Cytokine and Chemokine Retention Profile in COVID-19 Patients with Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR < 30 (n = 23), 30 < eGFR < 60 (n = 33), eGFR > 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.

Targeting IL-6 trans-signalling by sgp130Fc attenuates severity in SARS-CoV-2 -infected mice and reduces endotheliopathy

“… 11 However, in surviving mice (15 dpi), sgp130Fc treatment significantly decreased serum IL-6 and sIL-6R levels along with lung mRNA expression of Tnf α, Il1ß, Ifnγ and other cytokines belonging to IL-6 family related with severity of COVID-19 such as Osm, Lif and Il11 . 40 , 41 , 67 Regarding sIL-6R, our group and others have reported significant increased serum levels in survivor patients with severe COVID-19, 11 , 68 likely due to the release from activated T cells. 69 In this context, sgp130Fc treatment showed a clear anti-inflammatory effect with potential impact in long term consequences of the disease.…”

“…As expected, higher levels of pro-inflammatory genes were detected in non-survivors (<15 dpi). Notably, when we focused on infected surviving mice (15 dpi), those that received sgp130Fc showed significant decreased mRNA expression of pro-inflammatory cytokines ( Tnfα , Il1ß and Ifnγ ), as well as IL-6 family of cytokines and receptors related with severe COVID-19: Il6r , Il6st , Osm , Osmr , Lif , Lifr , 40 , 41 ( Fig. 3 b).…”

Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells

“…All farnesol target genes identified in our study were linked to CKD development and progression, which have been associated with chronic inflammation, oxidative stress, and ischemia [40]. TNFRSF9 and FAS receptor were identified as biomarkers of impaired kidney function and CKD in epidemiological studies [41,42]. Similarly, serum CD27 levels were strongly associated with kidney dysfunction and a low glomerular filtration rate in type 1 diabetes [43].…”

IL-6 and IL-17 as potential links between pre-existing hypertension and long-COVID sequelae in patients undergoing hemodialysis: A multicenter cross-sectional study

“…In contrast to the general population of COVID-infected patients, the baseline chronic in ammation in patients undergoing HD prevents a sustained increase in cytokines 23,26 . This discrepancy suggests that the accumulation of cytokines and chemokines during COVID-19 is primarily attributed to impaired renal clearance in HD patients 27 . Our ndings support the impact of these unique characteristics on long-term immune-related COVID-19 outcomes in HD patients, shown by signi cant differences in IL-6 and IL-17 concentrations between convalescent HD patients and non-CKD controls.…”