A Framework for Risk-Based Implementation of Combination Therapy in CKD

Therapeutic options for CKD have expanded substantially in recent years, creating new opportunities to reduce residual kidney and cardiovascular risk through combination therapy. Evidence from large randomized trials and meta-analyses demonstrates that sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide 1 receptor agonists provide independent and additive benefits, with emerging data showing that select combinations may also improve safety. A risk-based approach, anchored in albuminuria and supported by validated risk equations, can guide treatment intensity, support more timely initiation of multidrug regimens, and improve health system efficiency. Addressing implementation barriers, advancing single-pill combinations, and leveraging adaptive and combination therapy trials will be essential to translate these therapeutic advances into improved long-term outcomes for people with CKD.