The role of medications and their management in acute kidney injury.

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.

Peramivir pharmacokinetics in a patient receiving continuous veno-venous hemodiafiltration during the 2009 H1N1 influenza A pandemic.

OBJECTIVE: Peramivir is a neuraminidase inhibitor having activity against various influenza A and B subtypes. The main route of elimination is the kidney and a dose reduction is justified for multiple-day therapy when the creatinine clearance is < 50 mL/min. Before the 2009 influenza pandemic, dosing guidelines did not exist for patients receiving continuous renal replacement therapy (CRRT). This case report provides data on the dialysis membrane saturation coefficient (SA) and pharmacokinetic parameters of peramivir in a 29-year-old female receiving continuous veno-venous hemodiafiltration (CVVHDF), a mode of CRRT. METHODS: Plasma and effluent samples were collected to calculate the saturation coefficient, plasma half-life, maximum and minimum plasma concentrations, and area under the plasma drug concentration-time curve (AUC) for peramivir. CVVHDF was performed using a Prisma pump and an AN69 filter. During peramivir sampling, the dialysate flow rate was 16.7 mL/min. The mean total ultrafiltrate produced was 14.2 mL/min. To calculate a saturation coefficient (SA), simultaneous sampling of blood and effluent was performed. Pre- and post-filter as well as effluent samples were obtained 4.5 and 8.5 hours following the 3rd dose of 480 mg. Plasma concentrations were also obtained at several time points and the AUC estimated from 0 to 24 hours (AUC0-24). RESULTS: The maximum plasma concentration (C30min) was 19,477 ng/mL, the minimum plasma concentration (Cmin) 2,750 ng/mL, and AUC0-24 196,166 ng x h/mL. The estimated plasma half-life was 8.2 hours with a log-linear decrease over the 24-hour period suggesting significant extracorporeal clearance. The calculated SA was 0.98, similar to an estimated SA of 1. CONCLUSION: Peramivir is readily cleared by CVVHDF having a calculated SA close to 1. The maximum and minimum plasma concentrations, AUC0-24, and plasma half-life was similar to those previously reported. These data will be useful in determining appropriate peramivir dosing regimens for severely ill influenza patients with acute renal impairment managed by CVVHDF.

Process indicators of quality clinical pharmacy services during transitions of care.

The American College of Clinical Pharmacy charged the Public and Professional Relations Committee to develop a short white paper describing quality measures of clinical pharmacists' patient care services in transitional care settings. Transitional care describes patient movement from one health care setting or service to another. Care transitions are associated with an increased risk of adverse events for patients. Pharmacists play an important role in ensuring that medication errors and adverse events are minimized during these transitions, largely through the reconciliation of medications and assurance of continuity of care. Quality measures are often divided into three domains: structure, process, and outcome. Given the typical nature of the pharmacist's role, process indicators are best suited to evaluate quality clinical pharmacist services. However, process indicators relevant to pharmacists' activities are not yet fully described in the literature. The committee searched available literature describing quality measures that are directly influenced by the pharmacist during care transitions. This white paper describes these process indicators as quality measures of clinical pharmacists' services, identifies the transitional settings and activities to which they are most applicable, and provides the published sources from which indicators were derived. For process indicators that could not be found in published sources, we propose relevant measures that can be adapted for use in a given setting. As pharmacists become more involved in diverse and emerging patient care areas such as transitional care, it will be critical that they use these types of measures to document the quality of new services and reinforce the need for pharmacist participation during transitions of care.

Acute kidney insufficiency in the critically ill.

Acute kidney insufficiency (AKI), or injury, is common in the critically ill patient. Minimal increases in serum creatinine (Scr) have been associated with greater morbidity, mortality, and hospital cost. In 2002, the Acute Dialysis Quality Initiative (ADQI) proposed a consensus definition (the RIFLE classification) which was modified after continuing evidence suggested that small changes in Scr (≥0.3 mg/dL) led to worsening outcomes. This group, known as the Acute Kidney Injury Network (AKIN), suggests 3 stages of worsening kidney function. Such definitions may aid in identifying patients at greatest risk and further the development of preventive strategies. This review will focus on the epidemiology and etiology of AKI as well as provide a mechanistic description of drug-induced AKI. In addition, a brief review of continuous renal replacement therapies is provided.

Drug-induced acute kidney injury in the critically ill adult: recognition and prevention strategies.

Acute kidney injury is common in critically ill patients, with an incidence of 20% to 30%. It has been associated with increased mortality, hospital length of stay, and total cost. A number of strategies may be beneficial in identifying at-risk patients. In addition, using preventive measures and avoiding nephrotoxic medications are paramount in reducing the overall incidence. Although multifactorial, drug-induced acute kidney injury may account for up to 25% of all cases of acute kidney injury in this population. This review focuses on the mechanisms of drug-induced acute kidney injury in critically ill adults and offers preventive strategies when appropriate.