohort study was based on the Medicare Provider Analysis and Review (MEDPAR) files from 2003 to 2006. The focus of this analysis was high-cost kidney transplant patients (patients that qualified for Medicare outlier payments and 30-day readmission payments). Using regression techniques, we explored relationships between high-cost kidney transplant patients, center-specific case mix, and center quality. Among 43 393 kidney transplants in Medicare recipients, 35.2% were categorized as high-cost patients. These payments represented 20% of total Medicare payments for kidney transplantation and exceeded $200 million over the study period. Case mix was associated with these payments and was an important factor underlying variation in hospital payments high-cost patients. Hospital quality was also a strong determinant of future Medicare payments for high-cost patients. Compared to high-quality centers, low-quality centers cost Medicare an additional $1185 per kidney transplant. Payments for high-cost patients represent a significant proportion of the total costs of kidney transplant surgical care. Quality improvement may be an important strategy for reducing the costs of kidney transplantation. [source] Effect of Comorbidity Adjustment on CMS Criteria for Kidney Transplant Center PerformanceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009E. D. Weinhandl The Centers for Medicare & Medicaid Services (CMS) uses kidney transplant outcomes, unadjusted for standard comorbidity, to identify centers with sufficiently higher than expected rates of graft failure or patient death (underperforming centers) that they may be denied Medicare participation. To examine whether comorbidity adjustment would affect this determination, we identified centers that would have failed to meet 1-year graft survival criteria, 1992,2005, with and without adjustment using the Elixhauser Comorbidity Index. Adjustment was performed for each U.S. center for 24 consecutive (overlapping) 30-month intervals, including 102 176 adult deceased-donor and living-donor kidney transplant patients with Medicare as primary payer 6 months pretransplant. For each interval, we determined percent positive agreement (PPA) (number of centers underperforming both before and after adjustment, divided by number underperforming either before or after adjustment). Overall PPA was 80.8%, with no evidence of a trend over time. Among deceased-donor recipients, 10 of 31 comorbid conditions were predictors of graft failure in at least half of the intervals, as were six conditions among living-donor recipients. Lack of comorbidity adjustment may disadvantage centers willing to accept higher risk patients. Risk of jeopardizing Medicare funding may give centers incentive to deny transplantation to higher risk patients. [source] Racial Disparity Trends for Graft Failure in the US Pediatric Kidney Transplant Population, 1980,2004AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009B. M. Chavers Graft survival among adult African American kidney transplant patients remains low compared to whites, but little information is available for children and adolescents. We examined trends in graft failure among US incident primary kidney transplant patients aged <19 years (n = 13 692), 1980,2004. Trends in 1-year and 2- to 5-year graft failure (for patients whose grafts survived the first year) were analyzed in 5-year intervals. One-year graft failure declined 70% for white and 77% for African American patients over the 25-year period, and 1-year graft failure rates improved at a slightly higher rate for African American compared to white patients (p = 0.02). In contrast, the graft failure rates for years 2,5 declined 53% for white and only 41% for African American patients over the 25 years (p = 0.29). In fully adjusted Cox proportional hazards analysis, the rate of graft failure among African Americans was approximately 2-fold higher than for white patients over the entire study period. Graft survival has improved slightly more for African American than white pediatric patients over the past 25 years. However, graft survival for African American pediatric patients remains poor compared with white patients. [source] Mammalian Target of Rapamycin Inhibitor Dyslipidemia in Kidney Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008B. L. Kasiske The incidence, pathogenesis, consequences and treatment of mammalian target of rapamycin (mTOR) inhibitor dyslipidemia are not well described. We conducted a systematic review of randomized controlled trials reporting cholesterol and triglycerides in mTOR versus non-mTOR inhibitor immunosuppressive treatment regimens in kidney transplant recipients. All but one of 17 trials reported higher levels of cholesterol and triglycerides, or an increased prevalence of treatment with lipid-lowering agents. Approximately 60% of mTOR inhibitor-treated patients received lipid-lowering agents (2-fold higher than controls). There appeared to be little difference between dyslipidemias caused by sirolimus (14 trials) versus everolimus (3 trials). It was difficult to determine the extent to which declines in lipids over time posttransplant were due to lipid-lowering therapy, changes in doses and/or discontinuations of mTOR inhibitors. From the four trials that measured lipoproteins, it appeared that at least some of the increase in total cholesterol with mTOR inhibitors was due to increased low-density lipoprotein cholesterol. What direct or indirect effects mTOR inhibitors have on atherosclerotic cardiovascular disease in kidney transplant patients are unknown. However, in the absence of the necessary clinical trials, dyslipidemia should be managed, as it would be in nontransplant patients at high risk for cardiovascular disease. [source] Immunoprophylaxis with Basiliximab Compared with Antithymocyte Globulin in Renal Transplant Patients Receiving MMF-containing Triple TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2002Yvon Lebranchu Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin® or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20 mg day 0, day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin® plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin® group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a nonsignificant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p =,0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft. [source] | |||||||||||||||||||||||||