Asahina Yuta, Sakaguchi Yusuke, Kajimoto Sachio, Hattori Koki, Doi Yohei, Oka Tatsufumi, Kaimori Jun-Ya, Isaka Yoshitaka
Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Inter-Organ Communication Research in Kidney Diseases, Osaka University Graduate School of Medicine, Suita, Japan.
Clin Kidney J. 2021 Dec 16;15(5):929-936. doi: 10.1093/ckj/sfab277. eCollection 2022 May.
Studies examining associations between metabolic acidosis and cardiovascular events in chronic kidney disease (CKD) have shown conflicting results and have not differentiated between normal anion gap (hyperchloremic) acidosis and high anion gap acidosis. We aimed to examine the impact of normal and high anion gap acidosis, separately, on the risk of cardiovascular events among patients with CKD.
This retrospective cohort study included 1168 patients with an estimated glomerular filtration rate (eGFR) of 10-60 mL/min/1.73 m and available data on anion gap. We analyzed the association of time-updated high anion gap (anion gap ≥9.2) with the rate of cardiovascular events using marginal structural models (MSMs) to account for time-dependent confounding. We also analyzed the association between time-updated normal anion gap acidosis (anion-gap-adjusted bicarbonate level ≤22.8 mEq/L) and cardiovascular events.
The mean baseline eGFR of the cohort was 28 mL/min/1.73 m. The prevalence rates of high anion gap in CKD stages G3a, G3b, G4 and G5 were 20%, 16%, 27% and 46%, respectively. During a median follow-up period of 2.9 years, 132 patients developed cardiovascular events (3.3/100 patient-years). In MSMs, high anion gap was associated with a higher rate of cardiovascular events [hazard ratio (HR) 1.87; 95% confidence interval (95% CI) 1.13‒3.09; P = 0.02] and the composite of cardiovascular events or all-cause death (HR 3.28; 95% CI 2.19‒4.91; P < 0.001). Normal anion gap acidosis was not associated with cardiovascular events (HR 0.74; 95% CI, 0.47‒1.17; P = 0.2).
Among patients with advanced CKD, high anion gap was associated with an increased risk of cardiovascular events.
研究慢性肾脏病（CKD）患者代谢性酸中毒与心血管事件之间的关联，结果相互矛盾，且未区分正常阴离子间隙（高氯性）酸中毒和高阴离子间隙酸中毒。我们旨在分别研究正常和高阴离子间隙酸中毒对CKD患者心血管事件风险的影响。
这项回顾性队列研究纳入了1168例估算肾小球滤过率（eGFR）为10 - 60 mL/min/1.73 m²且有阴离子间隙数据的患者。我们使用边际结构模型（MSMs）分析随时间变化的高阴离子间隙（阴离子间隙≥9.2）与心血管事件发生率之间的关联，以考虑时间依赖性混杂因素。我们还分析了随时间变化的正常阴离子间隙酸中毒（阴离子间隙校正后的碳酸氢盐水平≤22.8 mEq/L）与心血管事件之间的关联。
该队列的平均基线eGFR为28 mL/min/1.73 m²。CKD G3a、G3b、G4和G5期高阴离子间隙的患病率分别为20%、16%、27%和46%。在中位随访期2.9年期间，132例患者发生了心血管事件（3.3/100患者年）。在MSMs中，高阴离子间隙与较高的心血管事件发生率相关[风险比（HR）1.87；95%置信区间（95%CI）1.13 - 3.09；P = 0.02]以及心血管事件或全因死亡的复合终点（HR 3.28；95%CI 2.19 - 4.91；P < 0.001）。正常阴离子间隙酸中毒与心血管事件无关（HR 0.74；95%CI，0.47 - 1.17；P = 0.2）。
在晚期CKD患者中，高阴离子间隙与心血管事件风险增加相关。
