APPROACH TO PATIENT • Updated 23 Oct 2024

Acute Kidney Injury (AKI) in the Outpatient Setting - Approach to

the Patient
Overview and Recommendations
Acute kidney injury (AKI) is a rapid reduction in kidney function that can lead to chronic kidney disease. It is often not recognized
in the outpatient setting.

Evaluation
● AKI is generally asymptomatic until the onset of kidney failure. Mild-to-moderate AKI can have no symptoms at all, while symp-
toms in severe cases may include confusion, malaise, swelling, nausea, weight gain, poor appetite, shortness of breath, and
lethargy.
● The initial evaluation includes patient history to identify the following:
⚬ Use of nephrotoxic medications
⚬ Preexisting conditions which may impair kidney function or affect kidney perfusion
⚬ Travel history, particularly for exposure to infectious diseases
● Use findings from the history and physical exam to help identify prerenal, intrinsic, or postrenal causes of AKI.
● Diagnose AKI in patients with any of the following 3 criteria:
⚬ Increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 mcmol/L) within 48 hours
⚬ Increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within prior 7 days
⚬ Urine volume < 0.5 mL/kg/hour for 6 hours
⚬ Elevated creatinine in the outpatient setting often needs to be evaluated without recent baseline values available. Chronic
kidney disease needs to be considered and these 3 criteria are mostly applicable to hospitalized patients. The diagnosis of
AKI in the outpatient setting is usually made retrospectively if the patient's renal function improves.
● Initial blood tests should include blood urea nitrogen (BUN), creatinine, serum electrolytes, and complete blood count.
BUN:creatinine ratio and fractional excretion of sodium may help distinguish between prerenal and intrinsic causes of AKI.
⚬ Compare measured BUN and creatinine levels to baseline levels, if they are known, to rule out presence of chronic kidney
disease.
⚬ If baseline creatinine is not known and there is no evidence for chronic kidney disease, assume a previously normal
glomerular filtration rate.
● Imaging with renal ultrasound helps to evaluate renal size and rule out an obstruction.
● Initial urine studies should include volume, osmolality, creatinine and sodium, dipstick testing, and microscopy.
● A kidney biopsy may be considered when conditions such as glomerulonephritis, vasculitis, or interstitial nephritis are sus-
pected and prerenal and postrenal causes have been excluded.

Management
● Consider hospitalization for patients who require advanced diagnostic evaluation, have rapidly progressive renal failure which
may require renal biopsy, have complications, are critically ill, or may not be able to manage repeated outpatient visits for
testing.
● Monitor and adjust fluid and electrolyte balance to address volume depletion or overload, and electrolyte abnormalities.
● Stop exposure to nephrotoxic agents if possible, or consider dose adjustments to medications as appropriate.
● Exclude urinary obstruction and treat it if detected.
● Identify and treat any infectious cause.
● Nutritional advice may be appropriate, including restricted potassium and phosphorus.
● Consider consultation with a nephrologist.
● Timely follow-up is important for all patients with AKI, and may include referral to a nephrologist or urologist if appropriate.

Background Information

Definitions
● AKI is an abrupt reduction in renal function (within 48 hours) as measured by an increase in serum creatinine, a decrease in
urine output, and/or the need for renal replacement therapy. 2 ,3
● It is characterized by a direct injury to the kidney, an acute impairment of function, or both. 1
 CLINICIANS' PRACTICE POINT

In the outpatient setting, the time of injury may or may not be evident from the clinical circumstances and needs to be distinguished from
chronic kidney disease when no recent baseline laboratory values are available.

Also Called

● Acute renal failure

● Acute renal insufficiency

Types

● Types of AKI are as follows: 1

⚬ Community-acquired AKI, which is defined as AKI prior to hospitalization (Nat Rev Nephrol 2013 May;9(5):278)
⚬ Hospital-acquired AKI, which is defined as AKI occurring as a common and serious complication of another disease in hospi-
talized patients
⚬ AKI occurring in critically ill patients admitted to the intensive care unit

Incidence/Prevalence

● The reported incidence of nondialysis-dependent AKI is > 5,000 cases per 1,000,000 per year. 3
● Prevalence of in low- and lower-middle income countries:

STUDY
⚬ SUMMARY
community-acquired acute kidney injury reported to be higher in patients from low- and lower-middle income coun-
tries compared to patients from high-income countries
CROSS-SECTIONAL STUDY: Lancet 2016 May 14;387(10032):2017
Details
– based on cross-sectional study
– 4,018 patients (median age 60 years) with AKI from 72 countries were evaluated using Kidney Disease: Improving Global
Outcomes (KDIGO) criteria for acute kidney injury
– countries were classified according to gross national income per person as high-income (HIC), upper-middle-income
(UMI), and combined low- and lower-middle-income countries (LLMIC)
– percentage of patients with community-acquired and hospital-acquired AKI

Epidemiology of Community-Acquired AKI and Hospital-Acquired AKI by Gross National Income per Person

Community-Acquired AKI Hospital-Acquired AKI***

Overall 58% 40%

HIC 50% 48%

UMIC 51%* 49%

LLMIC 77%** 20%

Abbreviations: AKI, acute kidney injury; HIC, high-income country; LLMIC, low- and lower-middle income countries; UMIC, upper-mid-
dle-income country.

* p < 0.001 vs. LLMIC.

** p < 0.001 vs. HIC.

*** No p values reported for comparisons of hospital-acquired AKI.

Reference -

Lancet 2016 May 14;387(10032):201.

– Reference - Lancet 2016 May 14;387(10032):2017, editorial can be found in Lancet 2016 May 14;387(10032):1974, com-
mentary can be found in Nat Rev Nephrol 2016 Jul;12(7):379

● 50,560 cases of community-acquired AKI have been reported in adults in Wales from November 2013 to January 2017 (QJM
2017 Nov 1;110(11):741, editorial can be found in QJM 2017 Nov 1;110(11):693).
STUDY
● SUMMARY
1,811 per million overall incidence of acute kidney injury in Scotland in 2003
CROSS-SECTIONAL STUDY: J Am Soc Nephrol 2007 Apr;18(4):1292
Details
⚬ based on population-based cross-sectional study
⚬ 523,390 people in Grampian region of Scotland were evaluated using Risk, Injury, Failure, Loss of kidney function, and End-
stage kidney disease (RIFLE) classification for AKI from January to June 2003
– 474 had AKI (defined as increase in serum creatinine ≥ 1.5-fold above baseline)
– 88 patients had acute-on-chronic renal failure (chronic kidney disease defined as 3 serum creatinine values above
threshold before index creatinine, each separated by ≥ 1 month)
⚬ incidences of AKI
– 1,811 per million overall (median age 76 years)
– 336 per million with chronic kidney disease (median age 81 years)
⚬ 47% had sepsis as precipitating factor
⚬ Reference - J Am Soc Nephrol 2007 Apr;18(4):1292

● 384.1 per 100,000 person-years incidence of community-acquired, nondialysis-dependent AKI have been reported among the
members of Kaiser Permanente of Northern California, United States between 1996 and 2003 (Kidney Int 2007 Jul;72(2):208).

Risk Factors

Overview of Risk Factors

● The risk factors for AKI include certain medical conditions, such as underlying chronic kidney disease (CKD), the use of medica-
tions, environmental factors, and demographic factors, such as older age. 1 ,2
● Common risk factors for AKI outside of the intensive care unit setting include infections, for example, pneumonia, and medica-
tions (Lancet 2019 Nov 23;394(10212):1949).
● Patients with multiple medical conditions and are receiving medications that alter renal hemodynamics are at increased risk of
AKI (Nephrology (Carlton) 2016 Sep;21(9):729).

STUDY
● SUMMARY
preexisting conditions (including diabetes, hypertension, and cardiovascular disease) and use of medications (including
nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, diuretics, angiotensin-converting enzyme [ACE] inhibitors,
and insulin), each associated with risk of AKI in the outpatient setting
COHORT STUDY: Sci Rep 2019 Nov 27;9(1):17658
Details
⚬ based on prospective cohort study
⚬ 6,047 adults (median age 67.4 years) enrolled in the pre-end-stage renal disease (ESRD) program at the China Medical
University Hospital, Taichung, Taiwan, from 2003 were evaluated
⚬ all adults were followed until initiation of maintenance dialysis for ESRD, loss to follow-up, death, or until December 31,
2015, for 13,467.68 person-years total
⚬ all adults had serum creatinine levels measured up to 180 days before pre-ESRD enrollment
⚬ an AKI in the outpatient setting event was defined as an increase of > 50% in serum creatinine level or > 35% in estimated
glomerular filtration rate (GFR) in the 180-day period preceding pre-ERSD enrollment
⚬ 1,905 adults (31.5%) developed AKI in the outpatient setting
⚬ factors associated with risk of AKI in the outpatient setting comparing adults with AKI in the outpatient setting vs. adults
without AKI in the outpatient setting
– preexisting conditions
● diabetes in 53.5% vs. 38.8% (p < 0.001)
● hypertension in 67.9% vs. 59.9% (p < 0.001)
● cardiovascular disease in 48.4% vs. 38.5% (p < 0.001)
– use of medication
● NSAIDs in 38.2% vs. 25.4% (p < 0.001)
● aspirin in 35.9% vs. 28.8% (p < 0.001)
● other antiplatelet agents in 17.5% vs. 9.4% (p < 0.001)
● IV contrast in 32.4% vs. 14.2% (p < 0.001)
● diuretics in 72.2% vs. 45.3% (p < 0.001)
● ACE inhibitors in 30.7% vs. 23.4% (p < 0.001)
● urate-lowering or gout-related medications
⚬ febuxostat in 3.8% vs. 1.6% (p < 0.001)
⚬ colchicine in 15.4% vs. 12.1% (p = 0.001)
 ● oral hypoglycemic agents in 41% vs. 32.2% (p < 0.001)
● insulin in 45% vs. 19.2% (p < 0.001)
⚬ Reference - Sci Rep 2019 Nov 27;9(1):17658

