The relationship between Nephrocheck® test values, outcomes, and urinary output in critically ill patients at risk of acute kidney injury.

BACKGROUND: Nephrocheck® was approved for acute kidney injury (AKI) risk assessment in critically illness. However, new studies suggest that urinary concentration affects Nephrocheck® and previous studies did not provide data on urinary output (UO) at the time of measurement. METHODS: We performed a prospective cohort study of the Nephrocheck® in intensive care unit patients fulfilling standard inclusion criteria. The primary outcome was Stage 2 or 3 AKI defined by both UO and creatinine Kidney Disease Improving Global Outcomes (KDIGO) criteria in the subsequent 12 h. The secondary outcome was the relationship of UO with Nephrocheck® measurement. RESULTS: Among 98 patients, the primary outcome occurred in 53 (54.1%) overall, but in 23 (23.5%) by creatinine criteria alone. The median (interquartile range) Nephrocheck® in patients with subsequent Stage 2 or 3 AKI was greater than in Stage 1 or no-AKI patients (0.97 [0.48-1.99] vs. 0.46 [0.22-1.17]; p = .005). However, its area under the receiver characteristic curve was 0.66 (95% confidence interval [CI], 0.56-0.77). Moreover, Nephrocheck® was significantly and inversely correlated with UO (ρ = -.46, p < .001) at the time of measurement and, on a multivariable logistic regression, Nephrocheck® was not associated with subsequent Stage 2 or 3 AKI (OR 1.06 [95% CI, 0.74-1.53], p = .73). In contrast, the UO had an OR of 0.98 for each ml/h increase (95% CI, 0.97-1.00, p = .007). CONCLUSION: Nephrocheck®'s predictive performance was limited and its value was inversely correlated with UO. Nephrocheck® had no independent relationship with outcome once UO at measurement was considered.

NephroCheck® Quality Test.

BACKGROUND: The acute kidney injury (AKI) risk score helps detect moderate and severe AKI in the next 12-24 h. However, inappropriate urine collection may impact its results. AIM: The aim of this study was to evaluate the stability of NephroCheck® after urine storage at different temperatures. METHODS: The urine sample was centrifuged and split into 3 tubes. One was tested as soon as possible by the laboratory. The other 2 samples were frozen at -20 and -80°C, and the NephroCheck® test was performed 8 weeks later. RESULTS: The mean values of the AKI risk score were 1.19 ± 0.93, 1.15 ± 1.14, and 1.20 ± 1.11 (ng/mL)2/1,000 for fresh urine, -20, and -80°C, respectively (p = 0.70). Spearman's rank correlation for -20 and -80°C versus immediate processing was strong with a rho of 0.82 and 0.98, respectively. CONCLUSION: The AKI risk score was relatively stable. Urine could be collected without dry ice or liquid nitrogen and kept for up to 8 weeks with either -20 or -80°C freezing with stable NephroCheck® results.

Clinical evaluation of four commercial immunoassays for the detection of antibodies against established SARS-CoV-2 infection.

A comparison of the clinical performance of the Elecsys Anti-SARS-CoV-2, Liaison SARS-CoV-2 S1/S2 IgG, Access SARS-CoV-2 IgG and Vitros Immunodiagnostic Products Anti-SARS-CoV-2 IgG immunoassays for the diagnosis of COVID-19 infection was performed. Patient sera were collected at least 6 weeks following onset of COVID-19 infection symptoms. Negative control specimens were stored specimens from those without COVID-19, collected in April-May 2019. Sensitivity and specificity with 95% confidence intervals (CI) were calculated. Linear regression was used to examine the relationship between the magnitude of serological response and clinical characteristics. There were 80 patients from whom 86 sera specimens were collected; six patients had duplicate specimens. There were 95 negative control specimens from 95 patients. The clinical sensitivity of the Elecsys assay was 98.84% (95% CI 93.69-99.97), specificity was 100% (95% CI 96.19-100.00); the Liaison assay clinical sensitivity was 96.51% (95% CI 90.14-99.27), specificity was 97.89% (95% CI 92.60-99.74); the Access assay clinical sensitivity was 84.88% (95% CI 75.54-91.70), specificity was 98.95% (95% CI 94.27-99.97); and the Vitros assay clinical sensitivity was 97.67% (95% CI 91.85-99.72), specificity was 100% (95% CI 96.15-100.00). A requirement for hospitalisation for COVID-19 infection was associated with a larger Vitros, Liaison and Access IgG response whilst fever was associated with a larger Elecsys response. All assays evaluated with the exception of the Access assay demonstrated similar performance. The Elecsys assay demonstrated the highest sensitivity and specificity.

