Regulators of cell cycle as therapeutic drug-targets for cortical tubular hyperplasia in proteinuric renal disease

细胞周期调节剂作为蛋白尿性肾病皮质小管增生的治疗药物靶点

• 批准号: nhmrc : 230500
• 负责人: A/Pr Gopala Rangan
• 金额: $ 14.65万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulators-cell-cycle-renal-disease/97656
• 关键词: Regulators; cell; cycle; therapeutic; drug

Currently in Australia, it has been estimated that approximately 60 000 people suffer from chronic kidney failure (CKF). In at least 80% of people with CKF, the kidney function will continue to worsen (due to disease progression) to the point where end-stage kidney failure (ESKF) has developed. When the latter occurs daily treatment by either dialysis or kidney transplantation is mandatory for a person to survive. At present, there are nearly 10 000 patients with ESKF who are being treated by dialysis or transplantation, in Australia. Although these treatments have allowed patients to survive, they are associated with significant and unacceptable patient morbidity and mortality. Current medical treatments to reduce the disease progression of CKF (and thereby extend the time taken to reach ESKF) are non-specific, partially effective and have a variable response. Also, these treatments are NOT known to arrest the progression of CKF. To compound the overall problem even further, the number of new patients starting chronic dialysis programmes is increasing (by 6% per year). Consequently, ESKF has been described by leading authorities as a medical catastrophe of world-wide dimensions, and research into ways to reduce-arrest the progression of CKF has been recommended as an urgent priority by the Australian Kidney Foundation. In CKF, the kidneys undergo compensatory growth which is harmful and paradoxically contributes to disease progression. The aim of this research program is to advance knowledge about the molecular mechanisms of kidney growth in CKF, with specific goals of: (i) identifying new molecular targets for drug-based manipulation of kidney growth; and (ii) to test the efficacy of experimental drugs which have an ability to alter kidney growth, and thereby reduce the progression of CKF.

目前在澳大利亚，据估计约有6万人患有慢性肾衰竭（CKF）。在至少80%的CKF患者中，肾功能将继续恶化（由于疾病进展），直至发展为终末期肾衰竭（ESKF）。当后者发生时，通过透析或肾移植进行日常治疗是一个人生存的必要条件。目前，澳大利亚有近1万名ESKF患者正在接受透析或移植治疗。尽管这些治疗使患者得以存活，但它们与显著且不可接受的患者发病率和死亡率相关。目前减少CKF疾病进展（从而延长达到ESKF所需的时间）的药物治疗是非特异性的，部分有效，并且具有可变的反应。此外，这些治疗方法还不知道是否能阻止CKF的进展。使整个问题更加复杂的是，开始长期透析计划的新患者人数正在增加（每年增加6%）。因此，ESKF已被主要权威机构描述为世界范围的医学灾难，澳大利亚肾脏基金会已建议将研究减少-阻止CKF进展的方法作为紧急优先事项。在CKF中，肾脏经历代偿性生长，这是有害的，并且矛盾地有助于疾病进展。该研究计划的目的是推进有关CKF肾脏生长的分子机制的知识，具体目标是：（i）确定基于药物的肾脏生长操纵的新分子靶点;（ii）测试具有改变肾脏生长能力的实验药物的功效，从而减少CKF的进展。