Acute Renal Failure

Author: Mahendra Agraharkar, MD, MBBS, FACP, President, Space City Associates of Nephrology; Medical Director, Acute Dialysis Unit and
Chronic Home Dialysis Unit, Gambro Healthcare Reliant Dialysis Center
Coauthor(s): Rajiv Gupta, MD, Assistant Professor, Department of Medicine, Texas A & M University Health Science Center; Consulting Staff,
Veteran's Affairs Hospital, Temple, Texas; Aruna Agraharkar, MD FACP, Consulting Staff, Department of Gerontology, Space Center Clinic;
Biruh T Workeneh, MD, Fellow in Nephrology, Stanford University School of Medicine
Contributor Information and Disclosures
Updated: Sep 21, 2007

Introduction
Background
Acute renal failure (ARF) or acute kidney injury (AKI), as it is now referred to in the literature, is defined as an
abrupt or rapid decline in renal filtration function. This condition is usually marked by a rise in serum
creatinine concentration or azotemia (a rise in blood urea nitrogen [BUN] concentration). However,
immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney
injury may be decreased urine production. A rise in the creatinine level can result from medications (eg,
cimetidine, trimethoprim) that inhibit the kidneys tubular secretion. A rise in the BUN level can occur without
renal injury, such as in GI or mucosal bleeding, steroid use, or protein loading, so a careful inventory must be
taken before determining if a kidney injury is present.
Pathophysiology
AKI may occur in 3 clinical patterns, including the following: (1) as an adaptive response to severe volume
depletion and hypotension, with structurally intact nephrons; (2) in response to cytotoxic, ischemic, or
inflammatory insults to the kidney, with structural and functional damage; and (3) with obstruction to the
passage of urine. Therefore, in general terms, AKI may be classified as prerenal, intrinsic, and postrenal.
While these classifications are useful in establishing a differential diagnosis, many pathophysiologic features
are shared among the different categories.
Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in creatinine levels, and
may have qualitative differences in urine solute concentrations and cellular content. The reason for this lack
of a uniform clinical presentation is a reflection of the variable nature of the injury. Classifying AKI as oliguric
or nonoliguric based on daily urine excretion has prognostic value. Oliguria is defined as a daily urine volume
of less than 400 mL/d and has a worse prognosis, except in prerenal failure. Anuria is defined as a urine
output of less than 100 mL/d and, if abrupt in onset, is suggestive of bilateral obstruction or catastrophic
injury to both kidneys. Stratification of renal failure along these lines helps in decision-making (eg, timing of
dialysis) and can be an important criterion for patient response to therapy.
Pre renal AKI
Prerenal AKI represents the most common form of kidney injury and often leads to intrinsic AKI if it is not
promptly corrected. Volume loss from GI, renal, cutaneous (eg, burns), and internal or external hemorrhage
can result in this syndrome. Prerenal AKI can also result from decreased renal perfusion in patients with
heart failure or shock (eg, sepsis, anaphylaxis). Special classes of medications that can induce prerenal AKI
in volume-depleted states are angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor
blockers (ARBs), which are otherwise safely tolerated and beneficial in most patients with chronic kidney
disease. Arteriolar vasoconstriction leading to prerenal AKI can occur in hypercalcemic states, with the use of
radiocontrast agents, nonsteroidal anti-inflammatory drugs (NSAIDs), amphotereicin, calcineurin inhibitors,
norepinephrine, and other pressor agents. The hepatorenal syndrome can also be considered a form of
prerenal AKI because functional renal failure develops from diffuse vasoconstriction in vessels supplying the
kidney.
Intrinsic AKI
Structural injury in the kidney is the hallmark of intrinsic AKI, and the most common form is acute tubular
injury (ATN), either ischemic or cytotoxic. Frank necrosis is not prominent in most human cases of ATN and
tends to be patchy. Less obvious injury includes loss of brush borders, flattening of the epithelium,
detachment of cells, formation of intratubular casts, and dilatation of the lumen. Although these changes are
observed predominantly in proximal tubules, injury to the distal nephron can also be demonstrated. The
distal nephron may also be subjected to obstruction by desquamated cells and cellular debris.
In contrast to necrosis, the principal site of apoptotic cell death is the distal nephron. During the initial phase
of ischemic injury, loss of integrity of the actin cytoskeleton leads to flattening of the epithelium, with loss of
the brush border, loss of focal cell contacts, and subsequent disengagement of the cell from the underlying
substratum.
Many endogenous growth factors that participate in the process of regeneration have not been identified;
however, administration of growth factors exogenously has been shown to ameliorate and hasten recovery
from AKI. Depletion of neutrophils and blockage of neutrophil adhesion reduce renal injury following

