163 research outputs found
Calcineurin inhibitors differentially alter the circadian rhythm of T-cell functionality in transplant recipients
Background: Graft survival in transplant recipients depends on pharmacokinetics and on individual susceptibility
towards immunosuppressive drugs. Nevertheless, pharmacodynamic changes in T-cell functionality in response to
drugs and in relation to pharmacokinetics are poorly characterized. We therefore investigated the immunosuppressive
effect of calcineurin inhibitors and steroids on general T-cell functionality after polyclonal stimulation of whole blood
samples.
Methods: General T-cell functionality in the absence or presence of immunosuppressive drugs was determined in vitro
directly from whole blood based on cytokine induction after stimulation with the polyclonal stimulus Staphylococcus
aureus enterotoxin B. In addition, diurnal changes in leukocyte and lymphocyte subsets, and on T-cell function after
intake of immunosuppressive drugs were analyzed in 19 patients during one day and compared to respective kinetics
in six immunocompetent controls. Statistical analysis was performed using non-parametric and parametric tests.
Results: Susceptibility towards calcineurin inhibitors showed interindividual differences. When combined with steroids,
tacrolimus led to more pronounced increase in the inhibitory activity as compared to cyclosporine A. While circadian
alterations in leukocyte subpopulations and T-cell function in controls were related to endogenous cortisol levels, T-cell
functionality in transplant recipients decreased after intake of the morning medication, which was more pronounced in
patients with higher drug-dosages. Interestingly, calcineurin inhibitors differentially affected circadian rhythm of T-cell
function, as patients on cyclosporine A showed a biphasic decrease in T-cell reactivity after drug-intake in the morning
and evening, whereas T-cell reactivity in patients on tacrolimus remained rather stable.
Conclusions: The whole blood assay allows assessment of the inhibitory activity of immunosuppressive drugs in
clinically relevant concentrations. Circadian alterations in T-cell function are determined by dose and type of
immunosuppressive drugs and show distinct differences between cyclosporine A and tacrolimus. In future these
findings may have practical implications to estimate the net immunosuppressive effect of a given drug-regimen
that daily acts in an individual patient, and may contribute to individualize immunosuppressio
Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury
Calcineurin inhibitors differentially alter the circadian rhythm of T-cell functionality in transplant recipients
Background: Graft survival in transplant recipients depends on pharmacokinetics and on individual susceptibility
towards immunosuppressive drugs. Nevertheless, pharmacodynamic changes in T-cell functionality in response to
drugs and in relation to pharmacokinetics are poorly characterized. We therefore investigated the immunosuppressive
effect of calcineurin inhibitors and steroids on general T-cell functionality after polyclonal stimulation of whole blood
samples.
Methods: General T-cell functionality in the absence or presence of immunosuppressive drugs was determined in vitro
directly from whole blood based on cytokine induction after stimulation with the polyclonal stimulus Staphylococcus
aureus enterotoxin B. In addition, diurnal changes in leukocyte and lymphocyte subsets, and on T-cell function after
intake of immunosuppressive drugs were analyzed in 19 patients during one day and compared to respective kinetics
in six immunocompetent controls. Statistical analysis was performed using non-parametric and parametric tests.
Results: Susceptibility towards calcineurin inhibitors showed interindividual differences. When combined with steroids,
tacrolimus led to more pronounced increase in the inhibitory activity as compared to cyclosporine A. While circadian
alterations in leukocyte subpopulations and T-cell function in controls were related to endogenous cortisol levels, T-cell
functionality in transplant recipients decreased after intake of the morning medication, which was more pronounced in
patients with higher drug-dosages. Interestingly, calcineurin inhibitors differentially affected circadian rhythm of T-cell
function, as patients on cyclosporine A showed a biphasic decrease in T-cell reactivity after drug-intake in the morning
and evening, whereas T-cell reactivity in patients on tacrolimus remained rather stable.
Conclusions: The whole blood assay allows assessment of the inhibitory activity of immunosuppressive drugs in
clinically relevant concentrations. Circadian alterations in T-cell function are determined by dose and type of
immunosuppressive drugs and show distinct differences between cyclosporine A and tacrolimus. In future these
findings may have practical implications to estimate the net immunosuppressive effect of a given drug-regimen
that daily acts in an individual patient, and may contribute to individualize immunosuppressio
What should European nephrology do with the new CKD-EPI equation?
