Acute kidney injury (AKI) is a sudden loss of renal function with a subsequent rise in creatinine and blood urea nitrogen (BUN). It is most frequently caused by decreased renal perfusion (prerenal) but may also be due to direct damage to the kidneys (intrarenal or intrinsic) or inadequate urine drainage (postrenal). In AKI, the acid-base, fluid, and electrolyte balances are disturbed and the urinary excretion of substances such as drugs is impaired. AKI may be asymptomatic or manifest with oliguria or anuria and, when kidney dysfunction is severe, it may manifest with symptoms and signs of uremia; in some cases, polyuria may occur as a result of impaired tubular reabsorption. A diagnosis of AKI can be made based on an increase in serum creatinine concentration and/or decrease in urine output. Initial evaluation includes blood and urine studies, which may help identify the mechanism of kidney injury and any metabolic complications of AKI. Additional specific investigations are guided by the suspected cause. Rapid evaluation, diagnosis, and treatment are necessary to prevent irreversible loss of renal function. Management is based on the mechanism of kidney injury and the underlying causes. Treatment is primarily supportive and aims to ensure adequate kidney perfusion and prevent complications and further kidney damage.
Prerenal acute kidney injury 
- Hypovolemia: e.g., due to hemorrhage, vomiting, diarrhea, sweating, burns, diuretics, poor oral intake, dehydration, hypercalcemia
- Hypotension: e.g., due to sepsis, cardiogenic shock (decreased cardiac output), anaphylactic shock
- Decreased circulating volume (↓ )
- Renal artery stenosis
- Drugs that affect glomerular perfusion: e.g., cyclosporine, tacrolimus, NSAIDs , ACE inhibitors (ACE-Is)
Intrinsic acute kidney injury
Intrinsic causes include any condition that leads to severe direct kidney damage (∼ 35% of cases of AKI). 
Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs)
- Ischemia: e.g., due to prolonged hypotension
- Nephrotoxic drugs: e.g., radiographic contrast agents, aminoglycosides, cisplatin, methotrexate, ethylene glycol, amphotericin B
- Endogenous toxins: e.g., hemoglobin in intravascular hemolysis, myoglobin in rhabdomyolysis, uric acid in , Bence-Jones protein light chains in multiple myeloma
- Acute interstitial nephritis
- Vascular diseases
- Glomerulonephritis:e.g., rapidly progressive glomerulonephritis
Postrenal acute kidney injury
- Acquired obstructions
- Neurogenic bladder: e.g., due to multiple sclerosis, spinal cord lesions, or peripheral neuropathy
- Congenital malformations: e.g., posterior urethral valves
Overview of nephrotoxic medications
|Chemotherapeutic agents (e.g., platinum-based chemotherapeutic agents)|
|Antiinflammatories and immunosuppressants|
- Decreased blood supply to kidneys (due to hypovolemia, hypotension, or renal vasoconstriction); → failure of renal vascular autoregulation to maintain renal perfusion → decreased GFR → activation of renin-angiotensin system → increased aldosterone release → increased reabsorption of Na+, H2O → increased urine osmolality → secretion of antidiuretic hormone → increased reabsorption of H2O and urea
- Creatinine is still secreted in the proximal tubules, so the blood BUN:creatinine ratio increases.
- Damage to a vascular or tubular component of the nephron → necrosis or apoptosis of tubular cells → decreased reabsorption capacity of electrolytes (e.g., Na+), water, and/or urea; (depending on the location of injury along the tubular system) → increased Na+ and H2O in the urine → decreased urine osmolality
- Bilateral urinary outflow obstruction (e.g., stones, BPH, neoplasia, congenital anomalies) → increased retrograde hydrostatic pressure within renal tubules → decreased GFR and compression of the renal vasculature → acidosis, fluid overload, and increased BUN, Na+, and K+.
- A normal GFR can be maintained as long as one kidney functions normally.
Four phases of AKI
|Overview of the four phases of AKI|
|Phase||Characteristic features (some patients may not undergo all phases)||Duration|
Initiating event (kidney injury)
| || |
- May be asymptomatic.
