Acute Kidney Injury (AKI)

Etiology references

1. 1. Lameire NH, Bagga A, Cruz D, et al. Acute kidney injury: an increasing global concern. Lancet. 2013;382(9887):170-179. doi:10.1016/S0140-6736(13)60647-9

2. 2. Turgut F, Awad AS, Abdel-Rahman EM. Acute Kidney Injury: Medical Causes and Pathogenesis. J Clin Med. 2023;12(1):375. Published 2023 Jan 3. doi:10.3390/jcm12010375

3. 3. Hosohata K, Inada A, Oyama S, Furushima D, Yamada H, Iwanaga K. Surveillance of drugs that most frequently induce acute kidney injury: A pharmacovigilance approach. J Clin Pharm Ther. 2019;44(1):49-53. doi:10.1111/jcpt.12748

4. 4. Pierson-Marchandise M, Gras V, Moragny J, et al. The drugs that mostly frequently induce acute kidney injury: a case - noncase study of a pharmacovigilance database. Br J Clin Pharmacol. 2017;83(6):1341-1349. doi:10.1111/bcp.13216

5. 5. Legrand M, Bell S, Forni L, et al. Pathophysiology of COVID-19-associated acute kidney injury. Nat Rev Nephrol. 2021;17(11):751-764. doi:10.1038/s41581-021-00452-0

6. 6. Gembillo G, Spadaro G, Santoro D. Link between obstructive uropathy and acute kidney injury. World J Nephrol. 2025 Mar 25;14(1):99120. doi: 10.5527/wjn.v14.i1.99120.

Changes in urine output

Amount of urine output during acute kidney injury (AKI) does not clearly differentiate between prerenal, renal, or postrenal causes. However, measurement of urine output can allow for earlier detection of AKI before serum creatinine rise, and risk stratification, and prognosis of AKI (with low urine output posing a high risk) (1, 2).

In acute kidney injury, urine output may have 3 phases:

• The prodromal phase usually has normal urine output and varies in duration depending on causative factors (eg, the amount of toxin ingested, the duration and severity of hypotension).

• The oliguric phase has urine output typically between 50 and 500 mL/day. The duration of the oliguric phase is unpredictable, depending on etiology of AKI and time to treatment. However, many patients are never oliguric. Nonoliguric patients have lower mortality and morbidity and less need for dialysis.

• In the postoliguric phase, urine output gradually returns to normal, but serum creatinine and urea levels may not fall for several more days. Tubular dysfunction may persist for a few days or weeks and is manifested by sodium wasting, polyuria (possibly massive) unresponsive to vasopressin, or hyperchloremic metabolic acidosis.

Symptoms and signs references

1. 1. Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015 Sep;26(9):2231-8. doi: 10.1681/ASN.2014070724

2. 2. Parker RA, Himmelfarb J, Tolkoff-Rubin N, Chandran P, Wingard RL, Hakim RM. Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study. Am J Kidney Dis. 1998 Sep;32(3):432-43. doi: 10.1053/ajkd.1998.v32.pm9740160

Determination of cause

Immediately reversible prerenal or postrenal causes of acute kidney injury must be excluded first. Extracellular fluid (ECF) volume depletion and obstruction are considered in all patients. The medication history must be accurately reviewed and all potentially renal toxic agents stopped. Urinary diagnostic indices (see table Urinary Diagnostic Indices in Prerenal AKI and Acute Tubular Injury) may be helpful in distinguishing prerenal AKI from acute tubular injury in an oliguric state, which are the most common causes of AKI in hospitalized patients. Urinary diagnostic indices are not reliable in nonoliguric states (3).

Prerenal causes are often apparent clinically. If so, correction of an underlying hemodynamic abnormality should be attempted. For example, in hypovolemia, volume infusion can be tried; in heart failure (HF), diuretics and afterload-reducing medications can be tried. Abatement of AKI confirms a prerenal cause.

Clinical Calculators

Fractional Excretion of Sodium

Postrenal causes should be sought in most cases of AKI. Immediately after the patient voids, bedside ultrasound of the bladder is performed (or, alternatively, a urinary catheter is placed) to determine the residual urine in the bladder. A postvoid residual urine volume > 100 mL suggests inadequate bladder emptying (eg, due to bladder outlet obstruction or detrusor muscle weakness and neurogenic bladder). The catheter, if placed, may be kept in to accurately monitor urine output in response to therapies, but the catheter is removed in patients who are anuric (if bladder outlet obstruction is not present) to decrease the risk of infection.

