SUBCLINICAL KIDNEY INJURY IS CAUSED BY A MODERATE SINGLE INFLAMMATORY EVENT.

ABSTRACT: Background: Current means of diagnosis of acute kidney injury (AKI) based on serum creatinine have poor sensitivity and may miss possible therapeutic windows in subclinical kidney injury, especially in septic AKI. Kidney injury molecule-1 (KIM-1) may be a valuable biomarker to improve diagnostic algorithms for AKI. The understanding of septic AKI is still insufficient, and knowledge about KIM-1 kinetics in inflammation is scarce. The aim of this study was to investigate the possible effect of lipopolysaccharide (LPS) on KIM-1 as a marker of structural kidney injury in healthy volunteers. Methods: A single-blinded, placebo-controlled cross-over study using the human endotoxin model (LPS administration) was performed in 10 healthy men. Kidney injury molecule-1 and serum creatinine were measured repetitively for 48 hours. Results: We observed a significant elevation of serum KIM-1 levels after the administration of LPS ( P < 0.001). Furthermore, LPS caused a significant elevation of serum creatinine at an early time point ( P = 0.013) as compared with placebo. Conclusion: Even a relatively small inflammatory stimulus is sufficient to cause subclinical structural kidney injury with elevated KIM-1 and serum creatinine in healthy volunteers. This outlines the insufficiency of the current diagnostic approach regarding AKI and the urgency to develop novel diagnostic algorithms including markers of kidney injury. Clinical Trial Registration:www.clinicaltrials.gov . Unique identifier: NCT03392701 (August 1, 2018).

High Anti-CoV2S Antibody Levels at Hospitalization Are Associated with Improved Survival in Patients with COVID-19 Vaccine Breakthrough Infection.

BACKGROUND: Although vaccination against COVID-19 is highly effective, breakthrough infections occur, often leading to severe courses and death. The extent of protection provided by individual antibody levels in breakthrough infections is still unknown and cut-off levels have yet to be determined. METHODS: In 80 consecutive fully vaccinated patients hospitalized between August and December 2021 with COVID-19 breakthrough infection (Delta variant), anti-CoV2S antibody levels were analyzed for the endpoint of death. RESULTS: Ten out of the 12 patients who died (83.3%) had antibody levels < 600 U/mL; 5 (41.7%) of these had antibody levels < 200 U/mL. Only 2 patients with a level of >600 U/mL died from vaccine breakthrough infection. Correction for the number of comorbidities and age revealed that anti-CoV2S antibody levels at the time of hospitalization were a significant predictor for reduced risk of death (OR = 0.402 for every 1000 U/mL, p = 0.018). CONCLUSIONS: In this retrospective data analysis, we show that almost all patients who died from COVID-19 vaccine breakthrough infection had antibody levels < 600 U/mL, most of them below 200 U/mL. In logistic regression corrected for the number of comorbidities and age, anti-CoV2S antibody levels at the time of hospitalization proved to be a significantly protective predictor against death.

Effect of repeated bolus and continuous glucose infusion on a panel of circulating biomarkers in healthy volunteers.

HYPOTHESIS: Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals. METHODS: An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours. RESULTS: We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion. CONCLUSIONS: Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1. CLINICAL TRIAL REGISTRATION: NCT04488848.

Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity.

A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.