Impact of Levosimendan and Its Metabolites on Platelet Activation Mechanisms in Patients during Antiplatelet Therapy-Pilot Study.

Levosimendan is used for the short-term treatment of severe heart failure or other cardiac conditions. The area of existing clinical applications for levosimendan has increased significantly. This study aimed to assess whether levosimendan and its metabolites impact the mechanisms related to platelet activation. In this study, we included patients with coronary artery disease receiving antiplatelet therapy. We analyzed the pharmacodynamic profile using three independent methods to assess platelet activity. The results of the conducted studies indicate a mechanism of levosimendan that affects the function of platelets, causing higher inhibition of platelet receptors and, thus, their aggregation. It is essential to clarify whether levosimendan may affect platelets due to the need to maintain a balance between bleeding and thrombosis in patients treated with levosimendan. This is especially important in the case of perioperative bleeding. This study was conducted in vitro; the research should be continued and carried out in patients to check the complete pharmacokinetic and pharmacodynamic profile.

Some Non-Obvious Consequences of Non-Extensiveness of Entropy.

Non-additive (or non-extensive) entropies have long been intensively studied and used in various fields of scientific research. This was due to the desire to describe the commonly observed quasi-power rather than the exponential nature of various distributions of the variables of interest when considered in the full available space of their variability. In this work we will concentrate on the example of high energy multiparticle production processes and will limit ourselves to only one form of non-extensive entropy, namely the Tsallis entropy. We will discuss some points not yet fully clarified and present some non-obvious consequences of non-extensiveness of entropy when applied to production processes.

Candida auris Infection in a Meningococcal Septicemia Survivor, Poland.

BACKGROUND: Candida auris is an emerging pathogen that constitutes a serious global health threat. It is difficult to identify without specific approaches, and it can be misidentified with standard laboratory methods, what may lead to inappropriate management. CASE PRESENTATION: We report, probably the first in Poland, C. auris isolation from blood cultures and wound swabs of a young male following meningococcal septicaemia, in February 2019. The patient had been previously hospitalized in the United Arab Emirates. The isolate was rapidly identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and therefore clinicians were promptly informed on the alert pathogen isolation. The targeted antifungal treatment was successful and infection control measures seemed effective. ITS-based identification and subsequent whole genome sequencing showed that the C. auris isolate belongs to South Asian lineage (clade I). CONCLUSIONS: C. auris is able to cause outbreaks in healthcare settings. Therefore, it is important to quickly identify C. auris isolates in hospital settings so that healthcare facilities can take proper precautions to limit its spread.

Determinants of the Level of Anti-SARS-CoV-2 IgG ANTibodiEs after Vaccination (DANTE-SIRIO 7) Study in a Large Cohort of Healthcare Workers.

The aim of this study was to determine anti-SARS-CoV-2 IgG concentrations and their major determinants in healthcare workers (HCWs) after full vaccination with the BNT162b2 vaccine. We recruited 847 individuals vaccinated with two doses of the BNT162b2 vaccine, who completed the questionnaire, and whose antibody concentrations were tested after 3 and 6 months after full vaccination. Anti-SARS-CoV-2 IgG levels were measured on the routinely employed Siemens Atellica system. The cutoff for positivity was ≥21.8 BAU/mL. Three and 6 months after vaccination, the majority of participants were seropositive. Median concentrations of anti-SARS-CoV-2 IgG significantly decreased from 1145 BAU/mL (IQR: 543-2095) to 225 BAU/mL (IQR: 100-510). Major positive determinants of antibody levels were fever after both doses of vaccine, prior-COVID-19 exposure, and muscle pain after the first dose. Lack of symptoms after the second dose and time since vaccination were significant negative determinants of anti-SARS-CoV-2 IgG concentrations. No other factors, including age and gender, or underlying comorbidities had a significant effect on antibody levels in HCWs. The anti-SARS-CoV-2 response after two doses of BNT162b2 vaccine was independently associated with prior-COVID-19 exposure, time since vaccination, and the occurrence of symptoms after either dose of vaccine. Easily reportable adverse reactions may facilitate the identification of immune response in HCWs.