Renal ultrasound can also be obtained to identify a more proximal obstruction. However, ultrasound may not detect an obstructive pathology because the collecting system is not always dilated, especially when the condition is acute, the ureter is encased (eg, in retroperitoneal fibrosis or neoplasm), or the patient has concomitant hypovolemia. If obstruction is strongly suspected, noncontrast CT can establish the site of obstruction and guide therapy.

The urinary sediment may provide etiologic clues. A normal urine sediment occurs in prerenal AKI and sometimes in obstructive uropathy. With renal tubular injury, the sediment characteristically contains tubular cells, tubular cell casts, and many granular casts (often with brown pigmentation). Urinary eosinophils may indicate allergic tubulointerstitial nephritis, but the diagnostic accuracy of this finding is limited. Red blood cell (RBC) casts and dysmorphic RBCs indicate glomerulonephritis or vasculitis but rarely may occur in acute tubular necrosis.

Renal causes are sometimes suggested by clinical findings. Patients with glomerulonephritis often have edema, marked proteinuria (nephrotic syndrome), or signs of arteritis in the skin and retina, often without a history of intrinsic renal disease. Hemoptysis may result from granulomatosis with polyangiitis or anti-GBM disease (Goodpasture syndrome). Certain rashes (eg, erythema nodosum, cutaneous vasculitis, discoid lupus) may indicate cryoglobulinemia, systemic lupus erythematosus (SLE), or immunoglobulin A-associated vasculitis. Tubulointerstitial nephritis, drug allergy, and possibly microscopic polyangiitis are suggested by a history of drug ingestion and a maculopapular or purpuric rash.

To further differentiate renal causes, antistreptolysin-O and complement titers, antinuclear antibodies, and antineutrophil cytoplasmic antibodies are determined.

Renal biopsy may be done if the diagnosis remains elusive (see table Causes of Acute Kidney Injury Based on Laboratory Findings).

Imaging

In addition to renal ultrasound, other imaging tests are occasionally obtained. In evaluating for ureteral obstruction, noncontrast CT is preferred over antegrade and retrograde urography. In addition to its ability to delineate soft-tissue structures and calcium-containing calculi, CT can detect nonradiopaque calculi.

Iodinated contrast agents should be avoided if possible. However, conventional renal arteriography may occasionally be indicated if macrovascular causes are suggested clinically, and intervention is anticipated (eg, renal artery stenosis). Magnetic resonance angiography can be used for diagnosing renal artery stenosis as well as thrombosis of both arteries and veins because gadolinium is used as the contrast agent, which has a lower risk of AKI than the iodinated contrast agents used in angiography and contrast-enhanced CT. However, gadolinium is involved in the pathogenesis of nephrogenic systemic fibrosis, a serious complication that occurs in patients with AKI as well as chronic kidney disease. Thus, gadolinium should be avoided if possible in patients with renal function below an estimated glomerular filtration rate (eGFR) of 30 mL/minute/1.73m². If clinically indicated, then group II gadolinium agents should be used preferentially due to lower risk of nephrogenic systemic fibrosis. (See Disadvantages of MRI.)

Kidney size, as determined with imaging tests, is helpful to know because, a normal or enlarged kidney favors reversibility, whereas a small kidney suggests chronic renal insufficiency. However, some chronic kidney diseases tend to present with enlarged kidneys, including the following:

• Polycystic kidney disease

• HIV-associated nephropathy

• Diabetic nephropathy

• Sarcoidosis

• Infiltrative lymphoma

Staging of AKI

Once the patient's volume status is optimized and genitourinary obstruction is excluded, AKI can be classified into 3 stages based on serum creatinine level or the amount of urine output (see table Staging Criteria for Acute Kidney Injury [KDIGO 2012]). The staging criteria provide a useful framework for risk stratification and for guiding management, but clinical decisions should not be dictated by stage alone.

Diagnosis references

1. 1. KDIGO (Kidney Disease: Improving Global Outcomes) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. Suppl. 2:1-138, 2012.

