Mechanisms of diabetic kidney disease and established and emerging treatments

Abstract

Kidney disease is the leading cause of mortality in persons with diabetes mellitus. Diabetic kidney disease (DKD) typically presents with a reduced estimated glomerular filtration rate and, in many but not all cases, with marked proteinuria. Strict glycaemic control and blood pressure control remain foundational in managing DKD, and advances in the understanding of disease mechanisms have redefined the therapeutic landscape. Large outcome trials, such as EMPA-KIDNEY, DAPA-CKD and CREDENCE, have demonstrated that sodium–glucose cotransporter 2 inhibitors slow chronic kidney disease progression and improve cardiovascular outcomes. Glucagon-like peptide 1 receptor agonists reduce albuminuria and preserve estimated glomerular filtration rate, as shown most recently in the FLOW trial. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, lowered renal and cardiovascular risk in the FIDELIO-DKD and FIGARO-DKD trials. Combination approaches (for example, sodium–glucose cotransporter 2 inhibition plus endothelin receptor type A blockade in ZENITH-CKD), aldosterone synthase inhibition, and targeted anti-inflammatory or complement-modifying agents offer additional promise. We summarize the key pathophysiological drivers (glomerular hyperfiltration, podocyte injury, tubulointerstitial inflammation and fibrosis), review established treatments and highlight emerging strategies to prevent or halt DKD.