Early outcomes and long-term survival after kidney transplantation in elderly versus younger recipients from the same donor in a matched-pairs analysis.

ABSTRACT: The elderly are the fastest-growing population on waiting lists for kidney transplantation (KTx). Recognized barriers to KTx in the elderly is early post-transplant mortality and morbidity. To analyze the outcomes of KTx in recipients older than 60 years and, simultaneously, in their younger paired recipients, receiving a graft from the same donor.We included 328 kidney transplant recipients in the study. The elderly kidney transplant recipients (EKT) group included 164 patients aged 65 standard deviation (SD4) years. They were paired with younger kidney transplant recipients (YKT) aged 45 (SD12) years.The studied groups (EKT vs YKT) did not differ from the graft function estimated 1 year after the transplantation (50.7 mL/min vs 54.0 mL/min), while the estimated glomerular filtration rate decline was significantly faster in the YKT group. One-year patient survival (93.9% vs 97.0%), 1-year graft survival (90.4% vs 82.3%), and incidences of delayed graft function and acute rejection did not differ between the EKT and YKT groups. Significantly more cardiovascular complications and post-transplant diabetes mellitus were noticed in the EKT group. The long-term patient and graft survivals were poorer in the EKT group versus the YKT group, but death-censored graft survivals were the same. After having excluded donor-derived graft factors, there were no differences in the first-year outcome of KTx between recipients younger and older than 60 years. As life expectancy is lower in the EKT group, the probability of patient and graft survival was also significantly lower in this group. However, death-censored graft survival was not different in the EKT and YKT groups.

Analysis of Factors Affecting Employment Status of Kidney Transplant Recipients in Selected European Union Member States.

Despite an increasing quality of life after renal transplantation, the number of recipients undertaking paid professional work remains relatively low. Employment after kidney transplantation became a new important marker of clinically significant health recovery. Furthermore, for social and economic reasons, returning to work and participation in social life may be considered as an objective parameter that demonstrate the effectiveness of transplantation. The objectives of the following study were to evaluate the factors that determine resuming paid work after renal transplantation, to assess a patient's decision about returning to professional activity by comparative analysis of renal transplant recipients from Poland, Czech Republic and Germany, and to identify groups of patients exposed to professional exclusion in those EU countries. Five hundred renal transplant recipients from three EU countries were included into the study. The two main research methods used in the study were the SF-36 questionnaire, constructed and validated to assess the quality of life after kidney transplantation and a questionnaire constructed for the purposes of this study. Multifactorial analysis identified several risk factors associated with professional exclusions after kidney transplantation, namely young or advanced age, female gender, lack of education, place of residence in rural areas, long period of illness, and lack of occupational activity before transplantation. Despite the high standards of social care and rehabilitation support, patients in Germany failed to take up professional activity after kidney transplantation in more cases than those in Poland and Czech Republic. Surprisingly, the objective function of the kidney (creatinine level) and the multidimensional assessment of quality of life (SF-36 survey) did not have a significant association with the employment status after renal transplantation.

Abnormal diurnal blood pressure profile and hypertension-mediated organ damage in nondiabetic chronic kidney disease G1-G3b patients.

