接受免疫检查点抑制剂治疗的患者的低钠血症和其他电解质异常。
Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors.
机构信息
Department of Internal Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA.
Department of Internal Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA.
出版信息
Nephrol Dial Transplant. 2021 Dec 2;36(12):2241-2247. doi: 10.1093/ndt/gfaa272.
BACKGROUND
Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a 'real-world' sample of patients receiving ICIs to treat advanced malignancies.
METHODS
This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review.
RESULTS
A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%.
CONCLUSIONS
Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.
背景
在接受免疫检查点抑制剂（ICI）治疗的患者中，已报道过由于肾上腺功能不全和甲状腺功能减退等内分泌疾病引起的低钠血症。我们在接受 ICI 治疗晚期恶性肿瘤的“真实世界”患者样本中，确定了低钠血症和其他电解质异常的风险和预测因素。
方法
这是一项对 2011 年至 2018 年期间在单一癌症中心接受 ICI 治疗的所有患者进行的回顾性观察性研究。患者在开始 ICI 后 12 个月或直至死亡时进行随访。采用癌症治疗常见不良事件术语标准 5.0 版来对低钠血症和其他电解质异常的严重程度进行分级。采用多变量逻辑回归模型来确定严重（3 级或 4 级）低钠血症的预测因素。通过病历回顾确定 3 级或 4 级低钠血症的病因。
结果
共纳入 2458 例患者。他们的平均年龄为 64 岁（标准差 13），58%为男性，90%为白人。在开始 ICI 的第一年，62%的患者出现低钠血症（血清钠<134 mEq/L），136 例（6%）出现严重低钠血症（<124 mEq/L）。严重低钠血症平均发生在药物开始后 164 天（标准差 100）。只有 9 例严重低钠血症是由内分泌疾病引起的（总体发生率为 0.3%）。严重低钠血症的危险因素包括伊匹单抗（细胞毒性 T 淋巴细胞相关抗原-4 抑制剂）的使用、利尿剂的使用和非白种人种族。还观察到其他严重的电解质异常：严重低钾血症（血钾<3.0 mEq/L）发生率为 6%，严重高钾血症（血钾≥6.1 mEq/L）发生率为 0.6%，严重低磷血症（磷<2 mg/dL）发生率为 17%，严重低钙血症（校正钙<7.0 mg/dL）发生率为 0.2%。
结论
低钠血症在接受 ICI 治疗的癌症患者中很常见。然而，内分泌疾病是严重低钠血症的罕见原因。
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