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EPIGREN : a pharmaco-clinical cohort study in kidney transplantation – Objectives, methods, characteristics of kidney transplant recipients and of their quality of life
Abstract
Among all existing studies/cohorts in kidney transplantation, only a few study the impact of the pharmacological parameters. In addition to the clinical file, the use of a self-administered questionnaire has been validated to collect these data. Comparison between clinical file and self-administered questionnaire concerning the reporting of adverse events highlighted some differences. Infections were the most reported adverse events by the physicians while the patients declared only a few. Adherence evaluated with the self-administered questionnaire decreased between the first and third post-transplantation year and so did the feeling of euphoria and revival. The « Mental health » dimension of the quality of life (QOL) ReTransQol score decreased over this period. However patients’ fear of losing the graft increased as shown by the decrease of the « Fear of losing the graft » dimension of the QOL score. QOL, evaluated by generic and kidney-transplanted-specific questionnaires is also an important parameter that must be considered in patient follow-up. Psychometric properties of the second version of the ReTransQol, as well as its reproducibility and its sensitivity to changes have been validated as early as the 3rd post-kidney-transplantation month. The pharmacoeconomic study Ephegren, development of Epigren cohort, will study the cost-effectiveness and cost-utility ratio of immunosuppressive and anti-cytomegalovirus strategies. Guidelines will then be proposed to standardise the treatments and decrease the management costs of kidney-transplant recipients.
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End stage renal disease (ESRD) profoundly impacts the lives of patients. Kidney transplantation provides the greatest health-related quality of life (HRQOL) improvement. Its measurement has become an important outcome parameter and a very important criterion in the evaluation of any type of medical treatment, especially in the field of renal transplantation.In 2007, a specific self-administered questionnaire for renal transplant recipients was developed in the French language: the ReTransQol (RTQ).After 5 years of use, the properties of the RTQ needed to be re-evaluated in a larger sample.This paper describes the analysis of the ReTransQol and its adaptation to achieve an improved and revised version.
The study design included three analysis phases for two samples of adult renal transplant recipients which came from two cross-sectional multicenter studies carried out in France in 2007 and 2012. Psychometrics properties like construct validity, acceptability and feasibility, reliability and convergent validity were evaluated and every analysis resulted in a new version of the questionnaire: the RTQ V2. The construct validity of the new RTQ was assessed with a Confirmatory Factor Analysis on a large sample of patients.
The study samples included 1,059 patients and 1,591 patients, respectively.After a principal component analysis, item reduction was performed and a total of 13 items were deleted. A final version of the RTQ V2 was created and comprised of 32 items describing 5 domains: Physical Health, Social Functioning, Medical Care, Treatment and Fear of Losing Graft.The explained variance between the first and second RTQ versions improved from 46.3% to 53.1%. All psychometric properties of RTQ V2 were satisfactory: IIC >0.4, IDV (%) of 100% and Cronbach's Alpha >0.7 in every dimension. The confirmatory analysis showed that the overall scalability of the RTQ V2 was satisfactory; all items showed a good fit to the Rasch model within each dimension, and showed INFIT statistics inside the acceptable range.
Psychometric properties allow this new version of the questionnaire to be used to assess different specific dimensions for the renal transplant population, more effectively than previously possible.
To compare the influence of demographic and clinical variables on quality of life (QOL) amongst haemodialysis (HD) and renal transplantation clients in Nepal.
Renal replacement therapy in the form of renal transplant is a newer modality in Nepal. In this study, effectiveness of renal transplant and maintenance HD in clients with end-stage renal disease were evaluated in a Nepalese context.
A descriptive, cross-sectional study was conducted to compare the QOL of clients undergoing HD and renal transplantation in two treatment centres in Nepal. Information on QOL was collected by using the WHOQOL-BREF instrument through interviews.
The clients in the transplantation groups were significantly younger, highly educated and employed. The QOL score of clients with renal transplantation was significantly higher in the physical, psychological and social relationship domains. While assessing QOL score in transplantation groups, females scored significantly higher score in the environmental domain compared with males.
The QOL score in renal transplant recipients was significantly better than that of clients on HD in three of the four WHOQOL-BREF domains. The limited resources and facilities for renal transplantation and the post-transplant follow-up service in Nepal might have contributed to a poorer outcome on the environmental domain in this group.
Background:
This study aims to identify factors associated with health related quality of life (HRQOL) through a comprehensive analysis of sociodemographic and clinical variables among a representative sample size of renal transplant recipients (RTR) in France.
Methods:
A cross-sectional multicenter study was carried out in 2008. All RTR over 18 years old with a functioning graft for at least one year were included. Data included socio-demographic, health status, and treatment characteristics. To evaluate HRQOL, the Short Form-36 Health Survey (SF-36) and a HRQOL instrument for RTR (ReTransQol) were administered. Multivariate linear regression models were performed.
Results:
A total of 1061 RTR were included, with a return rate of 72.5%. The variance explained in regression models of SF-36 ranges from 20% to 40% and from 9% to 33% for ReTransQol.
Conclusions:
The originality of our study's findings was that novel variables, particularly treatment side effects and unemployment, have a negative effect on quality of life of RTR. The French Biomedicine Agency and the National Health Institute for Public Health Surveillance conduct specific actions for professional reintegration and therapeutic education programs in the national plan to improve the HRQOL of people living with chronic diseases.
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Registries in the area of renal replacement therapy (RRT) are intended to be a tool for epidemiological research, health care planning and improvement of quality of care. In this perspective, the value of a population-based RRT registry and its ability to achieve its goals rely heavily on the quality of its data and on quality control procedures. Data quality is of crucial importance to prevent 'garbage coming out from garbage going in'. Regular evaluations of the data quality within these registries are needed to assess various aspects of data quality like completeness, prevention of duplicates, data validity, comparability, timeliness, usefulness and responsiveness of different items and accuracy of reporting and interpretation. In this technical note, we will discuss the purposes of RRT registries and the importance of different aspects of data quality in relation to those purposes. In addition, we discuss how these data quality aspects can be assessed and, where possible, how data quality may be improved.
