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

Renin-angiotensin system inhibitors (RASis) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) 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 RASis and SGLT2is as soon as kidney function stabilises. For patients with mild-to-moderate hyperkalaemia on RASis, we advocate for thiazide-like diuretics and SGLT2is to avoid RASi discontinuation rather than routine dietary restrictions or potassium binders. We recommend against discontinuing RASis or SGLT2is when glomerular filtration rates decrease gradually. We review the evidence for sick-day rules and find it unconvincing. Withholding RASis 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 SGLT2is 2-3 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 SGLT2is but we do suggest considering temporarily withholding RASis, especially in patients with advanced CKD or dehydration. We suggest promptly restarting RASis and SGLT2is 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.