Nephrology; CKD-EPI equationNefrologia; Equació CKD-EPINefrología; Ecuación CKD-EP
Markers of cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD: An observational study
In dialysis patients, cholesterol-lowering therapy with statins is less effective than in other high-risk patients. This may be explained by a shift from cholesterol synthesis toward cholesterol absorption. In line, markers of cholesterol absorption-such as campesterol-better predict atherosclerotic cardiovascular events than markers of cholesterol synthesis-such as lathosterol-in dialysis patients. To test the association between markers of cholesterol absorption such as campesterol-and markers of cholesterol synthesis-such as lathosterol-against cardiovascular events in non-dialysis CKD patients. Altogether 251 patients those not on lipid-lowering agents were followed annually for the composite endpoint atherosclerotic cardiovascular disease (ASCVD) and all-cause death. During follow-up of 5.2 ± 2.1 years, 61 participants reached the primary endpoint atherosclerotic cardiovascular disease/all-cause death [ASCVD/D], 47 participants suffered from ASCVD, and 46 participants died. In univariate Cox regression analysis, campesterol/lathosterol ratio did not significantly predict ASCVD/D (HR 0.643; 0.358-1.155; 3rd vs. 1st tertile), all-cause death (HR 1.309; 0.604-2.838; 3rd vs. 1st tertile) nor ASCVD (HR 0.589; 0.311-1.118; 3rd vs. 1st tertile). We did not observe a shift from cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD. Campesterol/lathosterol ratio did not predict future ASCVD or all-cause death in non-dialysis CKD
Plasma biomarkers outperform echocardiographic measurements for cardiovascular risk prediction in kidney transplant recipients: results of the HOME ALONE study
Background
Since kidney transplant recipients (KTRs) have a high cardiovascular disease burden, adequate risk prediction is of importance. Whether echocardiographic parameters and plasma biomarkers, natriuretic peptides [N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and troponin T provide complementary or overlapping prognostic information on cardiovascular events remains uncertain.
Methods
The prospective Heterogeneity of Monocytes and Echocardiography Among Allograft Recipients in Nephrology (HOME ALONE) study followed 177 KTRs for 5.4 ± 1.7 years. Predefined endpoints were hospitalization for acute decompensated heart failure or all-cause death (HF/D) and major atherosclerotic cardiovascular events or all-cause death (MACE/D). At baseline, plasma NT-proBNP, plasma troponin T and echocardiographic parameters [left atrial volume index, left ventricular (LV) mass index, LV ejection fraction, and LV filling pressure] were assessed.
Results
Among all echocardiographic and plasma biomarkers measured, only NT-proBNP was consistently associated with HF/D in univariate and multivariate {third versus first tertile: hazard ratio [HR] 4.20 [95% confidence interval (CI) 1.02–17.27]} analysis, and only troponin T was consistently associated with MACE/D in univariate and multivariate [third versus first tertile: HR 8.15 (95% CI 2.75–24.18)] analysis.
Conclusion
Our data suggest that plasma biomarkers are robust and independent predictors of heart failure and atherosclerotic cardiovascular events after kidney transplantation, whereas standard echocardiographic follow-up does not add to risk prediction
What should European nephrology do with the new CKD-EPI equation?
Nephrology; CKD-EPI equationNefrologia; Equació CKD-EPINefrología; Ecuación CKD-EP
Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study
Background
In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively.
Methods
In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias.
Results
Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants.
Conclusions
While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI.
Trial registration
Clinical Trials.gov NCT02905539. Registered on 8 September 2016.
2015-004808-36 (EudraCT Number)
U1111-1176-4563 (WHO Universal Trial Number)
DRKS00010766 (Deutsches Register Klinischer Studien
Consequences of chronic kidney disease in chronic obstructive pulmonary disease
Background: The combination of chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)
is associated with a higher prevalence of comorbidities and increased mortality. The impact of kidney function on
patient-centered outcomes in COPD has not been evaluated.
Methods: Patients from the German COPD and Systemic Consequences - Comorbidities Network (COSYCONET)
cohort COPD were analysed. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) measurements
were < 60 mL/min/1.73m2 at study inclusion and six month later. The effect of CKD, on comorbidities, symptoms
[modified British Medical Research Council dyspnoea scale], physical capacity [six-minute walk test, and timed up
and go] and St George’s Respiratory Questionnaire were analysed. Restricted cubic spline models were used to
evaluate a nonlinear relationship between eGFR with patient-centered outcomes, cox survival analysis was applied
to evaluate mortality.
Results: 2274 patients were analysed, with CKD diagnosed in 161 (7.1%). Spline models adjusted for age, gender,
BMI, FEV1 and cardiovascular comorbidities revealed independent associations between eGFR with modified British
Medical Research Council dyspnoea scale, St George’s Respiratory Questionnaire, (p < 0.001 and p = 0.011), six-minute
walk test (p = 0.015) and timed up and go (p < 0.001). CKD was associated with increased mortality, independently
from for other cardiovascular comorbidities (hazard ratio 2.3; p < 0.001).
Conclusion: These data show that CKD is a relevant comorbidity in COPD patients which impacts on patient-centered
outcomes and mortality
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