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

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.

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

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 &lt; 30 (n = 23), 30 &lt; eGFR &lt; 60 (n = 33), eGFR &gt; 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.

Efficacy and Safety of COVID-19 Vaccine in Patients on Renal Replacement Therapy.

Patients with CKD on RRT are at high risk for severe disease and mortality in COVID-19 disease. We decided to conduct an observational prospective study to evaluate antibody response after vaccination for COVID-19 in a cohort of 210 adult patients on RRT (148 on HD; 20 on PD; and 42 kidney transplant recipients). Blood samples were taken before and 4 weeks after vaccination. Antibody levels were evaluated with CLIA immunoassay testing for IgG anti-trimeric spike protein of SARS-CoV-2. A positive antibody titer was present in 89.9% of HD patients, 90% of PD patients, and 52.4% of kidney transplant recipients. Non-responders were more frequent among patients on immunosuppressive therapy. Mycophenolate use in kidney transplant patients was associated with lower antibody response. The median antibody titer was 626 (228-1480) BAU/mL; higher in younger patients and those previously exposed to the virus and lower in HD patients with neoplasms and/or on immunosuppressive therapy. Only two patients developed COVID-19 in the observation period: they both had mild disease and antibody titers lower than 1000 BAU/mL. Our data show a valid response to COVID-19 mRNA vaccination in HD and PD patients and a reduced response in kidney transplant recipients. Mycophenolate was the most relevant factor associated with low response.

GDF-15 is a Predictor of Mortality in Chronic Kidney Disease Patients With Covid-19 Infection

BACKGROUND AND AIMS A cytokine storm drives the pathogenesis of severe coronavirus disease (COVID-19) and several biomarkers with different mechanisms of action have been linked to mortality. Chronic kidney disease (CKD) emerged as a very common risk factor for severe COVID-19. Indeed, CKD patients are at increased risk of premature death from many causes, including, but not limited to, cardiovascular disease (CVD) and infections. In this study, we aimed to investigate the associations between the growth differentiation factor 15 (GDF-15), an established cardiovascular and inflammatory biomarker and outcomes in CKD patients hospitalized for COVID-19. METHOD A retrospective study on COVID-19 hospitalized subjects in the acute phase of the disease. A broad range of cytokines (CD25, IL-18, TNF-α, TNF RI, TNF RII, GDF-15, IL-7, LIF, IL-6, CHITINASE3_LIKE1, RAGE and Pentraxin-3) were assessed in plasma (Luminex, ELISA) collected upon hospitalization. A total of 77 subjects were divided into two groups according to their estimated glomerular filtration rate (eGFR, by CKD-EPI formula), ≥45 mL/min (n = 44), or ˂45 mL/min (n = 33). RESULTS We found no statistical differences between the two groups in terms of demographic features. Among comorbidities, we found a higher percentage of patients with diabetes in the eGFR < 45 group. Likewise, the serum tests upon admission showed in the eGFR < 45 group a higher value of neutrophilic count. Upon hospital admission, the patient groups were comparable in terms of symptoms, time from symptom onset to admission and death or discharge, radiological evidence of pneumonia and respiratory parameters and time of hospitalization. Furthermore, there were no statistical differences between medical therapy during hospitalization, need for respiratory support with Continuous Positive Airways Pressure or Non-Invasive Mechanical Ventilation, or death rather than discharge as the clinical outcome. Serum levels of 20 different compounds were measured in COVID-19 patients admitted to the hospital 4–5 days after the onset of symptoms. Interestingly, we found that patients with lower renal function (eGFR < 45 mL/min) had a significant increase of GDF-15, CD-25 and RAGE and, furthermore, higher serum levels of these molecules were detected in non-survivor patients and in those who needed ventilation. Also, TNFα, TNFR I, TNFR II, IL-7 and LIF had a significant increase in patients with eGFR < 45 mL/min with more elevated levels in non-survivor patients. In 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 (Figure 1). Independent association between GDF-15 quartiles and mortality risk was confirmed in Cox model adjusted for eGFR, age, fever, dyspnoea and P/F [hazard ratio (HR) 2.28, 95% confidence interval (CI) 1.53–3.39, P < 0.0001) The strength of association between GDF-15 quartiles and mortality risk was increased in patients with eGFR < 45 mL/min/1.73 m2 (HR 2.53, CI 1.34–4.79) compared with the other eGFR group (HR 1.99, CI 1.17–3.39) (Table 1). CONCLUSION Our results demonstrate that GDF-15 is an independent predictor of COVID-19 mortality in CKD patients. Given the reported increase of this cytokine with age and its possible mechanistic role in various pathological conditions, our findings suggest that GDF-15 signalling pathway inhibitors may be included as possible therapeutic candidates for COVID-19 in CKD.FIGURE 2: Overall likelihood of survival according to quartile of GDF-15. Kaplan–Meier curves for GDF-15 quartiles adjusted for eGFR, age, fever, dyspnoea and P/F. GDF-15: Growth Differentiation Factor 15, eGFR: estimated glomerular filtration rate, P/F: PaO2/FiO2 ratio.