- Oliguria or anuria
- Signs of volume depletion (in prerenal AKI caused by volume loss)
- Signs of fluid overload (from Na+ and H2O retention)
- Signs of uremia
- Signs of renal obstruction (in postrenal AKI)
- Fatigue, confusion, and lethargy
- In severe cases: seizures or coma
- Affected individuals have a higher risk of secondary infection throughout all phases (most common reason for fatalities).
Subtypes and variants
Acute tubular necrosis
- Epidemiology: : causes ∼ 85% of intrinsic AKIs
- Ischemic: Injury occurs secondary to decreased renal blood flow.
Toxic: Injury occurs directly due to nephrotoxic substances.
- Medication: aminoglycosides, cisplatin, amphotericin, lead, ethylene glycol
- Pigment nephropathy: an acute kidney injury that occurs as a result of the toxic effects of heme-containing pigments (e.g., hemoglobin, myoglobin) on proximal renal tubular cells (toxin-induced acute tubular necrosis)
- Acute uric acid nephropathy
- Other: sepsis, infections
- Pathophysiology: necrotic proximal tubular cells fall into the tubular lumen → debris obstructs tubules → decreased GFR → sequence of pathophysiological events similar to prerenal failure (i.e., activation of RAAS; see “Pathophysiology” above)
- Clinical features: same as AKI (see “Clinical features” and four phases of AKI above)
Diagnostics (see “Diagnostics” below)
- Blood findings: azotemia, hyperkalemia, and metabolic acidosis
- Urinary findings
- Urinary sediment
- Management: See “Management” below.
Renal cortical necrosis
- Definition: rare cause of AKI caused by acute generalized ischemic necrosis of the renal cortex in both kidneys
- Etiology: septic shock, disseminated intravascular coagulation (DIC); , hemolytic uremic syndrome (HUS), obstetric complications; (e.g., abruptio placentae, septic abortion, postpartum hemorrhage)
- Pathophysiology: vasospasms and microvascular injury with vascular thrombosis → prolonged severe renal ischemia; → diffuse and/or patchy destruction of the renal cortex 
- Clinical features: flank pain, CVA tenderness and signs of AKI (see also “Clinical features” above and shock)
- Management: Dialysis can improve outcomes (see “Management” below).
- Prognosis: high mortality rates without treatment
- Definition: AKI after IV administration of iodinated contrast medium
- Risk factors
- Clinical features/diagnostics: See “Clinical features” above and “Diagnostics” below.
Prevention of contrast-induced nephropathy
- Always evaluate kidney function before administering a contrast agent.
- Use a low dose and low concentration of contrast medium.
- The patient should discontinue nephrotoxic substances before administration.
- Ensure hydration: isotonic NaCl before and after administration of contrast medium
- Acetylcysteine (no clear recommendations )
- Compare current and previous creatinine levels to determine if the process is acute.
- Check diagnostic criteria and perform staging of AKI.
- Determine the most likely mechanism of AKI (i.e., prerenal, intrinsic, or postrenal) based on:
- A comprehensive chart review, history, and physical examination
- Supportive diagnostic findings and response to initial interventions
- Consider further testing for specific underlying causes of AKI.
Clinical presentation, laboratory tests, imaging, response to initial therapy, and, in some cases, histopathology are required to determine the underlying cause of AKI.
Diagnostic criteria of acute kidney injury
- Acute kidney injury is defined as the presence of any of the following criteria: ; 
Staging of acute kidney injury
- The KDIGO stages are widely used and correlate with the risk of death, need for renal replacement therapy, and long-term outcomes (e.g., CKD).
- Other classifications include: 
RIFLE criteria: A classification system for acute kidney injury
- The acronym stands for Risk, Injury, Failure, Loss, and End-stage kidney disease.
- For the first three categories, patients are classified according to the level of kidney injury (i.e., degree of increase in serum creatinine and/or decrease in GFR and urine output) and for the last two categories, according to the duration of complete loss of kidney function.
