Acute Kidney Injury Clinical Presentation
- Author: Biruh T Workeneh, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
A detailed and accurate history is crucial for diagnosing acute kidney injury (AKI) and determining treatment. Distinguishing AKI from chronic kidney disease is important, yet making the distinction can be difficult; chronic kidney disease is itself an important risk factor for AKI. A history of chronic symptoms—months of fatigue, weight loss, anorexia, nocturia, sleep disturbance, and pruritus—suggests chronic kidney disease. AKI can cause identical symptoms, but over a shorter course.
It is important to elicit a history of any of the following etiologic factors:
Volume restriction (eg, low fluid intake, gastroenteritis)
Nephrotoxic drug ingestion (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], aminoglycosides) 
Exposure to iodinated contrast agents within the past week 
Trauma or unaccustomed exertion
Blood loss or transfusions
Exposure to toxic substances, such as ethyl alcohol or ethylene glycol
Exposure to mercury vapors, lead, cadmium, or other heavy metals, which can be encountered in welders and miners
People with the following comorbid conditions are at a higher risk for developing AKI:
Chronic heart failure
Obesity [31, 32, 33]
Connective tissue disorders
Urine output history can be useful. Oliguria generally favors AKI. Abrupt anuria suggests acute urinary obstruction, acute and severe glomerulonephritis, or embolic renal artery occlusion. A gradually diminishing urine output may indicate a urethral stricture or bladder outlet obstruction due to prostate enlargement.
Because of a decrease in functioning nephrons, even a trivial nephrotoxic insult may cause AKI to be superimposed on chronic renal insufficiency.
Acute kidney injury (AKI) has a long differential diagnosis. The history can help to classify the pathophysiology of AKI as prerenal, intrinsic renal, or postrenal failure, and it may suggest some specific etiologies.
Patients commonly present with symptoms related to hypovolemia, including thirst, decreased urine output, dizziness, and orthostatic hypotension. Ask about volume loss from vomiting, diarrhea, sweating, polyuria, or hemorrhage. Patients with advanced cardiac failure leading to depressed renal perfusion may present with orthopnea and paroxysmal nocturnal dyspnea.
Elders with vague mental status change are commonly found to have prerenal or normotensive ischemic AKI. Insensible fluid losses can result in severe hypovolemia in patients with restricted fluid access and should be suspected in elderly patients and in comatose or sedated patients.
Intrinsic renal failure
Patients can be divided into those with glomerular etiologies and those with tubular etiologies of AKI. Nephritic syndrome of hematuria, edema, and hypertension indicates a glomerular etiology for AKI. Query about prior throat or skin infections. Acute tubular necrosis (ATN) should be suspected in any patient presenting after a period of hypotension secondary to cardiac arrest, hemorrhage, sepsis, drug overdose, or surgery.
A careful search for exposure to nephrotoxins should include a detailed list of all current medications and any recent radiologic examinations (ie, exposure to radiologic contrast agents). Pigment-induced AKI should be suspected in patients with possible rhabdomyolysis (muscular pain, recent coma, seizure, intoxication, excessive exercise, limb ischemia) or hemolysis (recent blood transfusion). Allergic interstitial nephritis should be suspected with fevers, rash, arthralgias, and exposure to certain medications, including NSAIDs and antibiotics.
Postrenal failure usually occurs in older men with prostatic obstruction and symptoms of urgency, frequency, and hesitancy. Patients may present with asymptomatic, high-grade urinary obstruction because of the chronicity of their symptoms. A history of prior gynecologic surgery or abdominopelvic malignancy often can be helpful in providing clues to the level of obstruction.
Flank pain and hematuria should raise a concern about renal calculi or papillary necrosis as the source of urinary obstruction. Use of acyclovir, methotrexate, triamterene, indinavir, or sulfonamides implies the possibility that crystals of these medications have caused tubular obstruction.
Obtaining a thorough physical examination is extremely important when collecting evidence about the etiology of AKI. Clues may be found in any of the following:
Skin examination may reveal the following:
Livido reticularis, digital ischemia, butterfly rash, palpable purpura - Systemic vasculitis
Maculopapular rash - Allergic interstitial nephritis
Track marks (ie, intravenous drug abuse) - Endocarditis
Petechiae, purpura, ecchymosis, and livedo reticularis provide clues to inflammatory and vascular causes of AK. Infectious diseases, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and embolic phenomena can produce typical cutaneous changes.
