In a recent meta-analysis, Zhang and colleagues concluded that regional citrate anticoagulation (RCA) seems to be a safe anticoagulation method in liver failure patients undergoing continuous renal replacement therapy (CRRT) [1]. We would like to make some comments. Indeed, during RCA-CRRT, 30–70% of the administrated citrate can be removed by the dialyzer, and the remaining citrate enters the systemic circulation [1]. In the setting of severe liver dysfunction, citrate clearance is reduced by about 50%, which means liver failure patients are more susceptible to citrate accumulation [1]. Zhang et al. advocate the use of the “Khadzhynov rules” [2] to diagnose citrate accumulation in severe liver patients including the following diagnosis criteria: (i) decreased systemic ionized calcium (ionCa), (ii) increased demand for calcium substitution, (iii) elevated total calcium (totCa)/ionCa ratio, and (iv) metabolic acidosis. They conclude that most likely, the citrate accumulation incidences of the included studies were overestimated by only using the totCa/ionCa ratio [1, 2]. We somewhat disagree, as in the setting of citrate anticoagulation, with disturbed microvascular circulation causing altered hepatic function and citrate accumulation [3], it is our experience, like Klingele [3], that lactate better reflects citrate accumulation than calcium ratio and liver dysfunction itself [4]. Further, Zhang et al. state that theoretically, liver failure patients did not lose all of the liver citrate metabolization function [1]. Again, we do not totally agree. It is well known that in all cells, citrate can be metabolized within the Cori cycle (tricarboxylic acid cycle) [4], the linked metabolic pathways by which muscles, even in the absence of oxygen, remain capable of functioning, producing lactate. The Cori cycle is activated both by citrate [4] and adrenaline [4], the latter leading to the production of lactate [4]. The liver citrate anticoagulation threshold (L-CAT) trial showed the safety of CRRT-citrate in patients with severely impaired liver function [5]. We conclude that the Cori cycle is functional without oxygen [4] and that citrate metabolism is less dependent on the hepatic function itself and more dependent upon the whole microcirculation of the body, as suggested by Klingele, which makes lactate the best marker of liver failure associated with microcirculation failure. Whenever the liver is unable to metabolize citrate, the Cori cycle takes over the task of the failing liver [4].

中文翻译：

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在严重的肝病中，柠檬酸盐可以安全使用：问题仍然存在——通过哪种机制

在最近的一项荟萃​​分析中，Zhang 及其同事得出结论，局部柠檬酸盐抗凝 (RCA) 似乎是接受连续肾脏替代治疗 (CRRT) 的肝功能衰竭患者的安全抗凝方法 [1]。我们想发表一些意见。事实上，在 RCA-CRRT 期间，30-70% 的给药柠檬酸盐可以被透析器去除，剩余的柠檬酸盐进入体循环 [1]。在严重肝功能障碍的情况下，柠檬酸清除率降低约 50%，这意味着肝功能衰竭患者更容易发生柠檬酸积累 [1]。张等人。提倡使用“Khadzhynov 规则”[2] 来诊断重症肝脏患者的柠檬酸盐积累，包括以下诊断标准：(i) 全身离子钙 (ionCa) 降低，(ii) 对钙替代的需求增加，(iii) 总钙 (totCa)/ionCa 比率升高，以及 (iv) 代谢性酸中毒。他们得出的结论是，很可能仅使用 totCa/ionCa 比值高估了纳入研究的柠檬酸盐积累发生率 [1, 2]。我们有点不同意，因为在柠檬酸盐抗凝的情况下，微血管循环紊乱导致肝功能改变和柠檬酸盐积累 [3]，我们的经验，如 Klingele [3]，乳酸比钙比率和肝功能障碍更好地反映柠檬酸盐积累本身[4]。此外，张等人。国家认为，理论上，肝功能衰竭患者的肝柠檬酸代谢功能并未全部丧失[1]。同样，我们并不完全同意。众所周知，在所有细胞中，柠檬酸都可以在 Cori 循环（三羧酸循环）内代谢 [4]，即使在没有氧气的情况下，肌肉仍然能够发挥功能并产生乳酸的相关代谢途径。Cori 循环被柠檬酸盐 [4] 和肾上腺素 [4] 激活，后者导致乳酸的产生 [4]。肝柠檬酸盐抗凝阈值 (L-CAT) 试验表明，CRRT-柠檬酸盐在肝功能严重受损的患者中是安全的 [5]。我们得出结论，如 Klingele 所建议的，Cori 循环在没有氧气的情况下也能发挥作用 [4] 并且柠檬酸盐代谢较少依赖于肝功能本身，而更多地依赖于身体的整个微循环，这使得乳酸成为肝衰竭的最佳标志与微循环障碍有关。每当肝脏无法代谢柠檬酸盐时，Cori 循环就会接管衰竭肝脏的任务 [4]。