Hyperkalemia may cause life-threatening cardiac and neuromuscular alterations, and it is associated with high mortality rates. Its treatment includes a multifaceted approach, guided by potassium levels and clinical presentation. In general, treatment of hyperkalemia may be directed towards stabilizing cell membrane potential, promoting transcellular potassium shift and lowering total K⁺ body content. The latter can be obtained by dialysis, or by increasing potassium elimination by urine or the gastrointestinal tract. Until recently, the only therapeutic option for increasing fecal K⁺ excretion was represented by the cation-exchanging resin sodium polystyrene sulfonate. However, despite its common use, the efficacy of this drug has been poorly studied in controlled studies, and concerns about its safety have been reported. Interestingly, new drugs, namely patiromer and sodium zirconium cyclosilicate, have been developed to treat hyperkalemia by increasing gastrointestinal potassium elimination. These medications have proved their efficacy and safety in large clinical trials, involving subjects at high risk of hyperkalemia, such as patients with heart failure and chronic kidney disease. In this review, we discuss the mechanisms of action and the updated data of patiromer and sodium zirconium cyclosilicate, considering that the availability of these new treatment options offers the possibility of improving the management of both acute and chronic hyperkalemia.

A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.

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.

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.