Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.
AimsErythropoietin (EPO) resistance, an important cause of anaemia in patients with heart and renal failure, is associated with increased mortality. The hypothesis of the present study was that exogenous EPO decreases hepcidin levels and that the decrease in hepcidin levels upon EPO treatment is related to the bone marrow response. Methods and resultsIn the EPOCARES trial, patients with renal failure (glomerular filtration rate 20-70 mL/min), heart failure, and anaemia were randomized to receive 50 IU/kg/week EPO (n ¼ 20) or not (n ¼ 13). Haemoglobin (Hb), hepcidin-25, ferritin, reticulocytes, serum transferrin receptor (sTfR), IL-6, and high-sensitivity C-reactive protein were measured at baseline and during treatment. Hepcidin-25 was measured by weak cation exchange chromatography/ matrix assisted laser desorption ionization time-of-flight mass spectrometry. Baseline hepcidin levels were increased compared with a healthy reference population and were inversely correlated with Hb (r 2 ¼ 0.18, P ¼ 0.02), and positively with ferritin (r 2 ¼ 0.51, P , 0.001), but not with renal function, high-sensitivity C-reactive protein or IL-6. Erythropoietin treatment increased reticulocytes (P , 0.001) and sTfR (P , 0.001), and decreased hepcidin (P , 0.001). Baseline hepcidin levels and the magnitude of the decrease in hepcidin correlated with the increase in reticulocytes (r 2 ¼ 0.23, P ¼ 0.03) and sTfR (r 2 ¼ 0.23, P ¼ 0.03) and also with the Hb response after 6 months (r 2 ¼ 0.49, ConclusionIn this group of patients with combined heart and renal failure and anaemia, increased hepcidin levels were associated with markers of iron load and not with markers of inflammation. The (change in) hepcidin levels predicted early and long-term bone marrow response to exogenous EPO. In our group hepcidin seems to reflect iron load and response to EPO rather than inflammation and EPO resistance.--
ObjectiveTo externally validate four commonly used rules in computed tomography (CT) for minor head injury.DesignProspective, multicentre cohort study.SettingThree university and six non-university hospitals in the Netherlands.ParticipantsConsecutive adult patients aged 16 years and over who presented with minor head injury at the emergency department with a Glasgow coma scale score of 13-15 between March 2015 and December 2016.Main outcome measuresThe primary outcome was any intracranial traumatic finding on CT; the secondary outcome was a potential neurosurgical lesion on CT, which was defined as an intracranial traumatic finding on CT that could lead to a neurosurgical intervention or death. The sensitivity, specificity, and clinical usefulness (defined as net proportional benefit, a weighted sum of true positive classifications) of the four CT decision rules. The rules included the CT in head injury patients (CHIP) rule, New Orleans criteria (NOC), Canadian CT head rule (CCHR), and National Institute for Health and Care Excellence (NICE) guideline for head injury.ResultsFor the primary analysis, only six centres that included patients with and without CT were selected. Of 4557 eligible patients who presented with minor head injury, 3742 (82%) received a CT scan; 384 (8%) had a intracranial traumatic finding on CT, and 74 (2%) had a potential neurosurgical lesion. The sensitivity for any intracranial traumatic finding on CT ranged from 73% (NICE) to 99% (NOC); specificity ranged from 4% (NOC) to 61% (NICE). Sensitivity for a potential neurosurgical lesion ranged between 85% (NICE) and 100% (NOC); specificity from 4% (NOC) to 59% (NICE). Clinical usefulness depended on thresholds for performing CT scanning: the NOC rule was preferable at a low threshold, the NICE rule was preferable at a higher threshold, whereas the CHIP rule was preferable for an intermediate threshold.ConclusionsApplication of the CHIP, NOC, CCHR, or NICE decision rules can lead to a wide variation in CT scanning among patients with minor head injury, resulting in many unnecessary CT scans and some missed intracranial traumatic findings. Until an existing decision rule has been updated, any of the four rules can be used for patients presenting minor head injuries at the emergency department. Use of the CHIP rule is recommended because it leads to a substantial reduction in CT scans while missing few potential neurosurgical lesions.
Background. Endothelial dysfunction contributes to accelerated atherosclerosis in chronic kidney disease (CKD). Bone marrow-derived endothelial progenitor cells (EPC) constitute an endogenous vascular repair system protecting against atherosclerosis. Smooth muscle progenitor cells (SPC) may stimulate atherosclerosis development. We hypothesized that an imbalance in EPC and SPC occurs in CKD, which may contribute to the increased cardiovascular disease (CVD) risk. Methods. EPC and SPC outgrowth from mononuclear cells (MNC), EPC migratory function and circulating CD34+ KDR + -EPC were measured in 49 patients with varying degrees of CKD on regular therapy and 33 healthy volunteers. Renal function, CKD cause, CVD history and endothelial dysfunction parameters were determined as factors of influence on progenitor cells. Results. Patients had reduced EPC outgrowth compared to controls [9 (2-22) vs 12 (1-38) cells/10 3 MNC, P = 0.026], independent of CKD cause and degree, whereas SPC outgrowth levels were higher in patients with more impaired kidney function (r = −0.397, P = 0.008). Patients had lower CD34 + KDR + -EPC compared to controls [9 (0-52) vs 19 (4-110) cells/10 5 granulocytes, P = 0.004]. CVD history and increased endothelial dysfunction markers were related to lower EPC levels. Progenitor cell outgrowth was shifted towards SPC with progression of endothelial damage. Reduction in EPC could not be attributed to decreases in progenitor cell-mobilizing factors SDF-1α and VEGF as levels increased with progressive kidney and endothelial dysfunction, while EPC remained low. Conclusions. Our data suggest that, already in mild CKD, EPC-mediated endogenous vascular regeneration is impaired, while SPC levels increase with declining kidney function.
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