RESUMO
OBJECTIVES: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. METHODS: We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results <38â¯g/L for the diagnosis of protein energy wasting. RESULTS: Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2â¯%, respectively vs. 66.7â¯% for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3â¯%) as opposed to BCP (0.7-1.5â¯%). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8â¯% vs. 0.7-1.5â¯% vs. 0.4-1.6â¯%). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. CONCLUSIONS: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.
Assuntos
Verde de Bromocresol , Insuficiência Renal Crônica , Humanos , Albumina Sérica/análise , Púrpura de Bromocresol , Diálise Renal , Insuficiência Renal Crônica/diagnósticoRESUMO
Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4-1.1%/nM) and 16.7%/nM (IQR, 12.0-24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84-100% and 91-100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population.
Assuntos
Anemia Ferropriva/sangue , Hepcidinas/sangue , Proteínas de Membrana/genética , Serina Endopeptidases/genética , Transferrina/metabolismo , Adolescente , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/genética , Área Sob a Curva , Proteína C-Reativa/metabolismo , Criança , Humanos , Masculino , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Maternal hyperoxygenation is widely used during labor as an intrauterine resuscitation technique. However, robust evidence regarding its beneficial effect and potential side effects is scarce, and previous studies show conflicting results. OBJECTIVE: To assess the effect of maternal hyperoxygenation upon suspected fetal distress during the second stage of term labor on fetal heart rate, neonatal outcome, maternal side effects, and mode of delivery. MATERIALS AND METHODS: In a single-center randomized controlled trial in a tertiary hospital in The Netherlands, participants were randomized in case of an intermediary or abnormal fetal heart rate pattern during the second stage of term labor, to receive either conventional care or 100% oxygen at 10 L/min until delivery. The primary outcome was the change in fetal heart rate pattern. Prespecified secondary outcomes were Apgar score, umbilical cord blood gas analysis, neonatal intensive care unit admission, perinatal death, free oxygen radical activity, maternal side effects, and mode of delivery. We performed subgroup analyses for intermediary and abnormal fetal heart rate, and for small for gestational age fetuses. RESULTS: From March 2016 through April 2018, a total of 117 women were included. Fetal heart rate patterns could be analyzed in 71 women. Changes in fetal heart rate (defined as improvement, equal, or deterioration) in favor of maternal hyperoxygenation were significant (odds ratio, 5.7; 95% confidence interval, 1.7-19.1) using ordinal logistic regression. Apgar score, umbilical cord blood gas analysis, free oxygen radicals, and mode of delivery showed no significant differences between the intervention and control group. Among women with an abnormal fetal heart rate, there were fewer episiotomies on fetal indication in the intervention group (25%) than in the control group (65%, P < .01). CONCLUSION: Maternal hyperoxygenation has a positive effect on the fetal heart rate in the presence of suspected fetal distress during the second stage of labor. There was no significant difference in the mode of delivery or neonatal outcome; however, significantly fewer episiotomies on fetal indication were performed following maternal hyperoxygenation in the subgroup with abnormal fetal heart rate pattern.