- Acute Kidney Injury Network (AKIN) criteria
- RIFLE criteria: A classification system for acute kidney injury
|Kidney Disease Improving Global outcomes (KDIGO) criteria for staging of AKI |
|Stage||Serum creatinine||Urine output|
|AKI stage 1|| || |
|AKI stage 2|| || |
|AKI stage 3|| |
|If serum creatinine and urine output correlate with different stages, consider staging based on the criterion that corresponds to the highest stage. |
- Serum creatinine and BUN
- Serum electrolytes: sodium, potassium, magnesium, calcium, and phosphate
- Blood gases: ABG or VBG
- Urinalysis with microscopy
- Urine sodium, urea, creatinine, and osmolality
- Calculate excretion fractions: may help to differentiate prerenal AKI from intrinsic AKI 
Overview of diagnostic findings
|Determination of the likely mechanism of acute kidney injury|
| || || |
| || |
|FEUrea|| || |
|Urine sodium concentration|| || |
|Urine osmolality|| || || |
Despite the common use of BUN:creatinine ratio and urinary fractional excretions (i.e., FENa, FEUrea) in clinical practice, observational data suggest that they do not reliably distinguish prerenal AKI from intrinsic AKI. 
The most likely mechanism of AKI is primarily determined based on clinical presentation and response to therapy. Evaluating patients' response to initial interventions is key to confirming the mechanism of AKI and guiding further workup and management steps.
Prerenal AKI 
Blood study findings
- Elevated serum creatinine
- Serum ≥ 20:1 
- Urine study findings
- Clinical findings: rapid improvement in renal function following acute intervention
- Blood study findings
- Urine study findings
- Biopsy: e.g., in suspected
- Clinical findings: lack of response to acute intervention
- Blood study findings
- Urine study findings
- Imaging ( or )
- Clinical findings: rapid improvement in renal function following resolution of the obstruction
- Obtain urgently to assess for hydronephrosis in patients with . 
- Consider when evaluating renal dysfunction of unclear etiology.
- Noncontrast CT
- Not routinely indicated
- Consider if:
- The cause of AKI cannot be identified after a thorough initial evaluation
- Diagnostic confirmation of the cause (e.g., glomerulonephritis, myeloma nephropathy) is needed prior to initiating disease-specific therapy
Additional specific testing
Usually reserved for cases in which intrinsic AKI is initially suspected or interventions aimed at reversing presumed prerenal AKI or postrenal AKI fail to improve renal function. Studies should be guided by clinical suspicion.
|Noninvasive testing for specific underlying causes of AKI |
|Examples||Characteristic clinical features||Diagnostic findings|
| || |
| || |
|Rapidly progressive glomerulonephritis|
| || |
- Initiate treatment for the underlying cause of AKI based on the presumed mechanism.
- Consider and early nephrology consultation.
- Provide supportive care to all patients.
- Hold potentially , ACE-Is, ARBs, NSAIDs, and nonessential medications.
- Adjust the dosing of essential renally cleared medications.
- Manage volume status and blood pressure to optimize kidney perfusion.
- Identify and manage complications (e.g., electrolyte disturbances, acidosis, fluid overload).
- Consider additional supportive care measures (e.g., nutritional support, VTE prophylaxis).
- Provide patient education and ensure adequate post-discharge follow-up.
AKI management is primarily supportive. Currently, there are no specific pharmacotherapies for AKI. 
Avoid coadministering RAAS inhibitors and NSAIDs in patients with reduced renal perfusion (e.g., in congestive heart failure, renal artery stenosis) because doing so can significantly decrease their GFR.
Early nephrology consult
- Common indications 
Treatment of underlying causes 
|Treatment for the underlying cause of AKI|
Renal replacement therapy 
See also “.”
- Indications; consider urgently for:
- Modalities include: 
Medications and nephrotoxic substances 
- Avoid drugs that may have a detrimental effect on glomerular perfusion. and
- Discontinue all nonessential renally cleared medications.
- For essential medications that are renally cleared, adjust dosing daily based on the patient's presumed GFR, considering the following: 
- Conventional Cockcroft-Gault, CKD-EPI equation, MDRD equation) are inaccurate in patients with AKI. formulas (e.g.,
- GFR should be reestimated daily based on the patient's urine output and the trajectory of serum creatinine.
- The kinetic eGFR equation may provide an accurate estimation of GFR in this setting. 
- Avoid iodinated contrast media to prevent .
- Avoid gadolinium-based contrast agents to prevent .
Calculating eGFR using conventional equations does not accurately predict the true GFR in patients with AKI. Reestimate GFR daily based on the patient's urine output and the trajectory of serum creatinine.
