Diagnosis and Management of Acute Kidney Injury in the Emergency Department

Objectives

This chapter will:

1.
Describe the importance of timely acute kidney injury (AKI) diagnosis according to available guidelines.
2.
Discuss the importance of early diagnosis of AKI in the emergency department (ED) and how physicians should manage the patients with AKI in the ED properly.

The diagnosis of acute kidney injury includes an acute and broad condition of kidney dysfunction detected by serum creatinine (SCr) modification, estimated glomerular filtrate (eGFR) change, or urine output decrease in a given time frame, as recommended by the Acute Dialysis Quality Initiative group (ADQI). On the basis of impairment of kidney function the same group developed the so-called Risk, Injury, Failure, Loss and End-stage kidney (RIFLE) criteria. More recently, the Acute Kidney Injury Network (AKIN) approved a slightly modified set of criteria with a modification to include small changes in SCr (≥0.3 mg/dL or 26.5 µmol/L) when they occur within a 48-hour period. These criteria have been reconciled in the definitive scoring system called Kidney Disease: Improving Global Outcomes (KDIGO) ( Table 216.1 ). Despite the fact that the existing criteria are standardized, they appear as limited and imperfect methods to detect the development of early AKI in the emergency department (ED). Because clinical signs and symptoms of acute renal damage are not specific, it is difficult to promptly distinguish AKI at the time of patient ED presentation. The missing early diagnosis of kidney injury leads to a higher risk of death during hospitalization as consequence of a delay in prompt AKI treatment. A report by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) found that 30% of AKI cases occurring during hospital admission were avoidable and that only 50% of patients with AKI received a timely standard of care. The limitation of current criteria for diagnosis of AKI are related to the nonspecific sign of oliguria, imprecise evaluation of eGFR in the context of an acute dynamic condition, and to the wide spectrum of mechanisms and conditions of AKI that actually start from a subclinical form of kidney dysfunction and damage. The subclinical form of AKI often is unrecognized because no evident symptoms can be present in this phase. However, subclinical AKI could be the prelude to the progression of an established AKI, and eventually to a chronic kidney dysfunction (CKD), risk for need of renal replacement therapy (RRT), and risk of death. The limitations of SCr are related to (1) creatinine metabolism, which is influenced a variety of nonrenal factors such as age, gender, muscle mass, diet (particularly protein intake), and (2) nutritional status. Although some equations for eGFR calculation take into account some of these variables (i.e., age and gender in the Modification of Diet in Renal Diseases [MDRD] equation), muscle mass and nutritional considerations are not reflected by these equations. Tubular secretion of creatinine also can vary and cause error in creatinine-derived estimates of GFR. Under normal conditions, tubular secretion of creatinine accounts for roughly 10% of creatinine clearance, but this secretion is inhibited by certain medications such as trimethoprim and cimetidine, leading to elevations in serum creatinine that do not reflect true decrements in GFR. SCr finally is influenced by its volume of distribution, which can be altered significantly by volume overload (a condition commonly present in acute and chronic renal insufficiency). Most important, the temporal gap between decreases in GFR and resultant elevations in SCr precludes early recognition of significant GFR loss. Substantial loss of GFR (up to 50%) may not manifest with elevations in SCr, and this condition may last over a prolonged period of time. In addition, during non-steady-state conditions, creatinine-based estimates of GFR are inaccurate, making assessment of true renal function difficult. Furthermore, when GFR is reduced significantly, the proportion of creatinine cleared by tubular secretion proportionally increases, with a substantial overestimation of GFR until the level of 15 mL/min is reached. A false elevation of creatinine levels may be due to Jaffe assay interference, secondary to hyperglycemia, delayed centrifugation, and hemolysis.

TABLE 216.1

Acute Kidney Injury Criteria: KDIGO Criteria Classification, AKIN Criteria Classification, RIFLE Criteria Classification

CLASSIFICATION *	SERUM CREATININE, GFR, OR OTHER CRITERIA	URINE OUTPUT CRITERIA
KDIGO
Stage 1	1.5- to 1.9-fold increase in serum creatinine level from baseline or ≥0.3 mg/dL (26.5 µmol/L) increase in serum creatinine level	<0.5 mL/kg per hr for 6–12 hr
Stage 2	2.0- to 2.9-fold increase in serum creatinine level from baseline	<0.5 mL/kg per hr for 2 : 12 hr
Stage 3	Threefold increase in serum creatinine level from baseline or increase in serum creatinine level to ≥4.0 mg/dL (≥353.6 µmol/L) or initiation of renal replacement therapy or, in patients aged <18 years, decrease in eGFR to <35 mL/min/1.73 m ²	<0.3 mg/kg per hr for ≥24 hr or anuria for ≥12 hr
AKIN
Stage 1	Increase in serum creatinine level of >0.3 mg/dL (≥26.4 µmol/L) or increase to ≥150%–200% (1.5- to 2.0-fold) from baseline	<0.5 mL/kg per hr for >6 hr
Stage 2	Increase in serum creatinine level to >200%–300% (>2- to 3-fold) from baseline	<0.5 mL/kg per hr for >12 hr
Stage 3	Increase in serum creatinine level to >300% (>3-fold) from baseline (or serum creatinine level of >4.0 mg/dL [≥354 µmol/L] with an acute increase of at least 0.5 mg/dL [44 µmol/L])	<0.3 mL/kg per hr for 24 hr or anuria for 12 hr
RIFLE
Risk	1.5-fold increase in serum creatinine level or >25% decrease in GFR	<0.5 mL/kg per hr for 6 hr
Injury	Twofold increase in serum creatinine level or >50% decrease in GFR	<0.5 mL/kg per hr for 12 hr
Failure	Threefold increase in serum creatinine level or 75% decrease in GFR or increase in serum creatinine level to ≥4 mg/dL (≥354 µmol/L) with an acute increase ≥0.5 mg/dL (≥44 µmol/l)	<0.3 mg/kg per hr for 24 hr or anuria for 12 hr
Loss	Persistent AKI with complete loss of renal function (>4 weeks)	N/A
End-stage renal disease	ESRD (>3 months)	N/A