OBJECTIVE: Chronic kidney disease (CKD) is associated with high cardiovascular risk. Prevalence of hypertension and hypertension-mediated organ damage (HMOD) increases with CKD progression. Nocturnal blood pressure (BP) is a strong predictor of cardiovascular complications. This cross-sectional study investigated the link between the diurnal BP profile and HMOD in nondiabetic CKD G1-G3b patients. METHODS: We investigated 109 CKD patients and 41 apparently healthy persons as controls. All subjects underwent 24-ambulatory blood pressure monitoring (ABPM), echocardiography with left ventricular mass index (LVMI) calculation and pulse wave velocity (PWV) measurement. RESULTS: Hypertension was present in 84% of CKD patients. SBP-24 and DBP-24, SBP-day and DBP-day did not differ between CKD and controls. Significant differences were found in SBP-night and DBP-night. The nondipping BP profile (SBP-night/SBP-day ratio ≥0.9) was found in 62% of CKD patients and 32% of controls (P < 0.005). Nocturnal hypertension was found in 56% of CKD patients. LVMI was higher in CKD compared to controls, higher in nondipping than dipping CKD patients, and higher in patients with nocturnal hypertension than without nocturnal hypertension. Abnormal left ventricular geometry was found in 72% nondipping and 43% dipping CKD patients. PWV was higher in CKD than in controls, in patients with nocturnal hypertension than without nocturnal hypertension but did not differ between CKD nondippers and dippers. CONCLUSION: The nondipping BP profile and nocturnal hypertension are associated with HMOD in G1-G3b CKD patients. Hence, there is a need for more extensive use of ABPM for individual risk assessment and personalization of antihypertensive treatment in CKD patients.

Using a Chemical Biopsy for Graft Quality Assessment.

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated with an increased survival rate and greater quality of patient's life when compared to conventional dialysis. Regrettably, transplantology suffers from a lack of reliable methods for organ quality assessment. Standard diagnostic techniques are limited to macroscopic appearance inspection or invasive tissue biopsy, which do not provide comprehensive information about the graft. The proposed protocol aims to introduce solid phase microextraction (SPME) as an ideal analytical method for comprehensive metabolomics and lipidomic analysis of all low molecular compounds present in kidneys allocated for transplantation. The small size of the SPME probe enables performance of a chemical biopsy, which enables extraction of metabolites directly from the organ without any tissue collection. The minimum invasiveness of the method permits execution of multiple analyses over time: directly after organ harvesting, during its preservation, and immediately after revascularization at the recipient's body. It is hypothesized that the combination of this novel sampling method with a high-resolution mass spectrometer will allow for discrimination of a set of characteristic compounds that could serve as biological markers of graft quality and indicators of possible development of organ dysfunction.

Noninvasive evaluation of renal tissue oxygenation with blood oxygen level-dependent magnetic resonance imaging early after transplantation has a limited predictive value for the delayed graft function.

PURPOSE: The aim of this study was to evaluate the feasibility of renal oxygenation assessment using blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the early period after kidney transplantation and to estimate its prognostic value for delayed graft function. MATERIAL AND METHODS: Examinations were performed in 50 subjects: 40 patients within a week after the kidney transplantation and 10 healthy controls, using T2*-weighted sequence. Measurements in transplant patients were correlated to basic laboratory parameters in the early period after transplantation and at follow-up. RESULTS: Examinations of seven patients (18%) were rejected due to their poor technical quality. Mean R2* values in transplant recipients were lower than in controls (11.6 vs. 15.9 Hz; p = 0.0001). An R2* value of 0.28 Hz was calculated as the minimal detectable change. There was no relation between R2* values and laboratory parameters. However, patients eGFR ≥ 40 ml/min/1.73 m2 presented higher R2* values than recipients eGFR < 40 ml/min/1.73 m2 (12.0 vs. 11.1 Hz; p = 0.0189). In ROC analysis R2* of ≤ 11.7 predicted an early reduced graft function with 0.82 sensitivity and 56% specificity (AUC = 0.708; p = 0.024) but was not useful for delayed graft function prediction (p > 0.7). CONCLUSIONS: Evaluation of renal graft oxygenation using BOLD MRI is technically challenging in the early period after transplantation. An R2* value of 0.28 Hz may in practice be considered as the minimal detectable change. The delayed graft function seems not to be dependent on early oxygenation values. Further, large-scale studies are necessary to confirm the latter observation.

Coronary artery calcification and large artery stiffness in renal transplant recipients.

