Carlo Alfieri

Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome—coronavirus-2 (SARS-CoV-2)—is an ongoing pandemic with high morbidity and mortality rates. Preliminary evidence suggests that acute kidney injury (AKI) is uncommon in patients with COVID-19 and associated with poor outcomes. Study aims and design: we performed a systematic review of the literature with a meta-analysis of clinical studies to evaluate the frequency of AKI and dialysis requirement in patients who underwent hospitalization due to COVID-19. The incidence of AKI according to the death risk was calculated in these patients. The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. Results: thirty-nine clinical studies (n = 25,566 unique patients) were retrieved. The pooled incidence of AKI was 0.154 (95% CI, 0.107; 0.201; p < 0.0001) across the studies. Significant heterogeneity was found (p = 0.0001). The overall frequency of COVID-19-positive patients who underwent renal replacement therapy (RRT) was 0.043 (95% CI, 0.031; 0.055; p < 0.0001); no publication bias was found (Egger’s test, p = 0.11). The pooled estimate of AKI incidence in patients with severe COVID-19 was 0.53 (95% CI, 0.427; 0.633) and heterogeneity occurred (Q = 621.08, I2 = 97.26, p = 0.0001). According to our meta-regression, age (p < 0.007) and arterial hypertension (p < 0.001) were associated with AKI occurrence in hospitalized COVID-19 positive patients. The odds ratio (OR) for the incidence of AKI in deceased COVID-19 positive patients was greater than among survivors, 15.4 (95% CI, 20.99; 11.4; p < 0.001). Conclusions: AKI is a common complication in hospitalized COVID-19 positive patients. Additional studies are under way to assess the risk of AKI in COVID-19 patients and to deepen the mechanisms of kidney injury.

Secondary hyperparathyroidism (SHP) is a frequent complication of kidney diseases. At variance with all the other forms of SHP, which are compensatory conditions, renal SHP has many pathogenetic peculiarities, which have been only in part defined. Furthermore, in the long course of chronic kidney diseases (CKD), SHP sometimes transforms into a hypercalcemic condition resembling the autonomous form of hyperparathyroidism (tertiary hyperparathyroidism; THP). The clinical consequences of SHP in CKD patients are manifold, encompassing not only bone and mineral disorders, but also other metabolic and organic changes which frequently burden these patients. Although the medical therapeutic tools have substantially increased in number and improved in their efficacy in recent decades, we have as yet no demonstration of a clear benefit regarding the major clinical outcomes. Furthermore, some of these patients, particularly when the autonomous THP develops, still require a surgical approach.

Abstract Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation.

The widely differing functions of vitamin D are based both on a wide diffusion of its specific receptor (VDR) and on the ability of many cells, in addition to renal tubular cells, to synthesize calcitriol for autocrine and paracrine functions. In the last few years, many published studies have added new insights into some important points on this topic. Recent data suggest that the control of calcitriol synthesis at tissue levels other than kidneys might differ greatly from the control system working at the renal level. Furthermore, the mechanisms by which the VDR might mediate either the genomic and nongenomic (rapid) vitamin D-mediated effects became much clearer. However, new evidence accumulated suggests that some additional receptor(s), responsive to vitamin D and different from the VDR, could play a role in the rapid response to vitamin D, probably interfering also with the genomic pathway. In this context, there are new possible interpretations of the mechanisms by which different vitamin D metabolites might express variable activities at different levels. In addition, some recent data have challenged the role of the VDR in direct parathyroid hormone (PTH) control, at least in physiological conditions, suggesting that vitamin D-mediated PTH inhibition is mainly secondary to the intestinal effect on calcium absorption. Finally, there is a renewed interest in the field of polymorphic variants in the VDR gene in relation to some clinical conditions, though the mechanisms underlining these associations are far from being clear. The present review briefly addresses all of the above points.