Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Nephrol Dial Transplant. 2024 Nov 27;39(12):2048-2057. doi: 10.1093/ndt/gfae113.
Despite continuous advancement, treatment of lupus nephritis (LN) remains challenging. Recent guidelines now include a regimen incorporating tacrolimus as a first-line treatment option. Even though tacrolimus is effective in combination with mycophenolate and corticosteroids, concerns remain regarding long-term use, given its association with increased cardiovascular risks including nephrotoxicity, hypertension, dyslipidemia and hyperglycemia in kidney transplant recipients. However, in LN, long-term evaluations and head-to-head comparisons are lacking and thus the safety profile remains ill-defined. We hypothesized that chronic toxicity also occurs in LN patients. Therefore, this study aimed to assess long-term cardiovascular and renal outcomes of tacrolimus in LN patients.
This observational cohort study examined adult LN patients treated with tacrolimus, assessing renal outcomes, hypertension, diabetes, dyslipidemia, cardiovascular events and the Framingham risk score. The results were compared with a control group of CNI-naïve LN patients.
Of the 219 LN patients in this study, 43 (19.6%) had tacrolimus exposure. Over a median follow-up of 7.1 years, tacrolimus use was associated with significant kidney function decline (6.8 mL/min/1.73 m2, versus 0.8 in the control group). The incidence of end-stage kidney disease was similar. Cardiovascular event incidence was equally low in both groups. The 10-year risk of coronary heart disease was lower in the tacrolimus group, primarily due to age differences. HbA1c levels were higher in the tacrolimus group (37.4 mmol/mol) than in controls (33.6 mmol/mol), although the incidence of diabetes was similar. There were no differences in the occurrence of hypertension or dyslipidemia.
Our study demonstrated that tacrolimus exposure was associated with long-term kidney function loss in LN patients. Although cardiovascular risk factors and events were similar to patients never exposed to tacrolimus, there may be an increased risk of developing diabetes. Therefore, our study supports vigilance towards renal adverse effects in LN patients treated with tacrolimus.
尽管不断取得进展，但狼疮肾炎 (LN) 的治疗仍然具有挑战性。最近的指南现在包括将他克莫司作为一线治疗选择的方案。尽管他克莫司与吗替麦考酚酯和皮质类固醇联合使用有效，但由于与肾毒性、高血压、血脂异常和高血糖等心血管风险增加相关，长期使用仍存在担忧，在接受肾移植的患者中。然而，在 LN 中，缺乏长期评估和头对头比较，因此安全性仍未明确。我们假设慢性毒性也会发生在 LN 患者中。因此，本研究旨在评估 LN 患者他克莫司的长期心血管和肾脏结局。
这项观察性队列研究检查了接受他克莫司治疗的成年 LN 患者，评估了肾脏结局、高血压、糖尿病、血脂异常、心血管事件和弗雷明汉风险评分。结果与一组未接受 CNI 治疗的 LN 患者进行了比较。
在这项研究的 219 名 LN 患者中，有 43 名（19.6%）有他克莫司暴露。在中位数为 7.1 年的随访中，他克莫司的使用与肾功能显著下降相关（6.8 mL/min/1.73 m2，而对照组为 0.8）。终末期肾病的发病率相似。两组心血管事件的发病率同样较低。由于年龄差异，他克莫司组 10 年患冠心病的风险较低。他克莫司组的 HbA1c 水平（37.4 mmol/mol）高于对照组（33.6 mmol/mol），尽管糖尿病的发病率相似。高血压或血脂异常的发生率没有差异。
我们的研究表明，他克莫司暴露与 LN 患者的长期肾功能丧失有关。尽管与从未接触过他克莫司的患者相比，心血管危险因素和事件相似，但发生糖尿病的风险可能会增加。因此，我们的研究支持对接受他克莫司治疗的 LN 患者的肾脏不良反应保持警惕。