Argument mining as rapid screening tool of COVID-19 literature quality: Preliminary evidence

Background The COVID-19 pandemic prompted the scientific community to share timely evidence, also in the form of pre-printed papers, not peer reviewed yet. Purpose To develop an artificial intelligence system for the analysis of the scientific literature by leveraging on recent developments in the field of Argument Mining. Methodology Scientific quality criteria were borrowed from two selected Cochrane systematic reviews. Four independent reviewers gave a blind evaluation on a 1–5 scale to 40 papers for each review. These scores were matched with the automatic analysis performed by an AM system named MARGOT, which detected claims and supporting evidence for the cited papers. Outcomes were evaluated with inter-rater indices (Cohen's Kappa, Krippendorff's Alpha, s* statistics). Results MARGOT performs differently on the two selected Cochrane reviews: the inter-rater indices show a fair-to-moderate agreement of the most relevant MARGOT metrics both with Cochrane and the skilled interval scores, with larger values for one of the two reviews. Discussion and conclusions The noted discrepancy could rely on a limitation of the MARGOT system that can be improved;yet, the level of agreement between human reviewers also suggests a different complexity between the two reviews in debating controversial arguments. These preliminary results encourage to expand and deepen the investigation to other topics and a larger number of highly specialized reviewers, to reduce uncertainty in the evaluation process, thus supporting the retraining of AM systems.

COVID-19 in Chronic Kidney Disease: The Impact of Old and Novel Cardiovascular Risk Factors.

Cardiovascular disease is a frequent complication and the most common cause of death in patients with CKD. Despite landmark medical advancements, mortality due to cardiovascular disease is still 20 times higher in CKD patients than in the general population, which is mainly due to the high prevalence of risk factors in this group. Indeed, in addition to traditional cardiovascular risk factors, CKD patients are exposed to nontraditional ones, which include metabolic, hormonal, and inflammatory alterations. The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought novel challenges for both cardiologists and nephrologists alike. Emerging evidence indicates that coronavirus disease 2019 (COVID-19) increases the risk of cardiovascular events and that several aspects of the disease may synergize with pre-existing cardiovascular risk factors in CKD patients. A better understanding of these mechanisms is pivotal for the prevention and treatment of cardiovascular events in this context, and we believe that additional clinical and experimental studies are needed to improve cardiovascular outcomes in CKD patients with COVID-19. In this review, we provide a summary of traditional and nontraditional cardiovascular risk factors in CKD patients, discussing their interaction with SARS-CoV-2 infection and focusing on CO-VID-19-related cardiovascular complications that may severely affect short- and long-term outcomes in this high-risk population.

COVID-19 pandemic era: is it time to promote home dialysis and peritoneal dialysis?

The novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020 by the World Health Organization. Older individuals and patients with comorbid conditions such as hypertension, heart disease, diabetes, lung disease, chronic kidney disease (CKD) and immunologic diseases are at higher risk of contracting this severe infection. In particular, patients with advanced CKD constitute a vulnerable population and a challenge in the prevention and control of the disease. Home-based renal replacement therapies offer an opportunity to manage patients remotely, thus reducing the likelihood of infection due to direct human interaction. Patients are seen less frequently, limiting the close interaction between patients and healthcare workers who may contract and spread the disease. However, while home dialysis is a reasonable choice at this time due to the advantage of isolation of patients, measures must be assured to implement the program. Despite its logistical benefits, outpatient haemodialysis also presents certain challenges during times of crises such as the coronavirus disease 2019 (COVID-19) pandemic and potentially future ones.

SARS-CoV-2-related ARDS in a maintenance hemodialysis patient: case report on tailored approach by daily hemodialysis, noninvasive ventilation, tocilizumab, anxiolytics, and point-of-care ultrasound.

Without rescue drugs approved, holistic approach by daily hemodialysis, noninvasive ventilation, anti-inflammatory medications, fluid assessment by bedside ultrasound, and anxiolytics improved outcomes of a maintenance hemodialysis patient affected by severe COVID-19.