Abstract The aim of the present study was to differentially determine quality of life (QOL) in patients with end-stage renal disease (ESRD) after successful kidney transplantation (RT, Group A) compared with ESRD patients on a waiting list for RT (Group B). and with healthy controls (Group C) because opinions vary as to which treatment modality can best assure ESRD patients a high QOL. Groups A, B and C each consisted of 149 persons, matched for age and gender. The Munich Quality of Life Dimensions List (MLDL) was used to measure global aspects of QOL. Distinct aspects of QOL were investigated by the Brief Symptom Inventory (BSI) and the Questionnaire for Social Support (K-22). Groups A and C reported similar QOL. Which was significantly higher than in group B (p < .0001). This was particularly true for the physical and psychological status and daily activities, but not for the social situation. Groups A and B reported similar social support, which was significantly, lower than in group C (p < 006). Both ESRD groups reported higher satisfaction with social support than healthy controls (p < .0001). Successful RT nor only improved distinct aspects of QOL in patients with ESRD, but even put them on par with healthy controls regarding physical and psychological QOL. Lower social support and higher satisfaction with social support in both groups of ESRD patients should be evaluated further. From a clinical viewpoint. the improvement of physical and psychological aspects of QOL in RT patients is impressive; but more attention should be paid to constantly low social support in this group of patients. International multi center longitudinal studies to investigate QOL in ESRD patients under different treatments am necessary.
Background
In the Eurotransplant Senior Programme (ESP), kidneys from donors aged ≥65 years are preferentially allocated locally and transplanted into patients aged ≥65 years on dialysis. The purpose of this study was to analyse whether the results of transplantation in the ESP can be improved by preservation of organs by hypothermic machine perfusion (MP) compared with simple cold storage (CS).Methods
Overall, 85 deceased heart-beating donors ≥65 years of age were included in this analysis with follow-up until 1 year post-transplant. For each donor, one kidney was randomly assigned to preservation by CS and the contralateral kidney to MP from organ procurement until transplantation. Delayed graft function (DGF), primary non-function (PNF) and 1-year patient and graft survival rates were evaluated as primary and secondary endpoints.ResultsThe median recipient age was 66 years in both groups and the median cold ischaemia time was 11 h for MP and 10.5 h for CS (P = 0.69). The DGF rate was 29.4% for MP and 34.1% for CS (P = 0.58). Only extended duration of cold ischaemia time was an independent risk factor for the development of DGF (odds ratio 1.2, P < 0.0001). PNF was significantly reduced (3.5% MP versus 12.9% CS, P = 0.02). The 1-year patient and graft survival rates were similar for MP and CS (94% versus 95% and 89 versus 81%, P > 0.05). The 1-year graft survival rate was significantly improved after MP in recipients who developed DGF (84% MP versus 48% CS, P = 0.01).Conclusions
Continuous pulsatile hypothermic MP for kidneys from donors aged ≥65 years can reduce the rate of never-functioning kidneys and improve the 1-year graft survival rate of kidneys with DGF. In this small cohort, the known advantage of MP for the reduction of DGF could not be confirmed, possibly due to relatively short cold ischaemia times.
The International Quality of Life Assesment (IQOLA) Project is a 4-year project to translate and adapt the widely used MOS SF-36 Health Survey Questionnaire in up to 15 countries and validate, norm, and document the new translations as required for their use in international studies of health outcomes. In addition to the eight-scale SF-36 health profile, the project will also validate psychometrically based physical and mental health summary scores, as well as health utility indexes incorporating SF-36 scales for use in cost-utility studies.
The term ‘internal consistency’ has been used extensively in classical psychometrics to refer to the reliability of a scale based on the degree of within-scale item intercorrelation, as measured by say the split-half method, or more adequately by Cronbach's (1951) (Psychometrika, 16, 297–334) alpha, as well as the KR20 and KR21 coefficients. This term is a misnomer, as a high estimate of internal item consistency/item homogeneity may also suggest a high level of item redundancy, wherein essentially the same item is rephrased in several different ways.
Chronic gastrointestinal diseases, such as inflammatory bowel disease (IBD) and celiac disease (CD), might have impact not only on the affected child but also on their parents since inside the family framework, a change in each member may have influence on the whole system. The aim of this study was to test the hypothesis that parents whose children have IBD or CD will have a lower quality of life (QoL) compared to parents of healthy children, as well as that lower QoL will be found among parents who perceive lower health related quality of life (HRQOL) of their child. 55 parents of children with IBD, 49 of CD and 53 parents of healthy children were included in the study. Children were aged 7-18 years. In order to measure parental QoL, a Croatian version of the WHOQOL-BREF questionnaire was administered, with four domains: physical health, psychological health, social relationship and environment. The Total QoL was calculated as a sum of all domain items. The parent-proxy report of children's HRQOL, PedsQL 4.0 Generic Core Scales was used. Main result shows that parents of children with IBD report a significantly lower psychological health, compared to parents of other children, and significantly lower physical health compared to parents of healthy children. Among parents of children with CD and parents of healthy children, better parental Total QoL was significantly correlated with better parental report of children's HRQOL, while for parents of children with IBD those associations were not found. Results of study show association between presence of the disease in offspring with poorer parental QoL, thus highlight the importance of supporting not only children with chronic disease but also involving their parents in psychosocial interventions, as well as supporting the patient's association groups which gather both children with chronic disease and their parents.
The Eurotransplant Senior Program (ESP) allocates kidneys from elderly donors to elderly recipients (> or = 65 years old). During the last 39 years, 922 kidney transplantations were performed in our transplant center. We retrospectively analysed patients included in the ESP from the our center. Eleven patients > or = 65 years old recieved kidney from donors 65 years old. Cold ischemia time was approximately 15 hours. Dual kidney transplantation was performed in one patient. Appropriate immunosuppressive protocol was given to all patients. Surgical complications were relatively common and included dissection of renal artery (1 patient), thrombosis of renal artery (1 patient), ureterovesical obstruction (1), lymphocele (1), bleeding (1), acute abdomen (2) and wound dehiscence (1). One rejection episode was registered. Delayed graft function was observed in the two patients with full recovery of kidney function. Seven patients until now have good functioning graft. Four kidneys were lost. One patient died because of pneumonia. Kidney transplantation in elderly is feasible procedure but with greater number of complications than usually.