Noncontrast imaging studies are preferred if possible. When the use of iodinated contrast is required for a critical diagnostic study or procedure (e.g., for the treatment of STEMI), the lowest clinical diagnostic dose should be used.
Volume status and blood pressure 
- Goal: optimize renal perfusion and reverse prerenal insults while avoiding fluid overload
- Management: Provide hemodynamic support and ensure are met; see also “Daily fluid requirements for special patient groups.” 
|Hypovolemia (and/or hypotension)|
|Euvolemia or indeterminate volume status|
Patients with AKI are at high risk of developing fluid overload, which can compromise renal function and may increase mortality. Avoid aggressive fluid resuscitation in patients who are not volume responsive.
Consider loop diuretics ONLY in patients with signs of fluid overload. Diuretics should not be used routinely to improve urine output in patients with AKI because of their lack of benefit and potential for harm. 
Choice of parenteral fluid 
- Use crystalloid solutions: Balanced IV fluid solutions, (e.g., lactated Ringer's, Plasma-Lyte A) may be preferred for most patients. 
- Avoid artificial colloids (e.g., hydroxyethyl starch). 
- Reserve IV albumin for select patients under specialist guidance. 
The use of normal saline in patients with AKI. has been associated with lower mortality and better renal outcomes compared with the use of
- To assess response to treatment and prevent complications of electrolyte disturbances
- To assess for
- Monitoring parameters: BMP, calcium, phosphorus, magnesium, and or
- Management 
- Nutritional support 
- Consider insulin therapy to maintain serum glucose between 110 and 149 mg/L (6.1 and 8.3 mmol/L) in critically ill patients. 
- See also “ .”
- PPI (e.g., pantoprazole) in critically ill patients who are at risk of GI bleeding.  : Consider starting a
- unfractionated heparin may be preferred over low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) in patients with severe renal impairment. : If indicated,
- Uremia: Monitor for signs and symptoms; if present, consider renal replacement therapy.
Consider a nutrition consult for all patients with AKI. 
Follow-up care 
- Educate patients on medication management and the prevention of AKI.
- Monitor serum creatinine, , blood pressure, and weight following discharge. 
- Ensure that patients who require ongoing renal replacement therapy have access to outpatient dialysis services.
- Consider referral for outpatient nephrology follow-up in patients with significant residual renal dysfunction (i.e., eGFR < 60 mL/min).
Patients who recover from AKI are at high risk of readmission, mortality, cardiovascular events, progressive renal function deterioration, and developing de novo CKD. 
Adequate discharge planning and follow-up may help improve patient outcomes. 
- Confirm diagnosis (see “Diagnostic criteria for AKI”) and stage AKI (see “Staging of AKI”).
- Send initial laboratory evaluation
- Consider urgent ultrasound and/or foley catheter placement (if urinary tract obstruction is suspected).
- Consider early nephrology consult.
- Optimize volume status.
- Identify and treat any metabolic complications (e.g., acidosis, hyperkalemia).
- Identify and treat the underlying cause.
- Hold nephrotoxic medications and renally-dose other medications.
- Strict input/output monitoring
- Provide additional supportive care (e.g., nutritional support, VTE prophylaxis)
Special patient groups
Neonatal acute kidney injury 
- Epidemiology: AKI is common in critically ill newborns (approx. 30% of NICU patients). 
- ∼85% prerenal
- ∼10% renal
- ∼5% postrenal
- Infant risk factors
Diagnostics: Modifications to KDIGO staging 
- Baseline serum creatinine in neonates is defined as the lowest previously measured value.
- The cut-off for AKI stage 3 is a serum creatinine level ≥ 3 times baseline OR ≥ 2.5 mg/dL.
- Accurate measurement of urine output in neonates poses challenges (esp. regarding urine collection) but is still being used to diagnose and stage AKI.
- Other diagnostic biomarkers, e.g., cystatin C, are currently being investigated to improve early and accurate detection of AKI in neonates. 
- See “Diagnostics” section above.
Identify patients who are at risk of AKI and implement appropriate preventive strategies. 
|Prevention of acute kidney injury|
|Risk factors||Preventive strategies|
|Acute illness|| |
|Nephrotoxic medication exposure|| |
|Iodinated radiocontrast agent exposure|
|Endogenous nephrotoxins|| |
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