Gut Microbiota and Diabetic Kidney Diseases

Diabetic kidney disease (DKD) is a well-known risk factor for cardiovascular morbidity and mortality, as well as the first cause of end-stage renal disease. The need for renal replacement therapy in the form of dialysis or kidney transplant at this stage still points to DKD as a major public health challenge worldwide. The onset and progression of DKD are driven by a great number of molecular mechanisms, among them, the most characterized include: alterations of the cellular metabolism due to increased glucose uptake; renal hypoxia and ROS production with subsequent tissue inflammation and fibrosis; changes in the renal and systemic hemodynamics, and, importantly, dysbiosis of the gut microbiota. There is growing evidence for a bidirectional microbiota-kidney interaction in the setting of DKD. Indeed, alterations within the gut microbiome composition encourage the expansion of microbial pathobionts and is associated with a significant increase in uremic solutes and inflammatory mediators that gradually intensify kidney damage, creating a vicious cycle in which dysbiosis and renal dysfunction are progressively worsened. Novel strategies aimed at targeting the intestinal microbiome in the setting of DKD have been suggested. Expanding our knowledge regarding the mechanisms through which the intestinal microbiota promotes renal damage in diabetes will be crucial in the clinical management of DKD as it could result in immediate applications in the daily approach to patients with DKD.