Pathologic kidney specimen showing marked pallor of thecortex, contrasting to the darker areas of survivingmedullary tissue. The patient died with acute kidney injury.
Acute kidney injury (AKI), previously calledacute renal failure (ARF),[1][2] is a sudden decrease inkidney function that develops within seven days,[3] as shown by an increase inserum creatinine or a decrease in urine output, or both.[4]
The diagnosis of AKI is made based on a person's signs and symptoms, along with lab tests for serum creatinine and measurement of urine output. Other tests includeurine microscopy andurine electrolytes.Renal ultrasound can be obtained when a postrenal cause is suspected. Akidney biopsy may be obtained when intrinsic renal AKI is suspected and the cause is unclear.[5]
The clinical presentation is often dominated by the underlying cause. The various symptoms of acute kidney injury result from the various disturbances of kidney function that are associated with the disease. Accumulation of urea and other nitrogen-containing substances in the bloodstream lead to a number of symptoms, such asfatigue,loss of appetite,headache,nausea, andvomiting.[6] Marked increases in thepotassium level can lead toabnormal heart rhythms, which can be severe and life-threatening.[7] Fluidbalance is frequently affected, though blood pressure can be high, low, or normal.[8]
Pain in the flanks may be encountered in some conditions (such asclotting of the kidneys' blood vessels orinflammation of the kidney). This is the result of stretching of thefibrous tissue capsule surrounding the kidney.[9] If the kidney injury is the result of dehydration, there may bethirst as well as evidence of fluid depletion onphysical examination.[9] Physical examination may also provide other clues as to the underlying cause of the kidney problem, such as arash in interstitial nephritis (orvasculitis) and a palpablebladder in obstructive nephropathy.[9]
Postrenal AKI refers to acute kidney injury caused by disease states downstream of the kidney and most often occurs as a consequence ofurinary tract obstruction. This may be related to:[14]
TheRIFLE criteria, proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in assessment of the severity of a person's acute kidney injury. The acronym RIFLE is used to define the spectrum of progressive kidney injury seen in AKI:[16][17]
Pathophysiology of acute kidney injury in the proximal renal tubule
Risk: 1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR) decrease by 25 percent, or urine output <0.5 mL/kg per hour for six hours.
Injury: Two-fold increase in the serum creatinine, or GFR decrease by 50 percent, or urine output <0.5 mL/kg per hour for 12 hours.
Failure: Three-fold increase in the serum creatinine, or GFR decrease by 75 percent, or urine output of <0.3 mL/kg per hour for 24 hours, or no urine output (anuria) for 12 hours.
Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than four weeks.
End-stage kidney disease: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than three months.
The deterioration of kidney function may be signaled by a measurable decrease in urine output. Often, it is diagnosed on the basis ofblood tests for substances normally eliminated by the kidney:urea andcreatinine. Additionally, theratio of BUN to creatinine is used to evaluate kidney injury. Both tests have their disadvantages. For instance, it takes about 24 hours for the creatinine level to rise, even if both kidneys have ceased to function. A number of alternative markers have been proposed (such asNGAL,HAVCR1,IL18 andcystatin C), but none of them are established enough as of 2018 to replace creatinine as a marker of kidney function.[18]
These may include urine sediment analysis,renal ultrasound and/orkidney biopsy. Indications for kidney biopsy in the setting of AKI include the following:[19]
Unexplained AKI, in a patient with two non-obstructed normal sized kidneys.
Inmedical imaging, the acute changes in the kidney are often examined withrenal ultrasonography as the first-line modality, whereCT scan and magnetic resonance imaging (MRI) are used for the follow-up examinations and when US fails to demonstrate abnormalities. In evaluation of the acute changes in the kidney, the echogenicity of the renal structures, the delineation of the kidney, the renal vascularity, kidney size and focal abnormalities are observed.[20] CT is preferred in renal traumas, but US is used for follow-up, especially in the patients suspected for the formation ofurinomas. A CT scan of the abdomen will also demonstrate bladder distension or hydronephrosis.[21]
Acute kidney injury is diagnosed on the basis ofclinical history and laboratory data. A diagnosis is made when there is a rapid reduction inkidney function, as measured by serumcreatinine, or based on a rapid reduction in urine output, termedoliguria (less than 0.5 mL/kg/h for at least 6 hours).[22]
AKI can be caused by systemic disease (such as a manifestation of an autoimmune disease, e.g.,lupus nephritis),crush injury,contrast agents, some antibiotics, and more. AKI often occurs due to multiple processes.[10]: 31-32
The causes of acute kidney injury are commonly categorized intoprerenal,intrinsic, andpostrenal.
