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肾脏疾病的基因治疗:对老年人有哪些益处?

Gene therapy for renal disorders: what are the benefits for the elderly?

作者信息

Lien Yeong-Hau H, Lai Li-Wen

机构信息

Department of Medicine, University of Arizona Health Sciences Center, Tucson 85724, USA.

出版信息

Drugs Aging. 2002;19(8):553-60. doi: 10.2165/00002512-200219080-00001.

Abstract

Chronic renal failure is one of the major health problems for the elderly. Currently, about 50% of all patients receiving chronic dialysis for end-stage renal disease (ESRD) are aged 65 years or older. Their first-year mortality rate is as high as 30%. The leading causes of ESRD in the elderly are diabetic nephropathy, hypertension and large vessel diseases, and glomerulonephritis. The elderly are also prone to developing acute renal failure induced by ischaemic injury or nephrotoxic drugs. Gene transfer in experimental animals have been tested in all of these conditions, as well as in animal kidney transplantation models, with various degrees of success. However, there are many obstacles to be overcome before gene therapy can be tested clinically for renal disorders. In particular, the major challenges include determining how to prolong and control transgene expression or antisense inhibition and how to minimise the adverse effects of viral or nonviral vectors. Once these problems are solved, gene therapy will have a role in treating age-related renal impairment.

摘要

慢性肾衰竭是老年人面临的主要健康问题之一。目前,所有接受终末期肾病(ESRD)长期透析治疗的患者中,约50%年龄在65岁及以上。他们的第一年死亡率高达30%。老年人ESRD的主要病因是糖尿病肾病、高血压和大血管疾病以及肾小球肾炎。老年人也容易发生由缺血性损伤或肾毒性药物引起的急性肾衰竭。在所有这些病症以及动物肾脏移植模型中,均已在实验动物中对基因转移进行了测试,并取得了不同程度的成功。然而,在基因疗法能够用于肾脏疾病的临床测试之前,还有许多障碍需要克服。特别是,主要挑战包括确定如何延长和控制转基因表达或反义抑制,以及如何将病毒或非病毒载体的不良影响降至最低。一旦这些问题得到解决,基因疗法将在治疗与年龄相关的肾功能损害方面发挥作用。

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