History and exam
Key diagnostic factors
Hypotension and/or hypovolaemia is a common cause of reduced kidney perfusion and resulting pre-kidney AKI.[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
[62]Royal College of Physicians. Acute care toolkit 12: acute kidney injury and intravenous fluid therapy. October 2015 [internet publication].
https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
Often due to acute illness (e.g., sepsis and vasodilatation; haemorrhage; vomiting and diarrhoea), particularly in a patient with background risk factors.
Can also result from dehydration due to poor fluid intake, over-diuresis, or insufficient replacement fluids in a hospital inpatient.[3]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. December 2019 [internet publication].
https://www.nice.org.uk/guidance/ng148
Hypovolaemia due to reduced fluid intake is a particular risk for frail, older patients especially those with cognitive or neurological impairment.[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
Hypotension may be absolute (SBP <90 mmHg) or relative to the patient’s usual BP (a drop of >40 mmHg from baseline).
Assessing volume status is a crucial part of your initial examination - signs of hypovolaemia are often present.[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Check:
Peripheral perfusion (capillary refill)
Pulse rate
Blood pressure (including a check for postural hypotension)
Jugular venous pressure
Dry axillae/mucous membranes.
Treat hypovolaemia promptly with an immediate bolus of crystalloid intravenous fluid.[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
[62]Royal College of Physicians. Acute care toolkit 12: acute kidney injury and intravenous fluid therapy. October 2015 [internet publication].
https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Prolonged hypotension can cause pre-kidney AKI to progress to cell damage and acute tubular injury (intrinsic AKI).
AKI is commonly asymptomatic so is easily missed. Whenever a patient presents with an acute illness, ensure your history covers characteristics that increase the risk of AKI. Check for:[17]Mehta R, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004 Oct;66(4):1613-21.
http://www.ncbi.nlm.nih.gov/pubmed/15458458?tool=bestpractice.com
[18]Liaño F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int. 1996 Sep;50(3):811-8.
http://www.ncbi.nlm.nih.gov/pubmed/8872955?tool=bestpractice.com
[67]National Confidential Enquiry into Patient Outcome and Death. Adding insult to injury: a review of care of patients who died in hospital with a primary diagnosis of acute kidney injury (acute renal failure). 2009 [internet publication].
https://www.ncepod.org.uk/2009aki.html
[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
Risk factors[3]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. December 2019 [internet publication].
https://www.nice.org.uk/guidance/ng148
[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Age ≥65 years (frail older people are at particular increased risk).[65]Anathhanam S, Lewington AJ. Acute kidney injury. J R Coll Physicians Edinb. 2013;43(4):323-8; quiz 329.
http://www.ncbi.nlm.nih.gov/pubmed/24350317?tool=bestpractice.com
History of any one or more of chronic kidney disease (CKD), heart failure, liver disease, diabetes, dementia (or any other neurological/cognitive impairment that may result in limited access to oral fluids).
Previous AKI.
Myeloproliferative disorder (e.g., multiple myeloma).[5]Sharfuddin AA, Weisbord SD, Palevsky PM, et al. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, et al, eds. Brenner and Rector's the kidney. 9th ed. Philadelphia, PA: Saunders; 2012.[53]McCarthy CS, Becker JA. Multiple myeloma and contrast media. Radiology. 1992 May;183(2):519-21.
http://www.ncbi.nlm.nih.gov/pubmed/1561361?tool=bestpractice.com
Medication history[3]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. December 2019 [internet publication].
https://www.nice.org.uk/guidance/ng148
[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
[62]Royal College of Physicians. Acute care toolkit 12: acute kidney injury and intravenous fluid therapy. October 2015 [internet publication].
https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
Non-steroidal anti-inflammatory drug (NSAID) or aminoglycoside antibiotic use (nephrotoxic potential - can cause drug-induced interstitial nephritis).
ACE inhibitor/angiotensin-II receptor antagonist use.
Renin-angiotensin system modifying agents reduce the kidney’s ability to adapt to changes in perfusion pressure by lowering efferent glomerular arteriolar tone, making it more difficult for the kidney to maintain glomerular filtration pressure in the event of hypovolaemia/hypotension.[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
Diuretic or any other antihypertensive - particularly if started (or dose changed) in the last 7 days.
