Uremic toxins and cardiovascular mortality in diabetic chronic kidney disease

Cardiovascular diseases are undeniably a major cause of morbidity and mortality in patients with chronic kidney disease (CKD), particularly when diabetes is the underlying cause. However, traditional cardiovascular risk factors alone do not fully explain the pathophysiology and increased risk in these patients. The accumulation of certain uremic toxins, particularly trimethylamine-N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), has been linked to cardiovascular events in patients with end-stage renal disease (ESRD) requiring renal replacement therapy. However, data on diabetic patients with earlier stages of CKD remain limited. SDMA and ADMA originate from protein metabolism, while TMAO is derived from metabolic byproducts of gut microbiota processing of quaternary ammonium compounds such as choline and L-carnitine. These toxins are primarily excreted via the kidneys. Could these specific toxins serve as new prognostic biomarkers in diabetic CKD patients?A random subcohort from the REGARDS (REasons for Geographic And Racial Differences in Stroke) prospective study, conducted between 2003 and 2007, included 555 diabetic patients aged over 45 years with at least moderate CKD (baseline eGFR < 60 ml/min/1.73m²). For these patients, plasma and urinary concentrations of…