INTRODUCTION Acute kidney injury (AKI) is the abrupt loss of kidney function, resulting

in the retention of urea and other nitrogenous waste products and in the dysregulation of

extracellular volume and electrolytes. The term AKI has largely replaced acute renal failure

(ARF), reflecting the recognition that smaller decrements in kidney function that do not result

in overt organ failure are of substantial clinical relevance and are associated with increased

morbidity and mortality. The term ARF is now reserved for severe AKI, usually implying the

need for renal replacement therapy.

The loss of kidney function that defines AKI is most easily detected by measurement of the

serum creatinine, which is used to estimate the glomerular filtration rate (GFR). Three

problems are associated with the use of serum creatinine to quantitatively define AKI:

Serum creatinine does not accurately reflect the GFR in a patient in whom it is not

in steady state. In the early stages of AKI, the serum creatinine may be low, even

though the actual (not estimated) GFR is markedly reduced, since there may not

have been sufficient time for the creatinine to accumulate (see "Assessment of kidney

function"). When the serum creatinine is rising, estimates of GFR based on creatinine

values will overestimate the true GFR; conversely, estimates of GFR will

underestimate the true GFR during recovery of kidney function, when the serum

creatinine concentration is declining.

Creatinine is removed by dialysis. As a result, it is usually not possible to assess

kidney function by measuring the serum creatinine once dialysis is initiated. One

exception is when the serum creatinine continues to fall on days when hemodialysis

is not performed, indicating recovery of renal function.

Numerous epidemiologic studies and clinical trials have used diferent cut-of values

for serum creatinine to quantitatively define AKI [1].

Prior lack of consensus in the quantitative definition of AKI, in particular, has hindered clinical

research since it confounds comparisons between studies. Some definitions employed in

clinical studies have been extremely complex, with graded increments in serum creatinine for

diferent baseline serum creatinine values [1,2].

In an iterative process, several consensus definitions of AKI have been sequentially

developed in order to provide a uniform definition of AKI. In 2004, the Acute Dialysis Quality

Initiative (ADQI) group, which included expert intensivists and nephrologists, proposed

consensus- and evidence-based guidelines for the treatment and prevention of AKI [3].

Recognizing the need for a uniform definition for AKI, the ADQI group proposed a consensus

graded definition, called the RIFLE criteria [3]. A modification of the RIFLE criteria was

subsequently proposed by the Acute Kidney Injury Network (AKIN, which included the ADQI

group), as well as representatives from other nephrology and intensive care societies [4-6].

More recently, the Kidney Disease: Improving Global Outcomes (KDIGO) AKI Workgroup

proposed a modified definition, harmonizing diferences between the RIFLE and AKIN

definitions [7].

This topic reviews these definitions of AKI, highlighting the diferences between the original

RIFLE criteria and the subsequent AKIN and KDIGO revisions. While it is important to

understand the diferences among these definitions, the KDIGO definition and staging

system, which is the most recent, should be considered the preferred definition.

The potential etiologies, diagnosis, and management of AKI are discussed elsewhere. (See

"Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury

(acute renal failure)" and "Diagnostic approach to the patient with subacute kidney injury in

an outpatient setting" and "Overview of the management of acute kidney injury (acute renal

failure)".)

RIFLE CRITERIA The RIFLE criteria consists of three graded levels of kidney dysfunction

(Risk, Injury, and Failure), based upon either the magnitude of increase in serum creatinine

or urine output, and two outcome measures (Loss and End-stage renal disease [ESRD]).

Conceptually, the first three of these criteria were considered to be graded definitions of AKI,

providing increasing specificity at the expense of sensitivity, rather than "staging" criteria for

patients meeting a minimal definition of AKI. The RIFLE strata are as follows [3]:

Risk 1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR)

decrease by 25 percent, or urine output <0.5 mL/kg per hour for six hours
 Injury Twofold increase in the serum creatinine, or GFR decrease by 50 percent,

or urine output <0.5 mL/kg per hour for 12 hours

Failure Threefold increase in the serum creatinine, or GFR decrease by 75

percent, or urine output of <0.3 mL/kg per hour for 24 hours, or anuria for 12 hours

Loss Complete loss of kidney function (eg, need for renal replacement therapy) for

more than four weeks

ESRD Complete loss of kidney function (eg, need for renal replacement therapy)

for more than three months

The change in serum creatinine was specified as occurring over not more than seven days.

Subsequent to publication of RIFLE, it was noted that the change in serum creatinine

concentrations do not correlate with the percent decrease in GFR that is cited in the RIFLE

classification; a 1.5-fold increase in serum creatinine corresponds to a 33 rather than 25

percent decrease in GFR [8].

However, given the absence of readily available methods for measurement of GFR when

serum creatinine is not in steady state, as is the case during AKI, changes in GFR are not

included in the Acute Kidney Injury Network (AKIN) classification system (see 'AKIN criteria'

below) and in the Kidney Disease: Improving Global Outcomes (KDIGO) AKI classification

system, except for the classification of children under the age of 18 years. (See 'KDIGO

modifications to RIFLE and AKIN' below.)

The RIFLE criteria correlated with prognosis in a number of studies [9-18]. As an example, a

systematic review of 13 studies demonstrated a stepwise increase in the relative risk of

death in patients who met the RIFLE criteria for various stages of AKI [15]. Compared with

patients who did not have AKI, patients in the RIFLE stages of "risk," "injury," and "failure"

had increased relative mortality risks of 2.4 (CI 1.94-2.97), 4.15 (CI 3.14-5.48), and 6.37 (CI

5.14-7.9). Despite significant heterogeneity among studies, results from most individual

reports were qualitatively similar.

The relative risk for mortality by RIFLE stage, based on change in serum creatinine, does not

correlate well with the mortality risk by RIFLE stage, calculated based on the urine output

criteria. The observed relative risk was greater in studies that used the creatinine criteria
alone, compared with those that used both the creatinine and urine output criteria to

determine RIFLE stage, with a much smaller increment between the "risk" and "injury"

stages using urine output than with creatinine. These results suggest that the calibration

between the serum creatinine and urine output criteria for staging is poor.

AKIN CRITERIA A modification of the RIFLE criteria was developed by the Acute Kidney

Injury Network (AKIN), providing both diagnostic criteria and a staging system for acute

kidney injury [4-6].

Diagnostic criteria The AKIN diagnostic criteria for AKI specify an abrupt (within 48

hours), absolute increase in the serum creatinine concentration of 0.3 mg/dL (26.4

micromol/L) from baseline; a percentage increase in the serum creatinine concentration of

50 percent; or oliguria of <0.5 mL/kg per hour for more than six hours (table 1).