Acute kidney injury occurs in up to 30% of patients following cardiac surgery.[24] Mortality increases by 60-80% in post-cardiopulmonary bypass patients who go on to require renal replacement therapy. Preoperative creatinine greater than 1.2 mg/dL, combined valve and bypass procedures, emergency surgery, and preoperative intra-aortic balloon pump are risk factors most strongly correlated with post-cardiopulmonary bypass acute kidney injury. Other well-known minor risk factors include female gender, congestive heart failure, chronic obstructive pulmonary disease, insulin-requiring diabetes, and depressed left ventricular ejection fraction.[24] Volatile anesthetic agents have been shown to increase renal sympathetic nerve activity (RSNA), which causes retention of salts and water, diminished renal blood flow (RBF) and an increase in serum renin levels, but not in antidiuretic hormone (ADH).[25]
Postoperative acute kidney injury is defined as an AKI based on the KDIGO criteria occurring within 7 days of an operative intervention.[26]
Pediatric AKI is defined using the KDIGO definition and the modified neonatal KDIGO criteria for neonates.[27][28]
The management of AKI hinges on identification and treatment of the underlying cause. The main objectives of initial management are to prevent cardiovascular collapse and death and to call for specialist advice from anephrologist. In addition to treatment of the underlying disorder, management of AKI routinely includes the avoidance of substances that are toxic to the kidneys, callednephrotoxins. These includeNSAIDs such asibuprofen ornaproxen,iodinated contrasts such as those used forCT scans, manyantibiotics such asgentamicin, and a range of other substances.[29]
Monitoring of kidney function, by serial serum creatinine measurements and monitoring of urine output, is routinely performed. In the hospital, insertion of aurinary catheter helps monitor urine output and relieves possible bladder outlet obstruction, such as with an enlarged prostate.[10]: 39
In prerenal AKI withoutfluid overload, administration ofintravenous fluids is typically the first step to improving kidney function. Volume status may be monitored with the use of acentral venous catheter to avoid over- or under-replacement of fluid.[10]: 29
Iflow blood pressure persists despite providing a person with adequate amounts of intravenous fluid, medications that increase blood pressure (vasopressors) such asnorepinephrine, and in certain circumstances medications that improve the heart's ability to pump (known asinotropes) such asdobutamine may be given to improve blood flow to the kidney. While a useful vasopressor, there is no evidence to suggest thatdopamine is of any specific benefit and may in fact be harmful.[30]
The myriad causes of intrinsic AKI require specific therapies. For example, intrinsic AKI due to vasculitis or glomerulonephritis may respond tosteroid medication,cyclophosphamide, and (in some cases)plasma exchange. Toxin-induced prerenal AKI often responds to discontinuation of the offending agent, such as ACE inhibitors, ARB antagonists,aminoglycosides,penicillins, NSAIDs, orparacetamol.[9]
The use ofdiuretics such asfurosemide, is widespread and sometimes convenient in improving fluid overload. It is not associated with higher mortality (risk of death),[31] nor with any reduced mortality or length ofintensive care unit or hospital stay.[32]
Renal replacement therapy, such as withhemodialysis, may be instituted in some cases of AKI. Renal replacement therapy can be applied intermittently (IRRT) and continuously (CRRT). Study results regarding differences in outcomes between IRRT and CRRT are inconsistent. A systematic review of the literature in 2008 demonstrated no difference in outcomes between the use ofintermittent hemodialysis andcontinuous venovenous hemofiltration (CVVH) (a type of continuous hemodialysis).[33] Among critically ill patients, intensive renal replacement therapy with CVVH does not appear to improve outcomes compared to less intensive intermittent hemodialysis.[29][34] However, other clinical and health economic studies demonstrated that, initiation of CRRT is associated with a lower likelihood of chronic dialysis and was cost-effective compared with IRRT in patients with acute kidney injury.[35][36][37]
