|Year : 2018 | Volume
| Issue : 4 | Page : 121-125
Acute kidney injury: A definition with a rich past and an evolution
Dimitrios C Karathanasis1, C Androula Karaolia2
1 Department of Nephrology, 404 General Military Hospital, Larissa, Greece
2 Department of Neurosurgery, University of Thessaly, Larissa, Greece
|Date of Web Publication||27-May-2019|
Dr. Dimitrios C Karathanasis
Andrea Papandreou 49, Terpsithea-Larisa, 41500 Larisa
Source of Support: None, Conflict of Interest: None
The term acute kidney injury (AKI) appeared in the society of nephrology in 2004 mirroring a key station of the constant development of the whole entity of acute renal failure. The long route from “acute Bright's disease” in the 19th century to modern “acute kidney stress” reflects the continuous effort of the society of nephrology to set the appropriate criteria and finally to formulate a precise and consensus definition in nomenclature of kidney injury. The most important definitions were the Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease in 2004, Acute Kidney Injury Network (AKIN) in 2007, and Kidney Disease Improving Global Outcomes (KDIGO) in 2012 which had been proposed by the committees of Acute Dialysis Quality Initiative, AKIN, and KDIGO, respectively. Common basis of the above definitions was the clinical-laboratory criteria of urine output and serum creatinine while the target of every newer attempt was to increase the sensitivity of AKI and to offer a globally unified perception in terms of diagnosis and prevention. Since the emersion of KDIGO definition, the interest in defining AKI has been focused on the stage that precedes renal damage by the detection of clinically reliable biomarkers. Subsequently, the concept of acute injury is being lately realized as an attack in correspondence with heart attack or even more as an acute stress which can only be witnessed by the appropriate biomarkers. Recent research is focusing on the discovery of the ideal biomarker which must meet the requirements of high specificity, low cost, and ease of application.
Keywords: Acute kidney injury, acute kidney stress, acute renal failure
|How to cite this article:|
Karathanasis DC, Karaolia C A. Acute kidney injury: A definition with a rich past and an evolution. J Integr Nephrol Androl 2018;5:121-5
| Introduction|| |
The term acute kidney injury (AKI) was introduced in the nephrological terminology in 2004 as a replacement for the older term acute renal failure (ARF)., The inevitable need for the replacement of the term ARF had two main reasons. On one hand, >35 definitions were in use for this term in clinical practice, causing confusion and disorientation. On the other hand, this term was focusing only on the clinical-laboratory result of the reduction of kidney function, ignoring the fact that this is a result of a kidney injury process that has commenced much earlier, owed to a complex etiology and pathophysiology. Since then, the international nephrological community has concentrated on the evolution of the new definition and the more precise definition of the prerequisites for its implementation.,
| Historical Review|| |
To investigate the historical course in the definition of ARF, one can define four major periods:
The period before World War I
Already in the antiquity, Galenus connected renal disease with a reduced urine production. Much later, in the 18th century, Morgagni attributed the reduction of urine production to damages along the urinary tract, whereas in the 19th century, ARF was described by Bright receiving the name “acute Bright's disease.” Despite the aforementioned stations of the period, in general lines, renal disease was combined with a reduction in the production of urine.
The period of World Wars I and II
The abundance of related cases during the war has led to the appearance at first in the German literature, during World War I and later in the English literature (during World War II) of references that correlated for the first-time kidney damage with various elements of the metabolism.
The postwar period and until 2000
This period opens with the introduction in literature of the term ARF by Frank in 1946, despite the fact that this was attributed by many to the kidney physiologist Homer Smith. This introduction was followed by a continuous publication of different definitions of ARF, depending on the clinical and laboratory criteria that each definition emphasized. This polyphony led to incomparable conclusions of the performed clinical studies and caused differentiation in the results on the incidence and mortality of the disease.,
The initial abundance of definitions for ARF led gradually to the formation of a definition with the main features of rapid reduction of renal function with subsequent retention of metabolic products as well as disorders related to the extracellular fluid volume, electrolytes, and acid–base balance., Frequently, the term ARF was combined with a determination of gravity, ranging from mild, in cases of a small increase in serum creatinine values, to severe, in cases demanding mechanical support of the kidney function.
