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      Prof. Patrick M. Honore, MD, PhD, FCCM

      Professor of Medicine, Deputy Chairman of ICU Department

      Director of ICU Research Unit

      Centre Hospitalier Universitaire Brugmann

      Place Van GehuchtenPlein, BE–4-1020 Brussels (Belgium)

      E-mail [email protected]

      Bellomo R, Kellum JA, La Manna G, Ronco C (eds): 40 Years of Continuous Renal Replacement Therapy.

      Contrib Nephrol. Basel, Karger, 2018, vol 194, pp 25–37 (DOI: 10.1159/000485598)

      ______________________

Indications and Timing of Continuous Renal Replacement Therapy Application

      Sean M. Bagshaw^a · Ron Wald^b

      ^aDepartment of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, and ^bDivision of Nephrology, St. Michael’s Hospital, Toronto, ON, Canada

      ______________________

      Abstract

      Renal replacement therapy (RRT) is increasingly utilized to support critically ill patients with severe acute kidney injury (AKI). The clinical dilemma of when to ideally start RRT in these patients has been a longstanding issue that is in need of higher quality evidence to guide clinical practice. When clinicians are confronted with patients with life-threatening complications of AKI, the decision to start RRT is straightforward. However, in the absence of clear indications, the ideal circumstances and timing that balance the perceived benefits and risks of early versus delayed RRT remain uncertain. Survey data have confirmed substantial practice variation in the timing of RRT initiation. Most observational data and small clinical trials have limitations related to confounding by indication, heterogeneity in case-mix and illness severity, and variation in defining timing thresholds for starting RRT. Recently published trials have further added to the clinical uncertainty. This concise review provides an overview of prevailing and evolving evidence on the optimal time to start RRT in critically ill patients with AKI.

      © 2018 S. Karger AG, Basel

      Introduction

Recent temporal trends show increasing utilization of renal replacement therapy (RRT) in critically ill patients in intensive care unit (ICU) settings [1]. Continuous RRT (CRRT), a core life-support technology unique to the ICU, remains the most common form of renal support provided to critically ill patients.

The dilemma of when to ideally start CRRT in critically ill patients, specifically in those with acute kidney injury (AKI) or in those confronted with grossly impaired kidney function and multiorgan dysfunction, has been a longstanding challenge for intensivists and nephrologists. The decision to start RRT is often relatively straightforward in patients with medically refractory complications associated with AKI (i.e., hyperkalemia, acidemia, pulmonary edema, uremia); however, these complications are increasingly infrequent among critically ill patients [2]. In the absence of clearly urgent indications, the optimal time for starting CRRT remains uncertain. In these circumstances, the utilization of CRRT is driven largely by the perception of clinicians in terms of greater relative benefit than risk and often started in response to trends in illness acuity, non-renal organ dysfunction (i.e., acute lung injury) and kidney function recovery [3]. This issue, when to ideally start RRT in critically ill patients with AKI, has been identified as high priority for new knowledge in critical care and nephrology [4].

      How Is “Timing” Relative to Starting CRRT Defined?

There is no consensus on how to define ”timing” relative to starting CRRT in critically ill patients with AKI. Observational studies have employed a spectrum of definitions for “early,” “delayed” and “late” start of CRRT [5]. These studies have incorporated physiological measures (e.g., urine output), biochemical measures (e.g., serum creatinine, urea), start relative to AKI onset, start relative ICU admission, and start relative to the occurrence of a complication associated with AKI (i.e., a conventional indication). However, reference to “early,” “delayed,” or “late” is relative and susceptible to bias. What may represent an “early” start of RRT in one context may constitute “late” in another, where the spectrum of clinical characteristics, diagnoses, and illness severity vary. This heterogeneity in definitions for “timing” or “thresholds” or “criteria” across observational studies has contributed to lack of clarity to guide clinical practice and practice variation [2].

A common feature of observational data has been a general focus only on patients who received RRT, with omission of patients also with severe AKI not treated with RRT [6]. Although clinicians may have difficulty prospectively identifying such patients, it is well known that a subgroup of these patients will survive and recover kidney function, despite severe AKI, without ever receiving RRT [7]. The exclusion of the subgroup from observational data has contributed to “delayed” groups disproportionately comprised of patients with less favorable outcome. This result may be an overestimation of the relative survival advantage of earlier RRT initiation [5].

Survey data suggest the decision by clinicians to start CRRT in critically ill patients with AKI is largely subjective based on a wide spectrum of clinical information and the relative perception of benefit, and likely further modified by both patient-specific (i.e., age, multimorbidity, kidney reserve, response to a diuretic challenge, acuity of illness) and health-system-specific factors (i.e., prescribing service, time of day, day of week) [3]. Moreover, survey data also showed substantial variation in the minimum severity of indications that would

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