Longitudinal Analysis of Urinary Cytokines and Biomarkers in COVID-19 Patients with Subclinical Acute Kidney Injury.

In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1ß were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm.

Clinical utility of tubular markers in kidney disease: a narrative review

Background and Objective: Various tubular markers have been established for the diagnosis of kidney diseases and evaluation of treatment efficacy. Currently, there are limited treatments available for advanced kidney disease. Therefore, early identification of patients at high risk of progression to end-stage renal disease (ESRD) is necessary for the provision of appropriate treatment at an early phase. The present review focuses on newly established urinary tubular markers, i.e., urinary [tissue inhibitor of metalloproteinases-2 (TIMP-2)]*[insulin-like growth factor binding protein-7 (IGFBP7)] and L-type fatty acid binding protein (L-FABP). Methods: A literature search of the electronic databases MEDLINE (January 2014 to February 2022) was conducted using search terms of “urinary [TIMP-2]*[IGFBP7]”, “urinary L-FABP”, “kidney disease”, and “COVID-19”. Original articles, which were written in English and show clinical usefulness of urinary [TIMP-2]*[IGFBP7] or urinary L-FABP, were mainly reviewed. Key Content and Findings: These proteins are expressed in human tubules and are reported to have renoprotective functions against kidney disease. In 2014, the U.S. Food and Drug Administration approved the clinical application of NephroCheck, measuring urinary [TIMP-2]*[IGFBP7], for the diagnosis of acute kidney injury (AKI). Notably, the usefulness of urinary L-FABP in AKI, chronic kidney disease (CKD), diabetic kidney disease, aging, and coronavirus disease 2019 (COVID-19) has been widely reported. Furthermore, various methods have been established for the easy, rapid, and highly sensitive measurements of c in various situations. In 2011, urinary L-FABP was approved by the Ministry of Health, Labor and Welfare in Japan. Conclusions: Early utilization of an accurate marker may improve the prognosis of kidney disease and patient survival. © Journal of Laboratory and Precision Medicine. All rights reserved.

Association of Salivary IGF and IGF/IGFBP-3 Molar Ratio with Cervical Vertebral Maturation Stages from Pre-Adolescent to Post-Adolescent Transition Period—A Cross-Sectional Exploratory Study

Background: The relevance of growth determination in orthodontics is driving the search for the most precise and least invasive way of tracking the pubertal growth spurt. Objectives: The aim was to explore whether minimally invasive salivary estimation of biomarkers Insulin-like growth factor (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) could be used to estimate skeletal maturity with diagnostic accuracy, especially in children and adolescent age groups. Subjects and methods: The cross-sectional study was conducted on 105 participants aged 6–25 years from the out-patient Department of Preventive Dental Science at Majmaah University between the period 2 January 2021 and 12 July 2021. Each subject’s lateral cephalogram radiograph was categorized based on skeletal maturity, and saliva samples were estimated for IGF-1 and IGFBP-3 using the respective ELISA kits. Two-way ANOVA with interaction was applied to examine the main effects due to cervical vertebral maturation staging (CVS), Sex and interaction effect due to CVS, and Sex on study parameters. Karl Pearson’s Product Moment Correlation Coefficient was calculated for finding a significant association between IGF, IGFBP3, and the IGF-1/IGFBP3 molar ratio. Results: Highest mean salivary IGF-1 was observed in the pubertal peak stage, which coincides with cervical vertebral maturity stages 3 and 4 (CVS3 and CVS4) for both males (2.57 ng/mL) and females (1.57 ng/mL) and the lowest mean level of IGF-1 for females (0.85 ng/mL) and males (1.22 ng/mL) was observed during the prepubertal stage. There exists a significant variation in IGF-1 between males and females in the pubertal stage (p < 0.01), but the difference is very narrow in the prepubertal and post-pubertal groups (p > 0.05). There was no significant interaction effect of different skeletal stages and gender on the IGFBP3 and the IGF-1/IGFBP3 molar ratio (p > 0.05), but there exists a significant interaction effect on IGF-1 (p < 0.05). Conclusion: Estimation of the IGF-1 and the IGF-1/IGFBP3 molar ratio in saliva, being a non-invasive biological marker, could serve as an adjunctive tool along with radiographic assessment in estimating growth maturity in the adolescence age group. By initiating orthodontic treatment during the mandibular growth peak in adolescence, a positive outcome is ensured in managing skeletal deformities within the craniofacial complex.

Correlation between Salivary Levels of IGF-1, IGFBP-3, IGF-1/IGFBP3 Ratio with Skeletal Maturity Using Hand-Wrist Radiographs.

OBJECTIVE: The relevance of growth determination in orthodontics is driving the search for the most precise and least invasive way of tracking the pubertal growth spurt. Our aim was to explore whether minimally invasive salivary estimation of biomarkers Insulin-like growth factor (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) could be used to estimate skeletal maturity for clinical convenience, especially in children and adolescent age groups. MATERIALS AND METHOD: The cross-sectional study was conducted on 90 participants (56 girls and 34 males) with ages ranging from 6 to 25 years. Each subject's hand-wrist radiograph was categorized based on skeletal maturity, and saliva samples were estimated for IGF-1 and IGFBP-3 using the respective ELISA kits. Kruskal-Wallis nonparametric ANOVA was applied to compare different skeletal stages. RESULTS: The study demonstrated low salivary IGF-1 levels at the prepubertal stage, with increase during pubertal onset and peak pubertal stage followed by a decline during pubertal deceleration to growth completion. Spearman's correlation coefficient demonstrated a strong positive association (r = 0.98 p < 0.01) between salivary IGF/IGFBP-3 ratio and different stages of skeletal maturity. CONCLUSION: Salivary IGF-1, IGFBP-3, and IGF/IGFBP-3 ratio could serve as a potential biochemical marker for predicting the completion of skeletal maturity.

Role of Urinary Kidney Stress Biomarkers for Early Recognition of Subclinical Acute Kidney Injury in Critically Ill COVID-19 Patients.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions.

INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.