Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulating levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-γ), were collected at diagnosis, and one and two weeks after. Compared with 14 non-infected HD patients, COVID-19 patients showed lymphopenia and higher ferritin and lactate dehydrogenase levels. Moreover, COVID-19 patients had higher levels of IL-10 (15.2 (12.5) vs. 1.2 (1.4) pg/mL, p = 0.02). Twenty-nine patients were randomized to HDx (n = 15) or PLD (n = 14). After a single treatment, IL-8 showed a significant reduction in both groups, whereas IL-10 decreased only in HDx. All over the study, there were no significant modifications in circulating cytokine levels between the two groups, except for a parallel increase of IL-8 and IL-10 at one week control in the HDx group. No correlations were found between cytokine levels and clinical outcomes. In maintenance HD patients, COVID-19 is not related to a sustained inflammatory response. Therefore, modulation of inflammation seems not to be a suitable therapeutic target in this specific population.

The only curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). PEA requires cardiopulmonary bypass (CPB) which is associated with a high acute kidney injury (AKI) risk. Circulating endothelin-1 (ET-1) levels are elevated in CTEPH, and ET-1 plays a pivotal role in AKI. Because AKI is burdened by high morbidity and mortality, we aimed to evaluate the association between preoperative ET-1 and the risk to develop AKI in CTEPH individuals who undergo PEA. We also evaluated the association of AKI and ET-1 with kidney function and mortality at 1 year after PEA.

Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. Methods: The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. Results: The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months (p < 0.001) and at 1 year (p = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses (p < 0.05). Conclusions: ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated.

Coronavirus disease 2019 (COVID-19) in hemodialysis patients (HD) is characterized by heterogeneity of clinical presentation and outcomes. To stratify patients, we collected clinical and laboratory data in two cohorts of HD patients at COVID-19 diagnosis and during the following 4 weeks. Baseline and longitudinal values were used to build a linear mixed effect model (LME) and define different clusters. The development of the LME model in the derivation cohort of 17 HD patients (66.7 ± 12.3 years, eight males) allowed the characterization of two clusters (cl1 and cl2). Patients in cl1 presented a prevalence of females, higher lymphocyte count, and lower levels of lactate dehydrogenase, C-reactive protein, and CD8 + T memory stem cells as a possible result of a milder inflammation. Then, this model was tested in an independent validation cohort of 30 HD patients (73.3 ± 16.3 years, 16 males) assigned to cl1 or cl2 (16 and 14 patients, respectively). The cluster comparison confirmed that cl1 presented a milder form of COVID-19 associated with reduced disease activity, hospitalization, mortality rate, and oxygen requirement. Clustering analysis on longitudinal data allowed patient stratification and identification of the patients at high risk of complications. This strategy could be suitable in different clinical settings.