#853 Kidney-protective medication and risk of adverse clinical outcomes in patients with chronic kidney disease: preliminary findings from DISCOVER CKD
Authors: Pecoits-Filho Roberto , Kashihara Naoki , Ofori-Asenso Richard , Chen Tony , Pentakota Surendra , Järbrink Krister , Sanchez Juan Jose Garcia , Lam Carolyn , Pollock Carol , Fishbane Steven , Kanda Eiichiro 
Published: May 2024

Abstract

Background and Aims
Renin-angiotensin-system inhibitors (RASi) have been a foundational therapy in chronic kidney disease (CKD) for several decades. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have also emerged as a critical disease-modifying therapy in CKD, with contemporary data from trials showing SGLT2i to significantly improve kidney and cardiovascular (CV) outcomes in patients with or without diabetes. Nonetheless, several studies have revealed sub-optimal prescribing of RASi and/or SGLT2i therapy (both herein referred to as kidney-protective medication) in patients with CKD. Using prospective data from the DISCOVER CKD study, we conducted an exploratory analysis to assess the association of kidney-protective medication real-world use with mortality risk, CV events (fatal and non-fatal), and hospitalisation in patients with CKD.

Method
DISCOVER CKD (NCT04034992) is a multi-country, non-interventional cohort study designed to characterise the epidemiology of CKD, including describing patient characteristics, disease progression, clinical outcomes, patient journey, practice patterns, and clinical management. In the prospective phase, patients with CKD were recruited from the UK, USA, Spain, Italy, Sweden and Japan between September 2019 and June 2022. Clinical data were extracted manually from patients’ health records into a standardised case report form. The current analysis includes 12 months’ follow-up data. A Cox proportional hazards model was used to compare the risk of all-cause mortality and CV events and a negative binomial regression model was used to compare the risk of all-cause hospitalisation between patients receiving and not receiving kidney-protective medication at baseline, with adjustments for age, sex, CKD stage, diabetes mellitus, hyperkalaemia, and heart failure. DISCOVER CKD received research ethics board approval, and informed consent was obtained from all patients.

Results
Of the 1052 patients enrolled in DISCOVER CKD, 643 (61.1%) were receiving kidney-protective medication in the form of RASi (n = 618) and SGLT2i (n = 147) at baseline. The mean age of participants receiving and not receiving kidney-protective medication was 62.4 years and 62.7 years, respectively; 34.4% and 40.8%, respectively, were female. Most patients had CKD stage 3A (n = 332, 31.6%) or 3B (n = 308, 29.3%), and 8.4% (n = 88) had ongoing dialysis. Body mass index (30.4 vs 29.4 kg/m2) and blood pressure were similar for those receiving kidney-protective medication versus those who were not. Laboratory assessments were also generally similar, although estimated glomerular filtration rate (eGFR; 40.9 vs 33.7 mL/min/1.73 m2) and haemoglobin (132.0 g/L vs 124.0 g/L) were higher in patients receiving kidney-protective medication versus those not. During the follow-up, patients receiving kidney-protective medication had a 67% lower risk of all-cause mortality (hazard ratio [HR] 0.33; 95% confidence interval [CI] 0.12–0.80, p = 0.019), and a 20% lower risk of all-cause hospitalisation (HR, 0.80; 95% CI 0.64–0.99, p = 0.042) compared with patients not receiving kidney-protective medication. In the population without pre-existing CV disease, a trend towards a lower rate of CV events was observed in patients with kidney-protective medication (CV events rates: 2.2 vs 3.2 per 100 person-years; HR, 0.38; 95% CI 0.12–1.08, p = 0.074 (Figure).

Conclusion
In this multinational CKD cohort, preliminary analysis indicates that using kidney-protective medication was associated with lower risks of adverse outcomes including death. Further analysis to mitigate potential confounding will be performed to confirm these preliminary findings.