Renal, Dialysis and Transplant Unit, Department of Emergency and Transplantation, University of Bari, Bari, Italy.
Clin Exp Immunol. 2010 Mar;159(3):268-80. doi: 10.1111/j.1365-2249.2009.04065.x. Epub 2009 Nov 24.
Although notable progress has been made in the therapeutic management of patients with chronic kidney disease in both conservative and renal replacement treatments (dialysis and transplantation), the occurrence of medication-related problems (lack of efficacy, adverse drug reactions) still represents a key clinical issue. Recent evidence suggests that adverse drug reactions are major causes of death and hospital admission in Europe and the United States. The reasons for these conditions are represented by environmental/non-genetic and genetic factors responsible for the great inter-patient variability in drugs metabolism, disposition and therapeutic targets. Over the years several genetic settings have been linked, using pharmacogenetic approaches, to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, analysing single gene or candidate pathways, do not represent the gold standard, being the overall pharmacological effects of medications and not typically monogenic traits. Therefore, to identify multi-genetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole genomic high-throughput technologies. However, to date, only few pharmacogenomics reports have been published in nephrology underlying the need to enhance the number of projects and to increase the research budget for this important research field. In the future we would expect that, applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic make-up, to monitor carefully the efficacy/toxicity of a given drug and to modify the dosage or number of medications to obtain predefined clinical outcomes.
尽管在慢性肾脏病的保守治疗和肾脏替代治疗(透析和移植)方面已经取得了显著进展,但药物相关问题(疗效不足、药物不良反应)的发生仍然是一个关键的临床问题。最近的证据表明,药物不良反应是欧洲和美国患者死亡和住院的主要原因。造成这些情况的原因包括环境/非遗传和遗传因素,这些因素导致药物代谢、处置和治疗靶点在患者之间存在很大的变异性。多年来,已经使用药物遗传学方法将几种遗传背景与许多用于临床肾脏病学的药物的作用和毒性联系起来。然而,这些分析单个基因或候选途径的策略并不能代表金标准,因为药物的整体药理作用通常不是单基因特征。因此,为了确定药物反应的多基因影响,来自不同医学和药理学领域的研究人员和临床医生已经开始采用创新的全基因组高通量技术进行药物基因组学研究。然而,迄今为止,在肾脏病学中仅发表了少数药物基因组学报告,这表明需要增加项目数量并增加该重要研究领域的研究预算。在未来,我们希望应用关于个体对药物遗传反应的知识,肾病学家能够根据每个人的基因构成来开处方,仔细监测给定药物的疗效/毒性,并调整剂量或药物数量以获得预定的临床结果。