#5214 RENAL TOLERABILITY OF SGLT-2 INHIBITORS COMBINING WITH RENIN-ANGIOTENSIN SYSTEM BLOCKERS AND MINERALOCORTICOID RECEPTOR ANTAGONISTS IN CKD
Authors: Pampa-Saico Saul , Alexandru Simona , Frías Aida , Pizarro-Sánchez M Soledad , Burgos Elena , López-Picasso María , Puente-Suárez Laura García 
Published: June 2023

Abstract

Background and aims
Recently the sodium glucose cotransporter-2 (SGLT-2) inhibitors combining with angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor II blocker (ARBs) or angiotensin-receptor neprilysin inhibitor (ARNI)) and mineralocorticoid receptor antagonist (MRA) ((triple therapy (TT)), would help prevent further progression of renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease (ESKD). The degree to which data on TT initiation and discontinuation in cronic kidney disease (CKD) patients can be generalized to patients in real-world practice is unclear.

Aims
to evaluate renal tolerability to the TT at target doses as well as clinical incidents and dosage adjustments. To analyze the risk factors for TT discontinuation.

Method
A retrospective cohort study was carried out in patients ≥18 years old with chronic kidney disease (CKD) treated with TT in Rey Juan Carlos Hospital between January 2019 to December 2022. The collected clinical data included age, gender, associated morbidities, serum creatinine (Scr), estimated glomerular filtration rate (eGFR), potassium, sodium levels, dose adjustments before administration of TT and in the first year of follow up. Multivariate logistic models were performed to evaluate the risk factors to dosage adjusted and discontinuation of TT.

Results
Among 104 patients treated with TT were included. Medium age was 69 years old (range, 37-91). Most of them were men, 78% (81). The main cause to initiate TT was cardiorenal syndrome 59% (61). Before to initiate TT, in 35% patients the treatment was adjusted. The main modification was reduced or discontinuation of diuretics (loop or thiazide) therapy 23% (24/104). In the first year of follow up, in 69 patients (66%) it was necessary dosage adjustments, being the reduced of MRA (spironolactone and eplerenone) the main modification treatment 38% (26/69). The major cause of dose adjustment was developed of acute kidney injury (AKI) in 43 patients (41%). According to KDIGO criteria, 38 patients (88%) reached stage 1; 4 patients (9%) stage 2 and 1 case (2%) stage 3. The independent risk factor associated with dosage adjustment were AKI development (OR: 28.57; 95% CI 6.04-134.4; P = 0.0001) adjusted by sex and age. Despite the dosage adjustment and titers, in 29 patients (28%) TT was discontinued in a median time of 4 months (IQR 2–11) after its initiation. The risk factor associated with TT discontinuation were AKI developed (P = 0,003) and eGFR at the 12 months of follow up (P = 0,01). There were no significant excess risks of symptomatic hypotension, volume depletion, and hyperkalemia after a year of follow up.

Conclusions
The renal tolerability of use to triple therapy in chronic kidney disease appears to be low. The AKI development was the main risk factor of dosage adjustment and discontinuation of TT. Its necessary to clarify which is the best way to maximizing renal tolerability in this complex groups of patients. The use of early combination therapy requires careful assessment. Its important to find strategies to guide clinicians about the steps and challenges to improving overall use of triple therapy tolerability and dosage adjustment.