Lack of improvement withfluid resuscitation, therapy-resistant hyperkalemia, metabolic acidosis, or fluid overload may necessitateartificial support in the form ofdialysis orhemofiltration.[7] However, oliguria during anesthesia may predict AKI,[39][40] but the effect of a fluid load is highly variable. Striving toward a predefined urine output target to prevent AKI is futile.[25][41][42]
Mortality after AKI remains high. AKI has a death rate as high as 20%, which may reach up to 50% in theintensive care unit (ICU). Each year, around two million people die of AKI worldwide.[44]
AKI develops in 5% to 30% of patients who undergo cardiothoracic surgery, depending on the definition used for AKI.[45] If AKI develops after major abdominal surgery (13.4% of all people who have undergone major abdominal surgery) the risk of death is markedly increased (over 12-fold).[46]
Depending on the cause, a proportion of patients (5–10%) will never regain full kidney function, thus enteringend-stage kidney failure and requiring lifelong dialysis or akidney transplant. Patients with AKI are more likely to die prematurely after being discharged from hospital, even if their kidney function has recovered.[2]
New cases of AKI are unusual but not rare, affecting approximately 0.1% of the UK population per year (2000 ppm/year), 20x incidence of new ESKD (end-stage kidney disease). AKI requiring dialysis (10% of these) is rare (200 ppm/year), 2x incidence of new ESKD.[48]
Hot weather can increase the risk of AKI.[49][50] For example, there is an increased incidence of AKI in agricultural workers because of occupational hazards such as dehydration and heat illness.[51] No other traditional risk factors, including age, BMI, diabetes, or hypertension, were associated with incident AKI.
Acute kidney injury is common among hospitalized patients. It affects some 3–7% of patients admitted to the hospital and approximately 25–30% of patients in theintensive care unit.[52]
Acute kidney injury was one of the most expensive conditions seen in U.S. hospitals in 2011, with an aggregated cost of nearly $4.7 billion for approximately 498,000 hospital stays.[53] This was a 346% increase in hospitalizations from 1997, when there were 98,000 acute kidney injury stays.[54] According to a review article of 2015, there has been an increase in cases of acute kidney injury in the last 20 years which cannot be explained solely by changes to the manner of reporting.[55]
Clinical investigations have revealed a higher incidence of AKI and associated mortality in males compared to premenopausal women.[56][57]
Before the advancement ofmodern medicine, acute kidney injury was referred to asuremic poisoning whileuremia was contamination of theblood withurine. Starting around 1847,uremia came to be used for reduced urine output, a condition now calledoliguria, which was thought to be caused by the urine's mixing with the blood instead of being voided through theurethra.[58]
^abDan Longo, Anthony Fauci, Dennis Kasper, Stephen Hauser, J. Jameson, Joseph Loscalzo (July 21, 2011).Harrison's Principles of Internal Medicine, 18 edition.McGraw-Hill Professional.
^abcdeMercado MG, Smith DK, Guard EL (December 2019). "Acute Kidney Injury: Diagnosis and Management".American Family Physician.100 (11):687–694.PMID31790176.
^abcdeSluman C, Gudka PM, McCormick K (2020). "Acute Kidney Injury: Pre-renal, Intra-renal and Post-renal".Renal Medicine and Clinical Pharmacy. Advanced Clinical Pharmacy - Research, Development and Practical Applications. Vol. 1. pp. 23–44.doi:10.1007/978-3-030-37655-0_3.ISBN978-3-030-37654-3.