The latter two of these criteria are identical to the RIFLE "risk" criteria. The addition of an

absolute change in serum creatinine of 0.3 mg/dL was based on epidemiologic data that

demonstrated an 80 percent increase in mortality risk associated with changes in serum

creatinine concentration of as little as 0.3 to 0.5 mg/dL [19]. Including a time constraint of 48

hours is based upon data that showed that poorer outcomes were associated with small

changes in the creatinine when the rise in creatinine was observed within 24 to 48 hours

[20,21]; however, it should be recognized that this timeframe difered from the seven-day

time specified in the RIFLE criteria.

Two additional caveats were proposed by the AKIN group:

The diagnostic criteria should be applied only after volume status had been

optimized.

Urinary tract obstruction needed to be excluded if oliguria was used as the sole

diagnostic criterion.

Staging system Unlike the RIFLE criteria, which provided graded definitions of AKI with

increasing specificity but decreased sensitivity progressing sequentially from Risk to Injury to

Failure, the AKIN paradigm established a single definition for AKI followed by three staging

strata. These strata of increasing severity correspond to the Risk (stage 1), Injury (stage 2),
and Failure (stage 3) components of the RIFLE criteria, with the addition of the 0.3 mg/dL

increase in serum creatinine to the stage 1 criteria. Loss and End-stage renal disease

(ESRD) are removed from the staging system and defined as outcomes.

The AKIN modifications to RIFLE have not substantively changed the classification of

patients with AKI or improved its ability to predict hospital mortality [22].

KDIGO MODIFICATIONS TO RIFLE AND AKIN The Kidney Disease: Improving Global

Outcomes (KDIGO) Clinical Practice Guidelines for AKI included a revision to the definition

of AKI while retaining the Acute Kidney Injury Network (AKIN) staging criteria [7]. In the

KDIGO definition, the timeframe for an absolute increase in serum creatinine of 0.3 mg/dL

is retained from the AKIN definition (48 hours), while the timeframe for a 50 percent

increase in serum creatinine reverted to the seven days originally included in the Acute

Dialysis Quality Initiative (ADQI) RIFLE criteria.

According to KDIGO, AKI is defined by any of the following:

Increase in serum creatinine by 0.3 mg/dL (26.5 micromol/L) within 48 hours; or

Increase in serum creatinine to 1.5 times baseline, which is known or presumed to

have occurred within the prior seven days; or

Urine volume <0.5 mL/kg/h for six hours

The KDIGO criteria only utilize changes in serum creatinine and urine output, not changes in

glomerular filtration rate (GFR) for staging, with the exception of children under the age of 18

years, for whom an acute decrease in estimated GFR (eGFR) to <35 mL/min per 1.73 m2 is

included in the criteria for stage 3 AKI. As with the RIFLE and AKIN staging systems, KDIGO

suggested that patients be classified according to criteria that result in the highest (ie, most

severe) stage of injury. Using the KDIGO criteria, AKI is staged as follows:

Stage 1 Increase in serum creatinine to 1.5 to 1.9 times baseline, or increase in

serum creatinine by 0.3 mg/dL (26.5 micromol/L), or reduction in urine output to

<0.5 mL/kg per hour for 6 to 12 hours.

Stage 2 Increase in serum creatinine to 2.0 to 2.9 times baseline, or reduction in

urine output to <0.5 mL/kg per hour for 12 hours.

 Stage 3 Increase in serum creatinine to 3.0 times baseline, or increase in serum

creatinine to 4.0 mg/dL (353.6 micromol/L), or reduction in urine output to <0.3

mL/kg per hour for 24 hours, or anuria for 12 hours, or the initiation of renal

replacement therapy, or, in patients <18 years, decrease in eGFR to <35 mL/min per

1.73 m2.

LIMITATIONS Several commentaries have been published raising concerns regarding the

use of these criteria to diagnose AKI, although all commentaries stress the importance of a

consensus approach for research purposes [23-25].

In a commentary on the Kidney Disease: Improving Global Outcomes (KDIGO) AKI

guidelines, the European Renal Best Practice (ERBP) working group agreed that AKI be

defined on the basis of either a change in creatinine or reduction in urine output. The ERBP

group recommended that the first documented serum creatinine be used as the baseline,

rather than using historical creatinines (ie, prior to the acute illness) or a calculated value

based on a presumed baseline glomerular filtration rate (GFR) of 75 mL/min [23]. The ERBP

work group also recommended that urine output be assessed per shift using ideal body

weight rather than true weight.

Another important issue is the use of urine output as a sole criterion for AKI. By all criteria

discussed above, stages are defined by either change in serum creatinine or urine output.

However, the assignment of the corresponding changes in serum creatinine and changes in

urine output to the same strata is not based on robust evidence. Studies that have examined

the prognostic and diagnostic utility of urine output have yielded variable results. As an

example, in one assessment of the RIFLE classification, which compared the serum

creatinine and urine output criteria, the serum creatinine criteria were strong predictors of

intensive care unit (ICU) mortality, whereas the urine output criteria did not independently

predict mortality [13]. Another study, however, has suggested that urine output may be a

more sensitive marker for AKI than serum creatinine [26]. One study has suggested that

risks of death or renal replacement therapy were highest when both the serum creatinine and

urine output criteria were met [27].

The Kidney Disease Outcomes Quality Initiative (K/DOQI) and ERBP groups have ofered

opinions on the use of urine output as a criterion for AKI [23,24]. The ERBP group stressed

the importance of using both urine output and the serum creatinine and stated that, although

all criteria included the urine output, in practice, it is often omitted from studies [23]. The

K/DOQI working group noted that brief durations of oliguria do not prognostically correlate

with small changes in the serum creatinine and may just reflect insufficient volume

resuscitation [24]. Until this issue is resolved, it is reasonable to use the criteria that result in

the least favorable strata, as suggested in the Acute Dialysis Quality Initiative (ADQI) group

[3] and affirmed by KDIGO [7]. (See 'KDIGO modifications to RIFLE and AKIN' above.)

The determination of a baseline creatinine for individual patients is another issue that has

been raised as a potential criticism. It is impossible to calculate the change in serum

creatinine in patients who present with AKI, but without a baseline measurement of serum

creatinine. The authors of the RIFLE criteria had initially suggested back-calculating an

estimated baseline serum creatinine concentration using the four-variable Modification of

Diet in Renal Disease (MDRD) equation, assuming a baseline GFR of 75 mL/min/1.73 m2

[3]. However, this approach has been demonstrated to result in significant misclassification

[23] and should not be utilized. As noted above, the ERBP group recommended that the first

documented serum creatinine be used as the baseline, rather than using historical

creatinines (ie, prior to the acute illness) or a calculated value based on a presumed baseline

GFR of 75 mL/min [23]. One analysis has also highlighted concern that reliance on small

changes in serum creatinine for the diagnosis of AKI may be associated with a high rate of

misdiagnosis, especially in patients with a baseline serum creatinine 1.5 mg/dL [28].

