Fabry Nephropathy: An Evidence-Based Narrative Review.

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.

Ischemic preconditioning in solid organ transplantation: from experimental to clinics.

This study reviews the current understanding of ischemic preconditioning (IP) in experimental and clinical setting, and the mechanisms that mediate the complex processes involved as a tool to protect against ischemia and reperfusion (I/R) injury, but is not intended as a complete literature review of preconditioning. IP has been mainly elucidated in cardiac ischemia. Recent reports confirm the efficacy of pre- and postconditioning in cardiac surgery and percutaneous coronary interventions in humans. IP utilizes endogenous as well as distant mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. Specifically, preconditioned tissues exhibit altered energy metabolism, better electrolyte homeostasis and genetic reorganization, as well as less oxygen-free radicals and activated neutrophils release, reduced apoptosis and better microcirculatory perfusion. To date, there are few human studies, but recent trials suggest that human liver, lung and skeletal muscle acquire protection after IP. Present data address the potential therapeutic application of IP in the prevention of I/R damage specially aimed at clinical transplantation. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena.