McDaniel Bradford L, Bentley Michael L
Department of Pharmacy, Carilion Clinic, Roanoke, VA, USA.
Department of Biomedical Science, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
Integr Pharm Res Pract. 2015 May 18;4:21-29. doi: 10.2147/IPRP.S52930. eCollection 2015.
Prior to 2002, the incidence of acute renal failure (ARF) varied as there was no standard definition. To better understand its incidence and etiology and to develop treatment and prevention strategies, while moving research forward, the Acute Dialysis Quality Initiative workgroup developed the RIFLE (risk, injury, failure, loss, end-stage kidney disease) classification. After continued data suggesting that even small increases in serum creatinine lead to worse outcomes, the Acute Kidney Injury Network (AKIN) modified the RIFLE criteria and used the term acute kidney injury (AKI) instead of ARF. These classification and staging systems provide the clinician and researcher a starting point for refining the understanding and treatment of AKI. An important initial step in evaluating AKI is determining the likely location of injury, generally classified as prerenal, renal, or postrenal. There is no single biomarker or test that definitively defines the mechanism of the injury. Identifying the insult(s) requires a thorough assessment of the patient and their medical and medication histories. Prerenal injuries arise primarily due to renal hypoperfusion. This may be the result of systemic or focal conditions or secondary to the effects of drugs such as nonsteroidal anti-inflammatory drugs, calcineurin inhibitors (CIs), and modulators of the renin-angiotensin-aldosterone system. Renal, or intrinsic, injury is an overarching term that represents complex conditions leading to considerable damage to a component of the intrinsic renal system (renal tubules, glomerulus, vascular structures, inter-stitium, or renal tubule obstruction). Acute tubular necrosis and acute interstitial nephritis are the more common types of intrinsic renal injury. Each type of injury has several drugs that are implicated as a possible cause, with antiinfectives being the most common. Postrenal injuries that result from obstruction block the flow of urine, leading to hydronephrosis and subsequent damage to the renal parenchyma. Drugs associated with tubular obstruction include acyclovir, methotrexate, and several antiretrovirals. Renal recovery from drug-induced AKI begins once the offending agent has been removed, if clinically possible, and is complete in most cases. It is uncommon that renal replacement therapy will be needed while recovery occurs. Pharmacists can play a pivotal role in identifying possible causes of drug-induced AKI and limit their toxic effect by identifying those most likely to cause or contribute to injury. Dose adjustment is critical during changes in renal function, and the pharmacist can ensure that optimal therapy is provided during this critical time.
2002年以前，由于没有标准定义，急性肾衰竭（ARF）的发病率各不相同。为了更好地了解其发病率和病因，并制定治疗和预防策略，推动研究进展，急性透析质量倡议工作组制定了RIFLE（风险、损伤、衰竭、丧失、终末期肾病）分类法。后续数据持续表明，即使血清肌酐小幅升高也会导致更差的预后，急性肾损伤网络（AKIN）对RIFLE标准进行了修订，并使用急性肾损伤（AKI）一词取代ARF。这些分类和分期系统为临床医生和研究人员提供了一个起点，以完善对AKI的理解和治疗。评估AKI的一个重要初始步骤是确定可能的损伤部位，通常分为肾前性、肾性或肾后性。没有单一的生物标志物或检测方法能明确界定损伤机制。确定损伤因素需要对患者及其病史和用药史进行全面评估。肾前性损伤主要由于肾灌注不足引起。这可能是全身性或局部性疾病的结果，或继发于非甾体抗炎药、钙调神经磷酸酶抑制剂（CIs）以及肾素-血管紧张素-醛固酮系统调节剂等药物的作用。肾性或固有性损伤是一个总括性术语，代表导致固有肾系统（肾小管、肾小球、血管结构、间质或肾小管梗阻）某一组成部分受到严重损害的复杂情况。急性肾小管坏死和急性间质性肾炎是更常见的固有性肾损伤类型。每种损伤类型都有几种药物被认为可能是病因，其中抗感染药物最为常见。由梗阻导致的肾后性损伤会阻碍尿液流动，导致肾积水及随后的肾实质损伤。与肾小管梗阻相关的药物包括阿昔洛韦、甲氨蝶呤和几种抗逆转录病毒药物。一旦在临床可行的情况下停用致病药物，药物性AKI的肾脏功能开始恢复，且在大多数情况下可完全恢复。在恢复过程中通常不需要肾脏替代治疗。药剂师在识别药物性AKI的可能病因并通过确定最有可能导致或促成损伤的药物来限制其毒性作用方面可发挥关键作用。在肾功能变化期间，剂量调整至关重要，药剂师可确保在这个关键时期提供最佳治疗。
