Background Excessive activation of immune responses in coronavirus disease 2019 (COVID-19) is considered to be related to disease severity, complications and mortality. The complement system is an important component of innate immunity and can stimulate inflammation, but its role in COVID-19 is unknown. Methods A prospective, longitudinal, single center study was performed in hospitalized COVID-19 patients. Plasma concentrations of complement factors C3a, C3c, and terminal complement complex (TCC) were assessed at baseline and during hospital admission. In parallel, routine laboratory and clinical parameters were collected from medical files and analyzed. Results Complement factors C3a, C3c and TCC were significantly increased in plasma of COVID-19 patients compared to healthy controls (p<0.05). These complement factors were especially elevated in ICU patients during the entire disease course (p<0.005 for C3a and TCC). More intense complement activation was observed in patients that deceased and in patients with thromboembolic events. Conclusions COVID-19 patients demonstrate activation of the complement system, which is related to disease severity. This pathway may be involved in the dysregulated pro-inflammatory response associated with increased mortality and thromboembolic complications. Components of the complement system might have potential as prognostic markers for disease severity and as therapeutic targets in COVID-19.
Background: The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, e.g., using inulin or iohexol, is laborious and not feasible in daily practice. Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the “true GFR” measured using a gold standard method: iohexol plasma clearance. Methods: Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFR MDRD ), Endogenous Creatinine Clearance (GFR ECC ), and iohexol plasma clearance (GFR iohexol ) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay. Results: The eGFR MDRD and GFR ECC correlated with the GFR iohexol ( R 2 = 0.82, P < 0.0001 and R 2 = 0.82, P < 0.0001 respectively); however, bias and variability were considerable: the eGFR MDRD overestimated the true GFR with 31 ± 35% (95% limits of agreement: −37% to 100%) and the GFR ECC with 37 ± 49% (95% limits of agreement: −59% to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFR iohexol ( R 2 = 0.90, P < 0.0001) which tended to be better compared with the correlation of eGFR MDRD ( P = 0.06) and GFR ECC ( P = 0.08) with the GFR iohexol . Conclusions: In this pilot study in non-steady-state critically ill sepsis patients, GFR appears to be more accurately reflected by plasma PENK concentrations compared to conventional creatinine-based methods. Therefore, PENK holds promise as an accurate and feasible biomarker to determine kidney function during non-steady-state conditions in the critically ill.
Background: The assessment of kidney function and detection of acute kidney injury (AKI) remain cumbersome. On the one hand, because of limited accuracy of established tests: The most widely used methods are creatinine based, which lack in sensitivity, as creatinine is not purely filtrated by the kidney and rises relatively late after onset of AKI. On the other hand, because of labor-intensiveness: Gold standard inulin clearance and comparable methods involve intravenous compound infusion, blood sampling at several time points, and have error-sensitive determination methods. In recent years, several biomarkers have been put forward (e.g., NGAL, KIM-1, TIMP-2*IGFBP-7), but clinical implementation is limited up to now. Content: Proenkephalin (PENK) represents a new candidate to determine kidney function. This peptide is cleaved from the precursor peptide preproenkephalin A alongside enkephalins (endogenous opioids) and is filtrated in the glomerulus. PENK plasma concentration appears to accurately represent glomerular filtration rate in patients diagnosed with sepsis or cardiac diseases. Moreover, increased PENK concentration is found to be associated with longer-term outcome concerning AKI and cardiac diseases. Lastly, the predominant receptor of enkephalins, the δ-opioid receptor, is expressed with the highest density in the kidney, suggesting that enkephalins could also exert a direct effect on kidney function.
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