Eyes and ears
Eye examination may reveal the following:
Keratitis, iritis, uveitis, dry conjunctivae - Autoimmune vasculitis
Jaundice - Liver diseases
Band keratopathy (ie, hypercalcemia) - Multiple myeloma
Signs of diabetes mellitus
Signs of hypertension
Atheroemboli - Retinopathy
Evidence of uveitis may indicate interstitial nephritis and necrotizing vasculitis. Ocular palsy may indicate ethylene glycol poisoning or necrotizing vasculitis. Findings suggestive of severe hypertension, atheroembolic disease, and endocarditis may be observed on careful examination of the eyes.
Ear examination may reveal the following:
Hearing loss - Alport disease and aminoglycoside toxicity
Mucosal or cartilaginous ulcerations - Wegener granulomatosis
The most important part of the physical examination is the assessment of cardiovascular and volume status. The physical examination must include the following:
Pulse rate and blood pressure recordings measured in the supine and the standing position
Close inspection of the jugulovenous pulse
Careful examination of the heart and lungs, skin turgor, and mucous membranes
Assessment for peripheral edema
Cardiovascular examination may reveal the following:
Irregular rhythms (ie, atrial fibrillation) - Thromboemboli
Murmurs - Endocarditis
Pericardial friction rub - Uremic pericarditis
Increased jugulovenous distention, rales, S 3 - Heart failure
In hospitalized patients, accurate daily records of fluid intake and urine output, as well as daily measurements of patient weight, are important. Hypovolemia leads to hypotension; however, hypotension may not necessarily indicate hypovolemia.
Severe heart failure may also cause hypotension. Although patients with heart failure may have low blood pressure, volume expansion is present and effective renal perfusion is poor, which can result in AKI.
Severe hypertension with renal failure suggests one of the following disorders:
Abdominal examination may reveal the following:
Pulsatile mass or bruit - Atheroemboli
Abdominal or costovertebral angle tenderness - Nephrolithiasis, papillary necrosis, renal artery thrombosis, renal vein thrombosis
Pelvic, rectal masses; prostatic hypertrophy; distended bladder – Urinary obstruction
Limb ischemia, edema - Rhabdomyolysis
Abdominal examination findings can be useful in helping to detect obstruction at the bladder outlet as the cause of renal failure; such obstruction may be due to cancer or to an enlarged prostate.
The presence of tense ascites can indicate elevated intra-abdominal pressure that can retard renal venous return and result in AKI. The presence of an epigastric bruit suggests renal vascular hypertension, which may predispose to AKI.
Pulmonary examination may reveal the following:
Rales - Goodpasture syndrome, Wegener granulomatosis
Hemoptysis - Wegener granulomatosis
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Aug. 8(4):R204-12. [Medline]. [Full Text].
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007. 11(2):R31. [Medline]. [Full Text].
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008 Nov 4. 52(19):1527-39. [Medline].
Durand F, Graupera I, Ginès P, Olson JC, Nadim MK. Pathogenesis of Hepatorenal Syndrome: Implications for Therapy. Am J Kidney Dis. 2015 Oct 21. [Medline].
Talving P, Karamanos E, Skiada D, Lam L, Teixeira PG, Inaba K, et al. Relationship of creatine kinase elevation and acute kidney injury in pediatric trauma patients. J Trauma Acute Care Surg. 2013 Mar. 74(3):912-6. [Medline].
Mancini E, Caramelli F, Ranucci M, et al. Is time on cardiopulmonary bypass during cardiac surgery associated with acute kidney injury requiring dialysis?. Hemodial Int. 2011 Nov 8. [Medline].
Kheterpal S, Tremper KK, Heung M, Rosenberg AL, Englesbe M, Shanks AM, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009 Mar. 110(3):505-15. [Medline].
Goldberg R, Dennen P. Long-term outcomes of acute kidney injury. Adv Chronic Kidney Dis. 2008 Jul. 15(3):297-307. [Medline].
Panek R, Tennankore KK, Kiberd BA. Incidence, Etiology and Significance of Acute Kidney Injury in the Early Post Kidney Transplant Period. Clin Transplant. 2015 Oct 24. [Medline].
Feest TG, Mistry CD, Grimes DS, Mallick NP. Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment. BMJ. 1990 Oct 20. 301(6757):897-900. [Medline]. [Full Text].
Pannu N, James M, Hemmelgarn BR, Dong J, Tonelli M, Klarenbach S. Modification of Outcomes After Acute Kidney Injury by the Presence of CKD. Am J Kidney Dis. 2011 Aug. 58(2):206-13. [Medline].
Wang AY, Bellomo R, Cass A, Finfer S, Gattas D, Myburgh J, et al. Health-related quality of life in survivors of acute kidney injury: The Prolonged Outcomes Study of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy study outcomes. Nephrology (Carlton). 2015 Jul. 20 (7):492-8. [Medline].
Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17. 294(7):813-8. [Medline].
Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, et al. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007 May. 2(3):431-9. [Medline].
Ricci Z, Cruz D, Ronco C. The RIFLE criteria and mortality in acute kidney injury: A systematic review. Kidney Int. 2008 Mar. 73(5):538-46. [Medline].
James MT, Hemmelgarn BR, Wiebe N, Pannu N, Manns BJ, Klarenbach SW, et al. Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet. 2010 Dec 18. 376(9758):2096-103. [Medline].
Philips B, MacPhee I. Do statins prevent acute kidney injury?. Expert Opin Drug Saf. 2015 Oct. 14 (10):1547-61. [Medline].
Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, et al. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013 Mar 18. 346:f880. [Medline]. [Full Text].
Giacoppo D, Capodanno D, Capranzano P, Aruta P, Tamburino C. Meta-analysis of randomized controlled trials of preprocedural statin administration for reducing contrast-induced acute kidney injury in patients undergoing coronary catheterization. Am J Cardiol. 2014 Aug 15. 114 (4):541-8. [Medline].
Marenzi G, Cosentino N, Werba JP, Tedesco CC, Veglia F, Bartorelli AL. A meta-analysis of randomized controlled trials on statins for the prevention of contrast-induced acute kidney injury in patients with and without acute coronary syndromes. Int J Cardiol. 2015 Mar 15. 183:47-53. [Medline].
Molnar AO, Coca SG, Devereaux PJ, Jain AK, Kitchlu A, Luo J, et al. Statin use associates with a lower incidence of acute kidney injury after major elective surgery. J Am Soc Nephrol. 2011 May. 22(5):939-46. [Medline]. [Full Text].
Pan SY, Wu VC, Huang TM, Chou HC, Ko WJ, Wu KD, et al. Effect of preoperative statin therapy on postoperative acute kidney injury in patients undergoing major surgery: systemic review and meta-analysis. Nephrology (Carlton). 2014 Dec. 19 (12):750-63. [Medline].
Lewicki M, Ng I, Schneider AG. HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass. Cochrane Database Syst Rev. 2015 Mar 11. 3:CD010480. [Medline].
Kuhn EW, Slottosch I, Wahlers T, Liakopoulos OJ. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2015 Aug 13. 8:CD008493. [Medline].
Wang J, Gu C, Gao M, Yu W, Yu Y. Preoperative Statin Therapy and Renal Outcomes After Cardiac Surgery: A Meta-analysis and Meta-regression of 59,771 Patients. Can J Cardiol. 2015 Aug. 31 (8):1051-60. [Medline].
Boggs W. Poor Long-Term Survival After ICU Acute Kidney Injury. Medscape Medical News. Available at http://www.medscape.com/viewarticle/822384.. Accessed: April 1, 2014.
Gallagher M, Cass A, Bellomo R, Finfer S, Gattas D, Lee J, et al. Long-term survival and dialysis dependency following acute kidney injury in intensive care: extended follow-up of a randomized controlled trial. PLoS Med. 2014 Feb. 11(2):e1001601. [Medline]. [Full Text].
Billings FT 4th, Pretorius M, Schildcrout JS, Mercaldo ND, Byrne JG, Ikizler TA, et al. Obesity and oxidative stress predict AKI after cardiac surgery. J Am Soc Nephrol. 2012 Jul. 23 (7):1221-8. [Medline]. [Full Text].
Kelz RR, Reinke CE, Zubizarreta JR, Wang M, Saynisch P, Even-Shoshan O, et al. Acute kidney injury, renal function, and the elderly obese surgical patient: a matched case-control study. Ann Surg. 2013 Aug. 258 (2):359-63. [Medline]. [Full Text].
American College of Radiology. ACR Appropriateness Criteria® renal failure. National Guideline Clearinghouse. Available at http://guideline.gov/content.aspx?id=13685. Accessed: March 24, 2011.
Lowes R. FDA OKs NephroCheck to Assess Risk for Acute Kidney Injury. Medscape Medical News. Sep 5 2014. [Full Text].
Tuladhar SM, Püntmann VO, Soni M, Punjabi PP, Bogle RG. Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol. 2009 Mar. 53(3):261-6. [Medline].
Breidthardt T, Christ-Crain M, Stolz D, et al. A combined cardiorenal assessment for the prediction of acute kidney injury in lower respiratory tract infections. Am J Med. 2012 Feb. 125(2):168-75. [Medline].
Hall IE, Coca SG, Perazella MA, et al. Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis. Clin J Am Soc Nephrol. 2011 Dec. 6(12):2740-9. [Medline].
