Bahlmann-Kroll Elisabeth, Häckl Sebastian, Kramer Stefanie, Wulfmeyer Vera Christine, Glandorf Julian, Kaufeld Jessica, Koch Armin, Hartung Dagmar, Schmidt Bernhard M W, Schmidt-Ott Kai, Schmitt Roland
Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
BMJ Open. 2024 Dec 15;14(12):e088317. doi: 10.1136/bmjopen-2024-088317.
Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that causes the formation of cysts primarily in the kidneys. The continuous growth of multiple cysts leads to the destruction of functional parenchyma, which may progress to end-stage kidney disease. Tolvaptan is the only drug specifically approved for slowing down the progression of ADPKD. Sodium-glucose transporter 2 inhibitors might provide additional benefits but there is currently no information on safety and outcome effects of SGLT2i in patients with ADPKD, as these patients were excluded in SGLT2i trials. In particular, there has been speculation that SGLT2i might increase cyst growth and accelerate the loss of kidney function in ADPKD. The EMPA-PKD trial is assessing the safety of empagliflozin in patients with rapid progressive ADPKD with and without concomitant tolvaptan use by monitoring the total kidney volume and the loss of kidney function.
This is an investigator-initiated, double-blind, single-centre, placebo-controlled, randomised clinical trial including patients with rapidly progressive ADPKD (n=44). Participants will be randomly allocated (1:1) to receive a daily dose of either empagliflozin (10 mg/day) or placebo for 18 months. Patients will be stratified according to concomitant tolvaptan use. The primary endpoint is the progression of cystic kidney growth by monitoring MRI-based changes in total kidney volume and the secondary endpoint is the change in glomerular filtration rate. Additional endpoints include changes in copeptin levels, albuminuria and blood pressure.
The protocol has been approved by the German Federal Institute for Drugs and Medical Devices (BfArM) after review by the independent ethics committee Landesarztekammer Rheinland-Pfalz. Participation in this study will be voluntary and informed consent will be obtained. Regardless of the outcome, the results will be disseminated through a peer-reviewed international medical journal.
EU-CT number 2023-505890-34-00, NCT06391450.
常染色体显性多囊肾病（ADPKD）是一种遗传性疾病，主要导致肾脏中形成囊肿。多个囊肿的持续生长会导致功能性实质组织遭到破坏，进而可能发展为终末期肾病。托伐普坦是唯一被专门批准用于减缓ADPKD病情进展的药物。钠-葡萄糖协同转运蛋白2抑制剂可能会带来额外益处，但目前尚无关于ADPKD患者使用钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）的安全性和疗效的信息，因为这些患者在SGLT2i试验中被排除在外。特别是，有人猜测SGLT2i可能会增加ADPKD患者的囊肿生长并加速肾功能丧失。EMPA-PKD试验正在通过监测总肾体积和肾功能丧失情况，评估恩格列净在伴有或不伴有托伐普坦使用的快速进展性ADPKD患者中的安全性。
这是一项由研究者发起的、双盲、单中心、安慰剂对照的随机临床试验，纳入快速进展性ADPKD患者（n = 44）。参与者将被随机分配（1:1），接受每日一次的恩格列净（10毫克/天）或安慰剂治疗，为期18个月。患者将根据是否同时使用托伐普坦进行分层。主要终点是通过监测基于MRI的总肾体积变化来评估囊性肾脏生长的进展情况，次要终点是肾小球滤过率的变化。其他终点包括 copeptin 水平、蛋白尿和血压的变化。
该方案在经过独立伦理委员会莱茵兰-普法尔茨州医师协会审查后，已获得德国联邦药品和医疗器械研究所（BfArM）的批准。参与本研究将是自愿的，并将获得知情同意书。无论结果如何，研究结果都将通过同行评审的国际医学期刊进行传播。
欧盟临床试验编号2023 - 505890 - 34 - 00，美国国立医学图书馆临床试验注册编号NCT06391450。
