Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?

Albert Christian,Haase Michael,Albert Annemarie,Zapf Antonia,Braun-Dullaeus Rüdiger Christian,Haase-Fielitz Anja 대한진단검사의학회 2021 Annals of Laboratory Medicine Vol.41 No.1

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.

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study

Christian Albert,Michael Haase,Annemarie Albert,Siegfried Kropf,Rinaldo Bellomo,Sabine Westphal,Mark Westerman,Rüdiger Christian Braun-Dullaeus,Anja Haase-Fielitz 대한진단검사의학회 2020 Annals of Laboratory Medicine Vol.40 No.2

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 com

Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study

Albert Christian,Haase Michael,Albert Annemarie,Ernst Martin,Kropf Siegfried,Bellomo Rinaldo,Westphal Sabine,Braun-Dullaeus Rüdiger C.,Haase-Fielitz Anja,Elitok Saban 대한진단검사의학회 2021 Annals of Laboratory Medicine Vol.41 No.4

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.

Neutrophil Gelatinase-Associated Lipocalin Cutoff Value Selection and Acute Kidney Injury Classification System Determine Phenotype Allocation and Associated Outcomes

Albert Annemarie,Radtke Sebastian,Blume Louisa,Bellomo Rinaldo,Haase Michael,Stieger Philipp,Hinkel Ulrich Paul,Braun-Dullaeus Rüdiger C.,Albert Christian 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.6

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.

Housing Finance and Inclusive Growth in Africa: Benchmarking, Determinants and Effects

Nguena Christian-Lambert,Tchana Tchana Fulbert,Zeufack Albert G. 한국국제경제학회 2021 International Economic Journal Vol.35 No.2

Using a panel database of 48 Sub-Saharan African countries from 2000 to 2012 that we partially constructed, this paper analyses the structure of housing finance in Africa, its determinants, and its impact on inclusive growth. We find that market capitalization and urbanization are key positive determinants of housing finance, while a post-conflict environment is conducive to greater housing finance development. This result suggests that housing finance is driven by standard market forces of demand and supply. Besides, we find that housing finance development in Africa is not yet an effective tool for reducing economic inequality, at its current, very earlier stage. However, we show that above a given threshold, housing finance could be efficient at reducing inequality. Finally, there is a slightly positive relationship between housing finance and greater economic development in Africa. All these findings suggest that policies to boost housing finance development in Africa would be fruitful in the medium to long terms.

Effects of an Oil-Free Hydroethanolic Pumpkin Seed Extract on Symptom Frequency and Severity in Men with Benign Prostatic Hyperplasia: A Pilot Study in Humans

Martin Leibbrand,Simone Siefer,Christiane Scho¨ n,Tania Perrinjaquet-Moccetti,Albert Kompek,Anca Csernich,Franz Bucar,Matthias Heinrich Kreuter 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.6

Majority of men are affected by symptomatic benign prostatic hyperplasia (BPH) from a certain age. Botanical extracts are frequently used in the early management of the symptoms. In a single-arm, mono-center pilot study, the effects of a proprietary oil-free hydroethanolic pumpkin seed extract on the symptoms of BPH were investigated. A total of 60 men (62.3 years [95% confidence interval (CI): 60.3–64.3 years]) with a total International Prostate Symptom Score (IPSS) of 14.8 (95% CI: 13.5–16.1) participated between January 2017 and October 2017 in the study by ingesting the oil-free hydroethanolic pumpkin seed extract once daily before going to bed during 3 months. Change in IPSS within treatment period was assessed. Frequency of nocturia was recorded by bladder diary, and postvoid residual urine volume was determined through ultrasound. Between baseline and after 12 weeks of supplementation, a significant symptom reduction of an average 30.1% (95% CI: 23.1–37.1) was seen for the total IPSS. Symptom alleviation had a high impact on quality of life (P < .0001) and was significant after 8 and 12 weeks of intervention (P < .001). Nocturia significantly decreased over time (P < .0001), as confirmed by IPSS questionnaire and bladder diary. Postvoid residual urine volume was significantly reduced at the end of intervention (baseline: 83.67 mL [95% CI: 58.02–109.3]; after 12 weeks: 63.11 mL [95% CI: 45.37–80.85]; P = .0394). These results indicate that the oil-free hydroethanolic pumpkin seed extract seems to be a very well tolerable, appropriate plant extract to support health benefits in a collective suffering from BPH related symptoms without the need of medical treatment.