PURPOSE: Coronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in renal transplant recipients (RTR). Carotid-femoral pulse wave velocity (PWV), a non-invasive measure of large artery stiffness, also predicts CV events in RTR. The study investigated the relationship between CAC and PWV in RTR and assessed the performance of PWV measurement in predicting CAC. PATIENTS/METHODS: The study was performed as cross-sectional analysis in 104 RTR. CAC was determined as total calcium score (CS) and calcium mass (CM). Carotid-femoral PWV was also measured. Sensitivity, specificity and receiver operating characteristic (ROC) curve were used to assess the performance of PWV as diagnostic test for presence of CAC. RESULTS: CAC was found in 69% of participants. PWV was higher in RTR with CAC than in RTR without CAC (10.2±2.2 vs. 8.6±15; p<0.001). In univariate analysis CS was significantly correlated with age, duration of hypertension, waist circumference, PWV, hemoglobin concentration, and serum glucose. In multiple linear regression analysis CS was independently associated with age only, but not with PWV. Sensitivity and specificity of PWV>7.6m/s as cut-off for detecting CAC>0 was 0.889 and 0.406, respectively. Sensitivity and specificity of PWV>10.2m/s as cut-off for detecting severe CAC (CS>400) was 0.319 and 0.969, respectively. CONCLUSIONS: The study confirmed high prevalence of coronary artery calcification in renal transplant recipients. The study does not support the hypothesis that aortic stiffness is independently associated with coronary artery calcification in RTR. PWV measurement may be useful in excluding severe CAC in RTR.

Rho-kinase inhibitor reduces hypersensitivity to ANG II in human mesenteric arteries retrieved and conserved under the same conditions as transplanted organs.

Rho-kinase and GTP-ase Rho are important regulators of vascular tone and blood pressure. The aim of this study was to investigate the role of Rho-kinase in artery reactions induced by angiotensin II (ANG II) and the effects of ischemia-reperfusion injury as well as the function of intra- and extracellular calcium in these reactions. Experiments were performed on mesenteric superior arteries procured from cadaveric organ donors and conserved under the same conditions as transplanted kidneys. The vascular contraction in reaction to ANG II was measured in the presence of Rho-kinase inhibitor Y-27632, after ischemia and reperfusion, in Ca2+ and Ca2+-free solution. The maximal response to ANG II was reduced after ischemia, while an increase was observed after reperfusion. Vascular contraction induced by ANG II was decreased by Y-27632. Y-27632 reduced vascular contraction after reperfusion, both in Ca2+ and Ca2+-free solution. Reperfusion augments vascular contraction in reaction to ANG II. The Rho-kinase inhibitor Y-27632 reduces the hypersensitivity to ANG II after reperfusion mediated by both intra- and extracellular calcium. These results confirm the role of Rho-kinase in receptor-independent function of ANG II and in reperfusion-induced hypersensitivity.

Psychological principles in regard to the interview with the deceased donor's family.

The purpose of this article is to present the most important rules of the interview process with the family of a patient who has been diagnosed with brain death. Based on data from the literature and their own clinical experience, the authors also describe the psychological mechanisms that make contact with the family of a potential donor particularly difficult. The paper also discusses successive stages in the process of building contact with the family from the perspective of the dual advocacy approach that, in the light of recent data from the literature, can significantly increase the likelihood of the family's acceptance of organ donation, offering both the specific theoretical foundations as well as the strict principles in regard to the interview. The article contains practical suggestions for dealing with difficulties that can arise at all stages of contact with the family: making contact, providing information, providing information about brain death and talking with the family about organ donation from a deceased relative.

Diffusion-weighted MR imaging of transplanted kidneys: Preliminary report.

