ABSTRACT
Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.
Subject(s)
Death , Kidney/pathology , Kidney/surgery , Tissue Donors , Tissue and Organ Procurement , Biopsy , Cohort Studies , Graft Survival , Humans , Kidney Transplantation , Middle Aged , Organ SizeABSTRACT
Non-heart-beating donor (NHBD) kidneys may substantially expand the donor pool, but many transplant centers are reluctant to use these kidneys because of the relatively high incidence of primary nonfunction (PNF). In heart-beating donor kidneys, intravascular fluid depletion during transplant surgery is associated with delayed graft function (DGF). Therefore, we studied the effect of the recipients' hemodynamic status on the outcome of 177 NHBD kidney transplantations. Independent statistically significant predictors of PNF were average central venous pressure (CVP) below 6 cmH(2)O (adjusted odds ratio (AOR) 3.1 (95% CI: 1.4-7.1), p=0.007), average systolic blood pressure below 110 mmHg (AOR 2.6 (95% CI: 1.1-5.9), p=0.03) and pre-operative diastolic blood pressure below 80 mmHg (AOR 2.4 (95% CI: 1.0-5.9), p=0.05). Donor characteristics were not independently associated with PNF (p>0.10). In a subgroup analysis of 56 paired kidneys, 29% of the recipients with the lower CVP of the pair experienced PNF compared with 11% of their counterparts with higher CVP (p=0.09). Our study indicates that recipient hemodynamics during transplant surgery are major predictors of PNF. Therefore, improving recipient hemodynamics by expansion of the intravascular volume is expected to enhance the results of NHBD kidney transplantations and may enlarge the donor pool by increasing the acceptance of NHBD kidneys.
Subject(s)
Blood Pressure/physiology , Graft Rejection/physiopathology , Heart/physiology , Kidney Transplantation/physiology , Adult , Female , Heart Arrest , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Predictive Value of Tests , Prognosis , Reperfusion Injury/physiopathology , Retrospective Studies , Risk Factors , Tissue Donors , Treatment OutcomeABSTRACT
In a preliminary investigation an assay for tacrolimus based on fingerprick sampling and consecutive application as a blood spot on sampling paper has been developed. The dried blood spot was analysed by HPLC-tandem mass spectrometry. The validated range was 1-30 microg/l. Intra- and inter-assay variability for precision and accuracy was <7.5% and 15%, respectively. Tacrolimus concentrations of 24 stable out patients were compared after both blood spot sampling and conventional venous sampling. Method agreement was investigated with the methods of Passing and Bablok and Bland Altman and proved suitable for clinical use. The dried blood spot method for tacrolimus seems promising for patient monitoring.
Subject(s)
Drug Monitoring , Immunosuppressive Agents/blood , Tacrolimus/blood , Blood Specimen Collection/methods , Calibration , Chromatography, High Pressure Liquid , Fingers/blood supply , Humans , Immunosuppressive Agents/chemistry , Molecular Structure , Outpatients , Reference Standards , Regression Analysis , Reproducibility of Results , Tacrolimus/analogs & derivatives , Tacrolimus/chemistry , Tandem Mass SpectrometryABSTRACT
An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.
Subject(s)
Cardiovascular Diseases/chemically induced , Immunosuppressive Agents/adverse effects , Kidney Transplantation/immunology , Cardiovascular Diseases/epidemiology , Cyclosporine/adverse effects , Graft Survival/immunology , Hemodynamics/drug effects , Humans , Risk Factors , Tacrolimus/adverse effects , Treatment FailureABSTRACT
Although acceptable outcomes have been reported in both non-heart-beating (NHB) and elderly donors individually, the large pool of elderly NHB donors has not yet been fully utilized. In 1994, we expanded our transplant protocol to include NHB donors aged over 65 years and this study compares the clinical outcomes with regular NHB transplantations. Up to June 2005, 24 patients were transplanted at our center with kidneys from NHB donors aged 65 years or more, whereas 176 patients received grafts from conventional NHB donors during the same period. Grafts from older donors were associated with inferior glomerular filtration rates (29 vs. 44 mL/min after 1 year, p=0.01) and graft survival (52% vs. 68% after 5 years, p=0.19) compared to younger NHB donor grafts, although the difference in graft survival was not statistically significant. Exclusion of older NHB donor kidneys with severe vascular pathology resulted in similar graft survival of older and younger NHB donor kidneys. We conclude that the use of elderly NHB donors in order to expand the donor pool was associated with unacceptable clinical outcomes and cannot be justified without further refinement in their selection, for example, by histological assessment of pretransplant biopsies.