Spahillari A, Parikh CR, Sint K, Koyner JL, Patel UD et al. Serum cystatin C- versus creatinine-based definitions of acute kidney injury following cardiac surgery: a prospective cohort study. Am J Kidney Dis. 2012 Dec. 60(6):922-9. [Medline]. [Full Text].
Nainggolan L. Two Antihypertensives Plus NSAID Ups Risk of Acute Kidney Injury. Two Antihypertensives Plus NSAID Ups Risk of Acute Kidney Injury. Heartwire. Jan 9 2013. [Full Text].
Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ. 2013 Jan 8. 346:e8525. [Medline]. [Full Text].
Lauschke A, Teichgräber UK, Frei U, Eckardt KU. Low-dose' dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006 May. 69(9):1669-74. [Medline].
Macedo E, Mehta RL. When should renal replacement therapy be initiated for acute kidney injury?. Semin Dial. 2011 Mar-Apr. 24(2):132-7. [Medline].
Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3. 359(1):7-20. [Medline]. [Full Text].
Pannu N, Manns B, Lee H, Tonelli M. Systematic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney Int. 2004 Apr. 65(4):1366-74. [Medline].
Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. 2006 Jun 29. 354(26):2773-82. [Medline].
Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, et al. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015 Jun 2. 313 (21):2133-41. [Medline].
Zacharias M, Mugawar M, Herbison GP, Walker RJ, Hovhannisyan K, Sivalingam P, et al. Interventions for protecting renal function in the perioperative period. Cochrane Database Syst Rev. 2013 Sep 11. 9:CD003590. [Medline].
Ho KM, Morgan DJ. Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery. Am J Kidney Dis. 2009 Jan. 53(1):33-40. [Medline].
Acute kidney injury associated with synthetic cannabinoid use--multiple states, 2012. MMWR Morb Mortal Wkly Rep. 2013 Feb 15. 62(6):93-8. [Medline].
Gandhi S, Fleet JL, Bailey DG, et al. Calcium-Channel Blocker–Clarithromycin Drug Interactions and Acute Kidney Injury. JAMA. Nov 2013. [Full Text].
Melville N. Antibiotic and Calcium-Channel Blocker a Fatal Combination. Medscape Medical News. Available at http://www.medscape.com/viewarticle/814306. Accessed: November 20, 2013.
van der Wilden GM, Velmahos GC, Joseph DK, Jacobs L, Debusk MG, Adams CA, et al. Successful Nonoperative Management of the Most Severe Blunt Renal Injuries: A Multicenter Study of the Research Consortium of New England Centers for Trauma. JAMA Surg. 2013 Aug 14. [Medline].
Danziger J, Chen KP, Lee J, Feng M, Mark RG, Celi LA, et al. Obesity, Acute Kidney Injury, and Mortality in Critical Illness. Crit Care Med. 2015 Oct 22. [Medline].
|Stage||GFR** Criteria||Urine Output Criteria||Probability|
|Risk||SCreat† increased × 1.5
GFR decreased >25%
|UO‡ < 0.5 mL/kg/h × 6 h||High sensitivity (Risk >Injury >Failure)|
|Injury||SCreat increased × 2
GFR decreased >50%
|UO < 0.5 mL/kg/h × 12 h|
|Failure||SCreat increased × 3
GFR decreased 75%
SCreat ≥4 mg/dL; acute rise ≥0.5 mg/dL
|UO < 0.3 mL/kg/h × 24 h
anuria × 12 h
|Loss||Persistent acute renal failure: complete loss of kidney function >4 wk||High specificity|
|ESKD*||Complete loss of kidney function >3 mo|
|*ESKD—end-stage kidney disease; **GFR—glomerular filtration rate; †SCreat—serum creatinine; ‡UO—urine output
Note: Patients can be classified by GFR criteria and/or UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in SCreat is less than 3-fold, provided that the new SCreat is greater than 4.0 mg/dL (350 µmol/L) and results from an acute increase of at least 0.5 mg/dL (44 µmol/L).
|Stage||Serum Creatinine Criteria||Urine Output Criteria|
|1||Increase of ≥0.3 mg/dL (≥26.4 µmol/L) or 1.5- to 2-fold increase from baseline||< 0.5 mL/kg/h for >6 h|
|2||>2-fold to 3-fold increase from baseline||< 0.5 mL/kg/h for >12 h|
|3*||>3-fold increase from baseline, or increase of ≥ 4.0 mg/dL (≥35.4 µmol/L) with an acute increase of at least 0.5 mg/dL (44 µmol/L)||< 0.3 mL/kg/h for 24 h or anuria for 12 h|
|*Patients who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.|