SCARF Genes in COVID-19 and Kidney Disease: A Path to Comorbidity-Specific Therapies.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has killed ~7 million persons worldwide. Chronic kidney disease (CKD) is the most common risk factor for severe COVID-19 and one that most increases the risk of COVID-19-related death. Moreover, CKD increases the risk of acute kidney injury (AKI), and COVID-19 patients with AKI are at an increased risk of death. However, the molecular basis underlying this risk has not been well characterized. CKD patients are at increased risk of death from multiple infections, to which immune deficiency in non-specific host defenses may contribute. However, COVID-19-associated AKI has specific molecular features and CKD modulates the local (kidney) and systemic (lung, aorta) expression of host genes encoding coronavirus-associated receptors and factors (SCARFs), which SARS-CoV-2 hijacks to enter cells and replicate. We review the interaction between kidney disease and COVID-19, including the over 200 host genes that may influence the severity of COVID-19, and provide evidence suggesting that kidney disease may modulate the expression of SCARF genes and other key host genes involved in an effective adaptive defense against coronaviruses. Given the poor response of certain CKD populations (e.g., kidney transplant recipients) to SARS-CoV-2 vaccines and their suboptimal outcomes when infected, we propose a research agenda focusing on CKD to develop the concept of comorbidity-specific targeted therapeutic approaches to SARS-CoV-2 infection or to future coronavirus infections.

Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes.

Background: Matrix metalloproteinase-10 (MMP-10) levels increase progressively starting from early diabetic kidney disease (DKD) stages. Vitamin D3 (vitD3) deficit is associated with a higher risk of diabetic microangiopathy. Reduced MMP-10 expression has been observed after exposure to vitD3. Aim: to assess how vitD3 status is related to MMP-10 levels in patients with Type 2 diabetes (T2D). Methods: 256 patients with T2D were included in this cross-sectional study. Demographic, clinical and serum MMP-10 and 25-hydroxyvitamin D3 (25(OH)D3) levels were collected from each patient. The association between MMP-10 and (25(OH)D3) levels was assessed using a correlation analysis and fitting a multivariate linear regression model. Results: Serum MMP-10 levels were inversely correlated with circulating 25(OH)D3 (rho = −0.25; p < 0.001). In the subgroup analysis this correlation was significant in patients with DKD (rho = −0.28; p = 0.001) and in subjects with vitD3 deficit (rho = −0.24; p = 0.005). In the regression model adjusted for kidney function, body adiposity, smoking and vitD supplementation MMP-10 levels were 68.7 pg/mL lower in patients with 25(OH)D3 > 20 ng/mL, with respect to ≤20 ng/mL (p = 0.006). Conclusions: vitD3 repletion status is an independent predictor of MMP-10 levels in T2D patients. Perhaps, high 25(OH)D3 values should be targeted in these patients in order to prevent vascular complications.

Coffee Consumption and the Risk of Depression in a Middle-Aged Cohort: The SUN Project.

Coffee is one of the most widely consumed drinks around the world, while depression is considered the major contributor to the overall global burden of disease. However, the investigation on coffee consumption and depression is limited and results may be confounded by the overall dietary pattern. We assessed the relationship between coffee intake and the risk of depression, controlling for adherence to the Mediterranean diet. We studied 14,413 university graduates of the 'Seguimiento Universidad de Navarra' (SUN) cohort, initially free of depression. We evaluated coffee consumption using a validated food-frequency questionnaire (FFQ). Incident depression cases were adjudicated only if the participant met two criteria simultaneously: (a) validated physician-diagnosed depression together with (b) new onset of habitual antidepressant use. Both criteria were needed; participants meeting only one of them were not classified as cases. Participants who drank at least four cups of coffee per day showed a significantly lower risk of depression than participants who drank less than one cup of coffee per day (HR: 0.37 (95% CI 0.15⁻0.95)). However, overall, we did not observe an inverse linear dose⁻response association between coffee consumption and the incidence of depression (p for trend = 0.22).