Subject(s)
Kidney Transplantation/physiology , Tissue Donors/statistics & numerical data , Adolescent , Adult , Aged , Child , Female , Graft Survival , Heart Arrest , Humans , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Male , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
In 1998, a new organ donor registration system was implemented in the Netherlands to increase the number of potential donors. A high school education program was developed to prepare adolescents to make an informed decision about organ donation. A post-test only randomised controlled trial was conducted in 39 high schools including 2868 students. Students within schools were randomly allocated to either attend the organ donation education program or not. The impact of the program on students' intention to register their organ donation preference (and determinants thereof) were analysed using multivariate multileveling modelling (MlwiN). The results show that students who were exposed to the education program had more favourable registration intentions (B = .40), were more often willing to be donors (OR = 1.45), and had greater knowledge about (B = 3.84) and more positive social outcome expectations (B = .09) and self-efficacy regarding organ donation registration (B=.22). Lastly, they experienced significantly less negative outcome expectations related to organ donation registration (B = -.15). Students' evaluation of the school-based education program was favourable. The present organ donation registration program proved to be effective in changing determinants of organ donation registration, and a large-scale implementation in the Dutch high school curriculum is planned.
Subject(s)
Health Education/organization & administration , Health Knowledge, Attitudes, Practice , Psychology, Adolescent , Registries , School Health Services/organization & administration , Tissue and Organ Procurement , Adolescent , Decision Making , Female , Humans , Intention , Male , Multivariate Analysis , Netherlands , Program Evaluation , Self Efficacy , Surveys and Questionnaires , User-Computer InterfaceABSTRACT
This paper describes the process evaluation of an organ donation education program for high school students aged 15-18 years of which the effectiveness was established. The program consisted of three components: a video with group discussion, an interactive computer-tailored program and a registration training session. A cross-sectional survey was conducted among 50 teachers who had recently worked with the program. The results show that all teachers reported to have implemented at least two of the three intervention components, while a majority of teachers reported to have implemented all components. Teachers' attitudes toward the program were generally positive. They reported that the opinions of students and colleagues in their own department were most influential in their decision to provide the education program. Furthermore, teachers were very confident about their ability to apply the different parts of the education program. The educational quality of the program was evaluated as moderately positive and almost all teachers had the intention to use the program again in the future. Because of the positive evaluations and intentions for future implementation by teachers, and justified by its previously established effectiveness, the education program should be considered for large-scale dissemination among high schools in The Netherlands.
Subject(s)
Health Education , Schools , Teaching , Tissue Donors/education , Tissue and Organ Procurement , Adolescent , Cross-Sectional Studies , Female , Humans , Intention , Male , Netherlands , Program Evaluation , RegistriesABSTRACT
The present paper describes the impact and evaluation of two intervention components-a video with group discussion and an interactive computer-tailored program-in order to encourage adolescents to register their organ donation preference. Studies were conducted in school during regular school hours. The video with group discussion in class had a positive impact on the intention to register an organ donation preference as well as on the intention to register as a posthumous organ donor. The computer-tailored program had no surplus value when compared to reading an extensive brochure with general information on organ donation. However, participants appreciated the tailored information more than the brochure. It may be that having provided general information before exposure to the tailored program, the tailored intervention will be more effective. This needs to be tested in a further experiment.