ischemia, indicating that the inflammatory response is responsible, in part, for some features of ATN,
especially in postischemic injury after transplant.
Intrarenal vasoconstriction is the dominant mechanism for the reduced glomerular filtration rate (GFR) in
patients with ATN. The mediators of this vasoconstriction are unknown, but tubular injury seems to be an
important concomitant finding. Urine backflow and intratubular obstruction (from sloughed cells and debris)
are causes of reduced net ultrafiltration. The importance of this mechanism is highlighted by the
improvement in renal function that follows relief of such intratubular obstruction. In addition, when obstruction
is prolonged, intrarenal vasoconstriction is prominent in part due to the tubuloglomerular feedback
mechanism, which is thought to be mediated by adenosine and activated when there is proximal tubular
damage and the macula densa is presented with increased chloride load.
Apart from the increase in basal renal vascular tone, the stressed renal microvasculature is more sensitive to
potentially vasoconstrictive drugs and otherwise-tolerated changes in systemic blood pressure. The
vasculature of the injured kidney has an impaired vasodilatory response and loses its autoregulatory
behavior. This latter phenomenon has important clinical relevance because the frequent reduction in
systemic pressure during intermittent hemodialysis may provoke additional damage that can delay recovery
from ATN. Often, injury results in atubular glomeruli, where the glomerular function is preserved, but the lack
of tubular outflow precludes its function.
A physiologic hallmark of ATN is a failure to maximally dilute or concentrate urine (isosthenuria). This defect
is not responsive to pharmacologic doses of vasopressin. The injured kidney fails to generate and maintain a
high medullary solute gradient because the accumulation of solute in the medulla depends on normal distal
nephron function. Failure to excrete concentrated urine, even in the presence of oliguria, is a helpful
diagnostic clue to distinguish prerenal from intrinsic renal disease, in which urine osmolality is less than 300
mOsm/kg. In prerenal azotemia, urine osmolality is typically more than 500 mOsm/kg.
Glomerulonephritis can be a cause of AKI and usually falls into a class referred to as rapidly progressive
glomerulonephritis (RPGN). The pathologic correlation of RPGN is the presence of glomerular crescents
(glomerular injury) on biopsy; if more than 50% of glomeruli contain crescents, this usually results in a
significant decline in renal function. Although comparatively rare, acute glomerulonephritides should be part
of the diagnostic consideration in cases of AKI.
Postrenal AKI
Mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters, bladder, or
urethra, results in obstructive uropathy or postrenal AKI.
If the site of obstruction is unilateral, then a rise in the serum creatinine level may not be apparent due to
contralateral renal function. Although the serum creatinine level may remain low with unilateral obstruction, a
significant loss of GFR occurs, and patients with partial obstruction may develop progressive loss of GFR if
the obstruction is not relieved. Causes of obstruction include stone disease; stricture; and intraluminal,
extraluminal, or intramural tumors.
Bilateral obstruction is usually a result of prostate enlargement or tumors in men and urologic or gynecologic
tumors in women.
Patients who develop anuria typically have obstruction at the level of the bladder or downstream to it.
Frequency
United States
Approximately 1% of patients admitted to hospitals have AKI at the time of admission, and the estimated
incidence rate of AKI is 2-5% during hospitalization. Approximately 95% of consultations with nephrologists
are related to AKI. Feest and colleagues calculated in their report that the appropriate nephrologist referral
rate is approximately 70 cases per million population.1
Mortality/Morbidity
The mortality rate estimates vary from 25-90%. The in-hospital mortality rate is 40-50%; in intensive care
settings, the rate is 70-80%. Increments of 0.3 mg/dL in serum creatinine have important prognostic
significance.
Race
No racial predilection is recognized.
Clinical
History

A detailed and accurate history is crucial to aid in diagnosing the type of AKI and in determining its
subsequent treatment. A detailed history and a physical examination in combination with routine laboratory
tests are useful in making a correct diagnosis (see Lab Studies).