A more global concern raised by the K/DOQI work group is that the use of a definition based

upon a biomarker, such as serum creatinine, or a variable, such as urine output, may result

in a marked increase in the number of nephrology consultations, which would provide

uncertain benefit to the patient [24]. As noted by an accompanying editorial to the K/DOQI

commentary, discretion is required to determine the clinical significance of a diagnosis of AKI

[29].
CLINICAL UTILITY The clinical utility of these criteria is uncertain. This issue has been

raised by both a multidisciplinary work group convened by K/DOQI and the Canadian

Society of Nephrology [24,25].

We agree with both groups that these criteria have greatest utility in epidemiologic studies

and in defining consistent inclusion criteria and/or endpoints for clinical studies.

It seems likely that these criteria will eventually be replaced at least in part by sensitive and

specific biomarkers of renal tubular injury. The use of such biomarkers, analogous to

troponin as a marker of myocardial injury, will permit development of a new paradigm for

classifying AKI that is not solely dependent upon serum creatinine or other functional

markers.

We do believe that adoption of the term acute kidney injury to replace the older terminology

of acute renal failure (ARF) is highly appropriate. Just as acute lung injury is used to

describe acute pulmonary injury that has not progressed to overt organ failure, we believe

that AKI is more representative of the full spectrum of acute kidney dysfunction.

INFORMATION FOR PATIENTS UpToDate ofers two types of patient education

materials, The Basics and Beyond the Basics. The Basics patient education pieces are

written in plain language, at the 5th to 6th grade reading level, and they answer the four or five

key questions a patient might have about a given condition. These articles are best for

patients who want a general overview and who prefer short, easy-to-read materials. Beyond

the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10th to 12th grade reading level and are best for patients who

want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to

print or e-mail these topics to your patients. (You can also locate patient education articles

on a variety of subjects by searching on patient info and the keyword(s) of interest.)

Basics topic (see "Patient education: Acute kidney failure (The Basics)")

SUMMARY
Acute kidney injury (AKI) has traditionally been defined as the abrupt loss of kidney

function, resulting in the retention of urea and other nitrogenous waste products and

in the dysregulation of extracellular volume and electrolytes. (See 'Introduction'

above.)

Although the loss of kidney function is most easily detected by measurement of the

serum creatinine, several problems are associated with the use of this measure to

quantitatively define AKI, particularly the lack of consensus in the quantitative

definition. (See 'Introduction' above.)

The Acute Dialysis Quality Initiative (ADQI) proposed a graded definition of AKI

called the RIFLE criteria. The Acute Kidney Injury Network (AKIN) modified the

RIFLE criteria in order to include less severe AKI, to impose a time constraint of 48
hours, and to allow for correction of volume status and obstructive causes of AKI

prior to classification. (See 'RIFLE criteria' above and 'AKIN criteria' above.)

The AKIN proposed the term acute kidney injury to represent the entire spectrum of

acute renal failure (ARF). The proposed diagnostic criteria are an abrupt (within 48

hours), absolute increase in the serum creatinine concentration of 0.3 mg/dL (26.4

micromol/L) from baseline; a percentage increase in the serum creatinine

concentration of 50 percent; or oliguria of <0.5 mL/kg per hour for more than six

hours. (See 'AKIN criteria' above.)

Kidney Disease: Improving Global Outcomes (KDIGO) proposed a consensus

definition utilizing the 48-hour timeframe from AKIN for a 0.3 mg/dL change in serum

creatinine, while using a seven-day timeframe for the 50 percent change in serum

creatinine originally applied by the RIFLE criteria, while retaining the tripartite staging

of both systems. The KDIGO definition is the preferred definition at this time. (See

'KDIGO modifications to RIFLE and AKIN' above.)

These criteria have their greatest utility in epidemiologic studies. The clinical

applicability has been questioned by working groups convened by Kidney Disease

Outcomes Quality Initiative (K/DOQI), the European Renal Best Practice (ERBP)

group, and the Canadian Society of Nephrology. These criteria will likely be revised

and possibly replaced as biomarkers of tubular injury are developed. (See 'Clinical

utility' above and 'Limitations' above.)

 We agree that adoption of the term acute kidney injury to replace the older

terminology of acute renal failure is highly appropriate. AKI better represents the full

spectrum of acute kidney dysfunction. (See 'Clinical utility' above.)

INTRODUCTION Acute renal failure (ARF) is an abrupt and usually reversible decline in

the glomerular filtration rate (GFR). This results in an elevation of serum blood urea nitrogen

(BUN), creatinine, and other metabolic waste products that are normally excreted by the

kidney.

The term acute kidney injury (AKI), rather than ARF, is increasingly used by the nephrology

community to refer to the acute loss of kidney function. This term also highlights that injury to

the kidney that does not result in "failure" is also of great clinical significance. In this topic

review, the acute loss of kidney function will be referred to as AKI.

The initial assessment of patients with AKI and management of the major complications of

AKI are discussed here. The incidence, causes, diagnosis, and prevention of AKI are

presented separately. (See "Diagnostic approach to the patient with subacute kidney injury in

an outpatient setting" and "Renal and patient outcomes after acute tubular necrosis" and

"Possible prevention and therapy of postischemic (ischemic) acute tubular necrosis".)

PATHOGENESIS AKI has multiple possible etiologies. Among hospitalized patients, AKI

is most commonly due to acute tubular necrosis (ATN) from ischemia, nephrotoxin exposure,

or sepsis [1]. The pathogenesis of ATN is discussed elsewhere. (See "Pathogenesis and

etiology of postischemic (ischemic) acute tubular necrosis" and "Pathogenesis, clinical

features, and diagnosis of contrast-induced nephropathy".)

Other frequent causes of AKI among either ambulatory or hospitalized patients include

volume depletion, urinary obstruction, rapidly progressive glomerulonephritis, and acute

interstitial nephritis. The pathogeneses of these disorders are also discussed elsewhere.

(See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney

injury (acute renal failure)" and "Clinical manifestations and diagnosis of urinary tract

obstruction and hydronephrosis" and "Overview of the classification and treatment of rapidly

progressive (crescentic) glomerulonephritis" and "Clinical manifestations and diagnosis of

acute interstitial nephritis".)

