Laboratoire de Physiologie Rénale et Tubulopathies, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université, Université Paris Cité, F-75006 Paris, France.
Unité Métabolisme et Physiologie Rénale, Centre National de la Recherche Scientifique (CNRS) EMR8228, F-75006 Paris, France.
Genes (Basel). 2024 Sep 7;15(9):1175. doi: 10.3390/genes15091175.
Dent disease type 1 is a rare X-linked recessive inherited renal disorder affecting mainly young males, generally leading to end-stage renal failure and for which there is no cure. It is caused by inactivating mutations in the gene encoding ClC-5, a 2Cl/H exchanger found on endosomes in the renal proximal tubule. This transporter participates in reabsorbing all filtered plasma proteins, which justifies why proteinuria is commonly observed when ClC-5 is defective. In the context of Dent disease type 1, a proximal tubule dedifferentiation was shown to be accompanied by a dysfunctional cell metabolism. However, the exact mechanisms linking such alterations to chronic kidney disease are still unclear. In this review, we gather knowledge from several Dent disease type 1 models to summarize the current hypotheses generated to understand the progression of this disorder. We also highlight some urinary biomarkers for Dent disease type 1 suggested in different studies.
Dent 病 1 型是一种罕见的 X 连锁隐性遗传性肾脏疾病，主要影响年轻男性，通常导致终末期肾衰竭，目前尚无治愈方法。它是由编码 ClC-5 的基因失活突变引起的，ClC-5 是一种在肾脏近端小管内体中的 2Cl/H 交换器。这种转运蛋白参与重吸收所有滤过的血浆蛋白，这就是为什么 ClC-5 缺陷时通常会观察到蛋白尿的原因。在 Dent 病 1 型的背景下，已经表明近端小管去分化伴随着功能障碍的细胞代谢。然而，将这些改变与慢性肾脏病联系起来的确切机制仍不清楚。在这篇综述中，我们汇集了来自几种 Dent 病 1 型模型的知识，以总结目前为了解释该疾病进展而提出的假设。我们还强调了不同研究中提出的一些用于 Dent 病 1 型的尿生物标志物。