Subject(s)
Health Education/methods , Psychology, Adolescent , Students/psychology , Tissue and Organ Procurement/organization & administration , Adolescent , Chi-Square Distribution , Female , Humans , Male , Online Systems , Peer Group , Video RecordingABSTRACT
The occurrence of post-transplant diabetes mellitus (PTDM) is an important complication after renal transplantation associated with an increased risk of chronic transplant dysfunction and of cardiovascular morbidity and mortality. Both tacrolimus and cyclosporine have been associated with PTDM. In the initial studies, PTDM seemed to occur more often in tacrolimus treated patients than in cyclosporine treated patients. The mechanism by which tacrolimus could cause PTDM was unknown and the relative roles of tacrolimus and corticosteroids, which are often prescribed concomitantly with tacrolimus, were unknown. In several studies we used fasting glucose and insulin levels to assess (peripheral) insulin resistance, and intravenous glucose tolerance tests to assess insulin secretion by the pancreatic b-cells in response to a stimulus (glucose load). Thus, we evaluated the mechanism by which tacrolimus causes glucose metabolic disorders, risk factors for glucose metabolic disorders during tacrolimus treatment, the relative roles of corticosteroids and tacrolimus trough levels in glucose metabolic disorders, and also differences in glucose metabolism between patients using tacrolimus versus patients using cyclosporine. Based on the results of these studies and the available literature, the consequences for the choice of a primary immunosuppressive agent and guidelines for the treatment of PTDM during tacrolimus-based immunosuppression are discussed.
Subject(s)
Immunosuppressive Agents/metabolism , Kidney Transplantation , Tacrolimus/metabolism , Adrenal Cortex Hormones/blood , Clinical Protocols , Cyclosporine/adverse effects , Diabetes Mellitus/etiology , Glucose/metabolism , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/blood , Metabolic Diseases/chemically induced , Risk Factors , Tacrolimus/adverse effects , Tacrolimus/bloodSubject(s)
Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation/immunology , Tacrolimus/pharmacokinetics , Body Mass Index , Dose-Response Relationship, Drug , Female , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Multivariate Analysis , Postoperative Period , Predictive Value of Tests , Prospective Studies , Tacrolimus/blood , Tacrolimus/therapeutic useSubject(s)
Adrenal Cortex Hormones/therapeutic use , Kidney Transplantation/immunology , Mycophenolic Acid/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Cholesterol/blood , Drug Administration Schedule , Drug Therapy, Combination , Europe , Female , Histocompatibility Testing , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Lipoproteins, LDL/blood , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Mycophenolic Acid/analogs & derivatives , Reoperation , Tacrolimus/therapeutic use , Treatment OutcomeSubject(s)
Graft Survival/physiology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Mycophenolic Acid/therapeutic use , Tacrolimus/therapeutic use , Belgium , Female , Follow-Up Studies , Humans , Kidney Transplantation/mortality , Luxembourg , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Survival Rate , Time Factors , Tissue Donors/statistics & numerical dataSubject(s)
Adrenal Cortex Hormones/adverse effects , Health Status , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Quality of Life , Tacrolimus/therapeutic use , Adult , Attitude to Health , Cross-Sectional Studies , Drug Therapy, Combination , Female , Humans , Kidney Transplantation/psychology , Male , Middle Aged , Patient SelectionSubject(s)
Adrenal Cortex Hormones/adverse effects , Adrenal Insufficiency/chemically induced , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Adrenocorticotropic Hormone/blood , Body Mass Index , Cohort Studies , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Radioimmunoassay , Risk Factors , Tacrolimus/therapeutic use , Time Factors , Treatment OutcomeSubject(s)
Adrenal Cortex Hormones/therapeutic use , Graft Rejection/epidemiology , Kidney Transplantation/physiology , Tacrolimus/therapeutic use , Acute Disease , Administration, Oral , Adrenal Cortex Hormones/administration & dosage , Adult , Drug Administration Schedule , Graft Rejection/pathology , HLA-DR Antigens/blood , Histocompatibility Testing , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Incidence , Kidney Transplantation/immunology , Patient Selection , Pilot Projects , Tacrolimus/administration & dosageSubject(s)