Valid instrumentation in the assessment of health-related quality of life (HQoL) in renal transplant recipients is critical to identifying particular nuances and determinants of HQoL in this population. Therefore, the validity of disease-specific instruments to measure HQoL in renal transplant recipients, such as the Kidney Transplant Questionnaire (KTQ), needs further investigation. The objective of this study was to assess the concurrent validity of the KTQ in adult US renal transplant recipients using the well established SF-12 Health Survey version 2 (SF-12v2) as the comparison instrument.
One hundred and fourteen renal transplant recipients met the following inclusion criteria for this study, ie, were at least 21 years of age, more than two years post-transplant, and receiving immunosuppressant therapy. Subjects were asked to complete a series of HQoL instruments, ie, the KTQ and the SF-12v2 (physical component summary [PCS-12] and mental component summary [MCS-12]). Descriptive statistics were calculated, and correlational analyses were conducted to examine the concurrent validity of the HQoL instruments.
Among 100 participants (87.7% response rate), the majority of participants were male (52%), had deceased donor transplants (63%), and received Medicare benefits (84%). PCS-12 was positively correlated with three of five KTQ subscales (P < 0.05), ie, KTQ-physical (r = 0.43), KTQ-fatigue (r = 0.42), and KTQ-uncertainty/fear (r = 0.2). MCS-12 was positively correlated with all KTQ subscales (P < 0.01), ie, KTQ-physical (r = 0.26), KTQ-fatigue (r = 0.48), KTQ-uncertainty/fear (r = 0.33), KTQ-emotional (r = 0.47), and KTQ-appearance (r = 0.28).
The findings support the concurrent validity of the KTQ in US renal transplant recipients. Future studies should continue exploring the validity of the KTQ, as well as its practical and research utility in HQoL measurement in the renal transplant population.
We studied the impact of steroid use on kidney graft loss due to recurrent IgA nephropathy (IgAN). We used data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to conduct a survival analysis of adult recipients of a first kidney transplant for IgAN who received a graft between 1988 and 2007. Predictors of graft loss due to recurrent IgAN were analyzed in a competing risk survival analysis with steroid use modeled as a time-varying covariate. Fifteen hundred twenty-one recipients with kidney failure due to biopsy-proven IgAN received a first kidney transplant during the study period. Four hundred and twenty-eight recipients experienced graft loss, of which 54 losses (12.6%) were attributed to recurrent IgAN. The overall 10-year cumulative incidence of graft loss from recurrent IgAN was 4.3% (95% CI 3.1-5.8). Prevalence of steroid use was 92% at baseline, 84% at 1 year and 64% at 5 years. After adjusting for age, sex, HLA mismatch, dialysis duration and transplant era, steroid use was strongly associated with a reduced risk of recurrence (subhazard ratio 0.50, 95% CI 0.30-0.84). These results suggest that the risk of graft loss from recurrent disease should be considered when tailoring immunosuppression for patients with IgAN.
Nonadherence to oral immunosuppressive drugs in renal transplant patients remains a major challenge. The objective of this study was to develop an adherence-exposure model that 1) quantifies the impact of nonadherence patterns on cyclosporine levels and 2) identifies nonadherence patterns that are associated with unfavorable transplantation outcomes.
This model quantified variability in drug exposure, expressed as the coefficient of variation (CV%), for time-averaged and trough cyclosporine levels (C(avg) and C(min), respectively), and percentage of days spent below the therapeutic C(min) target. Simulated patterns of nonadherence closely matched those observed in clinical practice for four nonadherence clusters and an "Others" category.
Patients in simulated nonadherence clusters 1-3 spent a mean (standard deviation) 5.8% (4.9), 9.0% (5.0), and 6.5% (3.4) of days below the C(min) target, compared with 76.8% (6.5) for cluster 4 and 38.3% (6.4) for the "Others" category. Mean (standard deviation) CV% values for C(min) were 24.1 (7.9), 35.4 (11.7), and 34.1 (10.6) for clusters 1-3, compared with 136.4 (23.6) for cluster 4 and 64.8 (10.3) for the "Others" category. Findings for C(avg) were similar.
Based on nonadherence patterns and known relationships between CV% for C(min) and C(avg), and transplantation outcomes, patients in cluster 4 and the "Others" category are expected to be at high risk of allograft rejection. The proposed drug adherence-exposure model is useful to identify high-risk patients who can be targeted for interventions aimed at enhancing drug adherence to optimize clinical long-term outcomes.
Health-related quality of life (HRQoL) is becoming an important outcome measure in evaluation of various forms of renal replacement therapy (RRT). The Short Form-36 (SF-36), Giessen Subjective Complaints List (GBB-24), and Zerssen's Mood Scale (Bf-S) are internationally validated questionnaires for the assessment of HRQoL. The goal of the current study was to evaluate the HRQoL of renal transplant recipients and compare it with that of patients on different forms of RRT. The study population consisted of: (1) 120 patients on hemodialysis (HD); (2) 43 patients on peritoneal dialysis (PD); (3) nine recipients who lost their grafts and went back to dialysis; (4) 120 age- and sex-matched healthy individuals (controls); and (5) 48 renal transplant recipients. The mean SF-36 scores were not significantly different between control group and transplant recipients as well as HD and PD patients including previously transplanted patients. The dialysis patients scored significantly worse in all eight SF-36 domains compared with transplant recipients and healthy subjects. In all GBB-24 components, the transplant recipients scored significantly higher than HD and PD patients. In the "fatigue tendency," "limb pain," and "cardiac complaints" components, recipients scored significantly higher than control group subjects. The mood analysis (Bf-S) showed that the scores of transplant recipients and controls did not differ, being significantly higher than those of dialysis patients. The HRQoL of patients on HD and PD were similar and lower than that of the general population. Renal transplantation significantly improved HRQoL at least to the level of healthy individuals. Graft loss was associated with significant worsening of HRQoL.
