(B-038) Evaluating the Impact of Kidney Dysfunction on Cardiovascular Diseases Using the Global Burden of Disease Study

Background: Kidney dysfunction (KD) is a known risk factor for the leading causes of cardiovascular disease (CVD), ischemic heart disease (IHD) and ischemic stroke. As the number of prevalent cases of CVD increases globally, understanding the role of metabolic risk factors is crucial. This insight can help identify vulnerable groups, particularly those with cardio-renal-metabolic comorbidities, who may greatly benefit from targeted pharmaceutical therapies and interventions.

Objectives: We quantified the risk relationship between KD and IHD, ischemic stroke, and peripheral arterial disease (PAD) morbidity and mortality, using the Global Burden of Disease (GBD) study methodology.

Methods: We analyzed data from 73 cohorts, encompassing those 18 and older, identified through a systematic literature review or from the Chronic Kidney Disease Prognosis Consortium. To calculate the relative risks (RR) with 95% uncertainty intervals (UIs) across multiple stages (defined by eGFR mL/min/1.73m2) of KD and CVD types, we utilized a meta-regression Bayesian regularized trimming tool. This tool adjusts for selection bias and age using a cubic spline with 10% trimming on the left and right linear tails of the curve.

Results: Our analysis showed that PAD had the highest average RR associated with KD at 13.8 (95% UI: 6.0, 27.6). This was followed by IHD at 4.6 (2.8, 7.1) and stroke at 3.0 (1.9, 4.7). The risk of these CVDs was greatest for those with advanced KD (eGFR < 30 mL/min/1.73m2). In the most severe stage (eGFR < 15 mL/min/1.73m2), the average RR for PAD was 35.0 (13.7, 74.6), compared to 2.7 (1.3, 4.5) in the mildest stage (eGFR >= 30 mL/min/1.73m2). For IHD and stroke, a similar pattern was observed. In earlier KD stages, RRs across all CVD outcomes were still elevated, where for the mildest stage (eGFR >= 30 mL/min/1.73m2) the RR ranged from 1.6 (1.2, 1.9) to 2.6 (1.3, 4.5) , and for the moderate stage (eGFR 30-60 mL/min/1.73m2) the RRs ranged 1.8 (1.5, 2.2) to 3.9 (2.3, 6.1). Younger populations exhibited higher RRs across all KD stages and CVDs, with those under 50 showing particularly high RRs associated with PAD (25.4 (10.9,51.1) compared to those over 50 (8.0 (3.5,15.8).

Conclusions: Our study highlights that the risk of cardiovascular diseases is significant at all stages of KD, with the risk increasing as KD progresses. Early intervention in KD can help reduce the risk of CVD complications. Emerging research suggests that pharmaceutical therapies, such as SGLT-2i and GLP-1RAs, could offer benefits in reducing both cardiovascular and renal risk. Continued research is essential to developing targeted therapies that improve renal and cardiovascular health, underscoring the importance of early, proactive management of metabolic conditions.