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Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.

ABSTRACT: BACKGROUND:Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population. METHODS:We used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Fasting venous blood samples were obtained in the morning from all participants from 2001-2003. Serum erythropoietin concentrations were measured using a fully automated chemiluminescent enzyme-labeled immunometric assay. A genome-wide association study was performed to identify genetic determinants. RESULTS:Mean age (± SD) was 53 ± 12 years and 50% were female. Median (IQR) erythropoietin concentrations were 7.6 (5.8-9.9) IU/L in men and 7.9 (6.0-10.6) IU/L in women. A strong positive correlation was found between erythropoietin and waist circumference, glucose and systolic blood pressure (all P < 0.05). In subjects with normal renal function there was a strong exponential relation between hemoglobin and erythropoietin, whereas in renal impairment (eGFR < 60 mL/min/1.73m²) this relation was linear (men) or absent (women) (P < 0.001 for interaction). Single-nucleotide polymorphisms at the HBS1L-MYB locus were shown to be related to erythropoietin levels (P < 9x10-21), more significantly than other erythrocyte parameters. CONCLUSION:We provide age-specific reference ranges for endogenous serum erythropoietin. Erythropoietin levels are positively associated with the components of the metabolic syndrome, except cholesterol. We show that even mild renal failure blunts erythropoietin production and propose the HBS1L-MYB locus as a regulator of erythropoietin.

SUBMITTER: Grote Beverborg N

PROVIDER: S-EPMC4411129 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.

Grote Beverborg Niels N Verweij Niek N Klip Ijsbrand T IT van der Wal Haye H HH Voors Adriaan A AA van Veldhuisen Dirk J DJ Gansevoort Ron T RT Bakker Stephan J L SJ van der Harst Pim P van der Meer Peter P

PloS one 20150427 4

<h4>Background</h4>Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population.<h4>Methods</h4>We used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Fasting venous blood samples were obtained in the morning fro ...[more]

PMID: 25915923

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Project description:ImportanceAntibiotics are frequently prescribed for suspected pneumonia, but overdiagnosis is common and fixed regimens are often used despite randomized trials suggesting it is safe to stop antibiotics once clinical signs are normalizing.ObjectiveTo quantify potential excess antibiotic prescribing by characterizing antibiotic use relative to patients' initial clinical signs and subsequent trajectories.Design, setting, and participantsAn observational cohort study was conducted in 2 tertiary and 2 community hospitals in Eastern Massachusetts. All nonventilated adult patients admitted between May 1, 2017, and July 1, 2018 (194 521 hospitalizations), were included.Main outcomes and measuresIdentification of all antibiotic starts for possible community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP) per clinicians' stated indications. Potential excess antibiotic prescribing was quantified by characterizing the frequency of patients in whom all clinical signs were within reference ranges on the first day of antibiotic therapy and by how long antibiotic therapy was continued after all clinical signs were normal, including postdischarge antibiotics.ResultsAmong 194 521 hospitalizations, 9540 patients were treated for possible CAP (4574 [48.0%] women; mean [SD] age, 67.6 [17.0] years) and 2733 for possible HAP (1211 [44.3%] women; mean [SD] age, 66.7 [16.2] years). Temperature, respiratory rate, oxygen saturation, and white blood cell count were all within reference ranges on the first day of antibiotics in 1779 of 9540 (18.6%) episodes of CAP and 370 of 2733 (13.5%) episodes of HAP. Antibiotics were continued for 3 days or longer after all clinical signs were normal in 3322 of 9540 (34.8%) episodes of CAP and 1050 of 2733 (38.4%) episodes of HAP. Up to 24 978 of 71 706 (34.8%) antibiotic-days prescribed for possible pneumonia may have been unnecessary.Conclusions and relevanceIn this study, almost one-fifth of hospitalized patients treated for pneumonia did not have any of the cardinal signs of pneumonia on the first day of treatment and antibiotics were continued for 3 days or longer after all signs were normal in more than a third of patients. These observations suggest substantial opportunities to improve antibiotic prescribing.

Dataset Information

Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.

Publications

Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.

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