Tubular biomarkers and histology in lupus nephritis.

INTRODUCTION: The relevance of tubulo-interstitial involvement for kidney prognosis has recently been emphasized, but validated biomarkers for predicting histology are still lacking. The aim of our study was to evaluate different serum and urinary markers of tubular damage in patients with lupus nephritis (LN) and to correlate them with kidney histopathology. METHODS: A single-center retrospective study was conducted from January 2016 to December 2021. Serum and urine samples were collected on the same day of kidney biopsy and correlated with histologic data from a cohort of 15 LN patients. We analyzed the following urinary markers, adjusted for urine creatinine: beta 2-microglobulin, alpha 1-microglobulin, NGAL, uKIM-1, MCP-1, uDKK-3, and uUMOD. The serum markers sKIM-1 and sUMOD were also analyzed. RESULTS: A positive and strong correlation was observed between the degree of interstitial fibrosis (rho = 0.785, p = .001) and tubular atrophy (rho = 0.781, p = .001) and the levels of uDKK3. uUMOD also showed an inverse and moderate correlation with interstitial fibrosis (rho = -0.562, p = .037) and tubular atrophy (rho = -0.694, p = .006). Patients with >10% cortical interstitial inflammation had higher levels of uKIM-1 [4.9 (3.9, 5.5) vs. 0.8 (0.6, 1.5) mcg/mg, p = .001], MCP-1 [3.8 (2. 3, 4.2) vs. 0.7 (0.3, 1.2) mcg/mg, p = .001], sKIM-1 [9.2 (5.9, 32.7) vs. 1.4 (0, 3.5) pg/mL, p = .001], and lower sUMOD [8.7 (0, 39.7) vs. 46.1 (35.7, 53) ng/mL, p = .028]. CONCLUSION: The use of specific urinary and serum biomarkers of tubular dysfunction or injury may help to predict certain histologic parameters in LN patients.

Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers.

Background: Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. Methods: A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (ß2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Results: Multivariate regression analysis identified sUMOD (ß-0.357, P < .001) and uDKK3 (ß 0.483, P < .001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52-69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria. Conclusions: Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study.

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for mortality were 2.40 and 0.46, respectively. The LR+ and LR- for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62-0.81) and 0.72 (95% CI, 0.62-0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

Assessment of proadrenomedullin as diagnostic or prognostic biomarker of acute appendicitis in children with acute abdominal pain.

BACKGROUND: Acute appendicitis (AA) is one of the most frequent surgical pathologies in pediatrics. OBJECTIVES: To investigate the utility of proadrenomedullin (pro-ADM) for the diagnosis of AA. METHODS: Prospective, analytical, observational, and multicenter study conducted in 6 pediatric emergency departments. Children up to 18 years of age with suspected AA were included. Clinical, epidemiological, and analytical data were collected. RESULTS: We studied 285 children with an average age of 9.5 years (95% confidence interval [CI], 9.1-9.9). AA was diagnosed in 103 children (36.1%), with complications in 10 of them (9.7%). The mean concentration of pro-ADM (nmol/L) was higher in children with AA (0.51 nmol/L, SD 0.16) than in children with acute abdominal pain (AAP) of another etiology (0.44 nmol/L, SD 0.14; p < 0.001). This difference was greater in complicated cases compared with uncomplicated AA (0.64 nmol/L, SD 0.17 and 0.50 nmol/L, SD 0.15, respectively; p = 0.005). The areas under the receiver-operating characteristic curves were 0.66 (95% CI, 0.59-0.72) for pro-ADM, 0.70 (95% CI, 0.63-0.76) for C-reactive protein (CRP), 0.84 (95% CI, 0.79-0.89) for neutrophils, and 0.84 (95% CI, 0.79-0.89) for total leukocytes. The most reliable combination to rule out AA was CRP ≤1.25 mg/dL and pro-ADM ≤0.35 nmol/L with a sensitivity of 96% and a negative predictive value of 93%. CONCLUSION: Children with AA presented higher pro-ADM values than children with AAP of other etiologies, especially in cases of complicated AA. The combination of low values of pro-ADM and CRP can help to select children with low risk of AA.

Evaluation of proadrenomedullin as a diagnostic or prognostic biomarker of acute appendicitis in children.

INTRODUCTION: A delay in the diagnosis of acute appendicitis (AA), with the added complication of symptoms that mimic other self-limited causes of abdominal pain, can lead to an increase in ruptured appendices and morbimortality. None of the serum biomarkers evaluated to date have shown a predictive value for early diagnosis. OBJECTIVE: The objective of this study was to evaluate the usefulness of proadrenomedullin (MR-proADM) in the diagnosis of AA in children presenting with acute abdominal pain. METHODS: A single-center prospective observational study was conducted in 136 children who presented to the emergency department with suspected AA. RESULTS: Forty-four (32.5%) children had AA, and 9 (20.5%) had perforated appendicitis. The mean concentration of MR-proADM was significantly higher in children with AA than in children with nonspecific abdominal pain (NAP) (0.54 nmol/L; 95% confidence interval, 0.46-0.55 and 0.37 nmol/L; 95% confidence interval, 0.35-0.40, respectively). Performance characteristics of MR-proADM alone were not optimal. However, after combining best cutoff points, the combination of a C-reactive protein level of <0.3 mg/dL and a MR-proADM level of <0.34 nmol/L showed 100% sensitivity and negative predictive value, with 61% specificity. CONCLUSIONS: Although MR-proADM values are higher in children with AA than in children with nonspecific abdominal pain, these values do not help in the early diagnosis of AA. The combination of low C-reactive protein and low MR-proADM levels is useful for the identification of children with a low risk of AA.