Assuntos
Sofrimento Fetal , Trabalho de Parto , Feminino , Sofrimento Fetal/terapia , Frequência Cardíaca Fetal , Humanos , Recém-Nascido , Países Baixos/epidemiologia , Gravidez , RessuscitaçãoRESUMO
BACKGROUND: Use of serum hepcidin measurements in pediatrics would benefit from standardized age- and sex-specific reference ranges in children, in order to enable the establishment of clinical decision limits that are universally applicable. PROCEDURE: We measured serum hepcidin-25 levels in 266 healthy Dutch children aged 0.3-17 years, using an isotope dilution mass spectrometry assay, standardized with our commutable secondary reference material (RM), assigned by a candidate primary RM. RESULTS: We constructed age- and sex-specific values for serum hepcidin and its ratio with ferritin and transferrin saturation (TSAT). Serum hepcidin levels and hepcidin/ferritin and TSAT/hepcidin ratios were similar for both sexes. Serum hepcidin and hepcidin/ferritin ratio substantially declined after the age of 12 years and TSAT/hepcidin ratio gradually increased with increasing age. Serum hepcidin values for Dutch children <12 years (n = 170) and >12 years (n = 96) were 1.9 nmol/L (median); 0.1-13.1 nmol/L (p2.5-p97.5) and 0.9 nmol/L; 0.0-9.1 nmol/L, respectively. Serum ferritin was the most significant correlate of serum hepcidin in our study population, explaining 15.1% and 7.9% of variance in males and females, respectively. Multivariable linear regression analysis including age, blood sampling time, iron parameters, ALT, CRP, and body mass index as independent variables showed a statistically significant negative association between age as a dichotomous variable (≤12 vs >12 years) and log-transformed serum hepcidin levels in both sexes. CONCLUSIONS: We demonstrate that serum hepcidin relative to indicators of body iron is age dependent in children, suggesting that the set point of serum hepcidin relative to stored and circulating iron changes during childhood.
Assuntos
Biomarcadores/sangue , Índice de Massa Corporal , Ferritinas/sangue , Hepcidinas/sangue , Ferro/sangue , Transferrina/análise , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valores de Referência , Fatores SexuaisRESUMO
TMPRSS6 variants that affect protein function result in impaired matriptase-2 function and consequently uninhibited hepcidin production, leading to iron refractory iron deficiency anemia (IRIDA). This disease is characterized by microcytic, hypochromic anemia and serum hepcidin values that are inappropriately high for body iron levels. Much is still unknown about its pathophysiology, genotype-phenotype correlation, and optimal clinical management. We describe 14 different TMPRSS6 variants, of which 9 are novel, in 21 phenotypically affected IRIDA patients from 20 families living in the Netherlands; 16 out of 21 patients were female. In 7 out of 21 cases DNA sequencing and multiplex ligation dependent probe amplification demonstrated only heterozygous TMPRSS6 variants. The age at presentation, disease severity, and response to iron supplementation were highly variable, even for patients and relatives with similar TMPRSS6 genotypes. Mono-allelic IRIDA patients had a milder phenotype with respect to hemoglobin and MCV and presented significantly later in life with anemia than bi-allelic patients. Transferrin saturation (TSAT)/hepcidin ratios were lower in IRIDA probands than in healthy relatives. Most patients required parenteral iron. Genotype alone was not predictive for the response to oral iron. We conclude that IRIDA is a genotypically and phenotypically heterogeneous disease. The high proportion of female patients and the discrepancy between phenotypes of probands and relatives with the same genotype, suggest a complex interplay between genetic and acquired factors in the pathogenesis of IRIDA. In the absence of inflammation, the TSAT/hepcidin ratio is a promising diagnostic tool, even after iron supplementation has been given. Am. J. Hematol. 91:E482-E490, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Anemia Ferropriva , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Países Baixos , Adulto JovemRESUMO
BACKGROUND: The principle of the erythrocyte sedimentation rate (ESR) as assessed by TEST 1 is different from that of Westergren-based methods. This could result in different influences on the tests by paraproteins. METHODS: We investigated the effect of paraproteins on ESR readings by TEST 1 (y) and the StarrSed (x), a Westergren-based method, in 142 patients with paraproteinaemia. Agreement (Passing-Bablok) and bias (Bland-Altman) between methods was investigated and compared with that of a control population. RESULTS: A poor agreement between the two methods was found in patients with a paraprotein (y = 0.67x + 3.3) in comparison with that of the control population (y = 0.96x + 0.2). Large differences between methods were present when ESR readings were >40 mm/hour, but clinical interpretation was similar in 90% of cases. Linear regression showed a concentration dependent influence of paraproteins on ESR readings by the StarrSed, especially for immunoglobulin class IgM. CONCLUSION: ESR readings by TEST 1 result in similar clinical interpretation for most subjects, but readings are less influenced by the presence of a paraprotein than those of a Westergren-based method.