AKI, Acute kidney injury, AKIN, Acute Kidney Injury Network; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes; RIFLE, risk, injury, failure, loss, end-stage renal disease. KDIGO criteria permission obtained from Nature Publishing Group Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. Kidney Int Suppl. 2. 1–138 (2012). AKIN criteria reproduced from Metha, R. L. et al. Crit Care. 11, R31 (2007), which is published under an open access license by Biomed Central.

* In AKIN stage and RIFLE criteria. AKI classification is based on the more severe of urine output serum creatinine or eGFR criteria. In the KDIGO classification, AKI is defined as an increase in serum creatinine level of ≥0.3 mg/dL (≥26.5 µmol/L) within 48 hr or ≥1.5 times baseline within the prior 7 days or urine volume <0.5 mL/kg per hr for 6 hr. For AKIN criteria, the diagnosis of AKI is based on changes occurring during a 48-hr time period, staging may occur over a longer time frame. For RIFLE classification. AKI diagnosis is based on changes occurring during a period of 1–7 days, which must be sustained for more than 24 hr.

Diagnostic Utility of Biomarkers

Similarly to what happened with troponin for acute myocardial infarction diagnosis, in recent years eager research has been conducted to identify a biomarker for timely AKI diagnosis. Renal biomarkers levels, once elevated beyond a specific cutoff value or when changing over time, can detect a risk of AKI or subclinical kidney damage, allowing development of a new conceptual model for AKI. A continuum exists from initial kidney stress, susceptibility to insult and early injury to advanced kidney damage. Such acute early phase has also been defined “kidney attack,” whereas the subsequent phases in the time window of 90 days are described as acute kidney disease (AKD). In such conditions, a biomarker may trigger early preventive and protective measures before clinical AKI becomes manifest. The ADQI consensus group proposed the use of biomarkers to diagnose AKI with kidney damage even in the absence of renal dysfunction. Subclinical AKI may be diagnosed only with the use of biomarkers, when classic criteria are still within normal range showing the presence of reduced nephron mass. AKI implies injury or damage but not necessarily dysfunction in subclinical status. SCr and urine output only modify late with respect to the beginning of kidney injury. A recent revision of AKI criteria has been proposed recently, including novel biomarkers into the diagnostic flow chart and separating functional criteria (according to traditional biomarkers) and damage criteria (identified by novel biomarkers) ( Fig. 216.1 ). An ideal biomarker of AKI would be a substance that the kidney releases immediately in response to injury, not influenced by other clinical parameters or patient's characteristics and that can be detected in the blood or urine without significant metabolism. Biomarkers of kidney damage could result of great utility in emergency room to identify in a timely manner patients with high risk to develop AKI. Most clinical biomarkers were identified for early diagnosis of AKI, but the field is still developing.

FIGURE 216.1, Revision of acute kidney injury criteria, including novel biomarkers into the diagnostic flow chart, and separating functional criteria (according to traditional biomarkers) and damage criteria (identified by novel biomarkers).

Cystatin C

Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin, or neuroendocrine basic polypeptide) has been proposed as a valuable alternative marker tested in urine and in blood, particularly in situations in which creatinine-based estimates of GFR fail to provide an accurate estimate. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise. Serum levels of cystatin C are a more precise test of kidney function (as represented by the glomerular filtration rate, GFR) than serum creatinine levels.

Neutrophil Gelatinase-Associated Lipocalin

Neutrophil gelatinase-associated lipocalin (NGAL) is an independent biologic marker able to detect earlier AKI than SCr. In fact SCr is a marker of kidney function, whereas NGAL is a marker of kidney injury. Moreover, NGAL levels are useful to quantify the degree of tubular damage to establish the stratification of AKI. The clinical use of NGAL in ED to clinical judgement in acute kidney injury diagnosis is recognized largely in the scientific community. NGAL seems to be even a good marker in detecting AKI after cardiac surgery, and its concentration is related to risk to develop a tubular damage according a score ( Fig. 216.2 ). The limitations of using NGAL in ED seem to be related to the false-positive levels in septic patients or in chronic kidney diseases.

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