Overview of The Management of Acute Kidney Injury in Adults

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Overview of the management of acute kidney injury in adults
Authors: Mark D Okusa, MD, Mitchell H Rosner, MD

Section Editor: Paul M Palevsky, MD
Deputy Editor: John P Forman, MD, MSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2018. | This topic last updated: Nov 16, 2017.
INTRODUCTION — Acute kidney injury (AKI) 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 AKI, rather than acute renal failure (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 adult patients with subacute kidney injury in an outpatient setting" and "Kidney and patient
outcomes after acute kidney injury in adults" and "Possible prevention and therapy of ischemic acute tubular
necrosis".)
PATHOGENESIS — AKI has multiple possible etiologies. Among hospitalized patients, AKI is most
commonly due to either prerenal etiologies (volume depletion, "third spacing," effective volume depletion from
heart failure or cirrhosis) or acute tubular necrosis (ATN) from ischemia, nephrotoxin exposure, or sepsis [1].
The pathogenesis of ATN is discussed elsewhere. (See "Pathogenesis and etiology of 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 in adults" 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".)
RISK SCORE FOR PREDICTION — A number of risk scores for prediction of AKI in various clinical settings
have been developed. A risk score for AKI (defined as an increase in the creatinine of ≥0.3 mg/dL within 48
hours or 50 percent increase within seven days) among critically ill patients has been developed and
validated [2]. Using data from a prospective cohort of 573 patients, independent predictors of AKI within 48
hours of admission to the intensive care unit (ICU) were identified and used to develop a risk prediction
score:
● Chronic kidney disease (CKD) – 2 points
● Chronic liver disease – 2 points
● Heart failure – 2 points

