Acute Kidney Injury Is Important in the Hospital and Afterward

Acute kidney injury (AKI) is a major contributor to morbidity and mortality in hospitalized patients across the world.1 Affecting up to 20% of all admissions (depending on which definition of AKI is used),2 AKI is the most common reason for new-inpatient nephrology consultation. Recent data suggest that AKI incidence has risen rapidly, by up to 10% per year.3,4 AKI is associated with a variety of serious shortand longterm complications. Approximately 33% to 60% of critically ill patients who develop dialysis-requiring AKI do not survive to hospital discharge, and mortality associated with dialysis-requiring AKI is greater than that associated with other serious conditions such as myocardial infarction or acute respiratory distress syndrome.5 Even relatively mild AKI in the acute inpatient setting appears to be an independent risk factor for mortality.6 For several decades, many physicians believed that AKI was a self-limited process followed by complete recovery of renal function to pre-AKI levels among survivors. (Numerous trainees have been taught some variant of the old adage: “If the patients survive, so will their kidneys.”) But studies linking AKI with the development of new-onset chronic kidney disease (CKD) or the accelerated progression of pre-existing CKD have changed this view.7 One important reason the long-term impact of AKI hasn’t been appreciated is that, traditionally, clinical studies of AKI examined inhospital outcomes such as short-term mortality and resource usage and did not consider what transpired months to years after discharge. More recently, epidemiologic studies linking inpatient events with outpatient outcomes have filled this knowledge gap.8 Contemporary animal models of AKI have shed light on potential mechanisms of maladaptive repair after AKI, characterized by fibrosis, vascular rarefaction, tubular loss, glomerulosclerosis, and chronic interstitial inflammation, all of which result in renal function decline. So over the last decade there has been a paradigm shift in how we think about AKI and CKD. Rather than distinct entities, AKI and CKD are now viewed as interconnected syndromes since AKI is a risk factor for CKD progression and CKD is a risk factor for new episodes of AKI.9 Two studies published in this issue of the Journal of Hospital Medicine augment our understanding of AKI and its clinical impact in hospitalized patients. Analyzing data from the National Inpatient Sample, Silver et al.10 found that hospitalizations that include AKI are substantially costlier and associated with longer lengths of stay than hospitalizations without AKI. The authors also highlight that the additional economic costs of AKI exceeded those of many other higher-profile yet less-common acute medical conditions, such as myocardial infarction and gastrointestinal bleeding. These results re-emphasize the important economic burden of AKI at a national level and expand on prior literature by confirming findings previously limited to single-center and regional studies. Better defining the impact AKI has on our healthcare system could help ensure that adequate resources are invested to combat AKI. The second study, by Rutter et al.,11 found that among hospitalized patients with normal baseline renal function, use of vancomycin in combination with piperacillin-tazobactam is associated with a higher incidence of AKI after antibiotic exposure than use of either agent as monotherapy. This association persisted even after adjusting for potential confounders such as underlying comorbidities, exposure to nephrotoxic agents, documented hypotension, and baseline renal impairment. This study adds to a growing body of literature that suggests synergistic nephrotoxicity between vancomycin and piperacillin-tazobactam. It underscores that any medical intervention—even treatments typically envisioned as non-hazardous and frequently life-saving—involve inherent risks and should prompt the medical community to promote proper antimicrobial stewardship. Whether such exposures to vancomycin or beta-lactam derivatives cause AKI via direct tubular damage, interstitial nephritis, or some other novel mechanism remains to be elucidated. Better delineation of the contemporary causes of AKI, including increased antibiotic exposure, is the first step toward identifying ways to reduce AKI incidence. Both of these papers serve to highlight the clinical importance of AKI among hospitalized patients. Their findings re-emphasize the need for vigilance in detecting AKI and intervening early to achieve the best clinical outcomes. Given recent understanding that survivors of AKI are at greater risk for more rapid loss of renal function long after hospital discharge, one goal the US Department of Health and Human Services put forth for Healthy People 2020 is to “increase the proportion of hospital patients who incurred AKI who have follow-up renal evaluation in 6 months post-discharge” (10% improvement targeted).12 Transitions of care after hospitalizations complicated by AKI require special attention to ensure that patients’ needs are optimally *Address for correspondence and reprint requests: Benjamin J. Lee, MD, Division of Nephrology, University of California San Francisco, 533 Parnassus Avenue, U404, San Francisco, CA 94143; Telephone: 415-476-1812; Fax: 415476-3381; E-mail: bjlee@ucsf.edu