Characteristics and cardio-renal outcomes in CKD patients receiving guideline-directed therapy: insights from DISCOVER CKD

Abstract Background and Hypothesis In clinical trials, renin-angiotensin system inhibitors (RASi) and sodium-glucose co-transporter-2 inhibitors (SGLT2i), herein referred to as guideline-directed medical therapy (GDMT), alone or in combination, provide cardio-renal protection in patients with chronic kidney disease (CKD). However, data from real-world clinical practice on the impact of GDMT on clinical outcomes are limited. Methods DISCOVER CKD (NCT04034992) is a multinational, observational cohort study in adults with CKD. We used the prospective cohort (enrollment: September 2019 to June 2022) to assess patient characteristics and outcomes up to 15 months by baseline GDMT use, including: a composite renal outcome (initiation of dialysis, kidney transplantation, estimated glomerular filtration rate 15 ml/min/1.73 m2, or death attributable to renal causes); all-cause mortality and new cardiovascular (CV) events; and all-cause hospitalization. Inverse probability of treatment weighting method was employed in controlling confounding variables and estimating the effect of GDMT use. Results Of 1052 prospectively enrolled patients (62.5 ± 13.6 years, 36.9% female), most had CKD stage 3a (31.6%) or 3b (29.3%); 8.4% were receiving dialysis. At baseline, 643 (61.1%) were receiving GDMT (RASi only, n = 496; SGLT2i only, n = 25; both, n = 122; range 42.7% USA to 82.2% Spain, Sweden). Patients receiving GDMT had a higher comorbidity burden than those without GDMT. In patients with CKD stage 3–4, GDMT use was associated with significantly lower incidence of the composite renal outcome propensity score (PS)-weighted hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.27–0.84, P = 0.01. There was no significant difference between those receiving GDMT versus not in composite all-cause mortality and new CV events (PS-weighted HR 0.50, 95% CI 0.23–1.09; P = 0.08) or all-cause hospitalization rate (PS-weighted rate ratio 0.78, 95% CI 0.52–1.16; P = 0.216). Conclusions GDMT use was associated with reduced adverse renal outcomes in real-world patients with CKD, underscoring the need to address large gaps in GDMT implementation.