Psychiatric evaluation of organ transplant candidates is now routinely proposed also in Italy. This study purposed to assess the psychological status in patients on hemo-dialysis, peritoneal dialysis and renal transplantation; moreover other purpose is to investigate the possible differences among the three groups.
157 subjects were consecutively enrolled, to the service of U.O. Trapianti d'Organo of San Salvatore Hospital in L'Aquila (Italy), between October 2007 and August 2009; 127 were in dialysis (80.9%), of which 101 were in hemodialysis (64.3%) (HD group) and 26 in peritoneal dialysis (16.6%) (PD group) and 30 (19.1%) Kidney transplant (PT group). The subjects were examined with clinical evaluation and through the following psychometric instruments: HAM-D, HAM-A, Jalowiec Coping Scale, STAI-Y1, STAI-Y2, DISS, SF-36.
30% out of our sample showed the presence of some psychopathological signs and symptoms, especially depression and anxiety. At HAM-D there were no differences between HD group (6.73; DS + 5.58) and PD group (5.27, DS + 5.63); the mean value at HAM-D in PT group was 4.4 (DS + 3.16) (p < 0.05). At HAM-A there were no differences between three groups. The HD group showed an higher value at STAI-Y1 (38.61; DS + 10.64) than PD (34.95; DS + 6.75) and PT (33.89; DS + 6.14) groups (p < 0.05). The quality of life (physical role, general health, vitality and role emotional) was lower in HD and PD groups, higher in group PT. The HD e PD groups showed a higher level of disability than PT group (p < 0.05). All subjects used "positive: coping styles.
We consider essential to investigate the issues observed in this study, with the need to integrate psychosocial and functional needs assessment within a course of diagnosis and treatment for people who are undergoing dialysis procedures, or after waiting for a transplantation. Dialysis affects the quality of life, leading to limitations in activities and high level of disability. The PT group showed better quality of life and less impairment in functioning in the investigated areas. If the impact of psychological and/or psychiatric aid remains difficult to appraise, these results emphasize the impact of psychological status and the appropriateness of psychosocial support intervention on patients facing the transplant process or in dialysis treatments.
Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Données Informatisées et VAlidées en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre- and post-transplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver-operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.
Cytomegalovirus (CMV) continues to be one of the most common infections after solid-organ transplantation,
resulting in significant morbidity, graft loss, and adverse outcomes. Management of CMV varies considerably among transplant centers but has been become more standardized by publication of consensus guidelines by the Infectious Diseases Section of The Transplantation Society. An international panel of experts was reconvened in October 2012 to revise and expand evidence and expert opinion-based consensus guidelines on CMV management, including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues. The following report summarizes the recommendations.
Currently in the medical literature there is controversy about the role and effects of renal transplantation (RTx) on the sexual functioning of patients with terminal chronic renal disease (TCRD). There is no clear evidence of the real impact of RTx on sexual functioning in these patients. This article makes a brief summary of the literature, describing the most important clinical concepts, evaluates results, and compares the impact of renal transplantation on sexual function before and after the procedure.
Medline and the Embase database were consulted; Medical Subject Headings used were "Kidney Failure, Chronic," "Kidney Transplantation," "Sexual Dysfunction," "Pleasure," "Sexual Behavior," and "Quality of Life." Search was limited to articles within the last 15 years.
Sexual dysfunction affects almost 87% of male and 60% to 80% of female patients; 40% to 78% of male patients with RTx report a sense of improvement on global sexual function, 25% to 30% of female patients of reproductive age with RTx report improvement in sexual performance and decreasing of menstrual cycle alterations. Fewer than 10% of patients receiving an RTx reported a decrease of sexual satisfaction.
Despite controversy, reviewed results show significant improvement of sexual functioning after receiving an RTx. Those who report no improvement of sexual functioning may have conditions attributable to implicit characteristics of TCRD (age, neuroendocrine/metabolic problems) and/or RTx (immunosuppressive therapy). RTx improves sexual functioning by improving sexual desire and overall sexual satisfaction.
Identified determinants associated with improvement of sexual functioning are decreased prolactin serum level, age younger than 45 years, and onset of dialysis less than 6 months.
Analysis of data from the international Collaborative Transplant Study has revealed striking relationships between human leukocyte antigen mismatching and graft survival, the incidence of death from cardiovascular disease or infection, the occurrence of non-Hodgkin lymphoma, and onset of post-transplant osteoporosis and bone fracture following kidney transplantation from a deceased donor.
Background:
The shortage of organ donors has led to the introduction of the Eurotransplant Senior Program (ESP) to optimize the allocation of kidneys from elderly donors by age-matching. In the face of a rapidly aging population, identification of prognostic factors for kidney allograft survival within the ESP population will be of enormous significance.
Material and methods:
Donor and recipient data from 89 patients transplanted under the ESP protocol between 1999 and 2007 were retrospectively analyzed. Data were correlated with initial graft function, graft survival, acute rejection episodes, serum creatinine levels, glomerular filtration rates, and patient survival using univariate and multivariate analysis. Maximum follow-up was 5 years.
Results:
Cold ischemia time (CIT) >16 hours, body mass index (BMI) ≥25 kg/m(2), and kidney re-transplantation were significant risk factors for delayed graft function (DGF). Odds ratio for primary non-function was significantly increased with prolonged CIT, BMI ≥25 kg/m(2), and duration of renal replacement therapy >69 months. CIT >15 h, DGF, and kidney re-transplantation were associated with poor graft survival (P<0.05).
Conclusions:
Risk reduction (e.g., aiming at CIT <15 h) and close surveillance of patients at risk appear to be crucial for allograft survival in the ESP.
Background:
Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions.
Material and methods:
Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; <12, nonadherence). A logistic regression model was used to identify factors associated with nonadherence.
Results:
In total, 808/946 recipients (85.4%) provided ≥1 ITAS score. Nonadherence was reported by 24.8%, 31.5%, 33.0%, 39.8%, 35.4% and 26.4% at months 3, 6, 12, 24, 36 and 48, respectively. Mean ITAS score was higher with EC-MPS vs. MMF at months 24 (11.3[1.0] vs. 10.9[1.4], p=0.001) and 36 (11.4[1.0] vs. 11.1[11.3], p=0.024). The odds ratio for nonadherence was 1.60 (95% CI 1.17, 2.19; p=0.003) for African Americans vs. non-African Americans. The rate of biopsy-proven acute rejection was 12.7% (51/401) in nonadherent recipients vs. 11.3% (46/406) in adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013).