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● Hypertension – 2 points
● Coronary heart disease – 2 points
● pH <7.3 – 3 points
● Nephrotoxin exposure – 3 points
● Severe infection/sepsis – 2 points
● Mechanical ventilation – 2 points
● Anemia – 1 point
The risk prediction model was tested in an additional cohort of 144 patients and independently validated
among 1300 consecutive ICU patients. Using a threshold ≥5 to define high-risk individuals, the positive and
negative predictive values in the validation cohort were 32 and 95, respectively. Thus, using this model, 32
percent of patients with score ≥5 points are likely to develop AKI within 48 hours; 95 percent of patients with
score <5 points are unlikely to develop AKI.
The operating characteristics of this risk score are similar to others in that the positive predictive capability is
low to moderate while the negative predictive value is very high. These risk scores are helpful in situations
where the potential nephrotoxic insult is high and is anticipated (such as prior to coronary surgery or
angiography or contrast dye administration). In these settings, such scores allow for identification of risk
stratification and implementation of specific risk reduction programs targeting those patients at highest risk.
However, data are not provided in this study about severity or cause of ensuing AKI.
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. In addition, it is now recognized that even small increases in serum
creatinine (>0.3 mg/dL) can have important prognostic implications and are clinically relevant [3]. The
potential limitations of the different consensus criteria that have been proposed are discussed elsewhere.
(See "Definition and staging criteria of acute kidney injury in adults".)
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. In order to address this
non-steady state phenomena of serum creatinine, a kinetic GFR evaluation formula can be utilized [4].
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,
metabolic acidosis, and volume overload (see 'Management' below). The initial evaluation of the patient with
AKI is directed at determining the cause, removing any active insults, minimizing new injury, and identifying
the complications that may require immediate attention.
The diagnostic evaluation to determine the cause of AKI is discussed elsewhere. The use of urinary and
serum biomarkers of kidney injury and their evolving roles are also discussed in these sections. (See
"Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Etiology and
diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults", 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.
As these patients are often unstable and critically ill, we recommend careful attention to serial measurement
of these values as well as meticulous measurement of fluid balance.
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. Retrospective data have shown that even small degrees of fluid
overload are associated with poor outcomes and increased risk of mortality. Thus, fluid therapy should be
used with careful attention to net fluid balance and avoiding overload [5]. (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). This is
especially true for certain etiologies such as rhabdomyolysis (see "Crush-related acute kidney injury" and
"Prevention and treatment of heme pigment-induced acute kidney injury"). However, such fluid infusion is
contraindicated in those with obvious intravascular volume overload. In certain patients, such as those with
systolic or diastolic heart failure, cirrhosis, or the nephrotic syndrome, patients may appear to be volume
overloaded but have low effective circulating volume and may respond with increased urine output after fluid
therapy. In unclear cases, central hemodynamic measurements that assess volume responsiveness may be
helpful.
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 hypovolemia or hypovolemic shock in adults", section on 'Colloid versus crystalloid').
Potassium-containing crystalloid solutions, such as lactated Ringer's solution, should be used with caution
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 hypovolemia or hypovolemic shock in adults", section on 'Buffered crystalloid versus isotonic
saline'). However, randomized, controlled trials have not demonstrated the superiority of balanced solutions
over chloride-rich solutions such as 0.9 percent saline, and this debate continues [6].
The overall goal of fluid therapy is to increase cardiac output and improve tissue oxygenation in patients who
are preload dependent or volume responsive. Administering fluids in patients who are non-volume responsive
is detrimental and should be avoided. 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 [7]. 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). In critically ill, mechanically ventilated patients, mini-fluid boluses (100 mL) may demonstrate
fluid responsiveness by increase in stroke volume [8] while minimizing the potential for fluid overload
associated with large continuous fluid administration.
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 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 for a total of 1 to 3
liters. 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 (first three
hours)'.)
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 and which is associated with poor outcomes.
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 [9]. A higher furosemide dose was associated with decreased mortality, but this effect 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 or to postpone the initiation of dialysis,
since dialysis and ultrafiltration offer the most efficient method of volume removal in patients with AKI from
any cause and allow 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 [10-12], the benefit of early initiation of dialysis for volume
management remains uncertain (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 effect than thiazide diuretics. We often start with 40 to 80 mg of
intravenous furosemide. The dose of loop diuretics can be titrated upward to assess for responsiveness, and
a thiazide diuretic can be added to augment diuresis. As mentioned above, if there is minimal response to
high-dose loop diuretics (>80 to 120 mg of furosemide) combined with a thiazide diuretic, then
dialysis/ultrafiltration should be considered. (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 are 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 effects 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 effective.
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 staff), 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. Oral potassium binding resins
can be considered in mild hyperkalemia (see "Treatment and prevention of hyperkalemia in adults"). 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. In addition, administration of large amounts of chloride-rich solutions such as 0.9
percent saline may lead to a non-anion gap metabolic 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 [13-
20]. 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 or other etiologies. (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".)
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 [21]. 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 tissue 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 [22]. (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 (ICU) received, in random order, 2 mmol/kg of sodium
bicarbonate and an equivalent dose of sodium chloride [23]. 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 [18]. 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 effects.
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 [24]. (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 [25,26]. 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. This is
especially true for patients with tumor lysis syndrome. 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, Trousseau’s sign (carpal
spasm occurring after the occlusion of the brachial artery with a blood pressure cuff for three minutes),
Chvostek’s 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 [27].
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. This is especially true
for tumor lysis syndrome and rhabdomyolysis. (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 different 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).
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 effective.
● 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 remains controversial, with two randomized clinical
trials demonstrating disparate results, 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 [28].
Nutritional requirements are dependent on the severity of the underlying disease, pre-existing nutritional
status, and comorbidities [28]. (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 [29], despite the lack of specific data on underfeeding in AKI [30]. (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 [31].
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 [32]. (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 [33]. Other than
an increased incidence of nasogastric tube obstruction and high gastric residual volumes among dialyzed
patients, there was no difference 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 [34].
MONITORING — There are no data to guide the frequency with which serum electrolytes, pH, phosphate,
and calcium should be checked. 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 [35]. 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 "Kidney and patient outcomes after acute
kidney injury in adults".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected
countries and regions around the world are provided separately. (See "Society guideline links: Acute kidney
injury in adults".)
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.)
https://www.uptodate.com/contents/overview-of-the-management-of-acute-kidney-injury-in-adults/print?search=injuria%20renal%20aguda&sou… 10/13
● 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. However, a significant hyperchloremic metabolic acidosis
should be avoid when using 0.9 percent saline. (See 'Volume issues' above and "Maintenance and
replacement fluid therapy in adults".)
● Diuretics should not be used for prolonged therapy in place of dialysis, especially if the patient continues
in net positive fluid balance. Diuretics may be used for a limited period of time to relieve signs and
symptoms of volume overload. Loop diuretics may be more effective 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.
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Topic 14035 Version 22.0

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20/11/2018 Overview of the management of acute kidney injury in adults - UpToDate

Official reprint from UpToDate®

Authors: Mark D Okusa, MD, Mitchell H Rosner, MD

● Chronic kidney disease (CKD) – 2 points

● Chronic liver disease – 2 points

● Heart failure – 2 points

● Coronary heart disease – 2 points

● Nephrotoxin exposure – 3 points

● Severe infection/sepsis – 2 points

● Mechanical ventilation – 2 points

● 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)

Hyperkalemia — Hyperkalemia is a common and potentially life-threatening complication of AKI. It is

● Fluid overload that is refractory to diuretics.

SUMMARY AND RECOMMENDATIONS

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Topic 14035 Version 22.0

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