Distinguishing AKI from chronic renal failure is important, yet making the distinction can be difficult. A
history of chronic symptoms of fatigue, weight loss, anorexia, nocturia, and pruritus all suggest
chronic renal failure.
Take note of the following findings during the physical examination:
o Hypotension
o Volume contraction
o Congestive heart failure
o Nephrotoxic drug ingestion
o History of trauma or unaccustomed exertion
o Blood loss or transfusions
o Evidence of connective tissue disorders or autoimmune diseases
o Exposure to toxic substances, such as ethyl alcohol or ethylene glycol
o Exposure to mercury vapors, lead, cadmium, or other heavy metals, which can be
encountered in welders and miners
People with the following comorbid conditions are at a higher risk for developing AKI:
o Hypertension
o Congestive cardiac failure
o Diabetes
o Multiple myeloma
o Chronic infection
o Myeloproliferative disorder
Urine output history can be useful. Oliguria generally favors AKI. Abrupt anuria suggests an acute
obstruction, acute and severe glomerulonephritis, or an embolic event due to the renal artery
occlusion. A gradually diminishing urine output may indicate a urethral stricture or bladder outlet
obstruction due to prostate enlargement.
Because of a decrease in functioning nephrons, even a trivial nephrotoxic insult may cause AKI to be
superimposed on chronic renal insufficiency.

Physical
Obtaining a thorough physical examination is extremely important when collecting evidence about the
etiology of AKI.

Skin

Examination of the skin for petechiae, purpura, ecchymosis, and livedo reticularis provides
clues to inflammatory and vascular causes of AK
Infectious diseases, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular
coagulation (DIC), and embolic phenomena can present with typical cutaneous changes.

Eyes

Evidence of uveitis may indicate interstitial nephritis and necrotizing vasculitis.

Ocular palsy may indicate ethylene glycol poisoning or necrotizing vasculitis.
Findings suggestive of severe hypertension, atheroembolic disease, and endocarditis may
be observed after a careful examination of the eyes.
Cardiovascular system
The most important part of the physical examination is the assessment of cardiovascular
and volume status.
The physical examination must include pulse rate and blood pressure recordings measured
in both the supine position and the standing position; close inspection of the jugular venous
pulse; careful examination of the heart, lungs, skin turgor, and mucous membranes; and
assessment for the presence of peripheral edema.
Accurate daily records of fluid intake and urine output and daily measurements of patient
weight are important.
Blood pressure recordings can be important diagnostic tools.
Hypovolemia leads to hypotension; however, hypotension may not necessarily indicate
hypovolemia.
Severe congestive cardiac failure (CHF) may also cause hypotension. Although patients with
CHF may have low blood pressure, volume expansion is present and effective renal
perfusion is poor, which can result in AKI.
Severe hypertension with renal failure suggests renovascular disease, glomerulonephritis,
vasculitis, or atheroembolic disease.
Abdomen

Abdominal examination findings can be useful to help detect obstruction at the bladder outlet
as the cause of renal failure, which may be due to cancer or an enlarged prostate.
The presence of an epigastric bruit suggests renal vascular hypertension.

Causes
The causes of AKI traditionally are divided into 3 main categories: prerenal, intrinsic, and postrenal. The 3
main categories are summarized below.

