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

目前在澳大利亚，估计约有6万人患有慢性肾功能衰竭(CKF)。在至少80%的CKF患者中，肾功能将继续恶化(由于疾病的进展)，直到出现终末期肾功能衰竭(ESKF)。如果发生后一种情况，患者必须每天接受透析或肾移植治疗才能存活。目前，澳大利亚有近10000名ESKF患者正在接受透析或移植治疗。虽然这些治疗方法使患者得以存活，但它们与严重的和不可接受的患者发病率和死亡率有关。目前减少CKF疾病进展(从而延长达到ESKF的时间)的药物治疗是非特异性的、部分有效的，并且有不同的反应。此外，目前尚不清楚这些治疗方法能否阻止CKF的进展。使整个问题更加复杂的是，开始慢性透析计划的新患者数量正在增加(每年增加6%)。因此，ESKF被领导当局描述为一场世界性的医疗灾难，澳大利亚肾脏基金会建议将研究如何减少-阻止CKF的进展作为紧急优先事项。在CKF中，肾脏经历了补偿性生长，这是有害的，而且矛盾地促进了疾病的进展。该研究计划的目的是促进对肾纤维化肾脏生长的分子机制的了解，具体目标是：(I)为以药物为基础的肾脏生长调控寻找新的分子靶点；以及(Ii)测试能够改变肾脏生长从而减缓肾纤维化进展的实验药物的疗效。

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.