Clinical and experimental nephrology · 2025
Stage-specific risks of mortality and renal outcomes in cardiovascular-kidney-metabolic syndrome: findings from a nationwide Japanese cohort.
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Fujimoto Kenta, Kikuchi Masao, Nakai Michikazu, Konta Tsuneo, Iseki Kunitoshi, Tsuruya Kazuhiko, Yamagata Kunihiro, Narita Ichiei, Moriyama Toshiki, Shibagaki Yugo, Kasahara Masato, Kondo Masahide, Asahi Koichi, Watanabe Tsuyoshi, Kaikita Koichi, Fujimoto Shouichi
Аннотация
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome, integrating cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic dysfunction, is a construct proposed by the American heart association. Although associations with CVD are well recognized, evidence linking CKM stage to renal outcomes remains limited.
METHODS: We analyzed health checkup data of 266,256 Japanese aged 40-74 years. Participants were classified into CKM stages 0-4a. Outcomes included all-cause mortality, cardiovascular death, and a composite renal outcome (end-stage kidney disease [eGFR < 15 mL/min/1.73 m2], ≥ 40% eGFR decline, or doubling of serum creatinine). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs), with CKM stage 0 as the reference.
RESULTS: CKM stage 2 was the most prevalent stage (65.0%). Stage 4a showed the strongest association with all-cause and cardiovascular mortality (HRs 1.79, 3.16; 95% CIs 1.41-2.28, 1.92-5.20, respectively). In contrast, stage 3 conferred the highest risk of renal outcomes (HR 15.29, 95% CI 10.13-23.08). The number and type of metabolic risk factors correlated with outcomes, furthermore, severe CKD and prior CVD were stronger drivers of adverse outcomes than metabolic dysfunction.
CONCLUSION: CKM staging stratifies risk in the general population. No significant increase in risk was observed until CKM stage 2, and these findings underscore the progressive, cumulative nature of CKM syndrome. Metabolic dysfunction plays a crucial role in progression, stage 3 marks a pivotal inflection point for renal deterioration, and stage 4a identifies individuals at the greatest mortality risk. Early interventions targeting metabolic dysfunction may help prevent progression to advanced CKM stages and improve long-term outcomes.
METHODS: We analyzed health checkup data of 266,256 Japanese aged 40-74 years. Participants were classified into CKM stages 0-4a. Outcomes included all-cause mortality, cardiovascular death, and a composite renal outcome (end-stage kidney disease [eGFR < 15 mL/min/1.73 m2], ≥ 40% eGFR decline, or doubling of serum creatinine). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs), with CKM stage 0 as the reference.
RESULTS: CKM stage 2 was the most prevalent stage (65.0%). Stage 4a showed the strongest association with all-cause and cardiovascular mortality (HRs 1.79, 3.16; 95% CIs 1.41-2.28, 1.92-5.20, respectively). In contrast, stage 3 conferred the highest risk of renal outcomes (HR 15.29, 95% CI 10.13-23.08). The number and type of metabolic risk factors correlated with outcomes, furthermore, severe CKD and prior CVD were stronger drivers of adverse outcomes than metabolic dysfunction.
CONCLUSION: CKM staging stratifies risk in the general population. No significant increase in risk was observed until CKM stage 2, and these findings underscore the progressive, cumulative nature of CKM syndrome. Metabolic dysfunction plays a crucial role in progression, stage 3 marks a pivotal inflection point for renal deterioration, and stage 4a identifies individuals at the greatest mortality risk. Early interventions targeting metabolic dysfunction may help prevent progression to advanced CKM stages and improve long-term outcomes.