Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors for the Treatment of Hyperkalaemia in Children with Chronic Kidney Disease and Heart Failure receiving Renin-Angiotensin-Aldosterone System Inhibitors: A Systematic Review

Background: The primary objective of this systematic review was to determine whether sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy reduces the risk of hyperkalemia in children with chronic kidney disease (CKD) and heart failure receiving renin-angiotensin-aldosterone system (RAAS) inhibitors. Methods: Electronic databases, including EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and PubMed, were searched to identify studies involving children with CKD and/or heart failure, who were receiving RAAS inhibitors and treated with an SGLT2 inhibitor. Relevant English-language studies and those conducted in children were considered. Results: A total of 146 studies were identified, of which only 4 studies met the inclusion criteria, encompassing 632 patients, 50 with CKD and 48 with heart failure. Statistically significant improvements were reported in HbA1c levels, 24-hour protein excretion, and cardiovascular outcomes in patients with type 2 diabetes, CKD, and heart failure, respectively. However, none of the included studies reported basic metabolic panel results evaluating the effect of dual SGLT2 and RAAS inhibition on the incidence of hyperkalemia. Conclusions: SGLT2 inhibitors represent a significant advancement in the management of CKD, heart failure, and type 2 diabetes in adults, with expanding implications for pediatric clinical practice. The cardio-renal protective effects of SGLT2 inhibitors in both diabetic and non-diabetic adult patients underscore their potential as adjunctive therapy, alongside RAAS inhibitors, in pediatric patients with CKD and heart failure. Pediatric-specific pharmacologic data is still being refined. Keywords Chronic kidney disease, Heart failure, Hyperkalemia, Renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibitors Abbreviations CKD: Chronic Kidney Disease; ECG: Electrocardiogram; eGFR: Estimated Glomerular Filtration Rate; SGLT2: Sodium-Glucose Co-Transporter-2; RAAS: Renin-Angiotensin-Aldosterone System