Growth Differentiation Factor 15 (GDF-15) Levels Associate with Lower Survival in Chronic Kidney Disease Patients with COVID-19

Abstract

A cytokine storm drives the pathogenesis of severe COVID-19 infection and several biomarkers have been linked to mortality. Chronic kidney disease (CKD) emerged as a risk factor for severe COVID-19. We investigated the association between selected biomarkers and mortality in 77 patients hospitalized for COVID-19, and whether they differ in patients with eGFR higher and lower than 45 mL/min. The association between patients’ characteristics, plasma biomarkers and mortality was conducted by univariate logistic regression models and independent predictors of mortality were then used to create a multivariate prediction model through Cox regression. Patients with lower eGFR had a significant increase of GDF-15, CD-25 and RAGE, with higher plasma levels in non-survivors and in patients who needed ventilation. At univariate analysis, low and mid-low GDF-15 quartiles (<4.45 ng/mL) were associated with lower mortality risk, while mid-high and high quartiles (>4.45 ng/mL) were associated with higher mortality risk. Independent association between GDF-15 quartiles and mortality risk was confirmed in the Cox model and adjusted for eGFR, age, fever and dyspnea (HR 2.28, CI 1.53–3.39, p < 0.0001). The strength of the association between GDF-15 quartiles and mortality risk increased in patients with lower compared to higher eGFR (HR 2.53, CI 1.34–4.79 versus HR 1.99, CI 1.17–3.39). Our findings may suggest a further investigation of the effect of GDF-15 signaling pathway inhibition in CKD.

GDF-15 Levels and Other Laboratory Findings as Predictors of COVID-19 Severity and Mortality: A Pilot Study

“…To our knowledge, the reports on GDF-15 expression during COVID-19 are limited and somewhat contradictory. Some studies have been conducted on specific patient groups, such as patients on hemodialysis or those with chronic kidney disease, where underlying diseases could affect the GDF-15 levels [14,43]. Most of the previously performed studies support evidence of higher GDF-15 levels in COVID-19 patients requiring hospitalization and those with a more severe form of the disease [15][16][17][18][19][20][21][22], while others have provided data supporting lower levels of GDF-15 in hospitalized COVID-19 patients or no significant difference between hospitalized and discharged patients, nor between SARS-CoV-2-positive and -negative patients [18,23,24].…”

The prognostic value of estimated glomerular filtration rate on admission for death within 30 days among COVID-19 inpatients using fractional polynomial and spline smoothing

“…The percentage of eGFR < 60 ml/min/1.73 m 2 in our studies (33%) was similar to aforementioned previous studies [ 20 , 28 , 29 ]. It has been shown that Growth Differentiation Factor 15 (GDF-15) activity is only significant predictive cytokine for poor outcomes in COVID-19 patients, and the effect of GDF-15 tends to be stronger in the presence of eGFR < 45 ml/min/1.73 m 2 [ 30 ]. The results from a machine learning model indicate eGFR < 60 ml/min/1.73 m 2 , along with neutrophil and lymphocyte percentages were the leading predictors of mortality among COVID-19 patients [ 31 ].…”

Implication of serum growth differentiation factor-15 level in patients with renal diseases

“…Other systemic/infectious condition might affect GDF-15 levels. For example, circulating GDF-15 level is elevated in patients with chronic kidney disease suffering from COVID-19 probably due to systemic inflammation and multi-organ injury, and the elevated GDF-15 level is associated with mortality in this cohort [ 17 ]. We did not include any patients with COVID-19.…”