Aciclovir, methotrexate, triamterene, indinavir, or sulfonamides (can cause tubular obstruction by forming crystals).[77]Yarlagadda SG, Perazella MA. Drug-induced crystal nephropathy: an update. Expert Opin Drug Saf. 2008 Mar;7(2):147-58.
https://www.doi.org/10.1517/14740338.7.2.147
http://www.ncbi.nlm.nih.gov/pubmed/18324877?tool=bestpractice.com
Recreational drug use.
Over-the-counter drugs and herbal remedies.
Practical tip
AKI is often a ‘silent disease’ so a high index of suspicion is important, particularly in acutely ill patients.[62]Royal College of Physicians. Acute care toolkit 12: acute kidney injury and intravenous fluid therapy. October 2015 [internet publication].
https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
Most patients with AKI present asymptomatically, with non-specific symptoms or with symptoms solely related to the precipitating illness (e.g., sepsis).
A 2009 report from the UK’s National Confidential Enquiry into Patient Outcome and Death (NCEPOD) identified an unacceptable delay in post-admission diagnosis of AKI in 43% of patients who died in hospital from the condition.[67]National Confidential Enquiry into Patient Outcome and Death. Adding insult to injury: a review of care of patients who died in hospital with a primary diagnosis of acute kidney injury (acute renal failure). 2009 [internet publication].
https://www.ncepod.org.uk/2009aki.html
Many cases of AKI are precipitated by a kidney insult, particularly in patients with underlying risk factors. Examples include:[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
[3]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. December 2019 [internet publication].
https://www.nice.org.uk/guidance/ng148
[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
[62]Royal College of Physicians. Acute care toolkit 12: acute kidney injury and intravenous fluid therapy. October 2015 [internet publication].
https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
Sepsis or other acute illness (e.g., acute pancreatitis, burns)
Perform a septic screen and implement your local care bundle (e.g., Sepsis Six) if infection is suspected.[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
[63]Intensive Care Society. Standards and recommendations for the provision of renal replacement therapy on intensive care units in the United Kingdom. 2009.
Hypovolaemia (with or without hypotension)
Nephrotoxins
Exposure within the previous week to iodinated contrast agent
Use of an NSAID or aminoglycoside antibiotic[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
Recent surgery (especially cardiac)
Recent vascular intervention - raises the possibility of cholesterol embolisation (livedo reticularis), contrast-induced AKI.[52]Garg AX, Devereaux PJ, Yusuf S, et al. Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial. JAMA. 2014 Jun 4;311(21):2191-8.
http://jama.jamanetwork.com/article.aspx?articleid=1877182
http://www.ncbi.nlm.nih.gov/pubmed/24886787?tool=bestpractice.com
[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Oliguria is one of the diagnostic criteria for AKI and is an earlier indicator of impaired kidney function than rising creatinine.[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
Anuria suggests either an obstructive cause or severe AKI from a pre-kidney or intrinsic cause.
AKI can also be staged according to the extent to which urine output falls (or serum creatinine rises).[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
Stage the AKI using whichever one of serum creatinine or urine output gives the higher stage.[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
Stage 1 AKI: urine output <0.5 mL/kg/h for at least 6 consecutive hours
Stage 2 AKI: urine output <0.5 mL/kg/h for at least 12 consecutive hours
Stage 3 AKI: urine output <0.3 mL/kg/h for at least 24 consecutive hours or anuria for 12 hours
A higher stage of AKI is associated with a greater risk of death as well as increased likelihood of needing renal replacement therapy (RRT).[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
In practice, accurate and timely measurement of urine output is difficult unless the patient is catheterised.
Routine catheterisation is not recommended.[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
[68]Baum N, Dichoso CC, Carlton CE. Blood urea nitrogen and serum creatinine. Physiology and interpretations. Urology. 1975 May;5(5):583-8.
http://www.ncbi.nlm.nih.gov/pubmed/1093306?tool=bestpractice.com
Lower urinary tract symptoms such as urgency, frequency, or hesitancy are suggestive of a urinary tract obstruction.
