The basement membrane in the cross-roads between the lung and kidney.

The basement membrane (BM) is a specialized layer of extracellular matrix components that plays a central role in maintaining lung and kidney functions. Although the composition of the BM is usually tissue specific, the lung and the kidney preferentially use similar BM components. Unsurprisingly, diseases with BM defects often have severe pulmonary or renal manifestations, sometimes both. Excessive remodeling of the BM, which is a hallmark of both inflammatory and fibrosing diseases in the lung and the kidney, can lead to the release of BM-derived matrikines, proteolytic fragments with distinct biological functions. These matrikines can then influence disease activity at the site of liberation. However, they are also released to the circulation, where they can directly affect the vascular endothelium or target other organs, leading to extrapulmonary or extrarenal manifestations. In this review, we will summarize the current knowledge of the composition and function of the BM and its matrikines in health and disease, both in the lung and in the kidney. By comparison, we will highlight, why the BM and its matrikines may be central in establishing a renal-pulmonary interaction axis.

Plasma endostatin correlates with hypoxia and mortality in COVID-19-associated acute respiratory failure.

Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease. Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection. Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival. Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml. Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.