STUDY
● SUMMARY
use of nephrotoxic drugs, presence of heart failure, cerebrovascular disease, chronic pulmonary disease, rheumatologic
diseases, peptic ulcer disease, diabetes mellitus with complications, and tumors, each associated with increased risk of
community-acquired AKI
COHORT STUDY: Medicine (Baltimore) 2016 May;95(19):e3674
Details
⚬ based on retrospective cohort study
⚬ 11,542 adults (mean age 67 years) with AKI discharged from hospital from Chang Gung Medical Foundation records,
Taiyuan, Taiwan between 2010 and 2014 were evaluated
⚬ 6,287 adults (54.5%) had community-acquired AKI based on Risk, Injury, Failure, Loss of kidney function, and End-stage kid-
ney disease (RIFLE) classification
⚬ factors associated with increased risk of community-acquired AKI included
– prior use of nephrotoxic drugs (adjusted odds ratio [OR] 1.05, 95% CI 1.02-1.08)
– heart failure (adjusted OR 1.31, 95% CI 1.03-1.68)
– cerebrovascular disease (adjusted OR 1.52, 95% CI 1.25-1.85)
– chronic pulmonary disease (adjusted OR 1.31, 95% CI 1.05-1.64)
– rheumatologic diseases (adjusted OR 2.31, 95% CI 1.18-4.54)
– peptic ulcer disease (adjusted OR 1.32, 95% CI 1.06-1.64)
– liver disease (adjusted OR 2.03, 95% CI 1.62-2.54)
– diabetes mellitus with complications (adjusted OR 1.84, 95% CI 1.42-2.37)
– CKD (adjusted OR 1.58, 95% CI 1.37-1.84)
– tumors (adjusted OR 1.65, 95% CI 1.44-1.9)
⚬ Reference - Medicine (Baltimore) 2016 May;95(19):e3674

Conditions

● The following conditions can increase the susceptibility to AKI: 1 ,2 ,3

⚬ CKD
⚬ Hypertension
⚬ Heart failure or vascular disease
⚬ Dehydration/volume depletion
⚬ Diabetes mellitus and hyperglycemia
⚬ Chronic lung disease
⚬ Chronic liver disease
⚬ Cancer
⚬ Anemia
⚬ Hyperuricemia
⚬ Albuminuria

Medications

● The following medications are associated with AKI: 2 ,3

⚬ Nonsteroidal anti-inflammatory drugs (NSAIDs)
⚬ Radiocontrast agents
⚬ Aminoglycosides
⚬ Amphotericin
⚬ Beta-lactam antibiotics
⚬ Sulphonamides
⚬ Acyclovir
⚬ Methotrexate
⚬ Cisplatin
⚬ Cyclosporin
⚬ Tacrolimus
⚬ Angiotensin-converting enzyme (ACE) inhibitors
⚬ Angiotensin receptor blockers (ARBs)
⚬ vancomycin
⚬ Ifosfamide
⚬ Vascular endothelial growth factor (VEGF) inhibitors
⚬ Tenofovir
 ⚬ Proton pump inhibitors (PPIs)
⚬ Herbal and dietary supplements such as aristolochic acid, creatine, vitamin A, vitamin C, vitamin D, germanium, star fruit
● See Medications in Acute Kidney Injury in Adults - Approach to the Patient for additional information.
Environmental

● Gastrointestinal losses are a major risk for AKI, particularly in low-income countries (Lancet 2019 Nov 23;394(10212):1949).
● The following infections can increase the risk of AKI:
⚬ Malaria
⚬ Dengue fever
⚬ Scrub typhus
⚬ Leptospirosis
⚬ Hantavirus
⚬ Yellow fever
⚬ Rickettsiosis
⚬ Acute hepatitis
⚬ Brucellosis
⚬ Hemorrhagic rift valley fever
⚬ Mucormycosis
⚬ Diarrheal diseases (caused by Escherichia coli, Entamoeba histolytica, bacillary dysentery, cholera, and viral gastroenteritis)
⚬ Melioidosis
⚬ Typhoid
⚬ Chlamydia
⚬ Legionellosis
⚬ References - Nat Rev Nephrol 2013 May;9(5):278, Kidney Int 2017 May;91(5):1033
● The following plant and fungal toxins may increase the risk of AKI:
⚬ Herbal medicines
⚬ Impila food plants
⚬ Djenkol beans
⚬ Marking nut
⚬ Mushrooms
⚬ Plant-derived toxins that are used as insecticides and to kill fish
⚬ References - Nat Rev Nephrol 2013 May;9(5):278
● The following nephrotoxic animal venom may increase the risk of AKI:
⚬ Snake bites
⚬ Wasp, hornet, bee, spider, caterpillar, and scorpion stings
⚬ Reference - Kidney Int 2017 May;91(5):1033

Demographics

● Demographic risk factors of AKI are as follows: 2

⚬ Older age, and patients with the following conditions at older age can further increase the risk of community-acquired AKI:
– Diabetes mellitus
– Coronary artery disease
– Heart failure
– Baseline CKD
– Coexistent acute illness such as community-acquired pneumonia
– HIV infection
– Reference - Nephrology (Carlton) 2016 Sep;21(9):729
⚬ Female sex
⚬ Black race

Differential Diagnosis

Falsely Elevated Serum Creatinine and Blood Urea Nitrogen (BUN)

● Falsely elevated serum creatinine may be caused by medications, toxic ingestions, creatine supplements, and ketoacidosis.
⚬ The following medications can block tubular secretion of creatinine and elevate serum creatinine without reducing the
glomerular filtration rate: 1 ,2
– Cimetidine
– Pyrimethamine
– Trimethoprim
 – Fenofibrate
⚬ Toxic ingestions of the following substances can elevate serum creatinine:
– Methanol or nitromethane ingestion:
● Nitromethane interferes with measurements of serum creatinine by the Jaffe reaction leading to a falsely elevated
serum creatinine reading (correct reading can be obtained using specific enzymatic assay) (J Paediatr Child Health
1999 Oct;35(5):503).
● The presence and severity of spuriously elevated serum creatinine (Jaffe reaction) may act as early surrogate marker
or indicate severity of methanol poisoning after ingestion of radio controlled (R/C) vehicle fuels (J Emerg Med 2007
Oct;33(3):249).
● A 4-year-old girl who ingested model engine fuel (methanol/nitromethane) and was subsequently treated with fomepi-
zole for spuriously elevated creatinine level (Jaffe reaction) has been reported in a case report (Pediatr Crit Care Med
2007 Jul;8(4):392).
– Isopropyl alcohol intoxication (South Med J 2009 Aug;102(8):867)
⚬ Protein and creatine supplements leading to a high serum creatinine and low reported estimated glomerular filtration rate
in the absence of a kidney disease have been reported in a case presentation (BMJ 2010 Jan 8;340:b5027).
⚬ Ketoacidosis can also falsely elevate serum creatinine (J Intern Med 2000 Dec;248(6):511).
● Common causes of increased BUN are steroids (by increasing catabolic rate) and a high-protein diet.
● Other causes of BUN:serum creatinine ratio (usually < 8) are as follows:
⚬ Acute upper gastrointestinal bleeding, which may increase BUN:creatinine ratio independent of kidney function, as blood is
digested in the gastrointestinal tract
⚬ Rhabdomyolysis
⚬ Laboratory artifact, such as chemical interference with creatinine determination due to the presence of ketones, proteins,
sugars, or acetoacetate
⚬ Reference - Arch Intern Med 1998 Dec 7-21;158(22):2509

Causes

Prerenal Causes

● Prerenal causes of AKI are those that result in decreased renal perfusion without intrinsic damage, including intravascular vol-
ume depletion, systemic vasodilation, hemodynamically mediated intrarenal vasoconstriction, and reduced cardiac output. 1 , 2
,3

⚬ Intravascular volume depletion can be caused by the following processes:

– Renal loss due to overuse of diuretics or osmotic diuresis, such as in diabetic ketoacidosis
– Extrarenal loss due to vomiting, diarrhea, burns, sweating, blood loss, or hyperthermia
– Nephrotic syndrome
– Cirrhosis
– Capillary leak
⚬ Systemic vasodilation can caused by the following processes:
– Cirrhosis
– Medications
⚬ Hemodynamically mediated intrarenal vasoconstriction can caused by the following processes:
– Medications, such as cyclosporin (Sandimmune), andtacrolimus (Prograf)
– Radiocontrast agents
– Early sepsis
– Cardiorenal syndrome
– Hepatorenal syndrome
– Hypercalcemia
⚬ Reduced cardiac output can caused by the following conditions:
– Pericardial disease (restrictive, constrictive, tamponade)
– Heart failure
– Valvular heart disease
– Pulmonary hypertension
⚬ Reference - Nat Rev Nephrol 2011 Apr;7(4):189
● Prerenal causes account for approximately 70% of community-acquired AKI cases (Am Fam Physician 2012 Oct 1;86(7):631).

Normotensive Hemodynamic Causes

● AKI can result from interference with autoregulatory mechanisms that normally maintain glomerular filtration without causing
structural damage.
 ⚬ Failure to decrease afferent arteriolar resistance:
– Afferent vasodilation normally occurs in response to decreased renal perfusion, via prostaglandins.
– Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors prevent compensatory afferent
vasodilation.
⚬ Failure to increase efferent arteriolar resistance:
– Glomerular filtration rate (GFR) is normally maintained by efferent vasoconstriction mediated by angiotensin II.
– In reduced perfusion states, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
prevent compensatory efferent vasoconstriction, resulting in a decreased GFR.
⚬ Interference with afferent or efferent compensation may not lead to clinically apparent changes in GFR, but interfering with
both mechanisms may cause susceptibility to minor changes in perfusion from any cause of volume depletion.
⚬ Reference - N Engl J Med 2007 Aug 23;357(8):797, commentary can be found in N Engl J Med 2007 Nov 22;357(21):2204
Intrinsic Renal Causes

Tubular

● Ischemic or nephrotoxic forms of acute tubular necrosis (ATN) account for approximately 90% of parenchymal AKI (Contrib
Nephrol 2016;188:1).
● ATN is the most common type of intrinsic AKI. 2 ,3
⚬ Prolonged exposure to prerenal causes of acute kidney failure, such as hypotension and hypoperfusion, can cause ATN. 2 ,3
⚬ The following toxins can cause ATN:
– Medications:
● Aminoglycosides
● Cephaloridine
● Amphotericin
● Antiviral medications, such as acyclovir
● Carbamazepine
● Calcineurin inhibitors (such as, cyclosporine, tacrolimus)
● NSAIDs
● Quinolones
● HIV medication, such as tenofovir
● Bisphosphonates, such as pamidronate or zoledronate, but they are rare causes
– Contrast media
– Pigments, such as myoglobin or hemoglobin
– Ethylene glycol
– Recreational party drugs, such as N-benzylpiperazine or 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
– Synthetic cannabinoids, which have been reported in case series to cause ATN
⚬ Other causes of ATN:
– Metabolic causes include the following:
● Hypercalcemia
● Immunoglobulin light chain disease, including the following:
⚬ Amyloidosis
⚬ Multiple myeloma
⚬ Monoclonal gammopathy of renal significance (MGRS)
– Severe proteinuria, which may be seen with minimal change disease (“nephrosarca”).
⚬ See Acute Tubular Necrosis for additional information.
● Subnephrotic proteinuria and AKI have been reported in 10 elderly patients with primary tubulointerstitial disease resulting
from antibrush border antibodies (ABBA) in a case series (J Am Soc Nephrol 2018 Feb;29(2):644).