DIAGNOSIS AKI is generally detected by an increase in the serum creatinine and/or a

decrease in urine output. The magnitude of the increase in creatinine and/or decrease in

urine output that is required to establish a diagnosis of AKI has been the focus of multiple

expert consensus groups. The purpose of establishing a precise definition of AKI is to allow

better interpretation of epidemiologic and clinical studies and to identify potential therapies.

The potential limitations of the diferent consensus criteria that have been proposed are

discussed elsewhere. (See "Definition of acute kidney injury (acute renal failure)".)

INITIAL EVALUATION AFTER DIAGNOSIS Among many patients, AKI is mild and is

manifested only by a transient increase in the serum creatinine or fall in urine output.

However, AKI can cause life-threatening complications, even among those with relatively

less severe disease. In addition, the serum creatinine will not accurately reflect the

glomerular filtration rate (GFR) in patients who are not in steady state. Thus, among patients

who have just developed AKI and in whom the serum creatinine is actively increasing, the

estimated GFR (eGFR), based upon the serum creatinine, will overestimate the actual GFR.

Conversely, among patients who are recovering from AKI, the eGFR may underestimate the

actual GFR.

All patients who present with AKI must be carefully evaluated both for reversible causes,

such as hypotension, volume depletion, or obstruction, and for the presence of complications

such as hyperkalemia and volume overload (see 'Management' below). The initial evaluation

of the patient with AKI is directed at determining the cause and identifying the complications

that may require immediate attention.

The diagnostic evaluation to determine the cause of AKI is discussed elsewhere. (See

"Diagnostic approach to the patient with subacute kidney injury in an outpatient setting" and

"Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury

(acute renal failure)", section on 'Evaluation and diagnosis'.)

The major complications of AKI include volume overload, hyperkalemia, metabolic acidosis,

hypocalcemia, and hyperphosphatemia. With severe forms, mental status changes may be

present. Hyperuricemia and hypermagnesemia may also occur. The initial assessment

therefore should include the careful evaluation of volume status and measurement of serum
electrolytes, particularly potassium and bicarbonate, and serum phosphate, calcium, and

albumin. We also check serum uric acid, magnesium, and a complete blood count.

MANAGEMENT

Immediate therapy The management of life-threatening fluid and electrolyte

abnormalities due to AKI should be started immediately. Complications of AKI include the

following:

Fluid overload

Hyperkalemia (serum potassium >5.5 mEq/L) or a rapidly increasing serum

potassium

Signs of uremia, such as pericarditis, or an otherwise unexplained decline in mental

status

Severe metabolic acidosis (pH <7.1)

Patients with any of these complications despite appropriate medical therapy generally

require urgent dialysis. However, since hemodialysis often cannot be immediately provided,

such patients usually require medical treatment during the period prior to the initiation of

hemodialysis. Appropriate measures are discussed in sections below or in other topic

reviews, to which links are provided.

Volume issues An assessment of volume status is performed in all patients who present

with AKI since correction of volume depletion or volume overload (especially when

associated with worsening cardiac output) may reverse or ameliorate AKI. (See "Cardiorenal

syndrome: Definition, prevalence, diagnosis, and pathophysiology" and "Cardiorenal

syndrome: Prognosis and treatment".)

Volume depletion Unless contraindicated, the patient with a clinical history consistent

with fluid loss (such as vomiting and diarrhea), a physical examination consistent with

hypovolemia (hypotension and tachycardia), and/or oliguria should be administered

intravenous fluid therapy. This fluid challenge attempts to identify prerenal failure that can

progress to AKI if not treated promptly. Studies have shown that prompt reversal of volume

depletion may prevent or limit kidney injury due to acute tubular necrosis (ATN) (see "Crush-
related acute kidney injury (acute renal failure)" and "Prevention and treatment of heme

pigment-induced acute kidney injury (acute renal failure)"). However, such fluid infusion is

contraindicated in those with obvious volume overload or heart failure.

Fluids may be either crystalloid or colloid. Crystalloid solutions, such as isotonic saline, are

preferred for initial therapy since studies have shown that colloid solutions provide no

additional benefit and are more expensive (see "Treatment of severe hypovolemia or

hypovolemic shock in adults", section on 'Colloid versus crystalloid'). Potassium-containing

crystalloid solutions, such as lactated Ringer's solution, should be avoided since the kidney

may not be able to excrete potassium and hyperkalemia may result. There continues to be

much debate as to which intravenous fluid should be administered since large volumes of

normal saline may result in hyperchloremic metabolic acidosis and a more pH-balanced

solution may be of greater benefit. (See "Treatment of severe hypovolemia or hypovolemic

shock in adults", section on 'Bufered crystalloid'.)

Fluids should be targeted to physiologic endpoints such as mean arterial pressure or urine

output or, among patients in whom invasive monitoring is utilized, to dynamic changes in

cardiac output. The optimal infusion rate varies depending on the clinical status and

comorbidities of the patient. Overly aggressive volume repletion should be avoided as

excessive volume expansion may lead to pulmonary congestion, especially in septic patients

[2]. We suggest judicious administration, beginning with 1 to 3 liters of fluid, with careful and

repeated clinical assessment to assess the patient's response to this therapy. In some

cases, additional fluid therapy may be necessary (eg, severe burns, acute pancreatitis).

The total amount of administered volume depends upon the degree of volume depletion on

presentation and on ongoing losses. The restoration of adequate urine flow and

improvement in renal function with fluid resuscitation is consistent with a diagnosis of

prerenal disease. Patients who do not respond to administered volume with an increase in

urine output or decrease in the serum creatinine are unlikely to have prerenal disease and

more likely to have established ATN or other forms of intrinsic AKI such as acute or rapidly

progressive glomerulonephritis or acute interstitial nephritis. However, volume status may be

difficult to assess among some patients, and prerenal disease may not be reliably excluded

after the initial administration of fluid: Among selected patients in whom urine output is not
restored with administered volume, invasive monitoring may be required to adequately

assess the patient's fluid status and help guide further therapy. (See "Maintenance and

replacement fluid therapy in adults" and "Treatment of severe hypovolemia or hypovolemic

shock in adults".)

Some patients with relatively mild volume depletion may not have an obvious history of

volume loss. In addition, less severe volume depletion is difficult to accurately detect on

clinical examination, especially in older patients. In this setting, AKI may still be reversed, at

least in part, by fluid administration. Thus, in the absence of overt volume depletion, we

frequently administer intravenous saline at a variable rate based upon clinical status.

Although no consensus exists to guide therapy, among hemodynamically stable patients who

do not have overt evidence of volume depletion, we administer 75 to 100 mL per hour. If this

approach is undertaken, the patient's clinical status must be closely monitored to ensure that

volume overload does not occur and that the rate of administration is sufficient to keep up

with ongoing fluid losses. Once again, fluid therapy should be targeted to physiologic

endpoints.

