Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis.In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as “preclinical-” and “subclinical AKI” have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Purpose: Studies on the immune responses to severe acute respiratory syndrome coronavirus 2 vaccines are necessary to evaluate the ongoing vaccination programs by correlating serological response data and clinical effectiveness data. We performed a longitudinal immunological profiling of health care workers vaccinated with mRNA-1273 (Moderna, Cambridge, MA, USA). Half of these vaccinees had experienced a mild coronavirus disease 2019 (COVID-19) infection in the spring of 2020 (“COVID-recovered” cohort), whereas the other half of the vaccinees had no previous COVID-19 infection (“COVID-naive” cohort). Materials and Methods: Serum was drawn at multiple time points and subjected to assays measuring anti-Spike immunoglobulin G (IgG), avidity of anti-Spike IgG, avidity of anti-receptor binding domain (RBD) IgG, virus neutralizing activity, and interferon-γ release from stimulated lymphocytes. Results: Between both cohorts and within each cohort, we found remarkable inter-individual differences regarding cellular and humoral immune responses to the Moderna mRNA-1273 vaccine. Conclusion First, our study indicates that the success of mRNA-1273 vaccinations should be verified by serological assays in order to identify “low-responders” to vaccination. Second, the kinetics of anti-S IgG and neutralizing activity correlate well with clinical effectiveness data, thus explaining incipient protection against infection 2 weeks after the first dose of mRNA-1273 in COVID-naive vaccinees. Third, our IgG-avidity data indicate that this incipient protection is mediated by low-avidity anti-RBD IgG and low-avidity anti-S IgG.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods: We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI > 48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC < 0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients according to their MAKE and AKI status (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥ 0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P = 0.014). Conclusions Plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative MAKE.

BACKGROUND: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. METHODS: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. RESULTS: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. CONCLUSIONS NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.

Background: We explored the extent to which neutrophil gelatinase-associated lipocalin (NGAL) cutoff value selection and the acute kidney injury (AKI) classification system determine clinical AKI-phenotype allocation and associated outcomes. Methods: Cutoff values from ROC curves of data from two independent prospective cardiac surgery study cohorts (Magdeburg and Berlin, Germany) were used to predict Kidney Disease: Improving Global Outcome (KDIGO)- or Risk, Injury, Failure, Loss of kidney function, End-stage (RIFLE)-defined AKI. Statistical methodologies (maximum Youden index, lowest distance to [0, 1] in ROC space, sensitivity≈specificity) and cutoff values from two NGAL meta-analyses were evaluated. Associated risks of adverse outcomes (acute dialysis initiation and in-hospital mortality) were compared. Results: NGAL cutoff concentrations calculated from ROC curves to predict AKI varied according to the statistical methodology and AKI classification system (10.6–159.1 and 16.85–149.3 ng/mL in the Magdeburg and Berlin cohorts, respectively). Proportions of attributed subclinical AKI ranged 2%–33.0% and 10.1%–33.1% in the Magdeburg and Berlin cohorts, respectively. The difference in calculated risk for adverse outcomes (fraction of odds ratios for AKI-phenotype group differences) varied considerably when changing the cutoff concentration within the RIFLE or KDIGO classification (up to 18.33- and 16.11-times risk difference, respectively) and was even greater when comparing cutoff methodologies between RIFLE and KDIGO classifications (up to 25.7-times risk difference). Conclusions NGAL positivity adds prognostic information regardless of RIFLE or KDIGO classification or cutoff selection methodology. The risk of adverse events depends on the methodology of cutoff selection and AKI classification system.

BACKGROUND: Transfemoral aortic valve replacement (TAVR) is the standard treatment for elderly patients with aortic valve stenosis. Although safe and well-established, there is a risk of intraprocedural hemodynamic instability and silent cerebral embolism, which can lead to a decline in neurocognitive function and dementia. In clinical practice, comprehensive cognitive testing is difficult to perform. AI-assisted digital applications may help to optimize diagnosis and monitoring. METHODS: Neurocognitive function was assessed by validated psychometric tests using "∆elta -App", which uses artificial intelligence and computational linguistic methods for extraction and analysis. Memory function was assessed using the 'Consortium to Establish a Registry for Alzheimer's Disease' (CERAD) word list and digit span task (DST) before TAVR and before hospital discharge. The study is registered in the German Register of Clinical Trials (https://drks.de/search/de/trial/DRKS00020813). RESULTS: From October 2020 until March 2022, 141 patients were enrolled at University Hospital Heart Centre Brandenburg. Mean age was 81 ± 6 years, 42.6% were women. Time between the pre- and post-interventional test was on average 6 ± 3 days. Memory function before TAVR was found to be below average in relation to age and educational level. The pre-post TAVR comparison showed significant improvements in the wordlist repeat, P < 0.001 and wordlist recall test of CERAD, P < 0.001. There were no changes in the digital span test. CONCLUSIONS Despite impaired preoperative memory function before TAVR, no global negative effect on memory function after TVAR was detected. The improvements shown in the word list test should be interpreted as usual learning effects in this task.