^Das JA, Azad S, Liu W, Kapp ME, Nguyen V (4 March 2025). "Utility of Tissue Biopsy in Amoxicillin-Clavulanate-Induced Concomitant Hepatic Failure and Renal Failure: a Case Report".Springer Nature Comprehensive Clinical Medicine.7 (54) 54.doi:10.1007/s42399-025-01814-6.
^Stevens PE, Levin A (June 2013). "Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline".Annals of Internal Medicine.158 (11):825–830.doi:10.7326/0003-4819-158-11-201306040-00007.PMID23732715.S2CID46171014.
^Silverman SG, Leyendecker JR, Amis ES (February 2009). "What is the current role of CT urography and MR urography in the evaluation of the urinary tract?".Radiology.250 (2):309–323.doi:10.1148/radiol.2502080534.PMID19188307.
^abcGoldman L, Schafer AI (15 April 2015).Goldman-Cecil medicine (25th ed.). Philadelphia, PA: Elsevier/Saunders. p. 781.ISBN978-1-4557-5017-7.OCLC899727756.
^Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M (February 2008). "Renal replacement therapy in patients with acute renal failure: a systematic review".JAMA.299 (7):793–805.doi:10.1001/jama.299.7.793.PMID18285591.
^Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, et al. (October 2009). "Intensity of continuous renal-replacement therapy in critically ill patients".The New England Journal of Medicine.361 (17):1627–1638.doi:10.1056/NEJMoa0902413.PMID19846848.
^Schneider AG, Bellomo R, Bagshaw SM, Glassford NJ, Lo S, Jun M, et al. (June 2013). "Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis".Intensive Care Medicine.39 (6):987–997.doi:10.1007/s00134-013-2864-5.hdl:11343/218110.PMID23443311.S2CID25491242.
^Egal M, Erler NS, de Geus HR, van Bommel J, Groeneveld AB (January 2016). "Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis".Anesthesia and Analgesia.122 (1):173–185.doi:10.1213/ANE.0000000000001027.PMID26505575.S2CID5496234.
^Egal M, de Geus HR, van Bommel J, Groeneveld AB (June 2016). "Targeting oliguria reversal in perioperative restrictive fluid management does not influence the occurrence of renal dysfunction: A systematic review and meta-analysis".European Journal of Anaesthesiology.33 (6):425–435.doi:10.1097/EJA.0000000000000416.PMID26840829.S2CID11909307.
^O'Connor ME, Kirwan CJ, Pearse RM, Prowle JR (April 2016). "Incidence and associations of acute kidney injury after major abdominal surgery".Intensive Care Medicine.42 (4):521–530.doi:10.1007/s00134-015-4157-7.PMID26602784.S2CID9298414.
^Moyce S, Joseph J, Tancredi D, Mitchell D, Schenker M (April 2016). "Cumulative Incidence of Acute Kidney Injury in California's Agricultural Workers".Journal of Occupational and Environmental Medicine.58 (4):391–397.doi:10.1097/JOM.0000000000000668.PMID27058480.S2CID35174532.
^Torio CM, Andrews RM. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011. HCUP Statistical Brief #160. Agency for Healthcare Research and Quality, Rockville, MD. August 2013."Statistical Brief #160".Archived from the original on 2017-03-14. Retrieved2017-05-01.
^Pfuntner A., Wier L.M., Stocks C. Most Frequent Conditions in U.S. Hospitals, 2011. HCUP Statistical Brief #162. September 2013. Agency for Healthcare Research and Quality, Rockville, MD."Most Frequent Conditions in U.S. Hospitals, 2011 #162".Archived from the original on 2016-03-04. Retrieved2016-02-09.
![Renal ultrasonograph of acute pyelonephritis with increased cortical echogenicity and blurred delineation of the upper pole[20]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_acute_pyelonephritis.jpg)
![Renal ultrasonograph in renal failure after surgery with increased cortical echogenicity and kidney size. Biopsy showed acute tubular necrosis.[20]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_postoperative_renal_failure.jpg)
![Renal ultrasonograph in renal trauma with laceration of the lower pole and subcapsular fluid collection below the kidney[20]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_renal_trauma_with_laceration.jpg)