Conclusions:
Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.
Aims/hypothesis
The aim was to study geographic variations and recent trends in the incidence of end-stage renal disease (ESRD) by diabetes status and type, and in patient condition and modalities of care at initiation of renal replacement therapy.
Methods
Data from the French population-based dialysis and transplantation registry of all ESRD patients were used to study geographic variations in 5,857 patients without diabetes mellitus, 227 with type 1 diabetes mellitus, and 3,410 with type 2. Trends in incidence and patient care from 2007 to 2011 were estimated.
Results
Age- and sex-adjusted incidence rates were higher in the overseas territories than in continental France for ESRD unrelated to diabetes and related to type 2 diabetes, but quite similar for type 1 diabetes-related ESRD. ESRD incidence decreased significantly over time for patients with type 1 diabetes (−10% annually) and not significantly for non-diabetic patients (0.2%), but increased significantly for patients with type 2 diabetes (+7% annually until 2009 and seemingly stabilised thereafter). In type 2 diabetes, the net change in the absolute number was +21%, of which +3% can be attributed to population ageing, +2% to population growth and +16% to the residual effect of the disease. Patients with type 2 diabetes more often started dialysis as an emergency (32%) than those with type 1 (20%) or no diabetes.
Conclusions/interpretation
The major impact of diabetes on ESRD incidence is due to type 2 diabetes mellitus. Our data demonstrate the need to reinforce strategies for optimal management of patients with diabetes to improve prevention, or delay the onset, of diabetic nephropathy, ESRD and cardiovascular comorbidities, and to reduce the rate of emergency dialysis.
Data from the national French Renal Epidemiology and Information Network (REIN) registry were used to compare survival between transplant recipients under age 65 who resumed dialysis after graft failure during 2007-2009 and transplant-naïve incident dialysis patients matched for age, gender, diabetes mellitus, and year of starting dialysis. Among 911 transplant patients who returned to dialysis, 103 had died by 1 January 2011. Multivariate analysis showed that age over 48 years, coronary artery disease, peripheral artery disease, and inability to walk unassisted were significant predictors of death. In the case-control analysis, the observed mortality rates in 778 transplant failure and 778 transplant-naïve dialysis patients were 11.8 and 10.8%, respectively. Kaplan-Meier estimates of survival after transplant failure vs. the transplant-naïve controls were 95.2 vs. 94.1% at 1 year, 90.3 vs. 88.8% at 2 years, and 84.2 vs. 80.2% at 3 years (log rank P=0.197 overall). Dialysis in transplant failure vs. transplant-naïve patients was not associated with significantly increased mortality. At the start of dialysis, the serum creatinine levels and the rate of unplanned dialysis were significantly lower in transplant failure patients compared with transplant-naïve controls. Thus, in patients under 65 years of age in France, survival of dialysis patients after graft loss is similar to that of incident dialysis patients who have not undergone transplantation.Kidney International advance online publication, 19 February 2014; doi:10.1038/ki.2014.6.
In their study based on data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) census database, including 86,886 hemodialysis patients from 11 countries, Robinson and colleagues show that in all countries studied, mortality is higher in the first 120 days after the start of dialysis than after this period. We discuss factors that may affect international differences in early mortality, including current dialysis initiation practices and withdrawal from dialysis.
Background:
Subgroups of patients registered on a kidney transplant waiting list have higher than usual mortality levels. This study used data from the French Renal Epidemiology and Information Network (REIN) Registry to quantify the impact over time of various comorbidities on the excess risk of death among patients on the waiting list.
Methods:
Lexis diagrams were used to analyze time since onset of end-stage renal disease and time since registration on the waiting list. The number of excess deaths was calculated by comparison with the number of expected deaths in the general population of the same age and sex.
Results:
During 45,013 person-years of follow-up, 7,224 patients died, 5,956 (82%) more than expected relative to the general population. There were 101 deaths among wait-listed dialysis patients, 76 more than expected. The excess risk of death increased by 45% per additional year on the waiting list (18-79%, p = 0.0005). Time from end-stage renal disease onset until list registration (p = 0.004), time since registration (p < 0.001), age >65 years (p = 0.008), the presence of a primary renal disease (p = 0.028), and the number of comorbidities (p = 0.035) were independent predictors of death while on the waiting list.
Conclusions:
The excess risk of death while on the waiting list increased faster in patients with comorbidities. These results require consideration of ways to accelerate access to transplantation in high-risk patients.
The marked variation that exists in renal replacement therapy (RRT) epidemiology between countries and within countries requires
careful systematic examination if the root causes are to be understood. While individual patient-level studies are undoubtedly
important, there is a complementary role for more population-level, area-based studies—an aetiological approach. The EVEREST
Study adopted such an approach, bringing RRT incidence rates, survival and modality mix together with macroeconomic factors,
general population factors and renal service organizational factors for up to 46 countries. This review considers the background
to EVEREST, its key results and then the main methodological lessons and their potential application to ongoing work.
Transplant registries are a proven valuable source of data about transplantation. The inclusion of all transplants conducted in a region or country provides a different perspective from that of other observational studies. They allow examination of activity levels and trends, provide descriptions of outcomes which avoid the selection bias inherent in randomized clinical trials and facilitate hypothesis-generating studies. Examination of rare or unusual diseases and their outcomes is another area of strength. The models and structures of registries vary throughout the world. In Australia and New Zealand, kidney transplant outcomes are combined with dialysis in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Deceased solid-organ donor activity is recorded in the Australia and New Zealand Organ Donor (ANZOD) Registry. Both of these registries are conducted and governed along similar lines. Key factors include strong clinical links in data collection and governance, and the involvement of contributors in a wide variety of activities and output.