Interstitial

● Acute interstitial nephritis can cause AKI, and may occur secondary to several conditions.
⚬ Most cases of acute interstitial nephritis are related to medication use, including the following:
– Antibiotics:
● Penicillins: amoxicillin, ampicillin, aztreonam benzylpenicillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, methi-
cillin, nafcillin, oxacillin, and piperacillin/tazobactam
● Fluoroquinolones: ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin
● Cephalosporins: cefaclor, cefamandole, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, cefuroxime, ceftriax-
one, cephalexin, cephaloridine, cephalothin, and cephradine
● Sulfonamides: trimethoprim-sulfamethoxazole
 ● Macrolides: azithromycin, clarithromycin, erythromycin, and telithromycin
● Others: cefepime, chloramphenicol, clindamycin, colistin, doxycycline, ethambutol, flurithromycin, gentamicin, griseo-
fulvin, imipenem, isoniazid, lincomycin, linezolid, minocycline, nitrofurantoin, piromidic acid, polymyxin B, quinine, ri-
fampin, teicoplanin, and vancomycin
– Antiretrovirals: abacavir, acyclovir, atazanavir, azithromycin, foscarnet, indinavir, and interferon-alpha
– NSAIDs:
● Selective COX-2 inhibitors: celecoxib and rofecoxib
● Others: aceclofenac, benoxaprofen, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin,
ketoprofen, mefenamate, meloxicam, nabumetone, naproxen, noramidopyrine, nimesulide, oxaprozin, phenazone,
phenylbutazone, piroxicam, sulindac, tolmetin, and zomepirac
– 5-aminosalicylates: balsalazide, mesalazine, olsalazine, and sulfasalazine
– Gastrointestinal protective medications:
● Proton pump inhibitors: esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole
● H2 receptor antagonists: cimetidine, famotidine, and ranitidine

– Chemotherapeutic agents:
● Immune checkpoint inhibitors: atezolizumab, ipilimumab, nivolumab, and pembrolizumab
● Tyrosine kinase inhibitors: cediranib, sorafenib, and sunitinib
● Others: adriamycin, alendronate, azathioprine, Bacillus Calmette-Guerin (BCG), bevacizumab, bortezomib, carboplatin,
gemcitabine, interleukin-2, interferon, ifosfamide, lenalidomide, methotrexate, pemetrexed, and vemurafenib
– Diuretics:
● Thiazides: chlorothiazide, hydrochlorothiazide, indapamide, metolazone, and chlorthalidone (thiazide-like)
● Loop diuretics: bumetanide, furosemide, tienilic acid, and torsemide
● Potassium-sparing diuretics: amiloride and triamterene
– Antihypertensives:
● ACE inhibitors: captopril and lisinopril
● ARBs: candesartan and losartan
● Calcium channel blockers (CCBs): amlodipine and nifedipine
– Antiseizure medications: carbamazepine, diazepam, lamotrigine, levetiracetam, phenobarbital, phenytoin, and valproic
acid
– Other drugs: allopurinol, atorvastatin, carbimazole, chlorpropamide, cysteamine, deferasirox, exenatide, febuxostat, fle-

cainide, fluindione, gemfibrozil, leflunomide, metamizole, propranolol, propylthiouracil, risedronate, and sildenafil
– References - Adv Chronic Kidney Dis 2017 Mar;24(2):72, Nat Rev Nephrol 2010 Aug;6(8):461
⚬ Creatine in high doses (5 g orally 4 times daily) for prolonged period has been reported to relate to a case of acute intersti-
tial nephritis (N Engl J Med 1999 Mar 11;340(10):814)
⚬ Multiple hornet stings has been reported to lead to acute tubulointerstitial nephritis in a case report (BMC Nephrol 2006
Nov 21;7:18).
⚬ See also Acute Tubulointerstitial Nephritis (ATIN).
● In addition to acute interstitial nephritis, intrinsic AKI may also result from direct infiltration of renal parenchyma, due to the
following conditions: 1
⚬ Systemic infections
⚬ Malignancy, including lymphoma and leukemia
⚬ Systemic disease, including sarcoidosis
Glomerular

● The following glomerulonephritis (GN) may lead to AKI:

⚬ Immune complex mediated GN due to infection or autoimmune disease
⚬ Antineutrophil cytoplasmic antibodies (ANCA) associated GN (pauci-immune GN)
⚬ Antiglomerular basement membrane disease (Goodpasture disease)
⚬ Monoclonal immunoglobulin mediated GN (see Kidney Disease in Monoclonal Gammopathy of Renal Significance (MGRS)
for additional information)
⚬ Disorders of complement regulation and C3 glomerulopathy
⚬ Thrombotic microangiopathy
⚬ See Glomerular Disease - Approach to the Patient for additional information.

Vascular

● Intrinsic AKI can result from following acute events involving renal arteries or veins: 1 ,2
⚬ Renal atheroembolic disease
⚬ Renal vein thrombosis
⚬ Hypertension
 ⚬ Renal infarction
Postrenal Causes

● The following conditions that can lead to extrarenal obstruction of urinary flow may cause AKI: 1
⚬ Prostate hypertrophy
⚬ Neurogenic bladder
⚬ Retroperitoneal fibrosis
⚬ Kidney stones
⚬ Malignancy
● Intrarenal obstruction due to crystals, clots, or tumors can also cause AKI. 1

Causes of Community-Acquired Acute Kidney Injury in Developing Countries

● Causes of community-acquired AKI in developing tropical countries are markedly different from those in developed countries
with temperate climates (Nat Rev Nephrol 2013 May;9(5):278).

Table 1: Causes of Community-Acquired Acute Kidney Injury in Developing Tropical Countries

Infections Plant and Fungal Toxins Other Causes

⚬ Malaria ⚬ Herbal medicines ⚬ Chemical nephrotoxins

⚬ Dengue fever ⚬ Impila food plants – Ethylene glycol
⚬ Scrub typhus ⚬ Djenkol beans – N, N' -dimethyl-4, 4' -bipyri-
⚬ Hemorrhagic rift valley fever ⚬ Marking nut dinium dichloride
⚬ Leptospirosis ⚬ Mushrooms – Ethylene bromide
⚬ Hantavirosis ⚬ Plant-derived toxins used as insec- – Copper sulfate
⚬ Mucormycosis ticides and to kill fish – Chromic acid
⚬ Diarrheal diseases (caused by ⚬ Animal poisons
⚬ Environmental factors
Escherichia coli, Entamoeba histolyt- ⚬ Snake bites
ica, bacillary dysentery, cholera, ⚬ Wasp, hornet, and bee stings
– Heat stroke
and viral gastroenteritis) ⚬ Spider bite
– Poor sanitation
⚬ Melioidosis ⚬ Jellyfish sting
– Socioeconomic factors
⚬ Typhoid ⚬ Scorpion sting
– Natural disasters
⚬ Chlamydia ⚬ Carp gallbladder or bile ⚬ Others
⚬ Legionellosis – Intravascular hemolysis result-
ing from G6PD deficiency
– Obstetric complications

Abbreviations: G6PD, glucose-6-phosphate dehydrogenase.

Reference -

Nat Rev Nephrol 2013 May;9(5):278.

● Common causes of AKI in low and lower-middle income countries from International Society of Nephrology (ISN) Oby25 Global
Snapshot are as follows:
⚬ Dehydration (46%)
⚬ Sepsis (39%)
⚬ Hypotension or shock (38%)
⚬ Infection (36%)
⚬ Nephrotoxic agents (23%)
⚬ Reference - Lancet 2016 May 14;387(10032):2017, editorial can be found in Lancet 2016 May 14;387(10032):1974
● AKI in low-income Western countries:
⚬ Community-acquired AKI is more frequent compared to hospital-acquired AKI.
⚬ In urban areas, causes of community-acquired AKI are similar to those in urban areas of high-income countries, such as hy-
povolemia, use of drugs, and ischemia.
⚬ In rural areas, causes of community-acquired AKI typically include diarrhea, animal venoms, tropical diseases, and obstetric
complications.
⚬ Reference - Kidney Dis (Basel) 2016 Oct;2(3):103

Pathogenesis
● For general information on the pathogenesis of AKI, see Pathogenesis in Acute Kidney Injury in Adults - Approach to the
Patient.
● Pathogenesis of community-acquired AKI in tropical countries:
⚬ Direct kidney injury:
– Pathogens, plant and fungal toxins, and poisonous snake venom can cause local inflammation, as well as cellular prolif-
eration and infiltration, which can lead to direct injuries to the renal tubule.
– The interaction between erythrocytes infected with Plasmodium falciparum and the microvascular endothelium (cytoad-
herence) can cause direct injury to the glomerular endothelium.
⚬ Indirect kidney injury for patients with tropical infections and exposure to toxins:
– Malaria, leptospirosis, scrub typhus, and hantavirosis can lead to generalized arterial vasodilation with a reduced sys-
temic vascular resistance, which is a hemodynamic alterations that is similar to those observed in sepsis.
● The vasodilation activates the neurohumoral axis, sympathetic nervous system, and renin-angiotensin-aldosterone
pathway, leading to the nonosmotic release of vasopressin.
● The release of vasopressin results in intrarenal vasoconstriction with systemic vasodilation, which leads to kidney
injuries.
– Severe infections, such as diarrheal diseases and dengue hemorrhagic fever, can lead to hypovolemia due to increased
vascular permeability and fluid loss from the intravascular compartment, which can result in kidney injuries.
⚬ Reference - Nat Rev Nephrol 2013 May;9(5):278