BACKGROUND: An aim of this study was to assess the feasibility of DWI in the early period after kidney transplantation. We also aimed to compare ADC and eADC values in the cortex and medulla of the kidney, to estimate image noise and variability of measurements, and to verify possible relation between selected labolatory results and diffusion parameters in the transplanted kidney. MATERIAL/METHODS: Examinations were performed using a 1.5 T MR unit. DWI (SE/EPI) was performed in the axial plane using b-values of 600 and 1000. ADC and eADC measurements were performed in four regions of interest within the renal cortex and in three regions within the medulla. Relative variability of results and signal-to-noise ratio (SNR) were calculated. RESULTS: The analysis included 15 patients (mean age 52 years). The mean variability of ADC was significantly lower than that of eADC (6.8% vs. 10.8%, respectively; p<0.0001). The mean variability of measurements performed in the cortex was significantly lower than that in the medulla (6.2% vs. 11.5%, respectively; p<0.005). The mean SNR was higher in the measurements using b600 than b1000, it was higher in ADC maps than in the eADC maps, and it was higher in the cortex than in the medulla. ADC and eADC measured at b1000 in the cortex were higher in the group of the patients with eGFR ≤30 ml/min./1.73 m(2) as compared to patients with eGFR >30 ml/min./1.73 m(2) (p<0.05). CONCLUSIONS: Diffusion-weighted imaging of transplanted kidneys is technically challenging, especially in patients in the early period after transplantation. From a technical point of view, the best quality parameters offer quality ADC measurement in the renal cortex using b1000. ADC and eADC values in the renal cortex measured at b1000 present a relationship with eGFR.

Factors associated with glucose metabolism disorders after kidney transplantation.

INTRODUCTION: Post-transplant diabetes mellitus (PTDM), pre-diabetes-impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are frequent complications after organ transplantation. The aim of this study was to assess the frequency of PTDM, IFG and IGT in a group of renal transplant recipients, to compare the frequency of glucose metabolism disorders in subjects treated with tacrolimus and with cyclosporine, and to establish the influence of different risk factors on the development of glucose metabolism disorders. MATERIAL AND METHODS: We examined 206 non-diabetic kidney allograft recipients (age 46.4 ± 12.3 years, time since transplantation 45.5 ± ± 33.6 months, BMI 26.3 ± 4.5 kg/m2). Glucose metabolism disorders were diagnosed using an oral glucose tolerance test. Logistic regression was used to assess the influence of each risk factor (age, BMI, waist circumference, physical activity, the presence of cardiovascular disease, positive family history of diabetes, cholesterol and triglycerides concentration) on the development of glucose metabolism disorders. RESULTS: In 103 patients (50%), we diagnosed glucose metabolism disorders. 19% of patients had PTDM, 14% IFG, and 17% IGT. We did not find any differences in the frequency of glucose metabolism disorders between patients treated with tacrolimus and with cyclosporine. Multivariate analysis identified BMI and a family history of diabetes as independent risk factors of glucose metabolism disorders. CONCLUSIONS: We found a high prevalence of glucose metabolism disorders in the examined group. This suggests that kidney transplant recipients should be screened for these disturbances. Patients with higher BMI and with first-degree relatives with diabetes had an increased risk of glucose metabolism disorders after kidney transplantation.

A multicenter, randomized, double-blind study comparing different FK778 doses (manitimus) with tacrolimus and steroids vs. MMF with tacrolimus and steroids in renal transplantation.

BACKGROUND: This multicenter phase II study in renal transplantation compared 3 concentration-controlled ranges of FK778 (manitimus) with mycophenolate mofetil (MMF) both given in combination with tacrolimus and corticosteroids. METHODS: 364 patients were randomized to 12-month treatment: high-level FK778 group (H, N=87) received 4 x 600 mg/day (4 days) followed by 120 mg/day; mid-level FK778 group (M, N=92) received 3 x 600 mg/day (3 days) followed by 110 mg/day, low-level FK778 group (L, N=92) received 2 x 600 mg/day (2 days) followed by 100 mg/day, and control group received MMF 1 g/day (MMF, N=93). After week 6, FK778 doses were adjusted to trough ranges of 75-125 µg/mL (H), 50-100 µg/mL (M) and 25-75 µg/mL (L). Tacrolimus and steroids were administered at the same dose in each of the 4 groups. RESULTS: Biopsy proven acute rejection (BPAR) at 24 weeks, the primary study endpoint, was comparable in the L (22.8%) and MMF (17.2%) groups but higher in the H (34.5%) and M (29.3%) groups. BPAR at 12 months was comparable in the L (23.9%) and MMF (19.4%) groups but higher in the H (34.5%) and M (31.5%) groups. Graft and patient survival were lowest in the H group and renal function was poorest in the H and M groups. Premature study withdrawal was highest in the H group. CONCLUSIONS: Efficacy was similar between the low-level FK778 and MMF groups. Increased FK778 exposure was poorly tolerated and did not improve efficacy.