Prostatic hyperplasia is a common cause of obstructive AKI in older men.[4]Thomas ME, Blaine C, Dawnay A, et al. The definition of acute kidney injury and its use in practice. Kidney Int. 2015 Jan;87(1):62-73.
http://www.ncbi.nlm.nih.gov/pubmed/25317932?tool=bestpractice.com
Symptoms and signs of volume overload may be seen at presentation if the patient has obstructive AKI or any form of AKI against a background of pre-existing heart failure.
Otherwise the most common cause of volume overload is overenthusiastic fluid resuscitation.[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
Symptoms of volume overload that may be reported at presentation include:
Examination signs in a patient with volume overload might include:
Crackles on auscultation of lungs (suggests pulmonary oedema)
Tachypnoea (suggests fluid overload and/or acidosis).[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Vomiting may cause pre-kidney AKI or can be a later manifestation of AKI-related uraemia.[62]Royal College of Physicians. Acute care toolkit 12: acute kidney injury and intravenous fluid therapy. October 2015 [internet publication].
https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
If present, suspect small-vessel vasculitis (e.g., granulomatosis with polyangiitis, microscopic polyangiitis), or interstitial nephritis.[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Can occur with kidney stones, papillary necrosis, infection, tumour, or acute glomerulonephritis.
Point to an obstructive cause of AKI.[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
[65]Anathhanam S, Lewington AJ. Acute kidney injury. J R Coll Physicians Edinb. 2013;43(4):323-8; quiz 329.
http://www.ncbi.nlm.nih.gov/pubmed/24350317?tool=bestpractice.com
Other diagnostic factors
Orthostatic symptoms and postural hypotension confirmed on blood pressure monitoring are consistent with hypovolaemia and suggest pre-kidney AKI.
May be seen in AKI secondary to renal artery stenosis or a rapidly progressive glomerulonephritis.[18]Liaño F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int. 1996 Sep;50(3):811-8.
http://www.ncbi.nlm.nih.gov/pubmed/8872955?tool=bestpractice.com
[78]Feehally J, Gilmore I, Barasi S, et al. RCPE UK consensus conference statement: Management of acute kidney injury: the role of fluids, e-alerts and biomarkers. J R Coll Physicians Edinb. 2013;43(1):37-8.
https://www.doi.org/10.4997/JRCPE.2013.109
http://www.ncbi.nlm.nih.gov/pubmed/23516690?tool=bestpractice.com
[79]Academy of Medical Royal Colleges. Acute kidney injury: a competency framework. Defining the role of the expert clinician. November 2011 [internet publication].
https://www.aomrc.org.uk/reports-guidance/acute-kidney-injury-1111/
[9]Think Kidneys. Acute kidney injury best practice guidance: responding to AKI warning stage test results for adults in primary care. April 2016 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2016/10/RespondingtoAKI-Warning-Stage-Test-Results-for-Adults-in-Primary-Care.pdf
A change in mental status is usually secondary to a primary kidney insult (e.g., sepsis) that precipitated AKI.
Confusion can also result from encephalopathy in a patient with AKI-related uraemia.[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
Acute pericarditis is a complication associated with severe AKI and worsening uraemia (most often on a background of pre-existing CKD).[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
[65]Anathhanam S, Lewington AJ. Acute kidney injury. J R Coll Physicians Edinb. 2013;43(4):323-8; quiz 329.
http://www.ncbi.nlm.nih.gov/pubmed/24350317?tool=bestpractice.com
The presence of a pericardial friction rub on examination is an indication for renal replacement therapy (although it may be absent if there is a significant effusion).[1]Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.
https://kdigo.org/guidelines/acute-kidney-injury/
[13]Kanagasundaram S, Ashley C, Bhojani S, et al. Renal Association clinical practice guideline acute kidney injury (AKI). August 2019 [internet publication].
https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf
Asterixis is another possible symptom of uraemia.
Suspect intrinsic AKI secondary to rhabdomyolysis and tubular toxicity from myoglobin in the setting of acidosis.
Suspect an intrinsic cause of AKI (e.g., small vessel vasculitis or anti-glomerular basement membrane antibody disease).[64]Think Kidneys. Recommended minimum requirements of a care bundle for patients with AKI in hospital. December 2015 [internet publication].
https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2015/12/AKI-care-bundle-requirements-FINAL-12.07.16.pdf
Suspect renovascular disease.