Volume overload Hypervolemia may be present upon initial evaluation or occur due to

excessive fluid administration in the setting of impaired ability to excrete sodium and water.

This is especially true for patients with sepsis who commonly receive aggressive intravenous

fluid resuscitation. (See "Evaluation and management of suspected sepsis and septic shock

in adults", section on 'Intravenous fluids'.)

Daily fluid balance is commonly positive in critically ill patients with ATN as a result of

obligate fluid intake due to the administration of antibiotics, blood products, other intravenous

medications, and nutritional support. This may result in progressive volume expansion and

pulmonary edema, which may be especially poorly tolerated in patients with acute lung

injury.

Less commonly, volume overload may result from primary left ventricular dysfunction and

cause AKI or type 1 cardiorenal syndrome. The diagnosis and treatment of cardiorenal

syndrome are discussed elsewhere. (See "Cardiorenal syndrome: Definition, prevalence,

diagnosis, and pathophysiology" and "Cardiorenal syndrome: Prognosis and treatment".)

Diuretics may be used to relieve hypervolemia among patients with AKI. In a post-hoc

analysis of data from a multicenter, randomized trial that compared liberal versus

conservative fluid management among patients with acute lung injury, a positive fluid

balance was associated with mortality among 306 patients who developed AKI [3]. A higher

furosemide dose was associated with decreased mortality, but this efect was not significant

after adjusting for fluid balance. The full results of this trial are discussed elsewhere. (See

"Acute respiratory distress syndrome: Supportive care and oxygenation in adults", section on

'Fluid management'.)

However, we generally do not use diuretics for prolonged therapy to postpone the initiation of

dialysis, since dialysis ofers the most efficient method of volume removal in patients with AKI

from any cause and allows clinicians to optimize nutritional support and the use of

intravenous medications. However, although several observational studies have

demonstrated an association between the severity of volume overload at the time of initiation

of dialysis [4-6], there are no studies that have demonstrated a benefit of early initiation of

dialysis for volume management (see "Renal replacement therapy (dialysis) in acute kidney

injury in adults: Indications, timing, and dialysis dose"). If diuretics are used to treat volume

overload, then the patient should be regularly assessed to see if urine output responds. If

there is no increase in urine output, then alternative therapies such as dialysis should be

initiated.

If diuretics are used as temporizing agents to relieve volume overload, loop diuretics are the

preferred agents as they provide a greater natriuretic efect than thiazide diuretics. We often

start with 40 to 80 mg of intravenous furosemide. If unresponsive within 30 minutes to one

hour, we double the dose. In patients who are refractory to high doses of loop diuretics,

concomitant administration of a thiazide diuretic may achieve efective diuresis. (See

"Treatment of refractory edema in adults", section on 'Thiazide plus loop diuretics'.)

Among hospitalized patients, diuretics are generally given intravenously rather than orally

since the absorption of oral agents is variable in patients with decreased intestinal perfusion

and motility and in those with mucosal edema. The optimal diuretic dose and regimen is

discussed elsewhere. (See "Treatment of refractory edema in adults", section on 'Basic

principles of diuretic dosing'.)

Hyperkalemia Hyperkalemia is a common and potentially life-threatening complication of

AKI. It is especially prevalent in oliguric patients who are catabolic or have evidence of active

cellular breakdown, such as rhabdomyolysis and tumor lysis syndrome.

There are very few symptoms or signs of hyperkalemia, and these tend to occur only with

very high serum potassium levels and are related to impaired neuromuscular transmission

and cardiac conduction abnormalities. (See "Clinical manifestations of hyperkalemia in

adults".)

In general, all patients with AKI and hyperkalemia that is refractory to medical therapy should

be dialyzed unless hyperkalemia is mild (ie, <5.5 mEq/L) and the cause of AKI is known to

be easily reversed (such as prerenal AKI due to volume depletion or angiotensin-converting

enzyme [ACE] inhibitors).

Among patients who require dialysis, medical therapy of hyperkalemia is often required while

dialysis is being arranged. Immediate therapy is warranted if electrocardiographic changes or

peripheral neuromuscular abnormalities are present, regardless of the degree of

hyperkalemia. (See "Treatment and prevention of hyperkalemia in adults".)

Specific treatment of hyperkalemia is directed at antagonizing the membrane efects of

potassium, driving extracellular potassium into the cells, or removing excess potassium from

the body.

The indications for specific medical therapies are discussed at length elsewhere. (See

"Treatment and prevention of hyperkalemia in adults".)

We do not dialyze, at least initially, patients with mild hyperkalemia and AKI that is from a

known reversible cause (such as volume depletion or an ACE inhibitor/angiotensin receptor

blocker [ARB]). We treat such patients with a low-potassium diet and volume administration

and/or discontinuation of the ACE inhibitor or ARB. Such patients should be followed closely

to make certain that such conservative therapy is efective.

We also do not dialyze, at least initially, patients who have AKI from a cause that is not

readily reversible, such as ATN, and who have hyperkalemia that is adequately treated with

medical therapy. However, depending upon other variables (such as the time of day and
available medical staf), preparations for dialysis, such as placement of a dialysis catheter,

may be considered for such patients since hyperkalemia is likely to recur unless renal

function recovers. This is especially true among patients who are oliguric or anuric, but the

approach must be individualized for each patient.

In all patients with AKI, potassium in infusions and medications should be avoided as much

as possible. Dietary potassium intake should be restricted to approximately 2 grams daily.

Patients who have severe hyperkalemia (defined as K >6.5 mEq/L) or rapidly rising serum

potassium should not receive any dietary potassium until hyperkalemia can be addressed

(either by dialysis or medical therapy).

Metabolic acidosis The excretion of acid and regeneration of bicarbonate is impaired in

the setting of a low glomerular filtration rate (GFR) resulting in metabolic acidosis. Much of

the acid that is normally excreted by the kidney is the product of daily metabolism. However,

other factors usually contribute to severe acidosis among patients with AKI, who are often

critically ill. For example, patients with AKI due to sepsis, trauma, and multi-organ failure

often have increased production of lactic acid or ketoacids. Other patients who present with

AKI may have metabolic acidosis resulting from loss of bicarbonate or from diarrhea or, less

commonly, renal tubular acidosis.

Commonly used treatments for metabolic acidosis include dialysis and bicarbonate

administration. Among patients with AKI, the choice of therapy depends upon the absence or

presence of volume overload and the underlying cause and severity of the acidosis.