The role of the kidney in the systemic elimination of interleukin 6, platelet-derived growth factor and transforming growth factor beta.

STUDY GOAL: The aim of the study was to assess the role of the kidney in systemic elimination of IL-6 and growth factors (PDGF, TGF-ß) by comparison of their concentrations in renal arteries and veins, peripheral veins and urine. MATERIAL AND METHODS: 30 brain-dead kidney donors were included in the study. Samples were obtained during the harvesting procedure. 10 healthy volunteers served as controls. A mathematical model of elimination of investigated proteins from systemic circulation was developed. The elimination ratio (ER) formula indicates the predominance of renal synthesis or degradation and also quantifies the renal uptake (UR) and renal pass (PR) of investigated proteins. Serum levels of investigated proteins were estimated using an immunoenzymatic method (ELISA). RESULTS: Renal IL-6 uptake ratio (UR) amounted to 6.6%, elimination ratio (ER) amounted to 6.4% and pass ratio (PR) amounted to 0.2%. PDGF ratios amounted to 5.1%, 5.0% and 0.1% and TGF-ß ratios amounted to -9%, -9% and 0%, respectively. CONCLUSIONS: The kidney takes part in the elimination of IL-6 and PDGF from systemic circulation. The kidney does not take part in the elimination of TGF-ß.

Results of renal transplantation from expanded criteria deceased donors - a single-center experience.

BACKGROUND: Transplantation of kidneys retrieved from extended criteria donors is one of the options to expand the pool of available grafts, shorten the waiting time and increase the availability of this method of treatment. However, some factors (eg, donor age) may impair the results of transplantation. MATERIAL/METHODS: This study was a retrospective assessment of 327 patients who underwent renal transplants during the period 1995-2005, with kidneys harvested from expanded criteria donors (ECD) as defined by the United Network for Organ Sharing (UNOS). They formed 2 groups: group 1 (ECD - younger, n=255) consisted of recipients of kidneys obtained from donors aged 50-59 years; group 2 (ECD - older, n=72) consisted of patients who received kidneys from donors ≥ 60 years old. An analysis of the 1-, 3- and 5-year survival of grafts and patients and evaluation of graft function were performed. RESULTS: graft survival was significantly better in group 1 (ECD-younger) vs. group 2 (ECD-older), as was renal graft function. Survival 3 and 5 years after transplantation was 87.7% vs. 81.9%, 73.1% vs. 66.6%, and 60.1% vs. 51.7%, respectively. Delayed graft function occurred significantly more frequently in group 2 (group 1 vs. group 2-28.8% vs. 34.6%, p=0.0001). CONCLUSIONS: The transplantation of kidneys obtained from older donors fulfilling ECD definition is associated with shorter graft survival, deteriorated function and more frequent renal delayed graft function. However, this did not increase the mortality of recipients.

A brain dead woman, giving birth in the 23rd week of pregnancy, used as an organ donor: a case report.