Prerenal AKI
o Volume depletion
Renal losses (diuretics, polyuria)
GI losses (vomiting, diarrhea)
Cutaneous losses (burns, Stevens-Johnson syndrome)
Hemorrhage
Pancreatitis
o Decreased cardiac output
Heart failure
Pulmonary embolus
Acute myocardial infarction
Severe valvular disease
Abdominal compartment syndrome (tense ascites)
o Systemic vasodilation
Sepsis
Anaphylaxis
Anesthetics
Drug overdose
o Afferent arteriolar vasoconstriction
Hypercalcemia
Drugs (NSAIDs, amphotericin B, calcineurin inhibitors, norepinephrine, radiocontrast
agents)
Hepatorenal syndrome
o Efferent arteriolar vasodilation ACEI or ARB
Intrinsic AKI
o Vascular (large and small vessel)
Renal artery obstruction (thrombosis, emboli, dissection, vasculitis)
Renal vein obstruction (thrombosis)
Microangiopathy (TTP, hemolytic uremic syndrome [HUS], DIC, preeclampsia)
Malignant hypertension
Scleroderma renal crisis
Transplant rejection
Atheroembolic disease
o Glomerular
Antiglomerular basement membrane (GBM) disease (Goodpasture syndrome)
Antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCAassociated GN) (Wegener granulomatosis, Churg-Strauss syndrome, microscopic
polyangiitis)
Immune complex GN (lupus, postinfectious, cryoglobulinemia, primary
membranoproliferative glomerulonephritis)
o Tubular
Ischemi
Cytotoxic
Heme pigment (rhabdomyolysis, intravascular hemolysis)
Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning,
megadose vitamin C, acyclovir, indinavir, methotrexate)
Drugs (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatin,
ifosfamide, radiocontrast agents)
o Interstitial
Drugs (penicillins, cephalosporins, NSAIDs, proton-pump inhibitors, allopurinol,
rifampin, indinavir, mesalamine, sulfonamides)
Infection (pyelonephritis, viral nephritides)
Systemic disease (Sjogren syndrome, sarcoid, lupus, lymphoma, leukemia,
tubulonephritis, uveitis)
Postrenal AKI
o Ureteric obstruction (stone disease, tumor, fibrosis, ligation during pelvic surgery)

Bladder neck obstruction (benign prostatic hypertrophy [BPH], cancer of the prostate [CA
prostate or prostatic CA], neurogenic bladder, tricyclic antidepressants, ganglion blockers,
bladder tumor, stone disease, hemorrhage/clot)
Urethral obstruction (strictures, tumor, phimosis)

Differential Diagnoses
Acute Tubular Necrosis
Azotemia
Chronic Renal Failure
Other Problems to Be Considered
Obstructive uropathy
GI bleeding
Protein overloading
Steroid use
Workup
Laboratory Studies

Several laboratory tests are useful for assessing the etiology of AKI, and the findings can aid in
proper management. These tests include complete blood cell count, serum biochemistries, urine
analysis with microscopy, and urine electrolytes.
Blood urea nitrogen and serum creatinine
o Although increased levels of BUN and creatinine are the hallmarks of renal failure, the rate
of rise is dependent on the degree of renal insult as well as protein intake with respect to
BUN.
o The ratio of BUN to creatinine is an important finding because the ratio can exceed 20:1 in
conditions in which enhanced reabsorption of urea is favored (eg, in volume contraction) and
suggests prerenal AKI.
o BUN may be elevated in patients with GI or mucosal bleeding, steroid treatment, or protein
loading.
o Assuming no renal function, the rise in BUN over 24 hours can be roughly predicted using
the following formula: 24-hour protein intake in milligrams X 0.16 divided by total body water
in mg/dL added to the BUN value.
o Assuming no renal function, the rise in creatinine can be predicted using the following
formulas:
For males: weight in kilograms X [28 0.2(age)] divided by total body water in
mg/dL added to the creatinine value
For females: weight in kilograms X [23.8 0.17(age)] divided by total body water
added to the creatinine value
o As a general rule, if serum creatinine increases to more than 1.5 mg/dL/d, rhabdomyolysis
must be ruled out.
CBC, peripheral smear, and serology
o These tests may be useful, and the peripheral smear results may show schistocytes in
conditions such as HUS or TTP.
o A finding of increased rouleaux formation suggests multiple myeloma, and the workup
should be directed toward immunoelectrophoresis of serum and urine.
o The presence of myoglobin or free hemoglobin, increased serum uric acid level, and other
related findings may help further define the etiology of AKI.
o Serologic tests for antinuclear antibody (ANA), ANCA, anti-GBM antibody, hepatitis, and
antistreptolysin (ASO) and complement levels may help include and exclude glomerular
disease. Although serologic tests can be informative, the costs can be prohibitive if not
ordered judiciously.
Urinalysis
o Findings of granular muddy-brown casts are suggestive of tubular necrosis. The presence of
tubular cells or tubular cell casts also supports the diagnosis of ATN. Often, oxalate crystals
are observed in cases of ATN.
o Reddish brown or cola-colored urine suggests the presence of myoglobin or hemoglobin,
especially in the setting of a positive dipstick for heme and no RBCs in the microscopic
examination.
o Dipstick assay findings may show the presence of significant proteinuria, which would
suggest glomerular or interstitial disease.