We dialyze patients with severe oligo-anuric AKI who are volume overloaded and have

severe metabolic acidosis (a pH <7.1) regardless of the cause of acidosis. Physiologic

studies have suggested that this degree of acidemia may produce hemodynamic instability

related to reduced left ventricular contractility, arrhythmias, arterial vasodilation and

venoconstriction, and impaired responsiveness to catecholamine vasopressors [7-14].

Dialysis is preferred to the administration of bicarbonate among patients who are volume

overloaded because bicarbonate administration results in a large sodium load that may

cause or contribute to volume overload. Even among patients who are not volume
overloaded on exam, bicarbonate may cause volume overload among patients who are

oliguric or anuric and should be used cautiously.

In general, we also dialyze patients with AKI and organic acidosis (ie, lactic or ketoacidosis)

and pH <7.1, even if they are not volume overloaded and especially if they are oliguric or

anuric since such patients are at risk for becoming volume overloaded with bicarbonate

therapy.

However, among patients with AKI who are not volume overloaded and have no other

indication for acute dialysis, bicarbonate may be administered instead of dialysis in the

following settings:

Non-anion gap acidosis related to diarrhea. (See "Approach to the adult with

metabolic acidosis", section on 'Overview of therapy'.)

Severe organic acidosis (pH <7.1 mEq/L) while awaiting dialysis or in patients in

whom the cause of AKI is readily reversible (such as prerenal AKI due to volume

depletion or obstruction).

Intravenous bicarbonate may also be indicated among patients with AKI due to

rhabdomyolysis in order to prevent further renal injury (ie, ATN), providing other

indications for dialysis are not present and the patient is not volume overloaded. This

possible indication for bicarbonate is discussed elsewhere. (See "Crush-related acute

kidney injury (acute renal failure)".)

A reasonable goal for patients with metabolic acidosis due to bicarbonate loss from diarrhea

who are treated with bicarbonate is a serum bicarbonate between 20 and 22 mEq/L and pH

>7.2 [15]. Among such patients, the total amount of bicarbonate that will be needed can be

estimated from the calculated bicarbonate deficit (see "Approach to the adult with metabolic

acidosis", section on 'Dosing of alkali therapy (when given)'). The rate of bicarbonate

administration is dependent upon severity of acidosis and upon the volume status of the

patient.

We do not dialyze patients with mild organic acidosis (ie, pH 7.1), unless they have another

indication. The treatment of such patients is primarily directed at reversing the underlying

causes of excessive acid production. This includes the treatment of sepsis and the
optimization of ventilation and blood perfusion to minimize lactic acid production and the

administration of insulin to patients who have diabetic ketoacidosis. Exogenous sources of

acids (such as salicylates) should be removed. The use of bicarbonate is controversial

among such patients. We do not give bicarbonate to patients with mild organic acidosis, as

there are no data that suggest benefit [16]. (See "Bicarbonate therapy in lactic acidosis",

section on 'Which patients should receive bicarbonate therapy'.)

Two randomized trials failed to find a benefit of bicarbonate therapy in critically ill patients

with lactic acidosis and pH values >7.1:

In a crossover study, 14 patients with lactic acidosis (serum bicarbonate <17

mmol/L and arterial lactate >2.5 mmol/L) in a single intensive care unit received, in

random order, 2 mmol/kg of sodium bicarbonate and an equivalent dose of sodium

chloride [17]. Bicarbonate therapy produced a significant rise in arterial pH (from 7.22

to 7.36) and serum bicarbonate (from 12 to 18 mmol/L). However, the hemodynamic

responses to sodium bicarbonate and sodium chloride, including cardiac output,

mean arterial pressure, and pulmonary capillary wedge pressure, were identical.

In a similarly designed trial of 10 patients with lactic acidosis, sodium bicarbonate (1

mmol/kg) and an equivalent dose of sodium chloride were administered in random

order [12]. Bicarbonate therapy significantly increased the arterial pH (from 7.16 to

7.21) and serum bicarbonate (from 16 to 19 mmol/L). Again, the infusion of sodium

bicarbonate and sodium chloride produced similar changes in cardiac output, mean

arterial pressure, and pulmonary artery pressure.

These two trials were too small to detect a minor benefit of bicarbonate therapy; in addition,

patients with severe acidemia were not represented. Thus, we and other experts continue to

use bicarbonate therapy in patients who have an arterial pH <7.1. However, bicarbonate

therapy requires adequate ventilation, as discussed below. (See "Bicarbonate therapy in

lactic acidosis", section on 'Potential harms of bicarbonate and alternative agents'.)

Among patients who are receiving bicarbonate for the treatment of severe organic acidosis,

we initiate dialysis for those who have an ongoing and increasing demand for bicarbonate to

maintain pH despite administered bicarbonate, even if volume overload is not present.

However, there are no published data to suggest that a survival benefit is associated with

this approach. Thus, some clinicians would favor continuing bicarbonate administration,

providing there are no other indications for dialysis, and some would favor just treating the

underlying disease process that caused the acidosis. (See "Bicarbonate therapy in lactic

acidosis".)

Among patients with AKI, bicarbonate administration may be associated with serious side

efects. Bicarbonate administration may cause a decrease in the level of ionized or free

calcium because of a pH-dependent increase in the binding of calcium to albumin. This

could cause or worsen the symptoms of hypocalcemia since symptoms of hypocalcemia

reflect from the ionized, not total, calcium. (See 'Hypocalcemia' below.)

As in patients without AKI, bicarbonate administration could cause hypernatremia, an

increase in the partial pressure of carbon dioxide (pC02) among patients with circulatory or

ventilatory compromise, and increased intracranial pressure in patients with diabetic

ketoacidosis [18]. (See "Bicarbonate therapy in lactic acidosis".)

Hypocalcemia Serum calcium levels should be closely followed among patients with AKI.

Hypocalcemia is common among such patients and is primarily related to increases in serum

phosphorus levels caused by reduced GFR [19,20]. Other contributors to hypocalcemia

include skeletal resistance to parathyroid hormone and decreased synthesis of 1,25(OH)2D3.

(See "Etiology of hypocalcemia in adults".)

The serum ionized calcium should be measured in addition to the total serum calcium if a

laboratory known to reliably measure ionized calcium is available. The total serum calcium

concentration does not accurately reflect the ionized calcium concentration among patients

with low- or high-serum albumin levels, since calcium is bound to albumin. In addition, since

the binding of calcium to albumin is pH dependent, the amount of free calcium may be

altered by acid-base disorders or by the rapid correction of such disorders. (See "Diagnostic

approach to hypocalcemia" and "Relation between total and ionized serum calcium

concentrations".)

