Wang Wenda, Wang Zhan, Zhao Yang, Wang Xu, Li Hanzhong, Zhang Yushi
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Clin Pharm Ther. 2022 Jul;47(7):979-985. doi: 10.1111/jcpt.13631. Epub 2022 Mar 1.
Patients with tuberous sclerosis complex (TSC) demonstrate disrupted lipid homeostasis before and during treatment with mammalian target of rapamycin (mTOR) inhibitor. However, few previous reports focused on if the serum lipid status at baseline would influence lipid metabolic side-effects of mTOR inhibitors for TSC associated renal angiomyolipomas (TSC-AML). The present study was designed to evaluate the predictive function of serum lipid status at baseline for hyperlipidaemia by mTOR inhibitor treatment in TSC-AML patients.
The clinical data of TSC-AML patients who took mTOR inhibitors in Department of Urology of Peking Union Medical College Hospital (PUMCH) from 1 January 2014 to 1 January 2021, were retrospectively analysed. The record of lipid parameters at baseline and the highest levels of total cholesterol (TC) and triglyceride (TG) after treatment at least ≥3 months were collected. The correlation of serum lipid parameters at baseline with incidence of hyperlipidaemia during mTOR inhibitor treatment was analysed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of the serum lipid parameters in predicting hyperlipidaemia.
19 patients experienced hyperlipidaemia and 13 patients still had normal TC and TG levels during mTOR inhibitor treatment. The levels of high-density lipoprotein cholesterol (HDL-C) (0.98 ± 0.30 mmol/L vs. 1.23 ± 0.31 mmol/L, p = 0.030), low-density lipoprotein cholesterol (LDL-C) (2.47 ± 0.69 mmol/L vs. 1.95 ± 0.53 mmol/L, p = 0.029) and apolipoprotein B (ApoB) (0.82 ± 0.21 g/L vs. 0.65 ± 0.16 g/L, p = 0.019) are higher in the patients who experienced hyperlipidaemia during mTOR inhibition therapy. TC, TG, LDL-C, ApoB and high-sensitivity C-reactive protein (hsCRP) at baseline had positive correlation with TC after treatment; ApoB at baseline had positive correlation, while HDL-C and free fat acid (FFA) at baseline had negative correlation with TG after treatment. Therefore, ApoB concentration at baseline has statistically significant correlation with both TC (p < 0.001) and TG (p = 0.012) levels after mTOR inhibitor treatment. ROC curve and AUC revealed that ApoB with a cut-off value of 0.640g/L may be the best parameter for predicting hyperlipidaemia during mTOR inhibitor treatment in TSC-AML patients. The incidence rates of hyperlipidaemia were 27.3% and 76.2% among the patients with ApoB level ≤0.640 g/L and >0.640 g/L respectively.
Some baseline serum lipid parameters could be used for predicting incidence of hyperlipidaemia during mTOR inhibition therapy in TSC-AML patients, and ApoB with 0.640 g/L as a cut-off value may be a potentially optimal indicator, which could help for diagnosis and treatment decision-making.
结节性硬化症（TSC）患者在使用雷帕霉素靶蛋白（mTOR）抑制剂治疗前及治疗期间均表现出脂质稳态紊乱。然而，此前很少有报告关注基线时的血清脂质状态是否会影响mTOR抑制剂对TSC相关肾血管平滑肌脂肪瘤（TSC-AML）的脂质代谢副作用。本研究旨在评估TSC-AML患者基线时血清脂质状态对mTOR抑制剂治疗所致高脂血症的预测作用。
回顾性分析2014年1月1日至2021年1月1日在北京协和医院泌尿外科接受mTOR抑制剂治疗的TSC-AML患者的临床资料。收集基线时的脂质参数记录以及治疗至少≥3个月后总胆固醇（TC）和甘油三酯（TG）的最高水平。分析基线时血清脂质参数与mTOR抑制剂治疗期间高脂血症发生率的相关性。进行受试者操作特征（ROC）曲线分析以评估血清脂质参数预测高脂血症的能力。
19例患者在mTOR抑制剂治疗期间出现高脂血症，13例患者的TC和TG水平仍正常。mTOR抑制治疗期间出现高脂血症的患者，其高密度脂蛋白胆固醇（HDL-C）水平（0.98±0.30 mmol/L对1.23±0.31 mmol/L，p = 0.030）、低密度脂蛋白胆固醇（LDL-C）水平（2.47±0.69 mmol/L对1.95±0.53 mmol/L，p = 0.029）和载脂蛋白B（ApoB）水平（0.82±0.21 g/L对0.65±0.16 g/L，p = 0.019）更高。基线时的TC、TG、LDL-C、ApoB和高敏C反应蛋白（hsCRP）与治疗后的TC呈正相关；基线时的ApoB与治疗后的TG呈正相关，而基线时的HDL-C和游离脂肪酸（FFA）与治疗后的TG呈负相关。因此，基线时的ApoB浓度与mTOR抑制剂治疗后的TC（p < 0.001）和TG（p = 0.012）水平均具有统计学显著相关性。ROC曲线和AUC显示，截断值为0.640g/L的ApoB可能是预测TSC-AML患者mTOR抑制剂治疗期间高脂血症的最佳参数。ApoB水平≤0.640 g/L和>0.640 g/L的患者中，高脂血症的发生率分别为27.3%和76.2%。
一些基线血清脂质参数可用于预测TSC-AML患者mTOR抑制治疗期间高脂血症的发生率，截断值为0.640 g/L的ApoB可能是一个潜在的最佳指标，有助于诊断和治疗决策。
