Drug stewardship for RAS inhibitors and SGLT2 inhibitors in chronic kidney disease: stay on, restart

Renin-angiotensin system (RASi) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are the cornerstones of management for patients with chronic kidney disease (CKD). The use of these treatments is limited by frequent discontinuations, increasing the risk of death and compromising cardiovascular and renal health. This narrative review explores scenarios that lead to discontinuation: adverse effects (i.e. RASi-related acute kidney injury and hyperkalaemia); progression of CKD; acute illness; surgery and contrast administration. After AKI, we recommend restarting RASi and SGLT2i as soon as the kidney function stabilises. For patients with mild-to-moderate hyperkalaemia on RASi, we advocate for thiazide-like diuretics and SGLT2i to avoid RASi discontinuation, rather than routine dietary restrictions, or potassium binders. We recommend against discontinuing RASi or SGLT2i when glomerular filtration rates decrease gradually. We review the evidence for sick day rules and find it unconvincing. Withholding RASi before surgery has not been shown to reduce AKI. For low-risk procedures, the decision may be deferred to the anaesthetist. However, in settings where anaesthetists assess patients only shortly before surgery, or in high-risk cases, earlier multidisciplinary input is advised. We recommend stopping SGLT2i two to three days before elective procedures that involve fasting or anaesthesia. For the use of intra-arterial contrast, such as with coronary angiography, we do not recommend routinely withholding SGLT2i but we do suggest considering to temporarily withhold RASi, especially in patients with advanced CKD or dehydration. We suggest promptly restarting RASi and SGLT2i after events; if both drugs have been withheld for more than a few days, and both are indicated, we suggest a staggered start. By reconciling, reviewing, and thoughtfully prescribing medications, drug stewardship can maximize the time spent on these life-prolonging therapies, as long as this aligns with patients' goals of care.