The treatment of hypocalcemia depends on the severity and presence of symptoms. If the

patient is asymptomatic and hyperphosphatemia is present, initial therapy is the correction of

hyperphosphatemia. The reduction of serum phosphate as a result of treatment with oral

phosphate binders is often sufficient to improve the serum calcium. (See

'Hyperphosphatemia' below.)

Symptomatic patients should be more aggressively treated with intravenous calcium (see

"Treatment of hypocalcemia"). However, the administration of calcium to patients who are

severely hyperphosphatemic may result in the deposition of calcium phosphate into

vasculature and organs. Patients with symptomatic hypocalcemia in the presence of serum

phosphorus levels >8 to 10 mg/dL (2.6 to 3.2 mmol/L) should be dialyzed to correct both

hyperphosphatemia and hypocalcemia. Among such patients, we generally use high-calcium

dialysate.

Occasionally, patients will develop life-threatening symptoms of hypocalcemia while awaiting

dialysis. Such patients should be treated with intermittent intravenous calcium chloride or

calcium gluconate, even though there is a risk of metastatic calcification associated with

such therapy. We treat with intravenous calcium patients with symptoms of hypocalcemia

including paresthesias, tetany (especially carpopedal spasm), confusion, seizures,

Trousseaus sign (carpal spasm occurring after the occlusion of the brachial artery with a

blood pressure cuf for three minutes), Chvosteks sign (contraction of the facial muscle in

response to tapping the facial nerve anterior to the ear), or QT prolongation. Initially,

intravenous calcium (1 to 2 g of calcium gluconate, equivalent to 90 to 180 mg elemental

calcium, in 50 mL of 5 percent dextrose) can be infused over 10 to 20 minutes. The calcium

should not be given more rapidly, because of the risk of serious cardiac dysfunction,

including systolic arrest [21]. This dose of calcium gluconate will raise the serum calcium

concentration for only two or three hours while arrangements for dialysis are made. Either 10

percent calcium gluconate (90 mg of elemental calcium per 10 mL) or 10 percent calcium

chloride (270 mg of elemental calcium per 10 mL) can be used to prepare the infusion

solution. Calcium gluconate is usually preferred because it is less likely to cause tissue

necrosis if extravasated. (See "Treatment of hypocalcemia", section on 'Intravenous

calcium'.)

Hyperphosphatemia Hyperphosphatemia is observed in many patients with AKI. (See

"Overview of the causes and treatment of hyperphosphatemia" and "Tumor lysis syndrome:
Definition, pathogenesis, clinical manifestations, etiology and risk factors" and "Acute

phosphate nephropathy".)

We generally treat with dietary phosphate binders all patients with AKI who have moderately

to severely elevated serum phosphate concentrations (ie, >6 mg/dL), although there are no

published data that have shown that the treatment of acute hyperphosphatemia related to

AKI improves outcomes. We do not treat patients with mild hyperphosphatemia (ie, 4.5 to 6

mg/dL) that is due to AKI.

The selection of phosphate binder depends on the level of serum ionized calcium

concentration. If the serum ionized calcium concentration is low, calcium-containing

phosphate binders such as calcium acetate or calcium carbonate may be given to control

serum phosphate levels, providing patients can take oral medications. If the serum ionized

calcium concentration is high, non-calcium phosphate binders, such as lanthanum

carbonate, sevelamer, or Al(OH)3, should be given. Among such patients, non-calcium

binders are preferred in order to prevent increases in the calcium/phosphate product.

However, there are no data that have compared outcomes among patients treated with

diferent agents in the setting of AKI. The use of Al(OH)3 should be limited to several days to

minimize accumulation of aluminum.

There are no specific guidelines at which level to initiate hemodialysis in the setting of

hyperphosphatemia, and the decision to initiate hemodialysis is often based upon

concomitant clinical and laboratory findings (such as oliguria, development of hypervolemia,

hyperkalemia, etc). We generally dialyze patients with severe hyperphosphatemia (defined

as >12 mg/dL) since dialysis works more rapidly than phosphate binders and, thus, may be

more efective in preventing injury due to the precipitation of calcium and phosphate. As

noted above, we also dialyze patients with less severe hyperphosphatemia (serum

phosphorus levels defined as >8 to 10 mg/dL) who have symptomatic hypocalcemia. Dialysis

may also be used in patients who are unable to take oral medication.

Bleeding disorders AKI can cause a qualitative platelet dysfunction, which results in a

hemorrhagic diathesis. The major clinical manifestation of this is cutaneous bleeding, but

gastrointestinal bleeding can also occur. In the absence of symptoms, platelet function is
generally not assessed in patients with AKI. The clinical manifestations, indications for

treatment, and modes of therapy are discussed elsewhere. (See "Platelet dysfunction in

uremia".)

Indications for dialysis therapy Accepted indications for dialysis in patients with AKI

generally include:

Fluid overload that is refractory to diuretics.

Hyperkalemia (serum potassium concentration >6.5 mEq/L) or rapidly rising

potassium levels, refractory to medical therapy.

Metabolic acidosis (pH <7.1) in patients in whom the administration of bicarbonate

is not indicated, such as those with volume overload (who would not tolerate the

obligate sodium load), or those with lactic acidosis or ketoacidosis, in whom

bicarbonate administration has not been shown to be efective.

Signs of uremia such as pericarditis, neuropathy, or an otherwise unexplained

decline in mental status.

Nonemergent dialysis may also be indicated for patients with prolonged AKI, even in the

absence of the indications listed above. The optimal time to start dialysis is not known, and

the blood urea nitrogen (BUN) is only one of multiple parameters that may be used to assess

dialysis requirement. The optimal timing of the initiation of dialysis is discussed elsewhere.

(See "Renal replacement therapy (dialysis) in acute kidney injury in adults: Indications,

timing, and dialysis dose".)

NUTRITION The major goals of nutritional support for critically ill patients with AKI are to

provide adequate amounts of energy, protein, and nutrients [22].

Nutritional requirements are dependent on the severity of the underlying disease, pre-

existing nutritional status, and comorbidities [22]. (See "Nutrition support in critically ill

patients: An overview", section on 'Nutritional requirements'.)

Although requirements vary based upon the underlying catabolic state, some investigators

feel that patients need approximately 25 to 30 kcal/kg per day. Others, however, feel that

permissive underfeeding may actually be a preferred approach [23], despite the lack of
specific data on underfeeding in AKI [24]. (See "Nutrition support in critically ill patients: An

overview", section on 'Calories'.)