The continuous appearance of novel definitions for ARF renders the idea mature that a new, commonly acceptable definition is needed. The new definition must be simple, easily comprehensible, and be able to define at a high level of sensitivity and specificity for the diagnosis of ARF, also accurately contributing to its classification. The ground was prepared in 1999 by efforts aiming to determine and form a well-accepted definition for AKI caused by contrast agents, and in 2001 by formation of criteria to distinguish among AKI, syndrome of AKI and syndrome of severe AKI. Continuity was given by the USA National Institutes of Health and the research group of the American Society of Nephrology that propounded the characterization and term AKI, when studying ARF.
The period between 2004 and until today
This period starts from the insertion of the first commonly agreed and accepted definition of AKI in 2004, which gives prominence to the injury that preceded rather than to the following deficiency. This particular period is divided by three significant time spots, whereas some other less important new efforts occurred too:
Acute Dialysis Quality Initiative–Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (2004)
In 2004, a research group comprising nephrologists and intensivists being named Acute Dialysis Quality Initiative (ADQI), which was formed so as to study the quality of acute clearance, published the first, collectively formulated definition of AKI known as Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE). This new definition was based on the parameters, such as serum creatinine or glomerular filtration rate (GFR) and the volume of urine output, showing in this way the severity of AKI at the same time.
More specifically, the new definition consists of three clinical-laboratory criteria, which estimate the grade of injury (risk, injury, and failure), and two prognostic criteria (loss of kidney function and end-stage kidney disease), as shown in [Table 1]. The time in which these clinical-laboratory criteria appear, as in the context of the definition, is demanded to be recent, from 1 to 7 days, and have a persistent character.
|Table 1: Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease criteria|
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The central objective was to detect both cases of mild AKI and thus high sensitivity and low specificity and the cases of advanced AKI and thus low sensitivity and high specificity. A prerequisite is the knowledge of the previous serum creatinine value, and if this is not known, while at the same time there is an absence of history of chronic kidney disease, 75 mL/min/1.73 m2 is considered the baseline GFR. In the next few years, there was a cataclysmic invasion of the new definition in the literature of nephrology with a wide clinical and research application.,,,
The positive points of the RIFLE definition include the first systematic attempt of a commonly accepted definition and the increased predictive value for the determination of mortality., However, the need for serum creatinine to be used with all known factors of endogenous production such as age, diet, and medication were shown and recorded. Nevertheless, the recommendation of the RIFLE definition for arbitrary consideration of the baseline serum creatinine, when not available, was pointed out and underlined negatively. Several limitations, such as the administration of diuretics, may still influence the urine output or its exact measurement, such as the presence or absence of a urine catheter. An additional negative point of the definition is its failure to determine the cause of the injury., Finally, the incorrect equation in the risk and failure levels between the increase in serum creatinine and the reduction of GFR was recorded. At risk level, an increase in serum creatinine by 50% is equivalent to a 33.33% decrease in GFR and not 25%. At the failure level, the 200% increase in serum creatinine is equivalent to a 66.66% decrease in GFR and not 75%.
Acute Kidney Injury Network (2007)
One year after the publication of the RIFLE definition, it was shown that even minor changes in serum creatinine, from those identified by the above definition, could represent severe kidney injury. A study in 9,205 patients showed that even a small increase in serum creatinine by 0.3 mg/dL increased by 4.1 times the mortality rate, while the increase remained despite the adjustment based on the age and severity of the concomitant diseases.
These findings have paved the way for a new definition AKI using the RIFLE definition as the basis. In 2007, an international interdisciplinary committee of nephrologists and intensivists, named Acute Kidney Injury Network (AKIN), introduced the definition of AKIN, which is characterized by the three clinical-laboratory stages of AKI and is based on the parameters of serum creatinine and the urine output, while the time which is required for the clinical-laboratory criteria to occur is a period of 2 days. The AKIN definition is shown in [Table 2].