The presence of RBCs in the urine is always pathologic. Eumorphic RBCs suggest bleeding
along the collecting system. Dysmorphic RBCs or RBC casts indicate
glomerular inflammation, suggesting glomerulonephritis is present.
o The presence of WBCs or WBC casts suggests pyelonephritis or acute interstitial nephritis.
The presence of urine eosinophils is helpful in establishing a diagnosis but is not necessary
for allergic interstitial nephritis to be present.
o The presence of eosinophils, as visualized with Wright stain or Hansel stain, suggests
interstitial nephritis but can be seen in urinary tract infections, glomerulonephritis, and
atheroembolic disease.
o The presence of uric acid crystals may represent ATN associated with uric acid nephropathy.
o Calcium oxalate crystals are usually present in cases of ethylene glycol poisoning.
Urine electrolytes
o Urine electrolyte findings also can serve as valuable indicators of functioning renal tubules.
o The fractional excretion of sodium (FENa) is the commonly used indicator. However, the
interpretation of results from patients in nonoliguric states, those with glomerulonephritis,
and those receiving or ingesting diuretics can lead to an erroneous diagnosis. FENa can be
a valuable test for helping to detect extreme renal avidity for sodium in conditions such as
hepatorenal syndrome. The formula for calculating the FENa is as follows:
o

FENa = (UNa/PNa) / (UCr/PCr) X 100

o Calculating the FENa is useful in AKI only in the presence of oliguria.
o In patients with prerenal azotemia, the FENa is usually less than 1%. In ATN, the FENa is
greater than 1%. Exceptions to this rule are ATN caused by radiocontrast nephropathy,
severe burns, acute glomerulonephritis, and rhabdomyolysis.
o In the presence of liver disease, FENa can be less than 1% in the presence of ATN. On the
other hand, because administration of diuretics may cause the FENa to be greater than 1%,
these findings cannot be used as the sole indicators in AKI.
o In patients who are receiving diuretics, a fractional excretion of urea (FEUrea) can be
obtained since urea transport is not affected by diuretics. The formula for calculating the
FEUrea is as follows:
FEUrea = (Uurea/Purea) / (UCr/PCr) X 100
o FEUrea of less than 35% is suggestive of a prerenal state.
Imaging Studies

In some cases, renal imaging is useful, especially if the cause of renal failure is secondary to
obstruction.
Ultrasound
o Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the
urinary collecting system. The degree of hydronephrosis does not necessarily correlate with
the degree of obstruction. Mild hydronephrosis may be observed with complete obstruction
if found early.
o Obtaining images of the kidneys can be technically difficult in patients who are obese or in
those with abdominal distension due to ascites, gas, or retroperitoneal fluid collection.
o Ultrasound scans or other imaging studies showing small kidneys suggest chronic renal
failure.
Doppler scans
o Doppler scans are useful for detecting the presence and nature of renal blood flow.
o Because renal blood flow is reduced in prerenal or intrarenal AKI, test findings are of little
use in the diagnosis of AKI.
o Doppler scans can be quite useful in the diagnosis of thromboembolic or renovascular
disease.
o Increased resistive indices can be observed in patients with hepatorenal syndrome.
Nuclear scans
o Radionuclide imaging with a technetium Tc 99m diethylenetriamine pentaacetic acid (DTPA),
99m Tc-DTPA iodine I 131hippuran scan can be used to assess renal blood flow and
tubular functions.
o Because of a marked delay in tubular excretion of radionuclide in both prerenal disease and
intrarenal disease, the value of these scans is limited.
Aortorenal angiography can be helpful in establishing the diagnosis of renal vascular diseases,
including renal artery stenosis, renal atheroembolic disease, atherosclerosis with aortorenal
occlusion, and in certain cases of necrotizing vasculitis (eg, polyarteritis nodosa).

