Amyloidosis refers to the extracellular tissue deposition of fibrils composed of lowmolecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of b2 microglobulins (b2M), in the osteoarticular structures and viscera. Most of the b2M is eliminated through glomerular filtration and subsequent reabsorption and catabolism by the proximal tubules. As a consequence, the serum levels of b2M are inversely related to the glomerular filtration rate; therefore, in end-stage renal disease patients, b2M levels increase up to 60-fold. Serum levels of b2M are also elevated in several pathological conditions such as chronic inflammation, liver disease, and above all, in renal dysfunction. Retention of amyloidogenic protein has been attributed to several factors including type of dialysis membrane, prolonged uremic state and/or decreased diuresis, advanced glycation end products, elevated levels of cytokines and dialysate. Dialysis treatment per se has been considered to be an inflammatory stimulus, inducing cytokine production (such as interleukin-1, tumor necrosis factor-α, interleukin-6) and complement activation. The released cytokines are thought to stimulate the synthesis and release of b2M by the macrophages and/or augment the expression of human leukocyte antigens (class I), increasing b2M expression. Residual renal function is probably the best determinant of b2M levels. Therefore, it has to be maintained as long as possible. In this article, we will focus our attention on the etiology of dialysis-related amyloidosis, its prevention, therapy, and future solutions.

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The release of proinflammatory cytokines during inflammation represents an attempt to respond to injury, but it may produce detrimental effects. The inflammasome is a large, multiprotein complex that drives proinflammatory cytokine production in response to infection and tissue injury; the best-characterized inflammasome is the nod-like receptor protein-3 (NLRP3). Once activated, inflammasome leads to the active form of caspase-1, the enzyme required for the maturation of interleukin-1beta. Additional mechanisms bringing to renal inflammatory, systemic diseases and fibrotic processes were recently reported, via the activation of the inflammasome that consists of NLRP3, apoptosis associated speck-like protein and caspase-1. Several manuscripts seem to identify NLRP3 inflammasome as a possible therapeutic target in the treatment of progressive chronic kidney disease. Serum amyloid A (SAA), as acute-phase protein with also proinflammatory properties, has been shown to induce the secretion of cathepsin B and inflammasome components from human macrophages. SAA is a well recognised potent activator of the NLRP3. Here we will address our description on the involvement of the kidney in autoinflammatory diseases driven mainly by secondary, or reactive, AA amyloidosis with a particular attention on novel therapeutic approach which has to be addressed in suppressing underlying inflammatory disease and reducing the SAA concentration.

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On 31st December, 2019, a novel coronavirus, later named SARS-CoV-2, and whose clinical disease was to be named COVID-19, was isolated in China. First in Italy and then all over the world, viral circulation rapidly increased to a pandemic level, as defined by WHO on March 11th, 2020. In Italy, one of the most affected countries, where over 35,000 deaths have been recorded, lockdown was the only efficacious containment measure [1]. Unfortunately, hospitals soon became reservoirs of contagion [2]. In the northern Italian district of Piacenza in Emilia-Romagna, heavily hit by the shock wave of the virus, 1894 patients were hospitalized due to COVID-19 during March-April, 2020; dialysis patients were immediately identified as particularly frail. Home dialysis is the only means to allow dialysis patients to respect the lockdown, minimizing exposure to the hospital setting. In this regard, we would like to comment on our experience, from a center with a highly developed system of home dialysis. Indeed, patients on home dialysis (peritoneal dialysis [PD] and home hemodialysis [HHD]) represent 18% of our dialysis population (36/210 patients), a high figure by European standards. Our experience with home dialysis may be of particular interest, since we recorded a very high incidence of COVID-19 in patients on in-center hemodialysis (49/210 patients, 23%) [2], much higher than the overall incidence in Italy (about 3%), as recently reported by a survey of the Italian Society of Nephrology (available at: https ://sinit aly.org/ wp-conte nt/uploa ds/2020/05/2-Surve y-Covid-19-SIN-1. pdf, accessed on July 13th, 2020) involving 30,129 hemodialysis patients: among them, 1027 patients (3.41%) resulted affected by COVID-19.