The new definition differs from RIFLE,, to the following: (i) it replaced Risk, Injury, Failure with Stages I, II, III respectively and abolished the stages Loss and ESKD, considering that they concern future development stages of AKI, (ii) it limited the time required for the clinical-laboratory criteria to occur 2 days, (iii) it introduced the renal replacement therapy, regardless of the serum creatinine value, as a staging criterion, and (iv) it increased the sensitivity of AKI because it widened Stage I, corresponding to risk, by enrolling much more patients. This was achieved by setting the serum creatinine threshold to 0.3 mg/dL. The increase of occasions diagnosed with AKI was determined from 1% to 3.5%, depending on the study, while studies conducted, which included over a million patients, confirmed that the increase was 1%–2%.
The limit value of urine output both in stage risk and in Stage I of the AKIN definition was set at the high level of 0.5 mL/kg/h, whereas newer studies changed it to <0.3 mL/kg for 6 h.
Kidney disease improving global outcomes (2012)
In 2012, a nonprofit organization aiming at a global, unified challenge treatment to kidney disease called Kidney Disease Improving Global Outcomes (KDIGO), issued guidelines on the clinical, practical treatment of AKI, and provided a new definition of AKI that combined the pre-existing RIFLE and AKIN. The new definition was based on two clinical-laboratory criteria: serum creatinine and urine output, separating the AKI in three stages as shown in [Table 3]. According to the new definition, at least one of the following three criteria is demanded as a minimum prerequisite for the characterization of AKI: (i) increase of serum creatinine ≥0.3 mg/dL within 2 days, (ii) increase of serum creatinine at least 1.5 times within 7 days, and (iii) urine output <0.5 mL/kg/h for 6 h.,
Newer attempts to define acute kidney injury
Kidney attack (2012)
Gradually, the whole interest in the definition of AKI was moved to the stage which describes the moments immediately before the damage occurred, aiming at its earliest possible diagnosis. The corresponding trial in the heart aiming at analyzing myocardial infarction with or without ST elevation (STEMI and non-STEMI correspondingly) and unstable angina led to a concurrent effort to determine kidney attack.,
The adoption of the term kidney injury was serving the need for awareness and activation toward the early treatment of AKI. Initially, the term renal angina,,, was proposed, but its referral to pain and ischemic etiology led to its gradual retreat and eventually ended as a part of kidney attack. The analysis of kidney attack includes creatinine-increased AKI, noncreatinine-increased AKI, and renal angina. AKI with increased serum creatinine and concurrent presence of increased values in some corresponding biomarkers is paralleled with STEMI-type heart attack, whereas AKI that its only indication is an increase of the corresponding biomarkers is paralleled with non-STEMI-type heart attack. The presence of AKI without clinical indications and evidence of renal dysfunction which is only based on an increase of the biomarkers signified the turn from clinical to molecular level in the definition of AKI, something that was proposed by the ADQI team., The term renal angina was attributed to the intermediate stage and condition between creatinine-increased AKI and noncreatinine-increased AKI. The term was parallelized with unstable angina pectoris.
Subclinical kidney injury (2012)
Taking into consideration that the increase of serum creatinine appears 12 h to 2 days after the kidney attack, the need for early and timely detections of AKI led to the formulation of the term subclinical kidney injury. The new term reflects the precursor period when the increase of serum creatinine has not appeared yet, and the only indication for AKI is the presence of increased values of some biomarkers that suggest kidney tubular injury.
Acute kidney stress (2016)
Lately, the term “acute renal stress” was introduced to further determine the period before the manifestation of the injury and its symptoms. The term corresponds to the presence of increased biomarker values which imply tubular cells injury, and its use is tested in the level of intensive care units, where timely treatment is demanded, in the level of administrating medication and finally in the level of renal replacement therapy.
| Perspectives|| |
The modern trend and tendency concerning the definition of AKI is shifting from the clinical to the molecular level, concentrating and focusing on both increased sensitivity and specificity. This effort goes through the search for an ideal biomarker, the detection of which will ideally correspond uniquely to AKI, whereas at the same time, it will meet the requirements of low cost and ease of application. The prospect demands the discovery and emergence of “renal troponin,” contributing to the reformulation of a commonly accepted definition of AKI with beneficial effects on early diagnosis and treatment, on assessing more precisely its effect, and finally, on reducing the financial burdens that each health system shoulders.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]