Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
JAMA Netw Open. 2023 Jul 3;6(7):e2322056. doi: 10.1001/jamanetworkopen.2023.22056.
Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy.
To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden.
New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels.
Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users.
The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76).
In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.
在双相情感障碍患者中，关于锂治疗的肾毒性作用的研究结果存在不一致。
定量比较锂与丙戊酸盐治疗的患者慢性肾脏病（CKD）进展和急性肾损伤（AKI）的绝对和相对风险，并探讨累积使用和血锂水平升高与肾脏结局的关系。
设计、设置和参与者：本队列研究采用新使用者活性对照设计，并使用逆概率治疗权重最小化混杂。纳入 2007 年 1 月 1 日至 2018 年 12 月 31 日开始锂或丙戊酸盐治疗的患者，中位随访时间为 4.5 年（IQR，1.9-8.0 年）。数据分析于 2021 年 9 月开始，使用来自瑞典斯德哥尔摩肌酐测量项目的常规医疗保健数据，该项目是斯德哥尔摩所有成年居民的反复医疗保健使用队列。
新使用锂与新使用丙戊酸盐，以及高（>1.0 mmol/L）与低血清锂水平。
CKD 进展（相对于基线估计肾小球滤过率[eGFR]下降>30%的复合终点和肾衰竭）、AKI（通过诊断或短暂肌酐升高）、新出现的白蛋白尿和每年 eGFR 下降。还比较了锂使用者达到的锂水平的结局。
该研究纳入了 10946 人（中位数[IQR]年龄，45[32-59]岁；6227 名女性[56.9%]），其中 5308 人开始锂治疗，5638 人开始丙戊酸盐治疗。在随访期间，确定了 421 例 CKD 进展事件和 770 例 AKI 事件。与接受丙戊酸盐的患者相比，接受锂治疗的患者发生 CKD（危险比[HR]，1.11[95%CI，0.86-1.45]）或 AKI（HR，0.88[95%CI，0.70-1.10]）的风险没有增加。10 年的绝对 CKD 风险较低且相似：锂组为 8.4%，丙戊酸盐组为 8.2%。两组之间未发现发生白蛋白尿或 eGFR 年下降率的差异。在超过 35000 次常规锂检测中，只有 3%的结果处于毒性范围（>1.0 mmol/L）。与锂值 1.0 mmol/L 或更低相比，锂值>1.0 mmol/L 与 CKD 进展（HR，2.86；95%CI，0.97-8.45）和 AKI（HR，3.51；95%CI，1.41-8.76）的风险增加相关。
在这项队列研究中，与新使用丙戊酸盐相比，新使用锂与不良肾脏结局有明显关联，绝对风险较低，两种治疗方法之间无差异。然而，血清锂水平升高与未来的肾脏风险相关，尤其是 AKI，强调需要密切监测和调整锂剂量。