Procedures

Renal biopsy

A renal biopsy can be useful in establishing the diagnosis of intrarenal causes of AKI and
can be justified if it will change management (eg, initiation of immunosuppressive
medications). A renal biopsy may also be indicated when renal function does not return for a
prolonged period and a prognosis is required to develop long-term management.
In as many as 40% of cases, renal biopsy results reveal an unexpected diagnosis.
Acute cellular or humoral rejection in a renal transplant can be definitively diagnosed only by
performing a renal biopsy.

Treatment
Medical Care
The mortality rate for patients in the intensive care unit (ICU) is higher in those who have AKI, especially
when AKI is severe enough to require dialysis treatment. In addition, evidence suggests that the relative risk
of death is 4.9 in patients in the ICU who have renal failure that is not severe enough to require dialysis. This
reflects that the high mortality rate in patients with AKI who require dialysis may not be related to the dialysis
procedure or accompanying comorbidities and that AKI alone may be an independent indicator of mortality.

Aggressive treatment should begin at the earliest indication of renal dysfunction. A large proportion
of the renal mass is damaged before any biochemical evidence of renal dysfunction is appreciated
because the relationship between the GFR and the serum creatinine level is exponential, not linear.
The rise of serum creatinine may not be evident before 50% of the GFR is lost.
At this point, recognizing the presence of AKI and promptly initiating therapy aimed at minimizing the
damage to the remaining functional renal mass are important considerations. This may also aid in
reversing the renal damage that has already occurred. Reversing renal damage can be
accomplished only by identifying the underlying cause and directing the appropriate therapy.
Maintenance of volume homeostasis and correction of biochemical abnormalities remain the primary
goals of treatment. Furosemide can be used to correct volume overload when the patients are still
responsive to it. Furosemide plays no role in converting an oliguric AKI to a nonoliguric AKI or to
increase urine output when a patient is not hypervolemic. However, the response to furosemide can
be taken as a good prognostic sign. At this stage, the kidneys remain vulnerable to the toxic effects
of various chemicals. All nephrotoxic agents (eg, radiocontrast agents, antibiotics with nephrotoxic
potential, heavy metal preparations, cancer chemotherapeutic agents, NSAIDs) are either avoided or
used with extreme caution. Similarly, all medications cleared by renal excretion should be avoided or
their doses should be adjusted appropriately.
Correcting acidosis with bicarbonate administration is important. It cannot be overstated that the
current treatment of AKI is mainly supportive in nature and no therapeutic modalities to date have
shown efficacy in treating the condition. Therapeutic agents, such as dopamine, fenoldopam, and
mannitol, are not indicated in the management of AKI and may be harmful for the patient.
Hyperkalemia, which can be life-threatening, should be treated by decreasing the intake of
potassium, delaying the absorption of potassium, exchanging potassium across the gut lumen using
potassium-binding resins, controlling intracellular shifts, and instituting dialysis, as outlined
in Hyperkalemia.
Correcting hematologic abnormalities (eg, anemia, platelet dysfunction) warrants appropriate
measures, including transfusions and administration of desmopressin or estrogens.

Diet

Dietary modulation is an important facet of the treatment of AKI. Diet and fluid restriction become
crucial in the management of oliguric renal failure, wherein the kidneys do not adequately excrete
either toxins or fluids.
Because potassium and phosphorous are not excreted optimally in patients with AKI, blood levels of
these electrolytes tend to be high. Frequent measurements are mandatory to achieve acceptable
blood levels by modification of the diet or by intravenous supplementation.
In the polyuric phase of AKI, potassium and phosphorous may be depleted and patients require
dietary supplementation and intravenous fluids.
Calculation of the nitrogen balance can be challenging, especially in the presence of volume
contraction, hypercatabolic states, gastrointestinal bleeding, and diarrheal disease.

