Department of Pediatrics, Division of Nephrology, Duke University Medical Center, Durham, NC, USA.
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
Nat Rev Nephrol. 2023 Aug;19(8):479-480. doi: 10.1038/s41581-023-00721-0.
Chronic kidney disease (CKD) is highly prevalent World-Wide and it is an important cause of morbidity and mortality. In 2010, variants in ( gene was identified as a major risk factor for higher prevalence of CKD in individuals of African ancestry. The mechanisms by which toxic gain of function variants cause disease are the subjects of current investigations, and there is currently no effective targeted therapy for associated kidney disease. Egbuna and others recently reported that an orally administered small molecule compound inaxaplin (VX-147) that binds APOL1 may be useful in the treatment of associated kidney disease. This is a groundbreaking study, if confirmed in randomized control studies it may turn out to be one of the major advances in the therapy of proteinuric CKD this decade, and may also represent precision therapy for addressing health disparity in CKD. However, there is a need for a larger randomized control studies with stable eGFR and complete remission of proteinuria as end point, such studies should also be carried out in a more geographically diverse population.
慢性肾脏病（CKD）在全球范围内高发，是发病率和死亡率的重要原因。2010 年，（基因中的变异被确定为非裔个体 CKD 患病率较高的主要危险因素。目前正在研究毒性获得性功能变异导致疾病的机制，而针对 相关肾脏疾病目前尚无有效的靶向治疗方法。Egbuna 等人最近报道，一种口服小分子化合物 inaxaplin（VX-147）可与 APOL1 结合，可能对 相关肾脏疾病有治疗作用。这是一项具有开创性的研究，如果在随机对照研究中得到证实，它可能成为本十年治疗蛋白尿性 CKD 的主要进展之一，也可能代表针对 CKD 健康差异的精准治疗。然而，需要进行更大规模的随机对照研究，以稳定的 eGFR 和蛋白尿完全缓解为终点，此类研究还应在更具地域多样性的人群中进行。
