Epidemiology and pathogenesis of diabetic kidney disease

Diabetic nephropathy (diabetic kidney disease, DKD) describes the renal microangiopathic complications of diabetes mellitus (DM) and is one of the main causes of increased morbidity and mortality among patients with DM. The current definition comprises both classic nodular and diffuse glomerulosclerosis and also tubular interstitial and vascular lesions and includes non-albuminuric courses, whose prevalence is increasing. Due to increasing DM incidence, total DKD frequency is also rising. However, the ratio of DKD to the total cohort of patients with DM seems to be constant, at least in the Western world, probably due to earlier detection and subsequent implementation of inhibitors of disease progression. However, DKD and hypertensive nephropathy are still the main etiologies for chronic kidney disease and end-stage renal disease in the general population. Hyperglycemia may cause renal damage via different pathways. Reactive oxygen species (ROS) play a central role by inducing DNA damage. Simultaneously, in hyperglycemia accumulation of glycolytic intermediates represents a frequent phenomenon. These intermediates are subsequently metabolized and contribute both directly and indirectly to DKD onset. Metabolic, hemodynamic, and genetic risk factors constitute additional drivers of disease progression. DKD remains a main contributor to morbidity and mortality among patients with DM. Hyperglycemia-induced ROS and toxic glycolytic intermediates together with further risk factors play a central pathogenic role. These components constitute interesting novel therapeutic targets to prevent development and progression of DKD.