Risk prediction for severe acute kidney injury by integration of urine output, glomerular filtration, and urinary cell cycle arrest biomarkers.

BACKGROUND: Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. OBJECTIVE: To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. METHODS: We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. RESULTS: We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 µmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. CONCLUSION: In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.

Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction.

Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks' gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3rd, 5th, 10th and 20th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth.

Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients.

Objective: Angiotensin-converting enzyme 2 activity reflects non-classical renin-angiotensin system upregulation. We assessed the association of urinary angiotensin-converting enzyme 2 (uACE2) activity with acute kidney injury (AKI). Design, setting and participants: A prospective observational study in which we measured uACE2 activity in 105 critically ill patients at risk of AKI. We report AKI stage 2 or 3 at 12 hours of urine collection (AKI12h) and AKI stage 2 or 3 at any time during intensive care unit stay in patients free from any stage of AKI at inclusion (AKIICU). AKI prediction was assessed using area under the receiver-operating characteristics curve (AUROC) and net reclassification indices (NRIs). Main outcome measure: AKI stage 2 or 3 at 12 hours of urine collection. Results: Within 12 hours of inclusion, 32 of 105 patients (30%) had developed AKI12h. Corrected uACE2 activity was significantly higher in patients without AKI12h compared with those with AKI12h (median [interquartile range], 13 [6-24] v 7 [4-10] pmol/min/mL per mmol/L of urine creatinine; P < 0.01). A 10-unit increase in uACE2 was associated with a 28% decrease in AKI12h risk (odds ratio [95% CI], 0.72 [0.46-0.97]). During intensive care unit admission, 39 of 76 patients (51%) developed AKIICU. uACE2 had an AUROC for the prediction of AKI12h of 0.68 (95% CI, 0.57-0.79), and correctly reclassified 28% of patients (positive NRI) to AKI12h. Patients with uACE2 > 8.7 pmol/min/mL per mmol/L of urine creatinine had a significantly lower risk of AKIICU on log-rank analysis (52% v 84%; P < 0.01). Conclusions: Higher uACE2 activity was associated with a decreased risk of AKI stage 2 or 3. Our findings support future evaluations of the role of the non-classical renin-angiotensin system during AKI.

Longitudinal assessment of thyroid function in pregnancy.

BACKGROUND: Trimester-specific reference intervals (RIs) for thyroid function tests are lacking for Beckman Dxl 800 analysers. We aimed to establish RIs for thyroid stimulating hormone (TSH), free thyroxine (fT4) and to track intraindividual changes in thyroid function throughout pregnancy. METHODS: One hundred and thirty healthy women without antithyroid peroxidase antibodies were followed longitudinally. Thyroid function was determined at trimester-1 (T1): 9-13 weeks; trimester-2 (T2): 22-26 weeks; trimester-3 (T3): 35-39 weeks and postpartum (PP): 8-12 weeks. A subgroup (n = 47) was used to track intraindividual changes using PP as non-pregnant state (baseline). RESULTS: For trimesters 1-3, TSH (median (2.5th, 5th, 95th and 97.5th percentile)) was 0.77 (0.03, 0.05, 2.33, 3.05), 1.17 (0.42, 0.47, 2.71, 3.36) and 1.35 (0.34, 0.42, 2.65, 2.83) mIU/L, respectively. Free T4 (mean (95%CI)) was 10.7 (5.9-15.5), 8.1 (4.9-11.3), 7.8 (4.5-11.0) pmol/L, respectively. In T2 and T3, 36% and 41% of the fT4 values, respectively, fell below the non-pregnancy lower normal limit. In the subgroup assessed for longitudinal changes, of the women with baseline TSH ≤ median, 71-75% remained at or below the corresponding median for trimesters 1-3. Of the women with baseline fT4 ≤ median, 69-81% also remained at or below the corresponding median for trimesters 1-3. High correlation was observed at different trimesters and baseline for TSH (Spearman's r: 0.593-0.846, P < 0.001) and for fT4 (r: 0.480-0.739, P < 0.001). CONCLUSIONS: Use of trimester-specific RIs would prevent misclassification of thyroid function during pregnancy. In the majority of women, TSH and fT4 tracked on the same side of the median distribution, from a non-pregnant baseline, throughout pregnancy.