History and Physical

Clinical Presentation

● AKI is generally asymptomatic until the onset of kidney failure. 2 ,3

● Presentation may vary depending on cause of AKI: 1 ,2 ,3
⚬ Symptoms and conditions that may suggest prerenal AKI are as follows:
– Thirst and reduced fluid intake
– Vomiting
– Diarrhea
– Bleeding
– Burns
⚬ Symptoms and signs that may suggest intrinsic AKI, in addition to those seen with prerenal, are as follows:
– Fatigue
– Weight loss
– Hypotension
– Fever
– Myalgias, arthralgias, or arthritis
– Rash
– Cough including hemoptysis
⚬ Postrenal AKI is usually asymptomatic. Symptoms and signs, when present, that may suggest postrenal AKI are as follows:
– Urinary urgency or hesitancy
– Blood in urine
⚬ Reference - Am Fam Physician 2012 Oct 1;86(7):631
● Symptoms for patients with severe cases may include the following:
⚬ Confusion
⚬ Lethargy
⚬ Fatigue
⚬ Anorexia
⚬ Nausea and vomiting
⚬ Weight gain due to fluid retention
⚬ Swelling
⚬ Reference - Am Fam Physician 2012 Oct 1;86(7):631
● Ask patients for history of use of nephrotoxic medications or conditions which may impair kidney function or affect kidney
perfusion (Am Fam Physician 2012 Oct 1;86(7):631).
● Ask patients about travel history, particularly for exposure to infectious diseases.
● Assess intravascular volume status and check for skin rashes which may indicate underlying systemic conditions (Am Fam
Physician 2012 Oct 1;86(7):631).
History

History of Present Illness (HPI)

● Ask about symptoms and features that may suggest the cause of AKI. 2
⚬ History of vomiting, diarrhea, significant blood loss, or shock may indicate systemic volume depletion.
⚬ Trauma or prolonged immobilization may indicate rhabdomyolysis.
⚬ Fever, maculopapular erythematous rash, and arthralgias may suggest acute interstitial nephritis.
⚬ Presence of flank pain or history of urolithiasis, genitourinary tract neoplasia, or retroperitoneal disease may suggest ob-
struction of kidneys.
⚬ Dysuria, suprapubic pain, slow urine stream, and increased frequency of urination may indicate lower urinary tract disease.
⚬ Reference - Am Fam Physician 2012 Oct 1;86(7):631
● Ask about the following symptoms and history: 1
⚬ Symptoms indicative of fluid loss or sequestration, including intense thirst, salt craving, nonfluent speech, and muscle
cramps
⚬ Previous urea, serum creatinine, and electrolyte results
⚬ Previous health checks

Medication History

● The following medications that may contribute to or cause AKI: 2 ,3

⚬ Angiotensin converting-enzyme inhibitors
⚬ Angiotensin receptor blockers
⚬ Direct renin inhibitors, for example, aliskiren
⚬ Calcineurin inhibitors, for example, tacrolimus or cyclosporine
⚬ Nonsteroidal anti-inflammatory drugs (NSAIDs)
⚬ Amphotericin
⚬ Beta-lactam antibiotics
⚬ Sulfonamides
⚬ Vancomycin
⚬ Acyclovir
⚬ Tenofovir
⚬ Methotrexate
⚬ Cisplatin or carboplatin
⚬ Ifosfamide
⚬ Proton pump inhibitors
⚬ Herbal and dietary supplements, such as aristolochic acid, creatine, vitamin A, vitamin C, vitamin D, germanium, and star
fruit
⚬ Vascular endothelial growth factor inhibitors, for example, pazopanib or sunitinib
⚬ Aminoglycosides, for example, gentamicin, amikacin, or tobramycin
⚬ Iodinated radiocontrast media
⚬ Diuretics (overuse)
● Ask about use of the following drugs or substances: 1 ,2
⚬ Over-the-counter drugs
⚬ Herbal remedies
⚬ Recreational drugs

Past Medical History (PMH)

● Ask about history of the following chronic illnesses: 1 ,2 ,3

⚬ Chronic kidney disease
⚬ Diabetes mellitus
⚬ Hypertension
⚬ Heart failure
⚬ Peripheral artery disease (PAD)
⚬ Liver failure
⚬ Infections, such as HIV, hepatitis, or other infections
⚬ Autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis (RA), or systemic sclerosis
● Ask about the following medical history: 1 ,2
⚬ Previous urinary tract conditions, such as pyelonephritis or urinary tract infection
⚬ History of urolithiasis, genitourinary tract neoplasia, or retroperitoneal disease which may suggest obstruction of kidneys
⚬ Night sweats or arthralgias which may suggest the presence of parenchymal kidney disease
 ⚬ Known immunosuppressive therapy, including treatment for transplant patients and patients with malignancies
⚬ Recent procedures, including surgery, angiography, or other radiological procedures
Social History (SH)

● If warranted, obtain information about exposure to waterways, sewage systems, and rodents to identify possible causes, such
as malaria, leptospirosis, or hantavirus. 1
● Ask about recent travel or exposure to infectious diseases. 2
● Ask about fluid intake and output. 2

Physical

General Physical

● Check blood pressure. 2

⚬ Hypertension may occur with volume expansion and with glomerulonephritis. Malignant hypertension may also be present.
⚬ Hypotension may occur with volume depletion or sepsis .
⚬ Reference - Am Fam Physician 2012 Oct 1;86(7):631
● Evaluate fluid status by following assessments: 1 ,2
⚬ Jugular venous pressure or pulmonary capillary wedge pressure
⚬ Daily body weight (to estimate fluid balance)
⚬ Mucosal membrane
⚬ Capillary refill time
⚬ Axillary moisture
⚬ Furrowed tongue
⚬ Turgor of skin over forehead and sternum
⚬ See Dehydration and Hypovolemia in Adults for additional information.
● Look for signs of acute and chronic heart failure, infection, and sepsis. 1 ,2 ,3
● Fever may occur with infections or acute interstitial nephritis. 2 ,3

Skin

● Skin exam may identify features of underlying causes or associated conditions. 1 ,2

⚬ Skin lesions, for example, palpable purpura, may suggest vasculitis.
⚬ Fine maculopapular rash may suggest drug-induced interstitial nephritis.
⚬ Livedo reticularis, purple toes, and other signs may suggest atheroembolic disease.
⚬ Skin thickening may suggest systemic sclerosis (Am Fam Physician 2012 Oct 1;86(7):631).

HEENT

● Perform ophthalmic exam to look for following findings: 1

⚬ Evidence of plaques that may indicate atheroembolic disease (Hollenhorst plaques, such as intraluminal retinal
cholesterol/fibrin deposits)
⚬ Findings suggestive of bacterial endocarditis, vasculitis, or malignant hypertension

Neck

● Neck exam for jugular venous pressure and carotid pulses and sounds may help detect the following conditions: 1
⚬ Heart failure (jugular venous distention)
⚬ Aortic valve disease, for example, rapid rise and fall of carotid pulse in aortic regurgitation, and delayed carotid upstroke in
aortic stenosis
⚬ Vascular disease

Cardiac

● Cardiac exam to assess rate, rhythm, murmurs, gallops, and rubs may help detect the following conditions: 1
⚬ Heart failure
⚬ Possible sources of emboli
⚬ Endocarditis

Lungs

● Perform lung examination to determine the presence of heart failure or pulmonary-renal syndrome. 1

Abdomen
● The following abdominal findings are suggestive of AKI: 1 ,2
⚬ Evidence of vascular disease, including bruits or palpable abdominal aortic aneurysm
⚬ Masses that could be malignant
⚬ Enlarged or tender kidneys
⚬ Distended bladder
⚬ Possible sources of bacterial infection
⚬ Evidence of liver disease
⚬ Intra-abdominal pressure (may be assessed by measuring bladder pressure) > 20 mm Hg (may occur after trauma, abdomi-
nal surgery, or secondary to massive fluid resuscitation)
Extremities

● Check for edema and assess distal pulses. 1

● Muscle tenderness may occur with rhabdomyolysis (Am Fam Physician 2012 Oct 1;86(7):631).
● Check for signs of arthritis, such as painful and/or restricted movement and enlarged or swollen joints (Am Fam Physician
2012 Oct 1;86(7):631).

Neuro

● Presence of neurological signs may suggest the following systemic disorders: 1

⚬ Vasculitis
⚬ Thrombotic microangiopathy
⚬ Infective endocarditis
⚬ Malignant hypertension
● Presence of peripheral neuropathy in patients with AKI may suggest the following conditions: 1
⚬ Nerve compression caused by rhabdomyolysis
⚬ Heavy-metal intoxication
⚬ Plasma cell dyscrasia
⚬ Acute polyneuropathy of the critically ill patient

Rectal

● Rectal exam in both female and male patients may detect obstructive causes of AKI. 1

Pelvic

● Pelvic exam in female patients may detect obstructive causes of AKI. 1

Diagnostic Testing

Recommendations for Evaluation of Acute Kidney Injury

● Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline for AKI recommendations: 1
⚬ AKI is defined as any of the following:
– Increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 mcmol/L) within 48 hours
– Increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7
days
– Urine volume < 0.5 mL/kg/hour for 6 hours

CLINICIANS' PRACTICE POINT

In the outpatient setting, patients are seen with elevated creatinine levels but often recent baseline values may not be available.
Hence, these criteria are mostly applicable to hospitalized patients, and the diagnosis of AKI in the outpatient setting is usually made
retrospectively if the patient's renal function improves. If the patient's renal function does not improve, then the time frame of the
AKI may not be known.

⚬ Determine the cause of AKI whenever possible.