2. 2. Ostermann M, Lumlertgul N, Jeong R, See E, Joannidis M, James M. Acute kidney injury. Lancet. 2025;405(10474):241-256. doi:10.1016/S0140-6736(24)02385-7

3. 3. Hamadah A, Gharaibeh K. Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: PRO. . Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: PRO.Kidney360. 2023 Jun 1;4(6):e725-e727. doi: 10.34067/KID.0002492022

Emergency treatment

Life-threatening complications are addressed, preferably in a critical care unit. Pulmonary edema is treated with oxygen, IV vasodilators (eg, nitroglycerin), diuretics (often ineffective in AKI), or is treated with oxygen, IV vasodilators (eg, nitroglycerin), diuretics (often ineffective in AKI), ordialysis.

Hyperkalemia is treated as needed with IV infusion of 10 mL of 10% calcium gluconate, 50 g of dextrose, and 5 to 10 units of insulin. These medications do not reduce total body potassium, so further (but slower-acting) treatment is needed (eg, intestinal potassium binders, diuretics, dialysis). is treated as needed with IV infusion of 10 mL of 10% calcium gluconate, 50 g of dextrose, and 5 to 10 units of insulin. These medications do not reduce total body potassium, so further (but slower-acting) treatment is needed (eg, intestinal potassium binders, diuretics, dialysis).

Although correction of mild to moderate metabolic acidosis with sodium bicarbonate is controversial, IV sodium bicarbonate for the correction of severe Although correction of mild to moderate metabolic acidosis with sodium bicarbonate is controversial, IV sodium bicarbonate for the correction of severemetabolic acidosis (pH < 7.20) is often recommended to decrease mortality and need for dialysis treatment (1, 2). For patients without volume overload, bicarbonate can be administered as an infusion of isotonic bicarbonate (eg, 150 mEq of sodium bicarbonate in 1 liter of 5% dextrose) at a rate of 50 to 200 mL/hour. For patients with volume overload or a life-threatening condition (eg, cardiac arrest), a highly concentrated hypertonic bicarbonate (50 mEq of sodium bicarbonate in 50 mL) is administered over 1 to 2 minutes. Because variations in body buffer systems and the rate of acid production are highly variable, calculating the amount of bicarbonate needed to achieve a full correction is usually not recommended. Instead, the amount of sodium bicarbonate is titrated based on reassessment of serial laboratory tests when monitoring acidosis.). For patients without volume overload, bicarbonate can be administered as an infusion of isotonic bicarbonate (eg, 150 mEq of sodium bicarbonate in 1 liter of 5% dextrose) at a rate of 50 to 200 mL/hour. For patients with volume overload or a life-threatening condition (eg, cardiac arrest), a highly concentrated hypertonic bicarbonate (50 mEq of sodium bicarbonate in 50 mL) is administered over 1 to 2 minutes. Because variations in body buffer systems and the rate of acid production are highly variable, calculating the amount of bicarbonate needed to achieve a full correction is usually not recommended. Instead, the amount of sodium bicarbonate is titrated based on reassessment of serial laboratory tests when monitoring acidosis.

Hemodialysis or hemofiltration is initiated when

• Severe electrolyte abnormalities cannot otherwise be controlled (eg, potassium > 6 mmol/L)

• Pulmonary edema persists despite treatment with medication

• Metabolic acidosis is unresponsive to treatment

• Uremic symptoms occur (eg, vomiting thought to be due to uremia, asterixis, encephalopathy, pericarditis, seizures)

Blood urea nitrogen (BUN) and creatinine levels alone are not reliable indicators for determining when to initiate dialysis in acute kidney injury (AKI). In asymptomatic patients who are not seriously ill and likely to recover, dialysis can be deferred until (1) uremic symptoms (eg, encephalopathy, pericarditis) occur, or (2) electrolyte and/or volume complications are not amenable to medical therapies. This approach avoids the placement of a central venous catheter with its attendant complications and costs.

General measures

Nephrotoxic medications are discontinued, and all medications excreted by the kidneys (eg, digoxin, some antibiotics) are adjusted; serum levels are useful.Nephrotoxic medications are discontinued, and all medications excreted by the kidneys (eg, digoxin, some antibiotics) are adjusted; serum levels are useful.

Daily water intake is restricted to a volume equal to the previous day’s urine output plus measured extrarenal losses (eg, nasogastric tube suction fluid, vomitus, diarrhea) plus 500 to 1000 mL/day for insensible loss. Water intake can be further restricted for hyponatremia or increased for hypernatremia. Although weight gain indicates excess fluid, water intake is not decreased if serum sodium remains normal; instead, dietary sodium is restricted.

Sodium intake and potassium intake are minimized except in patients with prior deficiencies or gastrointestinal losses. An adequate diet should be provided, including daily protein intake of about 0.8 g/kg. If oral or enteral nutrition is impossible, parenteral nutrition is used; however, in AKI, risks of fluid overload, hyperosmolality, and infection are increased by IV nutrition. Calcium salts (calcium carbonate, calcium acetate) or iron-based or synthetic phosphate binders before meals help maintain serum phosphate at Sodium intake and potassium intake are minimized except in patients with prior deficiencies or gastrointestinal losses. An adequate diet should be provided, including daily protein intake of about 0.8 g/kg. If oral or enteral nutrition is impossible, parenteral nutrition is used; however, in AKI, risks of fluid overload, hyperosmolality, and infection are increased by IV nutrition. Calcium salts (calcium carbonate, calcium acetate) or iron-based or synthetic phosphate binders before meals help maintain serum phosphate at< 5.5 mg/dL (< 1.8 mmol/L).

If needed to help maintain serum potassium at < 6 mmol/L in the absence of dialysis (eg, if other therapies, such as diuretics, fail to lower potassium), a cation-exchange resin is prescribed when delayed onset of action of several hours is acceptable. Sodium polystyrene sulfonate is available in oral or rectal formulation, but it should be avoided in patients at high risk for bowel dysmotility (bowel obstruction, impaction, post-operative ileus); patiromer and sodium zirconium cyclosilicate are available via the oral route only.(eg, if other therapies, such as diuretics, fail to lower potassium), a cation-exchange resin is prescribed when delayed onset of action of several hours is acceptable. Sodium polystyrene sulfonate is available in oral or rectal formulation, but it should be avoided in patients at high risk for bowel dysmotility (bowel obstruction, impaction, post-operative ileus); patiromer and sodium zirconium cyclosilicate are available via the oral route only.

An indwelling bladder catheter is rarely needed and should be used only when necessary because of an increased risk of urinary tract infection and urosepsis.

In many patients, a brisk and even dramatic diuresis after relief of obstruction is a physiologic response to the expansion of extracellular fluid (ECF) during obstruction and does not compromise volume status. However, polyuria accompanied by the excretion of large amounts of sodium, potassium, magnesium, and other solutes may cause hypokalemia, hyponatremia, hypernatremia (if free water is not provided), hypomagnesemia, or marked contraction of ECF volume with peripheral vascular collapse. In this postoliguric phase, close attention to fluid and electrolyte balance is mandatory. Overzealous administration of salt and water after relief of obstruction can prolong diuresis. When postoliguric diuresis occurs, replacement of urine output with 0.45% saline at about 75% of urine output prevents volume depletion and the tendency for excessive free water loss while allowing the body to eliminate excessive volume if this is the cause of the polyuria.

Treatment references

1. 1. Jung B, Jabaudon M, De Jong A, et al. Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial. . Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial.JAMA. 2025;334(22):2000-2010. doi:10.1001/jama.2025.20231

2. 2. Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. . Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial.Lancet. 2018;392(10141):31-40. doi:10.1016/S0140-6736(18)31080-8

Prognosis references

1. 1. Parker RA, Himmelfarb J, Tolkoff-Rubin N, Chandran P, Wingard RL, Hakim RM. Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study. Am J Kidney Dis. 1998 Sep;32(3):432-43. doi: 10.1053/ajkd.1998.v32.pm9740160. PMID: 9740160.

2. 2. Sawhney S, Marks A, Fluck N, Levin A, McLernon D, Prescott G, Black C. Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury. Kidney Int. 2017 Aug;92(2):440-452. doi: 10.1016/j.kint.2017.02.019

3. 3. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), United States Renal Data System (USRDS). Acute Kidney Injury. Accessed November 23, 2025.

Prevention reference

1. 1. Rosner MH, Perazella MA. Acute Kidney Injury in Patients with Cancer. N Engl J Med. 2017;376(18):1770-1781. doi:10.1056/NEJMra1613984