Fasting/physiology , Kidney Transplantation/physiology , Tacrolimus/blood , Adult , Aged , Creatinine/blood , Diabetes Mellitus/epidemiology , Female , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Male , Metabolic Clearance Rate , Middle Aged , Postoperative Complications/epidemiology , Tacrolimus/pharmacokinetics , Tacrolimus/therapeutic useABSTRACT
Hypertension is an important risk factor for chronic transplant nephropathy. Therapy is usually based on casual office blood pressure (BP) measurements. However, it is not well known how casual BP predicts 24-hour BP in this population. The main focus of this study is to compare casual office BP with 24-hour ambulatory BP monitoring in renal transplant recipients with signs of chronic transplant nephropathy. Moreover, in this group, the day-night BP profile was assessed. In 36 renal transplant recipients with incipient or progressive proteinuria or an increase in serum creatinine level greater than 20%, 24-hour ambulatory BP was performed. Patients were defined as a nondipper if the mean BP decreased by less than 10% during the nighttime period. The correlation between single office and 24-hour ambulatory BPs was 0.61 for systolic BP and 0.55 for diastolic BP (P < 0.001). The mean difference between 24-hour ambulatory and single office BPs was -4.2 +/- 18.6 mm Hg (range, -44 to 36 mm Hg) for systolic BP and -1.1 +/- 10.7 mm Hg (range, -34 to 27 mm Hg) for diastolic BP; 94.5% of patients were classified as nondippers. There was a significant relation between the nightly decline in mean arterial pressure and calculated creatinine clearance (r = 0.34; P < 0.05). In conclusion, in renal transplant recipients with chronic transplant nephropathy, a large difference between office and ambulatory BPs is present, with both overestimation and underestimation of 24-hour BP by office BP measurements. Moreover, a severely disturbed day-night BP rhythm was observed. In transplant recipients with compromised graft function, office BP may not reflect 24-hour BP adequately, and ambulatory BP measurements should be considered.
Subject(s)
Blood Pressure Determination/methods , Blood Pressure Monitoring, Ambulatory , Kidney Diseases/physiopathology , Kidney Transplantation , Adult , Aged , Aged, 80 and over , Blood Pressure/physiology , Chronic Disease , Circadian Rhythm , Cyclosporine/therapeutic use , Female , Humans , Hypertension/physiopathology , Immunosuppressive Agents/therapeutic use , Kidney/drug effects , Kidney/physiopathology , Kidney Diseases/etiology , Kidney Function Tests , Kidney Transplantation/adverse effects , Male , Middle Aged , Tacrolimus/therapeutic useABSTRACT
Tacrolimus has proven to be superior to cyclosporine-Sandimmune with regard to the prevention of acute rejections, but data comparing tacrolimus with Neoral are scarce. A total of 128 consecutive renal transplant recipients was studied. The patients were treated with Neoral-based (n = 74) or tacrolimus-based (n = 54) immunosuppressive regimens. Survival analyses (Cox regression analysis) were performed on an intention-to-treat basis. Renal function and cardiovascular risk profile were analyzed by means of a repeated-measures analysis of variance (ANOVA) up to 12 months after transplantation. Immunological features were less favorable in the tacrolimus group. Two-year patient and graft survival were comparable. Acute-rejection-free survival was 82 % in the tacrolimus group versus 40 % in the Neoral group (P < 0.0001). The severity of the rejections (1997 Banff classification) was comparable (P = 0.43). Immunological graft loss (3.7 % vs. 12.2 %, P = 0.02) and conversion because of rejection (0 % vs. 28.4 %, P < 0.001) were less in the tacrolimus group. A higher proportion (68.5 % vs. 14.9 %, P < 0.001) was successfully put on monotherapy. Creatinine clearance, proteinuria, and fractional uric acid clearance were similar. In the tacrolimus group mean blood pressure was comparable, but patients needed less anti-hypertensive drugs (P < 0.001) and, even with fewer patients on lipid-lowering drugs, total cholesterol was lower (5.2 vs. 6.0 mmol/l, P = 0.003). Treatment for post-transplant diabetes mellitus was 18.5 % versus 10.8 % (P = 0.22). In both groups, antidiabetic medication could be withdrawn for most patients. This study indicates that tacrolimus is superior to cyclosporine-Neoral in preventing acute rejection with comparable patient and graft survival rates. Because of a lower need for treatment of hypertension and hypercholesterolemia, the cardiovascular risk profile is more favorable. A considerable proportion of patients can be successfully weaned off co-medication and treated with tacrolimus monotherapy.