Chronic kidney disease is associated with increased risk of sudden cardiac death

Abstract

Patients with chronic kidney disease (CKD) are recognized as a higher risk group for cardiovascular disease (CVD) due to various traditional risk factors, kidney-specific factors, and comorbidities, which have recently attracted significant attention. However, the long-term risk of acute CVD events such as sudden cardiac death (SCD) in CKD patients is unclear. Using the UK Biobank and Changsha cohorts, we find that CKD is associated with an increased risk of SCD. Patients with early-stage CKD, especially those with advanced CKD, faced an elevated risk of SCD. Furthermore, through proteomic analyses of the UK Biobank and Framingham Offspring Cohort, we identify five candidate proteins (NTproBNP, ANGPT2, FGF23, DTNB, and SEPTIN8) linked to SCD risk in CKD patients. Here, we show that patients with CKD have an increased risk of SCD in the long term, underscoring the imperative for strategies that address both cardiovascular risk and renal function in this population.

Fig. 1. Cumulative incidence of SCD among groups with and without CKD.

A in exploration cohort. B in validation cohort. CKD chronic kidney disease, SCD sudden cardiac death.

Fig. 2. Association of CKD and SCD risk in exploration cohort and validation cohort.

The central markers indicate hazard ratios, and the error bars represent 95% confidence intervals. In the exploration cohort (n = 349,648, SCD = 6815), model 1 was adjusted for age, sex, and ethnic; model 2 was adjusted for age, sex, ethnic, obesity, eGFR, smoking, drinking, household income, exercise, hypertension, diabetes, hyperlipidemia, CVD, medication for cholesterol, medication for BP, and medication for diabetes. In the validation cohort (n = 129,279, SCD = 154), model 1 was adjusted for age, sex; model 2 was adjusted for age, sex, obesity, eGFR, smoking, drinking, exercise, hypertension, diabetes, hyperlipidemia, CVD, medication for cholesterol, medication for BP, and medication for diabetes. Source data are provided as a Source data file. No Number, HR hazard ratio, CI confidence interval, CKD chronic kidney disease, SCD sudden cardiac death.

Fig. 3. Association of different CKD stages and SCD risk in exploration cohort.

The central markers indicate hazard ratios, and the error bars represent 95% confidence intervals. In this analysis, CKD staging was performed based on the ICD-10 codes and the eGFR levels of patients with CKD. Number of participants stratified by CKD stage: non-CKD (n = 344,077), CKD stage 1–3 (n = 4118), CKD stage 4 (n = 111), CKD stage 5 (n = 431). Model 1 was adjusted for age, sex, and ethnic; Model 2 was adjusted for age, sex, ethnic, obesity, smoking, drinking, household income, exercise, hypertension, diabetes, hyperlipidemia, CVD, medication for cholesterol, medication for BP, and medication for diabetes. Source data are provided as a Source data file. No. Number, HR hazard ratio, CI confidence interval, CKD chronic kidney disease.

Fig. 4. Association of 5 candidate circulating proteins and SCD risk in exploration cohort.

The central markers indicate hazard ratios, and the error bars represent 95% confidence intervals. Number of participants with avaliable proteomic data: NTproBNP (n = 2096, SCD = 94), ANGPT2 (n = 2167, SCD = 105), FGF23 (n = 2049, SCD = 89), DTNB (n = 1667, SCD = 72), SEPTIN8 (n = 1659, SCD = 69). Model 1 was adjusted for age, sex and ethnic; Model 2 was adjusted for age, sex, ethnic, obesity, eGFR, uACR, smoking, drinking, household income, exercise, hypertension, diabetes, hyperlipidemia, CVD, medication for cholesterol, medication for BP, and medication for diabetes. Source data are provided as a Source data file. No. Number, HR hazard ratio, CI confidence interval, CKD chronic kidney disease, NTproBNP N-terminal pro-brain natriuretic peptide, ANGPT2 angiopoietin 2, FGF23 fibroblast growth factor 23, DTNB dystrobrevin beta, SEPTIN8 septin 8.

Fig. 5. Sudden cardiac death in Chronic kidney disease.

The figures were created with Figdraw (Copyright ID: OAAWR8a7ff). CKD Chronic kidney disease, SCD Sudden cardiac death, HR Hazard ratio, NT-proBNP N-terminal pro-brain natriuretic peptide, ANGPT2 Angiopoietin 2, FGF23 Fibroblast growth factor 23, DTNB dystrobrevin beta, SEPTIN8 septin 8.