BACKGROUND: Maternal brain death during pregnancy is an exceptional case when somatic support might be continued despite diagnosed death. There are only a few cases of maternal brain death during pregnancy reported in the literature and detailed data regarding the frequency of such cases are lacking. CASE REPORT: The case of a 40-year-old woman, diagnosed brain dead due to a subarachnoid and intracranial hemorrhage in the 21st week of pregnancy is presented. The patient was admitted to the neurosurgery department and then to the intensive care unit, where brain death was diagnosed. The medical team decided to perform a caesarean section, and a living female infant was delivered. After delivery, maternal kidneys were recovered and successfully transplanted. CONCLUSIONS: This challenging case indicates that prompt diagnosis of maternal brain death is required to facilitate decision-making regarding somatic support prolongation to save the life of the fetus, as well as to allow procurement of the maternal organs.

Tacrolimus pharmacokinetics of once- versus twice-daily formulations in de novo kidney transplantation: a substudy of a randomized phase III trial.

BACKGROUND: Tacrolimus is a well-established immunosuppressive agent for the treatment and prevention of solid organ graft rejection. It is available as an immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged-release, once-daily formulation (Tacrolimus QD). In a previous study of the pharmacokinetics (PK) of these formulations, mean systemic exposure [area under the curve from 0 to 24 hours (AUC0-24)] of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure was similar; however, the mean dose of Tacrolimus QD was higher to achieve similar systemic exposure as Tacrolimus BID. METHODS: To further compare the PK of the tacrolimus formulations during the first 2 weeks posttransplant, a substudy was performed in a subset of patients enrolled into a phase III trial in de novo kidney transplant recipients comparing Tacrolimus QD and Tacrolimus BID. To minimize the difference in exposure observed in the earlier study, tacrolimus therapy was initiated before transplant. The PK analysis set comprised 34 patients (17 patients per treatment group) who had 4 complete PK profiles and no major PK-related protocol violations. RESULTS: Mean AUC0-24 of tacrolimus on day 1 was approximately 16% lower for Tacrolimus QD than for Tacrolimus BID, although by day 3 onward, the exposure was similar between treatment groups. Analysis of dose-normalized AUC0-24 (dose normalized to 0.1 mg/kg) showed a similar pattern. There was a good correlation between AUC0-24 and concentration of tacrolimus at 24 hours postdose for both formulations (Tacrolimus QD, r = 0.87; Tacrolimus BID, r = 0.92), and the slope of the line of best fit was similar. CONCLUSIONS: These results suggest that initiating tacrolimus therapy before transplant reduces the difference in exposure between Tacrolimus QD and Tacrolimus BID.

Progressive arterial stiffening in kidney transplant recipients.

BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness. Data from general population and end-stage renal disease patients suggest that PWV increases with age by about 0.1 m/s for each year of life and that PWV increase is steeper after the fifth decade. Recent follow-up studies showed decrease of arterial stiffness during the first year after kidney transplantation (KTx). This study aimed to investigate PWV change in kidney transplant recipients (KTR) during long-term follow-up. MATERIAL/METHODS: Carotid-femoral PWV was measured at baseline (PWV1) and then after at least 24 months (range 24-34, mean ±SD 28±3) of follow-up (PWV2) in 61 KTR aged 46±12 years. Baseline PWV measurements were performed at 36±27 months (range 4-121) after KTx. Clinical and laboratory data were also analyzed. GFR was calculated with MDRD formula (eGFR). ∆PWV was calculated as (PWV2-PWV1)/PWV1. RESULTS: Significant increase in PWV (9.1±1.7 vs. 9.8±2.0; p<0.002) and pulse pressure (PP) (50±11 vs. 53±14; p<0.05) was found during follow-up, but systolic, diastolic and mean arterial pressure did not change. eGFR did not change during follow-up (55±16 vs. 56±16 ml/min/1.73 m2). PWV increase was observed in patients aged ≥50 years (9.8±1.8 vs. 10.8±1.9; p<0.01), while not in younger patients (8.5±1.5 vs. 8.9±1.5; p=0.14). Significant positive correlation was found between ∆PWV and duration of the follow-up period. CONCLUSIONS: The study revealed progressive arterial stiffening in kidney transplant recipients during long-term follow-up. Further studies are necessary to explain the pathophysiology of this phenomenon.