⚬ Measure serum creatinine to detect worsening AKI.
⚬ Evaluate patients with AKI promptly to determine the cause with special attention to reversible causes.

Algorithm
● Rule out the presence of chronic kidney disease (CKD).
⚬ Evaluate renal size and cortical thickness using renal ultrasound. A reduction in size may indicate CKD.
 ⚬ In the absence of a previous serum creatinine measurement, assess for anemia, hyperphosphatemia, hypocalcemia, noc-
turia, acute illness, and duration of symptoms.
⚬ Reference - BMJ 2006 Oct 14;333(7572):786
● Suggested testing algorithm for determining the cause of AKI: 2 ,3
⚬ Identify or exclude postrenal causes (obstruction).
– Postrenal causes are suggested by findings of palpable bladder, pelvic mass, prostate enlargement, or complete anuria.
– Renal ultrasound is usually the first-line test to detect dilatation of renal pelvis and calyces, although obstruction may be
present without dilatation early in the course of malignancy.
⚬ Assessments to identify or exclude prerenal causes (hypovolemia):
– Physical exam findings, including pulse, jugular venous pressure, postural blood pressure, daily weights, and recorded
fluid balance, are helpful.
– A disproportional increase in serum urea:creatinine ratio suggests hypovolemia.
– A decrease in urinary sodium concentration suggests hypovolemia, unless the patient is on diuretics.
– IV fluid challenge to stimulate urinary output can be used. This test should be used with caution and only for patients
with functioning/nonobstructed kidneys.
⚬ For patients with no postrenal obstruction and no hypovolemia, look for evidence of renal parenchymal disease:
– Look for history or physical exam findings suggesting underlying systemic disease and/or use of antibiotics or nons-
teroidal anti-inflammatory drugs.
– Urinalysis findings of proteinuria or red blood cells/red cell casts suggest glomerulonephritis or urine eosinophils, which
can be indicative of acute interstitial nephritis.
⚬ Look for the following evidence that suggests that a major vascular occlusion has occurred:
– History of atherosclerotic vascular disease
– Renal asymmetry on ultrasound or computed tomography
– History of loin pain
– Macroscopic hematuria
⚬ Reference - BMJ 2006 Oct 14;333(7572):786, Am Fam Physician 2012 Oct 1;86(7):631

Testing Overview
● Diagnosis of AKI is based on serum creatinine levels and urine output (Am Fam Physician 2012 Oct 1;86(7):631).
● Initial testings for AKI are as follows:
⚬ Blood urea nitrogen (BUN)
⚬ Serum creatinine
⚬ Electrolytes
⚬ Fractional excretion of sodium (FENa)
⚬ Complete blood count
⚬ Urinalysis
⚬ Renal ultrasound as first-line imaging test to rule out obstruction
● Assess acute and chronic comorbidities to determine their impact on the outcome of AKI and risk for developing chronic kid-
ney disease. 1
● Identify and treat any infectious causes. 3

Blood Tests

General Testing

● Blood urea nitrogen (BUN):creatinine ratio:

⚬ BUN and creatinine: 1 ,2
– Compare BUN and creatine to the baseline levels if they are known.
– If baseline serum creatinine is not known and there is no evidence of chronic kidney disease, baseline serum creatinine
can be assumed to be an estimated glomerular filtration rate (GFR) of 75 mL/minute/1.73 m2.
⚬ Typical BUN:creatinine ratios:
– If it is an intrinsic cause of AKI, the ratio is typically 10:1-20:1.
– If it is a prerenal cause of AKI, the ratio is typically > 20:1.
– Reference - Am Fam Physician 2005 Nov 1;72(9):1739
● Other blood tests: 1 ,2
⚬ Check electrolytes, including sodium, potassium, chloride, calcium, magnesium, and phosphorus, which may be abnormal
with AKI.
⚬ Perform complete blood count (CBC) with differential to look for signs of infection or anemia.
⚬ Liver function tests and evaluation of muscle enzymes should be performed.
Additional Testing

● Consider measurement of biomarkers, including serum cystatin C to estimate GFR. 1 ,2 ,3

STUDY
● SUMMARY
serum cystatin C appears to have moderate sensitivity and specificity for detecting AKI DynaMed Level 2

SYSTEMATIC REVIEW: Am J Kidney Dis 2011 Sep;58(3):356

Details
⚬ based on systematic review limited by clinical heterogeneity
⚬ systematic review of 19 diagnostic cohort studies evaluating cystatin C for detection of AKI in 3,336 patients
⚬ reference standards were creatinine based and varied across studies
⚬ cutoff values for cystatin C, times when cystatin C was measured, and cystatin C assays varied across studies
⚬ pooled diagnostic performance of cystatin C for detection of AKI
– for serum cystatin C in analysis of 9 studies
● sensitivity 84% (95% CI 75%-90%)
● specificity 82% (95% CI 74%-88%)
● positive likelihood ratio 4.69 (95% CI 3.22-6.82)
● negative likelihood ratio 0.2 (95% CI 0.13-0.3)
– for early serum cystatin C (measured within 24 hours after intensive care admission or renal insult) in analysis of 7
studies
● sensitivity 84% (95% CI 74%-91%)
● specificity 78% (95% CI 67%-87%)
● positive likelihood ratio 3.87 (95% CI 2.6-5.75)
● negative likelihood ratio 0.21 (95% CI 0.13-0.32)
– for serum cystatin C after cardiac surgery in analysis of 3 studies
● sensitivity 82% (95% CI 58%-94%)
● specificity 79% (95% CI 50%-93%)
● positive likelihood ratio 3.93 (95% CI 1.59-9.74)
● negative likelihood ratio 0.22 (95% CI 0.1-0.5)
– for urinary cystatin C in analysis of 4 studies
● sensitivity 52% (95% CI 41%-64%)
● specificity 70% (95% CI 65%-75%)
● positive likelihood ratio 1.76 (95% CI 1.6-1.94)
● negative likelihood ratio 0.68 (95% CI 0.57-0.81)
⚬ Reference - Am J Kidney Dis 2011 Sep;58(3):356, commentary can be found in Am J Kidney Dis 2012 Apr;59(4):582

Urine Studies

Urinalysis

CLINICIANS' PRACTICE POINT

Urinalysis is critical to determining etiology of acute kidney injury (AKI).

● Urine dipstick testing: 2

⚬ Consider urine dipstick findings together with patient history (Crit Care 2016 Sep 27;20(1):299).
⚬ Consider measurement of hemoglobin, myoglobin, protein (specifically albumin), leukocytes, nitrites, and glucose to deter-
mine the potentially treatable causes of AKI, including the following causes:
– Glomerulonephritis, which usually has the findings of hematuria and proteinuria (> 1-2 g/day)
– Acute pyelonephritis, which usually has pyuria/leukocyturia and nitrites in urine
– Interstitial nephritis, which occasionally has eosinophiluria
– Rhabdomyolysis, which usually has hemoglobin in urine without red blood cells
– Reference - Crit Care 2016 Sep 27;20(1):299
⚬ National Institute for Health and Care Excellence (NICE) clinical guideline on prevention, detection, and management of AKI
recommendations:
 – In all patients with suspected or detected AKI, perform urine dipstick testing for blood, protein, leucocytes, nitrites, and
glucose. Record results and ensure appropriate management when test results are abnormal.
– In patients with no obvious cause of AKI but the urine dipstick results show hematuria and proteinuria without urinary
tract infection or trauma due to catheterization, suspect acute nephritis and consider referral to nephrologist.
– Reference - NICE 2019 Dec 18:NG148 PDF
Urine Microscopy

Table 2: Interpretation of Urine Microscopy Findings

Microscopy finding Significance

Epithelial cells Normal

Renal tubular cells Acute tubular injury

Nondysmorphic red cells Nonglomerular bleeding from anywhere in the urinary

tract

Dysmorphic red cells Glomerular disease, but also seen if urine sample is not
fresh at time of microscopy

Red cell casts Diagnostic of glomerular disease

Leukocytes ● Normal, ≤ 3 per high-power field

● > 3 per high-power field indicates inflammation in uri-
nary tract

White cell casts Renal infection or acute interstitial nephritis

Hyaline casts Any type of renal disease or volume depletion

Granular casts Significant renal disease

“Muddy brown cast” Necrotic tubular cells aggregated with Tamm Horsfall pro-
tein, indicating acute tubular injury

Crystals Abnormal crystals may indicate metabolic disorders or ex-

creted medications (some crystals may be found in
healthy urine)

Bacteria Urinary tract infection or sample contamination

Reference - Crit Care 2016 Sep 27;20(1):299.

● Urine sediment analysis: 1 ,2 ,3

⚬ Hematuria (gross or microscopic) may indicate glomerular, interstitial, vascular or other structural causes (such as trauma,
stone, tumor, or infection) of AKI, but it is rarely seen with the more common forms of AKI.
⚬ Red blood cell casts most commonly suggest glomerular or vascular causes but they have also been reported with acute in-
terstitial nephritis.
⚬ A lack of urinary red cells in the presence of positive dipstick reaction for blood typically is observed with AKI due to myo-
globinuria or hemoglobinuria.
⚬ White blood cells:
– Leukocyte casts may indicate pyelonephritis or interstitial nephritis.
– Elevated urine eosinophil count of > 1% is nonspecific but may support the suspicion of acute interstitial nephritis or
cholesterol embolism.
⚬ Crystals:
– Abundant uric acid crystals may indicate acute uric acid nephropathy or tumor lysis syndrome.
– Oxalate crystals suggest ethylene glycol intoxication, high doses of vitamin C, or jejunoileal bypass.
– Other crystals may occur in patients exposed to sulfonamides, indinavir, and triamterene.
 STUDY
⚬ SUMMARY
any granular casts or renal tubular epithelial cells in urine sediment appears to suggest acute tubular necrosis instead
of prerenal AKI DynaMed Level 2
DIAGNOSTIC COHORT STUDY: Clin J Am Soc Nephrol 2008 Nov;3(6):1615
Details
– based on diagnostic cohort study without blinding of microscopist from initial diagnostic impression
– final clinical diagnosis at discharge, renal biopsy, or death used as reference standard
– 267 consecutive patients with AKI had urine microscopy
● final diagnosis of acute tubular necrosis in 125 patients (47%)
● final diagnosis of prerenal AKI in 106 patients (40%)
● other causes of AKI excluded from analysis (13%)
– presence of any granular casts or renal tubular epithelial cells predicted acute tubular necrosis with
● sensitivity 83%
● specificity 77%
● positive predictive value 81%
● negative predictive value 80%
– Reference - Clin J Am Soc Nephrol 2008 Nov;3(6):1615, commentary can be found in Clin J Am Soc Nephrol 2009
Apr;4(4):691