Medication
Pharmacologic treatment of AKI has been attempted on an empiric basis, with varying success rates.
Several promising experimental therapies in animal models are awaiting human trials. Experimental
therapies include growth factors, vasoactive peptides, adhesion molecules, endothelin inhibitors, and
bioartificial kidneys. Aminophylline has also been used experimentally for prophylaxis against renal failure.
A prophylactic strategy shown to decrease the incidence of contrast nephropathy is the IV administration of
fluids. Although controversy exists regarding the ideal fluid, normal saline and isotonic NaHCO3 have proven

to be effective. Normal saline solution of 1 mL/kg/h administered 12 hours before the procedure and then 12
hours after the procedure is recommended. In patients who are at high risk for volume overload, isotonic
NaHCO3 solution should be administered before and after the procedure. It can be prepared by mixing 3
ampules of NaHCO3 in a liter of D5W and can be given at a rate of 3 mL/kg/h for 1 hour prior to the
procedure; 1 mL/kg/h during the procedure; and for 6 hours afterward. Another prophylactic agent used with
varying success is N -acetylcysteine at a dosage of 1200 mg PO q12h. This is administered to high-risk
patients the day before a contrast study is performed and is continued the day of the procedure. Diuretics,
NSAIDs, and possibly ACEIs should be withheld near the time of the procedure.
Diuretics
Although diuretics seem to have no effect on the outcome of established AKI, they appear useful in fluid
homeostasis and are used extensively. The use of isotonic sodium chloride solution in conjunction with
diuretics is debatable. The only therapeutic or preventive intervention that has an established beneficial
effect in the management of AKI is administration of isotonic sodium chloride solution to keep the patient
euvolemic or even hypervolemic.

Furosemide (Lasix)
Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits
sodium and chloride reabsorption in the thick ascending loop of Henle and the distal renal tubule. Potent and
rapid-acting agent with peak action at 60 min and lasting 6-8 h.
In renal failure, higher doses must be used for greater diuretic effects. Doses as high as 600 mg/d may be
needed under monitored conditions.
Frequently, IV doses are needed in AKI to maintain urine output. IV infusions are often helpful in ICU
settings, in which larger doses are necessary. This method promotes a sustained natriuresis with reduced
ototoxicity compared to conventional intermittent bolus dosing.
Adult
20-40 mg PO qd initially
Pediatric
Not established
Vasodilators
Dopamine in small doses (eg, 1-5 mcg/kg/min) causes selective dilatation of the renal vasculature,
enhancing renal perfusion. Dopamine also reduces sodium absorption, thereby decreasing the energy
requirement of the damaged tubules. This enhances urine flow, which, in turn, helps prevent tubular cast
obstruction. Most clinical studies have failed to establish this beneficial role of renal-dose dopamine infusion.

Dopamine (Intropin)
Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dose-dependent. Lower
doses predominantly stimulate dopaminergic receptors, which, in turn, produce renal and mesenteric
vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.
Adult
1-5 mcg/kg/min IV
Pediatric
Administer as in adults
Calcium channel blockers
Effective in animal models but efficacy not proven in humans. Effects are believed to be mediated through
vasodilation, and calcium channel blockers increasingly are used to enhance the function of transplanted
kidneys.

Nifedipine (Adalat, Procardia)

Relaxes smooth muscle and produces vasodilation, which, in turn, improves blood flow and oxygen delivery.
Adult
10-30 mg IR cap PO tid; not to exceed 120-180 mg/d
30-60 mg SR tab PO qd; not to exceed 90-120 mg/d

Pediatric
0.25-0.5 mg/kg/dose PO tid/qid prn
N-acetylcysteine
Used for prevention of contrast toxicity in susceptible individuals such as those with diabetes mellitus.

N-acetylcysteine (Mucosil, Mucomyst)

May provide substrate for conjugation with toxic metabolites.
Adult
For prevention of nephrotoxicity: 600 mg PO bid on day preceding and day of procedure
Pediatric
Not established
Follow-up
Further Outpatient Care

Always keep in mind that renal recovery in most cases is not complete and the kidneys remain
vulnerable to nephrotoxic effects of all therapeutic agents. Therefore, agents with nephrotoxic
potential are best avoided.