Usefulness of midregional proadrenomedullin to predict poor outcome in patients with community acquired pneumonia.

BACKGROUND: midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED). METHODS: Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was "poor outcome", defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis). RESULTS: 226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event. CONCLUSION: MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone.

Comparación entre 2 sistemas analíticos para la determinación de la hemoglobina A1c: inmunoturbidimetría versus cromatografía líquida de alta eficiencia / Comparison of 2 analytical systems for hemoglobin A1c: An immunoturbidimetric method versus high performance liquid chromatography

Introducción. La hemoglobina A1c (HbA1c) es ampliamente utilizada en la determinación del estado glucémico de pacientes con diabetes mellitus. El objetivo de este estudio fue comparar 2 métodos automatizados para medir HbA1c basados en diferentes principios de medida, evaluar la correlación entre ambos y su practicabilidad. Métodos. Se analizaron 622 muestras mediante 2 sistemas analíticos con fundamentos diferentes de medición: cromatografía líquida de alta eficiencia (HPLC) (analizador ADAMS A1c HA-8160; A. Menarini Diagnostics, Italia) e inmunoturbidimetría (Tina-quant Hemoglobin A1c Gen.3, plataforma Cobas 6000; Roche Diagnostics, Suiza). Ambos métodos fueron calibrados según el procedimiento de referencia de la IFCC. Se valoró la correlación entre ambos métodos mediante los análisis de regresión de mínimos cuadrados y Passing-Bablok (R programa v.2.11.1). También se registró el tiempo de puesta en marcha, las tareas de mantenimiento diario y el rendimiento de los 2 instrumentos. Resultados. La correlación fue muy alta tanto por mínimos cuadrados (ordenada en el origen 0.05, pendiente 0.98) como en Passing-Bablok (ordenada en el origen 0,10, pendiente 1,00). El tiempo invertido diariamente para la puesta en marcha del analizador HA-8160 fue de 25 min y el tiempo de finalización fue de 15 min. Las tareas de mantenimiento del Cobas 6000 al inicio y fin del día son procesos automatizados. El rendimiento de los analizadores fue 20 muestras/h en el HA-8160 y 100 muestras/h en el Cobas 6000. El sistema analítico cuyo principio de medida es HPLC incluye también el análisis manual de cada cromatograma. Conclusiones. Existe una correlación excelente entre los métodos de HPLC e inmunoturbidimétrico. La ventaja del sistema analítico que utiliza la inmunoturbidimetría es la optimización del tiempo de procesamiento de las determinaciones de HbA1c, lo que reduce el coste unitario de la prueba (AU)

Introduction. Hemoglobin A1c (HbA1c) is widely used to assess glycemic status in patients with diabetes mellitus. The purpose of this study was to compare 2 automated analytical systems to measure HbA1c that use different measurement principles, evaluating the correlation between the two methods, as well as their ease of use. Methods. A total of 622 samples were analyzed using 2 methods: high performance liquid chromatography (HPLC) (analyzer ADAMS A1c HA-8160; A. Menarini Diagnostics, Italy) and an immunoturbidimetric assay (Tina-quant Hemoglobin A1c Gen.3, Cobas 6000 analyzer; Roche Diagnostics, Switzerland). Both methods were calibrated in accordance with IFCC reference measurement procedure. The correlation between the two methods was assessed by least squares and Passing-Bablok linear regression analyses (R program v.2.11.1). The daily start-up time of the 2 instruments used, daily maintenance tasks, and determination of throughput were also recorded. Results. There was a strong correlation between the results generated by the two test methods using both the least squares (intercept 0.54; slope 0.98) and Passing-Bablok (intercept 0.10; slope 1.00) regression methods. The time spent daily for the start-up of the HA-8160 analyzer was 25 min and completion time was 15 min. Maintenance tasks for the Cobas 6000 analyzer at the beginning and end of the day are automated processes. The throughput for the HA-8160 analyzer was 20 samples/h, and 100 samples/h for the Cobas 6000 analyzer. The HPLC method also included a time-consuming manual analysis of each chromatogram. Conclusions. An excellent correlation was observed between the HPLC and immunoturbidimetric methods. The advantages of the immunoturbidimetric method are optimization of processing time of HbA1c tests and a reduction in the unit cost per test (AU)