Protein energy wasting is common among critically ill patients with AKI and contributes to

mortality [25]. Protein requirement increases with the severity of the underlying illness and

with initiation of dialysis. Whereas nondialysis patients with only mild to moderate illness

require only 0.8 to 1.2 g/kg per day, critically ill patients or patients who are on dialysis

generally require 1.2 to 1.5 g/kg per day or more [26]. (See "Nutrition support in critically ill

patients: An overview", section on 'Protein'.)

Providing adequate nutrition to patients with AKI who require dialysis may necessitate

parenteral or enteral nutrition. Among critically ill patients without AKI, most clinicians feel

that enteral nutrition should be employed in preference to parenteral nutrition whenever

possible because of its lower cost, less frequent and severe complications, less mucosal

permeability, greater wound healing, and lower rates of infection. (See "Nutrition support in

critically ill patients: An overview".)

Among patients with AKI, there are limited data concerning the efficacy and safety of enteral

nutrition. In one study, enteral nutrition-related outcomes were compared among 247

consecutive patients fed enterally: 114 required dialysis, 68 had AKI but did not require

dialysis, and 65 had normal renal function [27]. Other than an increased incidence of

nasogastric tube obstruction and high gastric residual volumes among dialyzed patients,

there was no diference in gastrointestinal and mechanical complications in the three groups.

The mean amounts of nonprotein calories and protein intake for dialyzed patients were 23.4

kcal/kg and 0.92 g/kg, respectively, with the amount of delivered protein calories being

slightly less than recommended. This can be overcome by administering parenteral amino

acids during daily dialysis.

There are few good studies that have evaluated the safety and efficacy of parenteral nutrition

among patients with AKI. A Cochrane review was unable to show an overall benefit of

parenteral nutrition on survival but was limited by poor quality of available studies [28].

MONITORING There are no data to guide the frequency with which serum electrolytes,

pH, phosphate, and calcium should be checked. In otherwise stable patients, we generally
check serum potassium, sodium, and bicarbonate twice daily, even if initial values are

normal, since, as discussed above, the initial creatinine may not reflect the true degree of

kidney dysfunction. In the setting of a glomerular filtration rate (GFR) of zero, a dangerous

increase in serum potassium may result from relatively small shifts of potassium from the

intracellular to extracellular compartment or from small amounts of potassium ingested in the

diet. Serum potassium should be checked more frequently in patients who have an elevated

serum potassium on presentation or who are oliguric or hemodynamically unstable.

Total serum calcium, phosphate, and albumin should be measured daily in stable patients.

The serum calcium should be measured more frequently (twice daily) in patients who require

calcium or bicarbonate.

It is important to carefully monitor daily weights, fluid intake, and urine output in order to

assess daily fluid balance [29]. In critically ill patients who are incontinent or otherwise

unable to monitor urine output due to compromised mental status, an indwelling catheter

may be necessary to ensure accurate measurement of urine output. The risks of an

indwelling catheter primarily include infection and must be weighed against the potential

benefit in each patient. This is discussed elsewhere. (See "Catheter-associated urinary tract

infection in adults".)

PROGNOSIS Most patients with AKI recover renal function, with recovery manifested by

an increase in urine output and a gradual decrease of the blood urea nitrogen (BUN) and

serum creatinine concentration. However many patients, including those with previously

normal renal function, do not return to baseline renal function. In addition, many studies have

demonstrated an increase in the risk of chronic kidney disease (CKD) and end-stage renal

disease (ESRD) among patients who recover from AKI. Even small, acute rises in serum

creatinine as low as 0.3 mg/dL (27 micromol/L) are associated with both short-term and long-

term increases in mortality. This issue is discussed elsewhere. (See "Renal and patient

outcomes after acute tubular necrosis".)

SUMMARY AND RECOMMENDATIONS

Acute kidney injury (AKI) is an abrupt decline in kidney function that results in an

elevation of serum blood urea nitrogen (BUN), creatinine, and other metabolic waste

products that are normally excreted by the kidney. (See 'Introduction' above.)

Potentially life-threatening complications of AKI include volume overload,

hyperkalemia, acidosis, and uremia. (See 'Immediate therapy' above.)

Volume status should be assessed in all patients with AKI. Fluid should be given to

restore intravascular volume in patients who are volume depleted. The amount of

administered fluid and the rate of replacement should be targeted to defined

endpoints, such as mean arterial pressure. Types of replacement fluid include colloid-

and crystalloid-containing solutions. For patients with AKI who require replacement

fluid, we generally use a non-potassium-containing crystalloid solution, such as

normal saline, rather than colloid-containing solutions. (See 'Volume issues' above

and "Maintenance and replacement fluid therapy in adults".)

Diuretics should not be used for prolonged therapy in place of dialysis. Diuretics

may be used for a limited period of time to relieve signs and symptoms of volume

overload. Loop diuretics may be more efective than thiazides at a glomerular filtration

rate (GFR) <30 mL/min/1.73 m2. (See 'Volume overload' above.)

The treatment of hyperkalemia is determined by severity and presence of any

associated signs, such as electrocardiographic changes or peripheral neuromuscular

abnormalities. The treatment of hyperkalemia includes both medical therapy and

dialysis. (See "Clinical manifestations of hyperkalemia in adults".)

Metabolic acidosis is common among patients with AKI. In general, we dialyze

patients with AKI who are volume overloaded and have a pH <7.1 mEq/L. Dialysis is

preferred to the administration of bicarbonate among such patients because

bicarbonate administration results in a large sodium load that may cause or

contribute to volume overload.

Among patients with AKI who are not volume overloaded and have no other

indication for acute dialysis, bicarbonate may be used in the setting of a non-anion

gap acidosis related to diarrhea or in patients with a severe organic acidosis while
awaiting dialysis. We do not use bicarbonate therapy in patients with a less severe

organic acidosis (pH 7.1). (See 'Metabolic acidosis' above.)

Hyperphosphatemia and hypocalcemia are commonly observed in patients with

AKI. The treatment depends on the degree of hyperphosphatemia and the presence

or absence of symptoms from hypocalcemia. (See 'Hyperphosphatemia' above.)

We treat with dietary phosphate binders all patients with AKI who have

moderately to severely elevated serum phosphate concentrations (ie, >6 mg/dL).

We do not treat patients with mild hyperphosphatemia (ie, 4.5 to 6 mg/dL) that is

due to AKI.

We generally dialyze patients with severe hyperphosphatemia (defined as >12

mg/dL [3.9 mmol/L]).

We dialyze patients with less severe hyperphosphatemia (serum phosphorus

levels defined as >8 to 10 mg/dL [2.6 to 3.2 mmol/L]) who have symptomatic

hypocalcemia.

Dialysis may also be used in patients who are unable to take oral medication.