Abstract

Abstract Background and Aims Few studies have investigated the prognosis in chronic kidney disease (CKD) patients with heart failure (HF) and diabetes (DM). In the clinical setting, treating a combination of these conditions is challenging but novel treatments such as SGLT2-inhibitors are now emerging. The aim of this study is to investigate the prevalence and outcomes of survival and major cardiovascular events (MACE) in CKD patients with HF and/or DM before these new treatments were commonly used. Method In this retrospective observational study, we extracted data from 26647 nephrology-referred patients ≥18 years old with eGFR 60 ≤ ml/min/1,73 m2 from the Swedish Renal Registry – Chronic Kidney Disease (SRR-CKD) and health registers at the National Board of Health and Welfare in Sweden during an observational period of January 2005 – June 2017. HF and DM was categorized based on International Classification of Disease 10 (ICD-10) diagnostic codes prior to inclusion in the SRR-CKD. Outcomes were death by any cause and MACE, defined as a composite of hospitalization for nonfatal myocardial infarction, coronary heart disease, congestive heart failure, nonfatal stroke or cardiovascular death. Secondary outcome was start of kidney replacement therapy (KRT) defined as start of dialysis or kidney transplantation. Results There were 12910 (47.7%) patients with CKD, 3458 (12.5%) with CKD+HF, 7595 (27.3%) with CKD+DM and 3684 (13.3%) with CKD+HF+DM. Median age was higher in the cohorts with heart failure (CKD+HF and CKD+HF+DM), 77 and 74 years vs 67 and 69 years (CKD and CKD+DM). Most patients were men in all four groups (62-66%). The use of evidence based therapies such as ACE-inhibitors/ARBs, varied across the groups between 62.9, 66.6, 78.5 and 78.7% (CKD, CKD+HF, CKD+DM, CKD+HF+DM). Statins were used in 42.0, 50.7, 71.1 and 73.7% and betablockers in 53.9, 83.7, 65.9, and 86.1%. Survival data is presented in a Kaplan-Meier curve (Figure 1). Adjusted hazard ratio (HR) for all cause-death was highest in the cohorts with heart failure CKD+HF (2.54 [95% CI 2.40–2.68]) and CKD+DM+HF (3.22 [3.05–3.39]) followed by CKD+DM (HR 1.53 [1.45–1.60]) compared to patients with only CKD. The cumulative incidence of MACE is illustrated below (Figure 2). Adjusted HR for MACE was substantially higher in patients with heart failure, 3.82 (3.62–4.03) and 4.82 (4.59–5.08) for CKD+HF and CKD+HF+DM respectively while it was 1.63 (1.56–1.72) for CKD+DM. The risk of initiation of KRT was similar in all four groups, but risk of death before start of KRT was higher in patients with HF. Conclusion In CKD-patients, a heart failure diagnosis comprises approximately three to four times greater risk of death and MACE compared to patients with only CKD. The combination of CKD+HF+DM is the most severe. In all patient groups the use of evidence-based therapies was surprisingly low. This may reflect both deviation from guidelines for CKD-patients and the clinical challenge in treating comorbidities in CKD-patients. The results underlie the importance of identifying CKD-patients with HF and DM early to optimize treatment.

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