DOUBLE PRO-TECT Alport: A confirmatory, multicenter, randomized, double-blind, placebo-controlled clinical trial to assess the effect of Dapagliflozin on the progression of chronic kidney disease in adolescents and young adult patients with Alport syndrom

遗传性肾病Alport综合征，如果不治疗，会导致生命早期的终末期肾衰竭-这对患者及其整个家庭来说是一个巨大的负担。Alport综合征导致肾脏过滤器的脆弱性增加。器官被破坏了。在BMBF资助的研究EARLY PRO-TECT Alport中，我们能够证明儿童早期使用抗高血压药物（ACE抑制剂雷米普利）治疗的益处和安全性。德国外交部制作了一个视频短片，配有英文字幕（https：//www.gesundheitsforschung-bmbf.de/de/videoportrait-hilfe-fur-nierenkranke-kinder-14890.php）。世界上第一项针对Alport综合征儿童的研究在全球范围内取得了巨大成功：由于这项研究，2020年重新编写了针对2岁以上儿童的国际治疗指南。ACE抑制剂可以减缓疾病，但不能治愈它：它仍然在发展。因此，在儿童和年轻人的DOUBLE PRO-TECT Alport研究中，我们现在想研究是否可以通过所谓的SGLT 2抑制剂进一步减缓疾病。这里使用的SGLT 2抑制剂达格列净几个月前被批准用于慢性肾脏疾病成人。然而，在这些获得批准的大型研究中，达格列净仅在不到8例Alport综合征患者中进行了试验。我们从以前的研究中了解到，ACE抑制剂和SGLT 2抑制剂通过降低肾脏过滤器中的压力而相互补充。在我们的研究中，我们想证明，在患有Alport综合征的青少年中，特别脆弱的肾脏过滤器可以得到保护。在德国，超过1000名患有Alport综合征的年轻人患有慢性肾脏疾病，他们希望有更好的治疗方法，这样他们就不需要过早透析。然而，Alport综合征太罕见（因此在商业上太无趣），制药公司无法研究特殊疗法。这就是为什么家庭和医生需要DOUBLE PRO-TECT Alport研究。只有这项研究才能显示SGLT 2抑制剂在延迟我们许多患者的肾脏疾病方面的潜力有多大，甚至可能延迟到退休年龄。

The genetic kidney disease Alport Syndrome, if untreated, leads to end-stage kidney failure early in life - an enormous burden for the patient and their entire family. Alport syndrome leads to increased vulnerability of the kidney filter. The organs get destroyed. In a BMBF-funded study, EARLY PRO-TECT Alport, we were able to demonstrate the benefits and safety of early treatment with antihypertensive drugs (the ACE inhibitor ramipril) in children. This is précised in a videoportrait by the German Ministry with English subtitles (https://www.gesundheitsforschung-bmbf.de/de/videoportrait-hilfe-fur-nierenkranke-kinder-14890.php). The world's first study in children with Alport Syndrome was a great success worldwide: Thanks to the study, the international therapy guidelines for children from 2 years of age were re-written in 2020. ACE inhibitors can slow the disease down, but not cure it: it still progresses. Therefore, in the DOUBLE PRO-TECT Alport study in children and young adults, we now want to investigate whether the disease can be further slowed down by so-called SGLT2 inhibitors. The SGLT2 inhibitor dapagliflozin used here was approved a few months ago for adults with chronic kidney disease. However, in these large studies, which led to approval, dapagliflozin has only been tested on fewer than 8 patients with Alport syndrome. We know from previous studies that ACE inhibitors and SGLT2 inhibitors complement each other by lowering the pressure in the kidney filter. In our study, we want to prove that in adolescents with Alport Syndrome, the particularly vulnerable kidney filters can be protected. In Germany, over 1000 young people with Alport syndrome have chronic kidney disease and are hoping for better therapies so that they do not need dialysis too early. However, Alport Syndrome is too rare (and therefore too uninteresting commercially) for pharmaceutical companies to be investigated for special therapies. This is why families and doctors need the DOUBLE PRO-TECT Alport study. Only this study can show how great the potential of SGLT2 inhibitors is to delay kidney disease in many of our patients, perhaps even until retirement age.