We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is characterized by severe pneumonia and/or acute respiratory distress syndrome in about 20% of infected patients. Computed tomography (CT) is the routine imaging technique for diagnosis and monitoring of COVID-19 pneumonia. Chest CT has high sensitivity for diagnosis of COVID-19, but is not universally available, requires an infected or unstable patient to be moved to the radiology unit with potential exposure of several people, necessitates proper sanification of the CT room after use and is underutilized in children and pregnant women because of concerns over radiation exposure. The increasing frequency of confirmed COVID-19 cases is striking, and new sensitive diagnostic tools are needed to guide clinical practice. Lung ultrasound (LUS) is an emerging non-invasive bedside technique that is used to diagnose interstitial lung syndrome through evaluation and quantitation of the number of B-lines, pleural irregularities and nodules or consolidations. In patients with COVID-19 pneumonia, LUS reveals a typical pattern of diffuse interstitial lung syndrome, characterized by multiple or confluent bilateral B-lines with spared areas, thickening of the pleural line with pleural line irregularity and peripheral consolidations. LUS has been found to be a promising tool for the diagnosis of COVID-19 pneumonia, and LUS findings correlate fairly with those of chest CT scan. Compared with CT, LUS has several other advantages, such as lack of exposure to radiation, bedside repeatability during follow-up, low cost and easier application in low-resource settings. Consequently, LUS may decrease utilization of conventional diagnostic imaging resources (CT scan and chest X-ray). LUS may help in early diagnosis, therapeutic decisions and follow-up monitoring of COVID-19 pneumonia, particularly in the critical care setting and in pregnant women, children and patients in areas with high rates of community transmission.

Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

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