Founded in 1987, the Scientific Registry of Transplant Recipients (SRTR) operates under a contract from the US government administered by the Health Resources and Services Administration (HRSA). SRTR maintains a database of comprehensive information on all solid organ transplantation in the US. The registry supports the ongoing evaluation of the clinical status of solid organ transplantation, including kidney, heart, liver, lung, intestine, pancreas, and multi-organ transplants. Data in the registry are from multiple sources, but most are collected by the Organ Procurement and Transplantation Network (OPTN) from hospitals, organ procurement organizations, and immunology laboratories. The data include information on current and past organ donors, transplant candidates, transplant recipients, transplant outcomes, and outcomes of living donors. SRTR uses these data to create reports and analyses for HRSA, OPTN committees that make organ allocation policy, and the Centers for Medicare & Medicaid Services to carry out quality assurance surveillance activities; SRTR also creates standard analysis files for scientific investigators. In addition, SRTR and OPTN produce an Annual Data Report and provide information upon request for the general public. Thus, SRTR supports the transplant community with information services and statistical analyses to improve patient access to and outcomes of organ transplant.
Background
Cytomegalovirus (CMV) remains an important pathogen in transplant patients, and valacyclovir (VACV) prophylaxis 8 g/day has been used in high-risk CMV-seromismatched [D+/R-] renal transplant patients to decrease CMV disease. Neurotoxic adverse effects have limited its use, and the aim of the present study was to retrospectively evaluate low-dose VACV prophylaxis, 3 g/day for 90 days after transplantation, in 102 D+/R- renal transplant patients.Methods
We compared patient and graft survival rates up to 5 years after transplantation with the data from the Collaborative Transplant Study Group (CTS) database. The incidence of CMV disease, rejection and neurotoxic adverse effects was analyzed up to 1 year after transplantation.ResultsThe patient and graft survival rates up to 5 years were comparable with those derived from the CTS. CMV disease was diagnosed in 25% of the patients and 2% developed tissue-invasive CMV disease. The rejection frequency was 22% and neurotoxic adverse effects were seen in 2% of the patients.Conclusions
Low-dose VACV prophylaxis (3 g/day) for 90 days post-transplantation results in high patient and graft survival rates and reduces the incidence of CMV disease. Neurotoxic adverse effects are minimal. We believe that low-dose VACV prophylaxis should be considered to form one of the arms in future prospective comparison studies for the prevention of CMV disease in the high-risk D+/R- population of renal transplant patients.
Anatomical differences between right and left kidneys could influence transplant outcome. We compared graft function and survival for left and right kidney recipients transplanted from the same deceased organ donor. Adult recipients of 4900 single kidneys procured from 2450 heart beating deceased donors in Australia and New Zealand from 1995 to 2009 were included in a paired analysis. Right kidneys were associated with more delayed graft function (DGF) (25 vs. 21% for left kidneys, p < 0.001) and, if not affected by DGF, a slower fall in serum creatinine. One-year graft survival was lower for right kidneys (89.1 vs. 91.1% for left kidneys, p = 0.001), primarily attributed to surgical complications (66 versus 35 failures for left kidneys). Beyond the first posttransplant year, kidney side was not associated with eGFR, graft or patient survival. Receipt of a right kidney is a risk factor for inferior outcomes in the first year after transplantation. A higher incidence of surgical complications suggests the shorter right renal vein may be contributory. The higher susceptibility of right kidneys to injury should be considered in organ allocation.
Background:
There have been few prospective studies on the natural history of nonadherence (NA) in kidney transplant recipients (KTRs) over time. The objective of this study was to prospectively evaluate the rate of and risk factors for NA in a French cohort of KTRs.
Method:
A total of 312 KTRs from eight French transplantation centers were included in this prospective, noninterventional cohort study. A computer-learning software package (the Organ Transplant Information System) was made available to all patients.
Results:
Using the four-item Morisky scale, we showed that 17.3%, 24.1%, 30.7%, and 34.6% of patients were nonadherent at posttransplant month 3 (M3), M6, M12, and M24, respectively. Young age was predictive of NA at M6, M12, and M24. Surprisingly, simple treatment regimens including a small number of doses per day and a small number of tablets per day were associated with NA at M3 and M12, respectively. Other factors predictive of NA included failure to use the Organ Transplant Information System software package at M6 and patient reports of adverse events at M12 and M24. Importantly, we observed that physicians underestimated the prevalence of adverse events when compared to patient self-reporting.
Conclusion:
Our observed rate of medication NA in France is consistent with rates reported in previous studies. We found variability in NA risk factors over time as well as an unexpected risk factor (simple treatment regimens). These findings will be useful in developing effective adherence-promoting interventions.
This article summarizes the administrative structure underlying the Unites States Renal Data System (USRDS); summarizes incidence, prevalence, patient characteristics, and treatment modalities; and describes data regarding clinical indicators and preventive care, hospitalization, survival, and costs. The USRDS recently instituted a comprehensive assessment system to characterize the transition to the new Centers for Medicare & Medicaid Services Prospective Payment System, which bundles into a single payment several integral components of dialysis care. This challenging initiative will be an important component of future USRDS Annual Data Reports. The main strengths of the USRDS are its size and representativeness, nearly complete inclusion of the US end-stage renal disease population, and linkage to Medicare claims. Limitations include lack of continuous validation of its methods, lack of complete comorbidity and laboratory data at registration, an initial survival bias, and lack of accuracy of cause-of-death reporting.
Using data representative of the national population 18 yrs of age and older, the author employs the major social variables of class, age, education, and income to explain variance in life satisfactions. Topics include residential environment, work experience, marriage and family life, personal resources and competence, the situation of women, and the quality of life for Blacks. Policy implications and the relationship between perceptual assessments and objective conditions are also evaluated. (61/2 p ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Background: The SF-36 is widely used as a significant health outcome or quality of life indicator and validated in many languages versions including Chinese. But the Chinese version of the SF-36 (CSF-36) is rarely used for those patients with hypertension, coronary heart diseases, chronic gastritis and peptic ulcer in China. Therefore, the CSF-36 needs to be validated in patients with chronic diseases.
Objectives: This paper is aimed to validate the CSF-36 using an in-patient sample of four chronic diseases from mainland China, with focusing on psychometric properties.