Imaging Studies

● National Institute for Health and Care Excellence (NICE) clinical guideline on prevention, detection, and management of AKI
recommendations:
⚬ Routine ultrasound of urinary tract is not recommended when a cause of AKI has been identified.
⚬ In patients with AKI and suspected pyonephrosis, offer urgent ultrasound of urinary tract within 24 hours of assessment.
⚬ Reference - NICE 2019 Dec 18:NG148 PDF
● Renal ultrasound 1 ,2 ,3
⚬ Renal ultrasound is suggested as the first-line imaging test for diagnosis of AKI.
⚬ Renal ultrasound may be challenging to perform in patients with abdominal distension. Consider other imaging methods in
these patients (Crit Care 2016 Sep 27;20(1):299).
⚬ Grayscale ultrasound may be useful to excluding postrenal causes of AKI, including bilateral obstruction and azotemia
– Bilateral obstruction:
● Grayscale ultrasound is the most effective method for excluding subacute or chronic obstruction but it is not useful
for detecting minimally dilated obstruction, such as retroperitoneal metastatic tumor or idiopathic retroperitoneal
fibrosis.
● Grayscale ultrasound may not be necessary unless for the following reasons:
⚬ The patient is at high-risk for obstruction
⚬ Clinical indications including flank pain, urolithiasis, or pelvic mass
⚬ The patient is classified as high-risk based on specific clinical factors
● Partial obstruction may be obscured by volume depletion in elderly patients. If obstruction is strongly suspected, re-
peat ultrasonographic examination after volume repletion.
– Azotemia: findings include postvoid residual bladder urine of < 50 mL and an absence of pelvicalyceal dilation.
– References - Intensive Care Med 2017 Jun;43(6):829, ACR 2020 PDF

STUDY
⚬ SUMMARY
7-factor risk score may help identify low-risk of hydronephrosis in adults with AKI DynaMed Level 2

DIAGNOSTIC COHORT STUDY: Arch Intern Med 2010 Nov 22;170(21):1900

Details
– based on retrospective diagnostic cohort study without independent validation
– ● derivation cohort included 200 patients with diagnosed AKI who had renal ultrasound
● validation cohort included 797 patients (mean age 66 years) from same institution with diagnosed AKI who had renal
ultrasound
● all patients were assessed for demographic and clinical factors from medical records
– patients excluded for pregnancy, renal transplant, or recent hydronephrosis diagnosis
– risk score for finding of hydronephrosis on ultrasound developed with 7 factors (1 point each)
● history of hydronephrosis
● recurrent urinary tract infections
● diagnosis consistent with obstruction
● non-Black race
● no exposure to nephrotoxic drugs
 ● no history of heart failure
● no prerenal AKI
– scores stratified to risk categories
● low-risk for score < 2 points
● medium-risk for score = 3 points
● high-risk for score > 3 points
– 10.6% of validation cohort diagnosed with hydronephrosis, 3.3% had hydronephrosis requiring treatment
– prevalence of hydronephrosis in validation cohort
● 3.1% of 223 patients classified as low-risk, 0.4% had hydronephrosis requiring treatment
● 10.7% of medium-risk group
● 16.1% of high-risk group
– predictive performance of low-risk classification for hydronephrosis
● sensitivity 91.8% (96.3% for hydronephrosis requiring treatment)
● specificity 30.3% (28.8% for hydronephrosis requiring treatment)
● negative predictive value 96.9% (99.6% for hydronephrosis requiring treatment)
● negative likelihood ratio 0.27 (0.13% for hydronephrosis requiring treatment)
– Reference - Arch Intern Med 2010 Nov 22;170(21):1900, commentary can be found in Arch Intern Med 2010 Nov
22;170(21):1907

Management

Management Overview

● Consider hospitalization for patients with AKI requiring advanced diagnostic evaluation, with rapidly progressive renal failure
requiring renal biopsy, with persistent AKI not responsive to initial management, with complications or critical illness, or those
who may not be able to manage repeated outpatient visits for testing.
● Consider dose adjustments for medications and stopping exposure to nephrotoxic agents if possible.
● Identify and treat any infectious causes. 3
● Exclude urinary obstruction and treat it if detected.
● Monitor fluid status to determine the need for fluid management (administration or restriction), including regular monitoring
of the following: 2
⚬ Intake and output of fluid
⚬ Body weight
⚬ Volume status
● Nutritional support may be appropriate, including the following: 2 ,3
⚬ Restricted potassium and phosphorus
⚬ Adequate calories
⚬ Adequate protein, but protein restriction is not recommended, although minimal nitrogenous waste production is ideal for
AKI
⚬ Recommended daily allowance for vitamins and trace elements
● Timely follow-up is important for all patients with AKI, and may include referral to a nephrologist or urologist if appropriate.
● See Management, Complications, and Prevention of Acute Kidney Injury (AKI) for additional information.

Considerations for Hospitalization

● Manage AKI based on the stage and the cause. 1
● Some complications of AKI can be avoided with prompt management. 3
● Consider whether hospitalization may be necessary or helpful for patients with AKI. 2
⚬ Hospitalization may be appropriate under any of the following situations:
– Additional intensive diagnostic evaluation that is necessary
– Rapidly progressive renal failure that may require renal biopsy
– Persistence of AKI which is not responsive to initial management
– Presence of complications
⚬ Hospitalization in intensive care unit may be appropriate if critical illness is also present.
● For management of early-stage AKI, treatment options are as follows: 2
⚬ IV fluids for volume resuscitation
⚬ Vasopressors
 ⚬ Medication monitoring and adjustments, including the following:
– Monitoring of medication levels to assure both level and dose are therapeutic
– Medication dose adjustment due to impaired renal function
● For management of late-stage AKI, treatment options are as follows: 2
⚬ Supportive measures, including maintained nutritional, fluid, and electrolyte balance
⚬ Monitoring and evaluation to detect complications of AKI that may indicate a need for renal replacement therapy
● See Management, Complications, and Prevention of Acute Kidney Injury (AKI) for additional information.

Medications

Medication Dosing Adjustment

● Medication dosing adjustments may be necessary in patients with AKI because of the following reasons: 2
⚬ Decreased excretion and metabolism by the kidney
⚬ Effects of kidney failure on other routes of drug excretion and metabolism
● The following common nephrotoxic medications can contribute to AKI: 2 ,3
⚬ Angiotensin converting-enzyme inhibitors
⚬ Angiotensin receptor blockers
⚬ Direct renin inhibitors, for example, aliskiren
⚬ Calcineurin inhibitors, for example, tacrolimus or cyclosporine)
⚬ Nonsteroidal anti-inflammatory drugs (NSAIDs) (see Nonsteroidal Anti-inflammatory Drug (NSAID) Toxicity - Emergency
Management or Renal Manifestations of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for additional information)
⚬ Amphotericin
⚬ Beta-lactam antibiotics
⚬ Sulfonamides
⚬ Vancomycin
⚬ Acyclovir
⚬ Tenofovir
⚬ Methotrexate
⚬ Cisplatin or carboplatin
⚬ Ifosfamide
⚬ Proton pump inhibitors (PPIs)
⚬ Herbal and dietary supplements, such as aristolochic acid, creatine, vitamin A, vitamin C, vitamin D, germanium, and star
fruit
⚬ Vascular endothelial growth factor inhibitors, for example, pazopanib or sunitinib
⚬ Aminoglycosides, for example, gentamicin, amikacin, or tobramycin
⚬ Iodinated radiocontrast media
⚬ Diuretics (overuse)
● Options for dosing adjustments are as follows: 3
⚬ Temporary discontinuation
⚬ Change in administration pattern
⚬ Switching to a less toxic alternative, if available

Anticoagulants

● Exercise caution when using anticoagulants in patients with AKI because of their increased risk of bleeding due to the follow-
ing reasons: 2
⚬ Uremic platelet dysfunction
⚬ Reduced excretion of low-molecular-weight heparins and direct oral anticoagulants
● Anticoagulant dosing adjustments: 2
⚬ Anticoagulant dosing adjustments may be appropriate for some low-molecular-weight heparins, such as enoxaparin, or di-
rect oral anticoagulants, such as dabigatran, based on creatinine clearance.
⚬ Anticoagulant dosing adjustments may be challenging in patients with changing glomerular filtration rate, in particular dur-
ing dialysis
● For patients with uremia and active bleeding, anticoagulants options are as follows: 2
⚬ Desmopressin 0.3 mcg/kg IV, subcutaneous, or intranasal
⚬ Cryoprecipitate
⚬ Conjugated estrogens and dialysis without anticoagulation, if prolonged bleeding control is required

