A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort.

Acute Kidney Injury (AKI) is a frequent complication in intensive care unit (ICU) patients that increases mortality and chronic kidney disease (CKD) development. AKI is associated with elevated plasma fibroblast growth factor 23 (FGF23), which can be modulated by erythropoietin (EPO) and Klotho. We aimed to evaluate whether a combined biomarker that includes these molecules predicted short-/long-term outcomes. We performed a prospective cohort of ICU patients with sepsis and previously normal renal function. They were followed during their inpatient stay and for one year after admission. We measured plasma FGF23, EPO, and Klotho levels at admission and calculated a combined biomarker (FEK). A total of 164 patients were recruited. Of these, 50 (30.5%) had AKI at admission, and 55 (33.5%) developed AKI within 48 h. Patients with AKI at admission and those who developed AKI within 48 h had 12- and 5-fold higher FEK values than non-AKI patients, respectively. Additionally, patients with higher FEK values had increased 1-year mortality (41.9% vs. 18.6%, p = 0.003) and CKD progression (26.2% vs. 8.3%, p = 0.023). Our data suggest that the FEK indicator predicts the risk of AKI, short-/long-term mortality, and CKD progression in ICU patients with sepsis. This new indicator can improve clinical outcome prediction and guide early therapeutic strategies.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI.

Assessment of Protein:Creatinine Ratio versus 24-Hour Urine Protein in the Diagnosis of Preeclampsia.

BACKGROUND/AIMS: Current evidence has tried to extrapolate the use of the protein:creatinine ratio (PCR) in a single urine sample as a rapid diagnostic tool for preeclampsia (PE). The present study addresses the effectiveness of the PCR in the differential diagnosis of the pregnancy hypertensive disorder (PHD). METHODS: This is a prospective study conducted on patients admitted during 1 year with a diagnosis of PHD. These pregnant women were assessed for the correlation between the 24-hour test and the PCR to detect significant proteinuria. A ROC curve was made to determine the PCR cutoff value that would offer the best positive predictive value (PPV) as an early predictor of global and severe PE. RESULTS: A total of 72 patients with 24-hour proteinuria and PCR were studied (49 with PE). A significant correlation between the quick and the deferred sampling was observed (r = 0.60; p < 0.001). The ROC analysis showed a PCR of 0.36 as the best cutoff value for the diagnosis of global PE (PPV 96.4%; false-positive rate 4.4%; AUC 0.8802) and a cutoff value of 4.58 (sensitivity: 100%; PPV 87.5%; false-positive rate 3.5%; AUC 0.9805) as the best cutoff for the diagnosis of severe proteinuria. CONCLUSIONS: PCR proved to be an effective test for the differential diagnosis of PHS.

Validación del test de troponinas en plasma a partir de una población sana: una experiencia local / Validation of normal values for troponin i plasma levels in a chilean population

Introducción: Las troponinas corresponden a proteínas estructurales del miocardiocito, su presencia en plasma se utiliza como marcador de injuria miocárdica. El test troponinas en plasma se utiliza actualmente para detectar daño miocárdico en pacientes en quienes se sospecha un infarto agudo al miocardio; para este propósito se toma como referencia valores de referencia validados en poblaciones de Inglaterra o Estados Unidos. Objetivo: El propósito de este estudio obtener valores de referencia para nuestra población local. Métodos y resultados: Se efectuó una determinación de troponina I en 500 sujetos sanos, se obtuvo el valor promedio de troponina I para esta población y el valor percentil 99 para esta población que se considera internacionalmente como el valor de referencia para determinar el límite normal, el valor P99 resultó significativamente menor en mujeres respecto a hombres. Conclusión: En conclusión, se han obtenido valores de referencia para aplicar el test de troponina I en nuestro medio local.

Background: Troponins are myocardiocyte proteins; their plasma level is used as a marker for myocardial injury. In the diagnosis of myocardial infarction values currently used as cut points are those validated elsewhere (USA, UK). Aim: In this study we aimed to determine normal limits of Troponin I in a sample of Chilean subjects. Methods and results: 500 healthy subjects had their troponin I levels measured, computing the mean and 99 percentile (p99) values. Both parameters were significantly lower in females compared to males (mean ± SD 0.089 +/- 0.047 vs 0.102 +/- 0.063, p<0.01; p99 0.02 vs 0.03, respectively). Conclusion: These troponin I values may be used to assess the likelihood of myocardial infarction in Chilean subjects.

Increase in C-reactive protein and lipids in adolescents with psychiatric disease.

Eighteen adolescent patients with severe psychiatric disorders were compared with healthy, eutrophics adolescents for the presence of inflammation and cardiovascular risk factors. We found significant differences in high-sensitivity C-reactive protein, total cholesterol, and triglycerides. Our results show, evidence of an inflammatory status and a deleterious lipid profile, in a very early state of psychiatric disease.