Zenjinkai Yokohama Daiichi Hospital, 2-5-15 Takashima Nishi-ku, Yokohama, Kanagawa, 220-0011, Japan.
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
CEN Case Rep. 2021 Nov;10(4):592-597. doi: 10.1007/s13730-021-00605-x. Epub 2021 Jun 7.
Familial hypercholesterolemia (FH) and chronic kidney disease, especially end-stage renal disease (ESRD), are common and put patients at a high risk of developing atherosclerotic cardiovascular disease (ASCVD). ESRD concomitant with FH may further increase the risk of ASCVD. Achieving target levels of low-density lipoprotein cholesterol (LDL-C) is difficult owing to the limitations of statin administration due to its side effects in ESRD. Therefore, some FH patients with ESRD require lipoprotein apheresis for the prevention of secondary ASCVD events. Although proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors may offer a safe and effective option for lowering lipid levels in such patients, no guidelines are available for their use. Here, we report the case of two male siblings with FH in secondary prevention undergoing hemodialysis combined with PCSK9 inhibitor treatment. The siblings, who showed a heterozygous c.1846-1G>A mutation in the LDLR gene, underwent hemodialysis. In combination with the lipoprotein apheresis, siblings were administered evolocumab, a PCSK9 inhibitor. Both the siblings had coronary artery disease, diabetes, and ESRD, and received hemodialysis. Their LDL-C levels did not reach the target values despite administering statin, ezetimibe, and biweekly lipoprotein apheresis. On the introduction of evolocumab treatment, their LDL-C levels were significantly reduced without any adverse effects, resulting in successful withdrawal from lipoprotein apheresis therapy. Although the effects of switching from lipoprotein apheresis to PCSK9 inhibitors for cardiovascular protection remain unclear in FH patients with and without ESRD, our case report will be helpful in guiding future therapeutic decisions.
家族性高胆固醇血症（FH）和慢性肾脏病，尤其是终末期肾病（ESRD），较为常见，使患者发生动脉粥样硬化性心血管疾病（ASCVD）的风险增高。ESRD 合并 FH 可能会进一步增加 ASCVD 风险。由于他汀类药物的副作用，ESRD 患者他汀类药物的应用受限，导致 LDL-C 目标水平难以实现。因此，一些 ESRD 合并 FH 的患者需要脂蛋白吸附治疗来预防二级 ASCVD 事件。虽然前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂可能为降低此类患者的血脂水平提供安全有效的选择，但目前尚无其使用指南。在此，我们报告了 2 例 FH 二级预防行血液透析联合 PCSK9 抑制剂治疗的男性同胞病例。这对兄弟携带 LDLR 基因 c.1846-1G>A 杂合突变，行血液透析。在与脂蛋白吸附治疗联合应用的同时，给予他们 PCSK9 抑制剂依洛尤单抗。这对兄弟均患有冠心病、糖尿病和 ESRD，并接受血液透析。尽管他们接受了他汀类药物、依折麦布和每两周 1 次的脂蛋白吸附治疗，但 LDL-C 水平仍未达到目标值。开始依洛尤单抗治疗后，他们的 LDL-C 水平显著降低，且无任何不良反应，成功停止了脂蛋白吸附治疗。尽管在 ESRD 合并或不合并 FH 的患者中，将脂蛋白吸附治疗转换为 PCSK9 抑制剂进行心血管保护的效果尚不清楚，但我们的病例报告将有助于指导未来的治疗决策。