Methods: The CSF-36 was used in a longitudinal study consisting of 534 patients in these four chronic disease groups. The psychometric properties of the scale were evaluated by indicators such as validity and reliability coefficients Cronbach α, Pearson r, standardized response mean employing correlational analyses, multi-trait scaling analysis, t-tests, factor analyses and structural equation models.
Results: Test–retest reliability coefficients for all domains were higher than 0.80 with a range of 0.83 to 0.96; the internal consistency (α) for most domains was higher than 0.70. Five of the eight domains as well as the Physical and Mental Health subscale summaries all had statistically significant changes after treatment with the SRM ranging from 0.18 to 0.28.
Conclusion: The CSF-36 showed good validity and reliability but small responsiveness when used in patients. It is a good and useful instrument for patients with chronic disease at some situations.
The principle methods for developing and validating new questionnaires are introduced, and the different approaches are described. These range from simple global questions to detailed psychometric and clinimetric methods. We review traditional psychometric techniques including summated scales and factor analysis models, as well as psychometric methods that place emphasis upon probabilistic item response models. Whereas psychometric methods lead to scales for QoL that are based upon items reflecting patients' level of QoL, the clinimetric approach makes use of composite scales that may include symptoms and side-effects of treatment.
As of January 14, 2011, 112,707 individuals were listed for kidney transplant. In the past 5 years the yearly average of deceased donor and living donor kidney-only transplants was 10,052 and 6,153, respectively. Compared with a previous decade, one-, 3- and 5-year graft survival rates for deceased donor kidney transplants increased 5%, 6%, and 6%, respectively. Long-term graft survival has not really improved over the past 2 decades. During the past decade, the percentage of kidneys from deceased donors over age 60 transplanted in patients of the same age group increased (from 29% to 60%) over the previous decade. The number of kidney transplants through paired-exchange donation was 109 in 2007. In 2010, that number almost quadrupled to 421. The number of unrelated living donors (LD) has also increased dramatically over the past decade, accounting for 28% of all LD transplants in 2010, and being the major source of LD kidney transplants since 2008. The combination of male donor and female recipient yielded the highest short- and long-term graft survival rates. Female donor and male recipient had the lowest short- and long-term graft survival rates. The risk of graft loss with female donor and male recipient was 23% higher than with male donor and female recipient. For re-transplants, risk of graft loss was 48% higher in patients who received no induction than in those who received IL-2RA + steroid. The impact of HLA mismatch on graft survival rates has declined, but it remains significant. There is still a 10% decrease in the 5-year graft survival from zero MM (77%) to 5&6 MM (67%) in the more recent years. National sharing of zero HLA-mismatched kidneys to sensitized adults with PRA > 20% has increased the transplant opportunity for more highly sensitized patients, nevertheless it will also indirectly decreased the benefits in survival that zero HLA-mismatches provides to about 6% of the kidney transplant population each year who were not sensitized. As of June 2011, 198,314 kidney transplant recipients were alive with a functioning graft.
A methodology for evaluating Likert-type scales is presented. Multitrait scaling is a straightforward approach to scale analysis
that focuses on items as the unit of analysis and utilizes the logic of convergent and discriminant validity. Multitrait scaling
is illustrated with the Multitrait Analysis Program, using patient satisfaction data from the Medical Outcomes Study.
A general formula (α) of which a special case is the Kuder-Richardson coefficient of equivalence is shown to be the mean of
all split-half coefficients resulting from different splittings of a test. α is therefore an estimate of the correlation between
two random samples of items from a universe of items like those in the test. α is found to be an appropriate index of equivalence
and, except for very short tests, of the first-factor concentration in the test. Tests divisible into distinct subtests should
be so divided before using the formula. The index
[`(r)]ij\bar r_{ij}
, derived from α, is shown to be an index of inter-item homogeneity. Comparison is made to the Guttman and Loevinger approaches.
Parallel split coefficients are shown to be unnecessary for tests of common types. In designing tests, maximum interpretability
of scores is obtained by increasing the first-factor concentration in any separately-scored subtest and avoiding substantial
group-factor clusters within a subtest. Scalability is not a requisite.
To examine the relationship between health-related quality of life (HQoL) and employment status in renal transplant recipients (RTRs).
Eighty-two RTRs met inclusion criteria: 21-65 yr of age; greater than one yr post-transplant; and received calcineurin inhibitors. A cross-sectional survey was conducted using a demographics questionnaire and the following HQoL instruments: SF-12 Health Survey version 2 (Physical Component Summary [PCS-12] and Mental Component Summary [MCS-12]) and Kidney Transplant Questionnaire (KTQ). Two multivariate logistic regression analyses (SF-12 model and KTQ model) were conducted to determine whether HQoL and demographic variables were independently associated with employment status.
Seventy-five RTRs were included in the analysis. Compared with employed RTRs, a greater number of unemployed RTRs were non-white, had lower education levels, and had deceased donor transplants (p < 0.05). Employed RTRs had significantly higher SF-12 scores (p < 0.05). In the SF-12 logistic regression model, PCS-12 and education level were significant predictors of employment status (p < 0.05). In the KTQ model, the Fatigue subscale and education level were significant predictors of employment status (p < 0.05).
Findings suggest higher PCS-12, higher KTQ-Fatigue, and education level are independently associated with employment status. Interventions targeted to improve HQoL, decrease fatigue, and increase education level are discussed.
Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.
This study investigates the difference in the incidence of renal replacement therapy (RRT) between Flanders and the Netherlands and possible explanations for this difference.
End-stage renal disease incidence data were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA). Additional sources were the National Institute of Statistics (NIS), the Central Bureau of Statistics (CBS), the Organisation for Economic Cooperation and Development (OECD) health data and the WHO Health For All database (WHO-HFA).
There is remarkable difference in incidence rate of RRT between Flanders and the Netherlands, with a higher rate in Flanders. This difference is already present in patients aged 45-64 years and increases with age, being >2-fold higher in subjects of ≥ 75 years. With respect to the renal diagnoses leading to need for RRT, a higher share of especially diabetes mellitus type 2 and renovascular disease was observed in Flanders. Remarkably, the difference in incidence rate of RRT is not associated with a difference in survival on RRT, not even in the elderly, arguing against a restricted access to RRT in the Netherlands. In the general population, the expected number of healthy life years at birth is lower in Belgium than in the Netherlands, and in Belgium, the hospital discharge rates for diabetes, acute myocardial infarction and cerebrovascular accident and the number of coronary bypass procedures and percutaneous coronary interventions per capitum is higher, as is the prevalence of obesity.