Consultation and Referral

● Consider the stage and the cause of AKI, and the severity of complications when referring to nephrologist. 2
● Indications for consultation with nephrologist: 2
⚬ The diagnosis or cause of AKI are unclear, especially if decreased perfusion and urinary tract obstruction have been treated
or ruled out.
⚬ Patient is at risk for long-term kidney failure.
⚬ Chronic kidney disease is suspected but the cause is unknown.
⚬ Assistance of management of parenchymal disease, not including acute tubular necrosis, is necessary.
⚬ There is a need for renal replacement therapy.
⚬ There is a poor response to treatments.
⚬ Complications of AKI are present.
⚬ The AKI is severe.
⚬ AKI is present in patient with chronic kidney disease stage 4-5 (baseline glomerular filtration rate [GFR] < 30
mL/minute/1.73 m2).
● National Institute for Health and Care Excellence (NICE) recommendations for referral:
⚬ Recommendations on referral to nephrologist:
– Refer adults with AKI to nephrologist or critical care specialist immediately if they meet the criteria for renal replacement
therapy.
– Do not refer adults to nephrologist when there is a clear cause for AKI and the condition is responding promptly to medi-
cal management, unless they have renal transplant.
– Consider discussing management with a nephrologist when the adults have severe illness which may benefit from treat-
ment but there is an uncertainty whether they are nearing the end of their life.
– Refer adults in intensive care to nephrology team when there is an uncertainty about the cause of AKI or when specialist
management of kidney injury may be needed.
– Early referral to nephrologist has the following potential benefits:
● Prevention of progressive AKI
● Possible avoidance of renal replacement therapy
● Timely transfer to critical care setting
● Improved likelihood of renal recovery
● Decreased length of hospital stay
● Improved long-term outcomes
– Discuss management of AKI with nephrologist as soon as possible and within 24 hours of detection when ≥ 1 of the fol-
lowing situations applies:
● There is a possible diagnosis that may need specialist treatment, such as vasculitis, glomerulonephritis, tubulointersti-
tial nephritis, or myeloma
● The AKI has no clear cause
● There is an inadequate response to treatments
● There are complications associated with AKI
● It is a stage 3 AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE), Acute
Kidney Injury Network (AKIN), or Kidney Disease Improving Global Outcomes (KDIGO) criteria
● Renal transplant is needed
● Chronic kidney disease stage 4-5
– Consider referral to nephrologist if estimated GFR rate is ≤ 30 mL/minute/1.73 m2 after recovering from an episode of
AKI.
– For patients with stage 2-3 AKI, rapid referral to nephrologist may allow:
● Early detection and treatment of primary renal diseases if it is present
● Timely correction of volume depletion and hypotension
● Guided investigation
⚬ Recommendations on referral to urologist:
– Immediately refer adults with any of the following conditions:
● Pyonephrosis
● Obstruction of solitary kidney
● Bilateral obstructions of upper urinary tract
● Complications of AKI related to obstruction
– Refer adults with upper tract urological obstruction.
● Following AKI, refer patients to a nephrologist if the renal function does not fully recover. These patients are at greater risk for
long-term kidney failure, cardiovascular events, and mortality. 2

Follow-Up

● Patients who are not hospitalized require early follow-up for renal function. 2
● Following AKI, refer patients to a nephrologist if the renal function does not fully recover. These patients are at greater risk for
long-term kidney failure, cardiovascular events, and mortality. 2
● Recommendations from professional organizations:
⚬ Kidney Disease Improving Global Outcomes recommendations for follow-up include additional monitoring to assess renal
function 3 months after an AKI episode (KDIGO Not Graded). Specifically, perform the following assessments:
– Assessment of resolution of AKI for patients without chronic kidney disease (CKD) following AKI, and providing manage-
ment for patients at increased risk for CKD (see Chronic Kidney Disease (CKD) in Adults for additional information)
– Assessment of new onset AKI
– Assessment of worsening of preexisting CKD (see Chronic Kidney Disease (CKD) in Adults for additional information)
⚬ National Institute for Health and Care Excellence recommendations include monitoring serum creatinine following an
episode of AKI. Consider referral to a nephrologist if the estimated GFR is ≤ 30 mL/minute/1.73 m2. 4

Education
● National Institute for Health and Care Excellence guidelines recommendations for patient education: 4
⚬ Discuss the options for immediate treatment, as well as monitoring, prognosis, and support with patients and/or caregivers
as soon as possible.
⚬ Provide information to patients and caregivers regarding long-term treatment, monitoring, self-management, and support.
⚬ For patients requiring renal replacement therapy after discharge, provide information regarding dialysis, such as the fre-
quency and length of dialysis and any necessary preparations, for example, placement of a fistula or a peritoneal catheter.
⚬ For patients at risk of AKI, discuss the risk of developing AKI, especially the risk associated with conditions that may cause
dehydration, such as diarrhea and vomiting, and nephrotoxic medications, such as nonsteroidal anti-inflammatory drugs.
The following patients are particularly at risk:
– Patients with chronic kidney disease who have an estimated glomerular filtration rate of < 60 mL/minute/1.73 m2
– Patients with neurological or cognitive impairment, especially if they are dependent on caregiver for access to fluids
⚬ Include caregivers in the discussion as appropriate.

Complications
● Assess for complications as soon as AKI is detected to allow for early treatment. 2
● The risk of complications depend on the stage (or severity) of the AKI. 2
● Complications of AKI are as follows:
⚬ Electrolyte disorders, including the following: 2
– Metabolic acidosis
– Hyperkalemia
– Hypokalemia
– Hyponatremia
– Hypernatremia
– Hypocalcemia
– Hypercalcemia
– Hyperphosphatemia
– Hypermagnesemia
⚬ Volume overload: 2
– Symptoms may include dyspnea, jugular venous distention, rales, ascites, and lower extremity edema.
– Volume overload may lead to life-threatening pulmonary edema.
– Volume overload is more likely to occur if oliguria is present.
– Volume overload is associated with poor prognosis.
⚬ Volume depletion, which can delay resolution of AKI 2
⚬ Chronic kidney disease (CKD), including end-stage kidney disease: 2 , 3 , 4
– The risk factors for development of CKD after AKI are as follows:
● Older age
● Comorbidities
● Lower baseline estimated glomerular filtration rate
● Higher baseline albuminuria
● Greater severity of AKI
⚬ Uremic complications, including the following: 2
– Encephalopathy, which may have the following symptoms: lethargy, asterixis, hyperreflexia, and myoclonus
– Pericarditis
– Bleeding associated with uremic platelet dysfunction
 – Pruritis
⚬ Medication toxicity 2
⚬ Anemia 2
⚬ Other potential long-term effects of AKI include the following: 4
– Decreased quality of life
– Depression
– Need for social or residential care

Prognosis
● Most causes of a community-acquired AKI are reversible, so it may have better long-term renal and patient outcomes com-
pared to a hospital-acquired AKI (Nephrology (Carlton) 2016 Sep;21(9):729).

STUDY
● SUMMARY
acute kidney injury in the outpatient setting associated with increased risk of end-stage kidney disease requiring dialysis
and all-cause mortality
COHORT STUDY: Sci Rep 2019 Nov 27;9(1):17658
Details
⚬ based on cohort study
⚬ 6,047 adults (median age 67.4 years) enrolled in the pre-end-stage kidney disease (ESRD) program at the China Medical
University Hospital, Taichung, Taiwan, from 2003 were evaluated
⚬ all adults were followed until initiation of maintenance dialysis for ESRD, loss to follow-up, death, or until December 31,
2015, for 13,467.68 person-years total
⚬ all adults had serum creatinine levels measured up to 180 days before pre-ESRD enrollment
⚬ an AKI in the outpatient setting event was defined as a fluctuation of > 50% in serum creatinine level or > 35% in estimated
glomerular filtration rate (GFR) in the 180-day period preceding pre-ERSD enrollment
⚬ 1,905 adults (31.5%) developed AKI in the outpatient setting
⚬ compared to adults without AKI in the outpatient setting, adults with AKI in the outpatient setting associated with increased
risk of
– ESRD requiring dialysis
● overall (adjusted hazard ratio [HR] 1.97, 95% CI 1.72-2.26)
● 1-year dialysis (adjusted HR 2.61, 95% CI 2.15-3.18)
– all-cause mortality
● overall (adjusted HR 1.84, 95% CI 1.56-2.17)
● 1-year mortality (adjusted HR 2.41, 95% CI 1.89-3.09)
⚬ Reference - Sci Rep 2019 Nov 27;9(1):17658

● See Prognosis in Management, Complications, and Prevention of Acute Kidney Injury (AKI) for additional information.

Prevention

Principles and Considerations

● Preventive measures to decrease the exposure of and susceptibility to AKI: 2 ,3
⚬ Correct volume depletion by using the following:
– Increasing oral sodium and fluid
– IV fluids, such as isotonic saline
⚬ Avoid or limit the use of the following medications:
– Diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with acute illness to
decrease the risks for volume depletion and hypotension
– Nephrotoxic medications, for example, nonsteroidal anti-inflammatory drugs, in patients with chronic kidney disease
(CKD)
– Iodinated contrast, particularly in patients with CKD
● See Prevention in Management, Complications, and Prevention of Acute Kidney Injury (AKI) for additional information.

Prevention of Contrast-Induced AKI

● Prevention of contrast-induced nephropathy:
⚬ Discontinue nephrotoxic drugs if possible.
⚬ Considerations on the use of contrast-enhanced imaging in patients at increased risk of contrast-induced AKI:
– Consider alternative imaging methods (KDIGO Not Graded).
 – Use the lowest possible dose of iodine-based contrast medium in patients at risk for contrast-induced AKI (KDIGO Not
Graded).
– Use either iso-osmolar or low-osmolar iodinated contrast media instead of high-osmolar iodinated contrast media
(KDIGO Level 1, Grade B).
⚬ Periprocedural hydration:
– Do not use oral fluids alone in patients at increased risk for contrast-induced AKI (KDIGO Level 1, Grade C).
– Use either isotonic sodium chloride or sodium bicarbonate solutions for IV volume expansion, rather than no IV volume
expansion, in patients at increased risk for contrast-induced AKI (KDIGO Level 1, Grade A).
– Hemodynamic-guided IV fluid administration may decrease the risk of contrast-induced AKI, all-cause death, and my-
ocardial infarction in patients having cardiac catheterization DynaMed Level 2 .
⚬ Medications use in patients at increased risk of contrast-induced AKI:
– Consider using oral acetylcysteine with isotonic crystalloids IV in patients at increased risk of contrast-induced AKI, de-
spite inconsistent evidence, because it appears to have a low risk of side effects and low cost (KDIGO Level 2, Grade D).
– Vitamin C (ascorbic acid):
● Use of high-dose vitamin C may be associated with lower risk of contrast-mediated nephropathy in high-risk patients
.
DynaMed Level 3

● Ascorbic acid associated with reduced risk of contrast-induced AKI in patients having coronary angiography
DynaMed Level 3 .
– Iloprost may prevent contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography
or interventions DynaMed Level 3 .
– Avoid or consider avoiding the following medications and procedures as a means of preventing contrast-induced AKI:
● Theophylline, because the risk of cardiovascular side effects and possible drug interactions may outweigh the benefits
(KDIGO Level 2, Grade C)
● Fenoldopam (KDIGO Level 1, Grade B)
⚬ Other strategies in patients at increased risk of contrast-induced AKI:
– Ischemic preconditioning may be associated with decreased risk of contrast-induced nephropathy in high-risk patients
DynaMed Level 3 .
– Prophylactic intermittent hemodialysis and prophylactic hemofiltration are not recommended for contrast media re-
moval in patients at increased risk of contrast-induced AKI (KDIGO Level 2, Grade C).
● See Complications Associated With Iodinated Contrast for details.