Prognosis

The prognosis of patients with AKI is directly related to the cause of renal failure and, to a great
extent, to the duration of renal failure prior to therapeutic intervention. If AKI is defined by a sudden
increment of serum creatinine of 0.5-1 mg/dL and is associated with a mild-to-moderate rise in
creatinine, the prognosis tends to be worse. However, even if renal failure is mild, the mortality rate
is 30-60%. If these patients need dialytic therapy, the mortality rate is 50-90%.
o The mortality rate is 31% in patients with normal urine sediment test results and is 74% in
patients with abnormal urine sediment test results.
o If using Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the survival
rate is nearly 0% among patients with AKI who have a score higher than 40 and is 40% in
patients with APACHE II scores of 10-19.
o Other prognostic factors include the following:
Older age
Multiorgan failure (ie, the more organs that fail, the worse the prognosis)
Oliguria
Hypotension
Vasopressor support
Number of transfusions
Noncavitary surgery
Prerenal azotemia due to volume contraction is treated with volume expansion; however, if left
untreated for a prolonged duration, tubular necrosis may result and may not be reversible.
Postrenal AKI, ie, urinary obstruction related renal failure, causes renal damage due to increased
pressure proximal to the obstruction, which results in a thinning of the renal cortex. If left untreated
for a long time, it may result in irreversible renal damage. Simple procedures such as catheter
placement, lithotripsy, prostatectomy, stent placement, or percutaneous nephrostomy can help
prevent permanent renal damage.
Timely identification of pyelonephritis, proper treatment, and further prevention using prophylactic
antibiotics may improve the prognosis, especially in females.
o Early diagnosis of crescentic glomerulonephritis via renal biopsy and other appropriate tests
may enhance early renal recovery because appropriate therapy can be initiated promptly
and aggressively.
o The number of crescents, the type of crescents (ie, cellular vs fibrous), and the serum
creatinine level at the time of presentation may dictate prognosis for renal recovery in this
subgroup of patients.

Patient Education

Educating patients about the nephrotoxic potential of common therapeutic agents is always helpful.
A good example is NSAIDs; most patients are unaware of their nephrotoxicity, and their universal
availability makes them a constant concern.
For excellent patient education resources, see eMedicine's Diabetes Center. Also, visit eMedicine's
patient education article Acute Kidney Failure.

Miscellaneous
Medicolegal Pitfalls

Although AKI potentially is a reversible condition, it can occur in patients with chronic renal failure.
Every effort should be made to identify reversibility, even if improvement in renal function is marginal.
The best way to identify reversibility is by tracking the rate of deterioration of renal function. If the
rate of worsening renal function accelerates, the cause should be sought and treated.
Renal recovery is usually observed within the first 2 weeks, and many nephrologists tend to
diagnose patients with end-stage (ie, irreversible) renal failure 6-8 weeks after onset of AKI. It is
always better to check these patients periodically because some patients may regain renal function
much later.

Special Concerns

Great controversy exists regarding the timing of dialysis. Dialysis, especially hemodialysis, may
delay the recovery of patients with AKI. Most authorities prefer using biocompatible membrane
dialyzers for hemodialysis. There seems to be no difference in outcome between the use of
intermittent hemodialysis and continuous renal replacement therapy (CRRT), but this is currently
under investigation. However, CCRT may have a role in patients who are hemodynamically unstable
and who have had prolonged renal failure after a stroke or liver failure. Such patients may not
tolerate the rapid shift of fluid and electrolytes caused during conventional hemodialysis. Although
not frequently used, peritoneal dialysis can also technically be used in acute cases and probably is
tolerated better hemodynamically than conventional hemodialysis.
Indications for dialysis in patients with AKI are as follows:
o Volume expansion that cannot be managed with diuretics
o Hyperkalemia refractory to medical therapy
o Correction of severe acid-base disturbances that are refractory to medical therapy
o Severe azotemia (BUN >80-100)
o Uremia