Our data do not support the assumption that the differences in RRT incidence in the elderly between Flanders and the Netherlands are due to a more restricted access to RRT in the Netherlands but may be due to differences in underlying comorbidity and life style between the two populations.
Snydman DR, Kistler KD, Ulsh P, Bergman GE, Vensak J, Morris J. The impact of CMV prevention on long-term recipient and graft survival in heart transplant recipients: analysis of the Scientific Registry of Transplant Recipients (SRTR) database. Clin Transplant 2011: 25: E455–E462. © 2011 John Wiley & Sons A/S.
Abstract: The association between cytomegalovirus immunoglobulin (CMVIG) and long-term clinical outcomes in heart transplantation has not been evaluated using data from large national databases. We examined the association between CMVIG, with and without antivirals, or antivirals alone, and long-term recipient and graft survival in heart transplantation using data from the Scientific Registry of Transplant Recipients. Recipients transplanted between January 1995 and October 2008, ≤80 yr old, of primary, single-organ heart transplants, recorded as receiving CMVIG with or without antivirals (n = 2112), antivirals without CMVIG (n = 12 089), or no prophylaxis (n = 14 661), at hospital discharge, were included. Kaplan–Meier analysis was used to examine death and graft loss at seven yr post-transplantation; Cox proportional hazards regression was used to estimate the adjusted risk of graft loss and death for prophylaxis vs. no prophylaxis. CMVIG use (± other antivirals) was associated with increased recipient (69% vs. 64%, p < 0.001) and graft (67% vs. 63%, p < 0.001) survival. Antivirals alone also demonstrated increased recipient (68% vs. 64%, p < 0.001) and graft survival (66% vs. 63%, p < 0.001). Cox models demonstrated that CMVIG (± other antivirals) was independently associated with decreased risk for death (hazard ratio, HR 0.79, p < 0.001) and graft loss (HR 0.78, p < 0.001) as were antivirals alone (mortality HR: 0.79, p < 0.001; graft loss: HR 0.78, p < 0.001).
The Kidney Transplant Questionnaire (KTQ) is a quality-of-life instrument designed specifically for renal transplant recipients.
The purpose of this work was to evaluate the validity and reliability of a Persian translation of the KTQ-25 questionnaire as a tool for use in Iran and also to compare the quality of life between dialysis and transplant patients.
We collected 143 subjects in a cross-sectional study. Their mean age was 40.3±13.3 years (range=15-72). All KDQ-25 scales met the criteria for internal consistency(Cronbach's alpha ranged from 0.8-0.95) and in construct validity, the correlation coefficient between 5 scales and the total scale was also acceptable (0.84-0.91). Furthermore, significant correlations were detected between the scales (P<.001).
The mean total score was 2.8±1.4 (range=5.8-1.5). The best mean score observed in uncertainty and fear item was 3.1±1.6 (range=0.5-7), while the lowest was detected in the emotional item, 2.4±1.3 (range=0.17-6). Mean follow-up was 50.1 (range=1-264) months. The most common physical problem was aching, tired legs in 77 (55%) subjects.In comparison between dialysis and transplant patients using the standard Iranian version of Kidney Disease Quality of Life (KDQOL) questionnaire, the total and disease-specific scores for dialysis patients were significantly better than the total score in the KDQ-25 (55.8±14 vs 40.7±20.2, P=.000) and (49.7±15.8 vs 40.7±20.2, P=.000), respectively.
Considering its validity and reliability, the Persian version of KTQ-25 questionnaire may be useful to assess the health-related quality of life among Iranian transplant recipients.
The Symphony study showed superior 1-year kidney graft outcome in patients on immunosuppression with tacrolimus/mycophenolate mofetil (Tacr/MMF). To analyze whether differences in clinical outcome between maintenance regimens may be explained by their impact on clinically relevant immune parameters, we assessed CD4 helper activity, immunoglobulin-secreting cell (ISC) formation, neopterin, sCD30, and intracellular cytokine production in a prospective study in 77 renal transplant recipients treated with cyclosporine A/azathioprine (CsA/Aza), CsA/MMF, Tacr/Aza or Tacr/MMF at 2 years post-transplant. Tacr- compared with CsA-based immunosuppression was independently associated with increased IL-2 (P < 0.0001, CD4 cells; P = 0.014, CD8 cells) and CD4 cell IL-4 responses (P = 0.046; stepwise logistic regression) resulting in physiological responses in Tacr/Aza patients as compared with 25 healthy controls. MMF versus Aza treatment was proven to be an independent variable associated with suppression of CD4 cell IL-10 responses (P = 0.008), B-cell IL-6R expression (P < 0.0001) and ISC formation [P = 0.020, staphylococcus cowan strain I (SAC I); P = 0.021, pokeweed mitogen (PWM)]. Our data suggest that Tacr/MMF had the most effective impact on graft protective Th2 responses (enhanced CD4 cell IL-4 by Tacr, decreased CD4 cell IL-10 responses by MMF) and suppression of B-cell functions (MMF), whereas Tacr/Aza was associated with physiological IL-2 and IL-4 and stronger humoral responses which may reduce the risk of infectious disease complications.
(ClinicalTrials.gov number: NCT00150891).
Use of capillary electrophoresis coupled to mass spectrometry (CE-MS) technology in proteome analysis has increased, with a focus on the identification of biomarker peptides in clinical proteomics. Among the reported applications, the main focus is on the urinary biomarkers for kidney disease. In this review, we discuss the principal, theoretical, and practical obstacles that are encountered when using CE-MS for the analysis of body fluids for biomarker discovery. We present several examples of a successful application of CE-MS for biomarker discovery in kidney disease, implications for disease diagnosis, prognosis, and therapy evaluation, and will also discuss current challenges and possible future improvements.