Screening
● AKI is typically asymptomatic. Therefore, screening is necessary for detection. 2
● Screening is especially important in patients with an increased risk of AKI. Risk factors include acute illness, certain medical
conditions and procedures, use of medications, and demographic factors. 1 ,2 ,4
⚬ Presence of the following conditions an increase susceptibility to AKI:
– Chronic kidney disease (CKD)
– Hypertension
– Heart failure or vascular disease
– Dehydration/volume depletion
– Diabetes mellitus and hyperglycemia
– Chronic lung disease
– Chronic liver disease
– Cancer
– Anemia
– Hyperuricemia
– Albuminuria
⚬ The following common nephrotoxic medications can contribute to AKI: 2 ,3
– Angiotensin converting-enzyme inhibitors
– Angiotensin receptor blockers
– Direct renin inhibitors, for example, aliskiren
– Calcineurin inhibitors, for example, tacrolimus or cyclosporine
– Nonsteroidal anti-inflammatory drugs (NSAIDs) (see Nonsteroidal Anti-inflammatory Drug (NSAID) Toxicity - Emergency
Management or Renal Manifestations of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for additional information)
– Amphotericin
– Beta-lactam antibiotics
– Sulfonamides
– Vancomycin
– Acyclovir
 – Tenofovir
– Methotrexate
– Cisplatin or carboplatin
– Ifosfamide
– Proton pump inhibitors (PPIs)
– Herbal and dietary supplements, such as aristolochic acid, creatine, vitamin A, vitamin C, vitamin D, germanium, and star
fruit
– Vascular endothelial growth factor (VEGF) inhibitors, for example, pazopanib or sunitinib
– Aminoglycosides, for example, gentamicin, amikacin, or tobramycin
– Iodinated radiocontrast media
– Diuretics (overuse)
⚬ The following demographic risk factors are associated with AKI:
– Older age
– Female sex
– Black race
● Screening may include evaluation and/or monitoring of serum creatinine, estimated glomerular filtration rate (GFR), urine out-
put, and urinalysis. 2
⚬ Consider severity of illness and lab values when deciding on the timing and frequency of repeat labs.
⚬ It may be difficult to obtain accurate urine output measurement outside of the intensive care unit.
⚬ Urinalysis may be useful to evaluate for acute or chronic kidney diseases.
⚬ An increase in serum creatinine and a decrease in urine output may occur several hours after the initial decline in esti-
mated GFR.
● National Institute for Health and Care Excellence (NICE) recommendations on screening for adults having iodinated contrast: 4
⚬ If the imaging is nonemergent, obtain estimated GFR (current or one available within last 3 months) to evaluate for CKD
prior to offering iodinated contrast.
⚬ If the imaging is nonemergent, assess the risk of AKI. The risk may be increased in patients with the following conditions or
factors:
– CKD, particularly those with estimated GFR of < 40 mL/minute/1.73 m2
– Diabetes in addition to CKD, particularly those with estimated GFR of < 40 mL/minute/1.73 m2
– Heart failure
– Renal transplant
– Age ≥ 75 years
– Hypovolemia
– Factors related to contrast, such as those requiring increased volume of contrast or intra-arterial administration of
contrast
● See Screening in Management, Complications, and Prevention of Acute Kidney Injury (AKI) for additional information.

Guidelines and Resources

Guidelines

International Guidelines

● Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline on acute kidney injury can be found at KDIGO
(2011) 2012 Mar PDF , commentary can be found in Am J Kidney Dis 2013 May;61(5):649.

United States Guidelines

● American College of Radiology (ACR) Appropriateness Criteria for renal failure can be found at J Am Coll Radiol 2021
May;18(5S):S174 .

United Kingdom Guidelines

● National Institute for Health and Care Excellence (NICE) guidance on prevention, detection and management of acute kidney
injury can be found at NICE 2019 Dec 18:NG148, updated Sep 2023 PDF .

Review Articles

● Review can be found in Nat Rev Dis Primers 2021 Jul 15;7(1):52.
● Review can be found in Lancet 2019 Nov 23;394(10212):1949.
● Review can be found in Ann Intern Med 2017 Nov 7;167(9):ITC66, commentary can be found in Ann Intern Med 2018 Jun
5;168(11):836.
● Review can be found in Am Fam Physician 2019 Dec 1;100(11):687.
● Review can be found in Lancet 2012 Aug 25;380(9843):756.
● Review of recognition and management of acute kidney injury in the International Society of Nephrology (ISN) 0by25 initiative
for acute kidney injury can be found in Lancet 2016 May 14;387(10032):2017, editorial can be found in Lancet 2016 May
14;387(10032):1974.
● Review of advances in pediatric acute kidney injury can be found in Pediatr Res 2022 Jan;91(1):44.
● Review of pathophysiology of acute kidney injury can be found in Compr Physiol 2012 Apr;2(2):1303.
● Review of pathophysiology due to ischemia in acute kidney injury can be found in Nat Rev Nephrol 2011 Apr;7(4):189.
● Review of pathogenesis of community-acquired acute kidney injury in:
⚬ Developed countries can be found in Nephrology (Carlton) 2016 Sep;21(9):729.
⚬ Tropical countries can be found in Nat Rev Nephrol 2013 May;9(5):278.
● Review of pathophysiology and clinical work-up for acute kidney injury can be found in Contrib Nephrol 2016;188:1.
● Review of drug-induced acute kidney injury: diverse mechanisms of tubular injury can be found in Curr Opin Crit Care 2019
Dec;25(6):550.
● Review of novel insights into crystal-induced acute kidney injury can be found in Kidney Dis (Basel) 2018 Jun;4(2):49.
● Review of diagnosis of acute kidney injury can be found in Curr Opin Crit Care 2014 Dec;20(6):581.
● Review of diagnosis and clinical workup of acute kidney injury can be found in Crit Care 2016 Sep 27;20(1):299.
● Review of diagnosis and specific causes of acute kidney injury can be found in Intensive Care Med 2017 Jun;43(6):829.
● Review of management of patients at risk for acute kidney injury can be found in Lancet 2017 May 27;389(10084):2139.
● Review of acute kidney injury and chronic kidney disease can be found in N Engl J Med 2014 Jul 3;371(1):58.
● Review of potential effects of anabolic-androgenic steroids and growth hormone as commonly used sport supplements on the
kidney can be found in BMC Nephrol 2019 May 31;20(1):198.
● Review of acute kidney injury in COVID-19: emerging evidence of a distinct pathophysiology can be found in J Am Soc Nephrol
2020 Jul;31(7):1380.

MEDLINE Search
● To search MEDLINE for (Acute Kidney Injury in the Outpatient Setting) with targeted search (Clinical Queries), click therapy ,
diagnosis , or prognosis .

Patient Information
● Handout from EBSCO Health or in Spanish
● Handout from National Kidney Foundation
● Handout from Patient UK

References

General References Used

1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for
Acute Kidney Injury. KDIGO (2011) 2012 Mar PDF , KDIGO Appendices 2012 Mar PDF , KDIGO Supplementary Tables 2012
Mar PDF .
2. Levey AS, James MT. Acute Kidney Injury. Ann Intern Med. 2017 Nov 7;167(9):ITC66-ITC80, correction can be found in Ann
Intern Med 2018 Jan 2;168(1):84, commentary can be found in Ann Intern Med 2018 Jun 5;168(11):836.

3. Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012 Aug 25;380(9843):756-66, editorial can be found in Lancet
2012 Dec 1;380(9857):1904.
4. National Institute for Health and Care Excellence (NICE) guidance on prevention, detection and management of acute kidney
injury up to point of renal replacement therapy can be found at NICE 2019 Dec 18:NG148 PDF , summary can be found
in BMJ 2013 Aug 28;347:f4930.

Recommendation Grading Systems Used

● Kidney Disease Improving Global Outcomes (KDIGO) recommendation grading system:

⚬ Strength of recommendation:
– Level 1 ("we recommend") - most patients should receive recommended course of action
– Level 2 ("we suggest") - different choices will be appropriate for different patients, based on patient's values and
preferences
 – Not Graded - topic does not allow adequate application of evidence, not meant to be interpreted as being stronger rec-
ommendations than Level 1 or 2
⚬ Quality of evidence:
– Grade A - high-quality evidence, true effect lies close to that of estimate of effect
– Grade B - moderate-quality evidence, true effect likely to be close to estimate of effect, but there is a possibility it is sub-
stantially different
– Grade C - low-quality evidence, true effect may be substantially different from estimate of effect
– Grade D - very low-quality evidence, estimate of effect very uncertain and often far from the truth
⚬ Reference - KDIGO clinical practice guideline on acute kidney injury (KDIGO (2011) 2012 Mar PDF , KDIGO Appendices
2012 Mar PDF )

Synthesized Recommendation Grading System for DynaMed Content

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evidence to support clinical decision-making (see 7-Step Evidence-Based Methodology ).
● Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading sys-
tem used in the original guideline(s) and allow users to quickly see where guidelines agree and where guidelines differ from
each other and from the current evidence.
● In DynaMed content, we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to
provide recommendations to support clinical decision-making in the Overview & Recommendations section.
● We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to classify synthe-
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⚬ Strong recommendations may be used when, based on the available evidence, clinicians (without conflicts of interest)
consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and bur-
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undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected conse-
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have limited confidence in their judgments.
⚬ Conditional recommendations may also be used when the range of patient values and preferences suggests that in-
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● DynaMed synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic
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Related Topics
● Acute Kidney Injury in Adults - Approach to the Patient
● Management, Complications, and Prevention of Acute Kidney Injury (AKI)

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