Combination therapy as a new standard of care in diabetic and non-diabetic chronic kidney disease.

Combination therapy, involving the use of multiple medications together, is becoming a new standard of care for chronic kidney disease (CKD). For people with CKD, combination therapy offers the promise of preventing kidney failure and reducing the risk of heart problems. This approach is appealing because different drugs target distinct mechanisms involved in CKD progression. For instance, some target immune responses, others reduce kidney inflammation and scarring, while others improve blood pressure within the kidneys. Data from large clinical trials suggest that each treatment works effectively on its own, regardless of other medications people are taking. Combining therapies can also reduce the risk of side effects of individual medications. This review highlights the evidence for combination therapy in CKD, explores how to improve its use, and discusses how future studies may answer remaining questions.
Abstract: A range of therapies now exists to reduce the risk of kidney failure and cardiovascular events in people with type 2 diabetes, including renin-angiotensin system blockade, sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists. With multiple clinical trials underway, it is likely that at least some of these therapies-as well as additional agents such as endothelin receptor antagonists-will further demonstrate kidney-protective effects in people with CKD who do not have diabetes in the near future. For conditions such as IgA nephropathy, several therapies have recently been approved or are being evaluated in late phase trials. Thus combination therapy is emerging as a new standard for diabetic and non-diabetic chronic kidney disease (CKD). This approach is supported by randomized data suggesting that each therapeutic class offers independent and additive benefits in diabetic kidney disease, regardless of background therapy. Notably, the reduction in hyperkalaemia and fluid retention with SGLT2 inhibitors may enhance the tolerability and safety of other treatments. In this review, we present the rationale for combination therapy with evidence-based kidney therapies in diabetic and non-diabetic CKD. We also summarize randomized evidence supporting a multi-medicine approach, address safety considerations, review ongoing trials, and propose frameworks for implementing treatments aligned with patient risk to optimize person-centred care and reduce long-term risks of kidney failure and related complications.
(© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)