The long‐term use of lithium salts has long been associated with tubular damage and chronic kidney disease development. Nevertheless, there is some interest in the potential role of these drugs in inflammatory pathways regulation including those pathways in the setting of acute kidney injury (AKI).

This therapeutic potential is based on lithium‐induced inhibitory phosphorylation of glycogen synthase kinase‐3 beta (GSK3b), a protein related to inflammatory response, through many mechanisms, including upregulation of interleukin‐6 (IL‐6) and tumor necrosis factor(TNF)expression.¹

Lithium anti‐inflammatory action is long known,and the resulting neuroprotective effects is a concept well‐established in medical literature. Also, GSK3b inhibition by lithium seems a promising pathway to improve tubular cell regeneration, as shown by a recent study, in which a single dose of lithium inhibited tubular cells apoptosis (through GSK3b phosphorylation) and promoted renal tubules recovery after ischemia‐reperfusion AKI and cisplatin‐induced AKI.²

Even though lithium induced nephropathy is a concern, the incidence of relevant chronic kidney disease is 1.2% and is related to long‐term use (10 years or more) and advanced age.¹ Nevertheless, there is an acute side effect of lithium on kidneys, namely nephrogenic diabetes insipidus. This condition is characterized by loss of ability of the kidney to concentrate urine, and may cause electrolytes disturbance, mainly hypernatremia, which can be managed as long as sodium levels are monitored. Therefore, it seems safe to use a single or few doses, as long as we monitor the levels of lithium and other electrolytes.

Of note, AKI is associated with increased mortality rates, especially in the acute care settings. The scientific community has dedicated many efforts in the last years to find a way to prevent AKI or treat it. Until now, only therapeutic alternative continues to be supportive with renal replacement therapy.

One cause of AKI that emerged recently and has called the scientific community attention is Coronavirus Disease 19(COVID‐19), caused by SARS‐Cov2, which is a health problem that overwhelmed the world in the last months. A putative mechanism for AKI in this context is the direct damage of kidney tubular cells and podocytes due to viral infection. Another mechanism, present in the most severe cases, is the Cytokine Release Syndrome (CRS), which is a well‐known cause of renal and pulmonary damage and is characterized by overexpression of IL‐6, TNF and Interleukin‐10.³

As GSK3b upregulates the expression of IL6 and TNF, we can hypothesize that its pharmacologic inhibition, such as that promoted by lithium, could be a way to reduce the inflammatory response that ultimately results in CRS.

Considering the exposure, we propose that bipolar‐disorder specialized centers should investigate the death rate, as well as AKI incidence, in COVID‐19 affected patients in use of lithium, in comparison to patients using other mood stabilizers. We also propose that it would be interesting to study the effects of lithium in a low or single dose in the most severe cases of COVID‐19, as a compassionate therapy.

长期使用锂盐与肾小管损害和慢性肾脏疾病的发展有关。然而，人们对这些药物在炎症途径调节中的潜在作用感兴趣，包括在急性肾损伤（AKI）发生中的那些途径。

这种治疗潜力基于锂诱导的糖原合酶激酶-3β（GSK3b）的抑制性磷酸化，GSK3b是与炎症反应相关的一种蛋白质，它通过多种机制，包括白介素-6（IL-6）和肿瘤坏死因子（TNF）的上调。 ）表达。^1个

锂的抗炎作用是众所周知的，其产生的神经保护作用是医学文献中公认的概念。此外，最近的一项研究表明，锂对GSK3b的抑制似乎是改善肾小管细胞再生的有希望的途径，其中单剂量的锂抑制肾小管细胞的凋亡（通过GSK3b磷酸化）并促进缺血再灌注AKI和肾小管的恢复。顺铂诱导的AKI。²

即使担心锂诱发的肾病，但相关的慢性肾脏疾病的发生率为1.2％，并且与长期使用（10年或更长时间）和高龄有关。¹然而，锂对肾脏有急性副作用，即肾病性尿崩症。这种情况的特征是肾脏浓缩尿液的能力下降，并可能引起电解质紊乱，主要是高钠血症，只要监测钠水平，就可以解决。因此，只要我们监测锂和其他电解质的水平，使用一次或几次剂量似乎是安全的。

值得注意的是，AKI与死亡率增加相关，特别是在急性护理环境中。在过去的几年中，科学界做出了许多努力，以寻找预防或治疗AKI的方法。到目前为止，只有替代疗法继续支持肾脏替代疗法。

最近出现的引起AKI的一个原因是引起SARS-Cov2感染的冠状病毒病19（COVID-19），这是一个健康问题，在过去的几个月中已席卷全球，引起了科学界的关注。在这种情况下，AKI的推定机制是由于病毒感染直接损害肾小管细胞和足细胞。在最严重的情况下，存在的另一种机制是细胞因子释放综合征（CRS），它是肾脏和肺部损伤的众所周知的原因，其特征在于IL-6，TNF和白介素10的过度表达。³

由于GSK3b上调IL6和TNF的表达，我们可以假设它的药理抑制作用（例如由锂促进的抑制作用）可能是减少最终导致CRS的炎症反应的一种方式。

考虑到暴露，我们建议与使用其他情绪稳定剂的患者相比，双相情感障碍专科中心应调查使用锂的COVID-19受影响患者的死亡率以及AKI发生率。我们还建议，在最严重的COVID-19病例中研究低剂量或单剂量锂的影响，将其作为一种富有同情心的疗法，将是有趣的。