The older term is 'acute renal failure' (ARF). The diagnosis of acute kidney injury (AKI) relies on decreased glomerular filtration rate (GFR), increased serum creatinine or cystatin C, or oliguria.
The consensus definition and classification RIFLE system is a mnemonic for three levels of severity - Risk, Injury, and Failure - and two outcomes - persistent ARF termed Loss and End-stage kidney disease.
Causes of acute kidney injury
- Volume depletion (eg haemorrhage, severe vomiting or diarrhoea, burns, inappropriate diuresis)
- Oedematous states: cardiac failure, cirrhosis, nephrotic syndrome
- Hypotension (eg cardiogenic shock, sepsis, anaphylaxis)
- Cardiovascular (eg severe cardiac failure, arrhythmias)
- Renal hypoperfusion: non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors, angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor antagonists, abdominal aortic aneurysm, renal artery stenosis or occlusion, hepatorenal syndrome
- Intrinsic acute kidney injury (AKI):
- Glomerular disease: glomerulonephritis, thrombosis, haemolytic uraemic syndrome
- Tubular injury: acute tubular necrosis (ATN) following prolonged ischaemia; nephrotoxins (eg aminoglycosides, radiocontrast media, myoglobin, cisplatin, heavy metals, light chains in myeloma kidney)
- Acute interstitial nephritis due to drugs (eg NSAIDs), infection or autoimmune diseases
- Vascular disease: vasculitis (usually associated with antineutrophil cytoplasmic antibody), cryoglobulinaemia, polyarteritis nodosa, thrombotic microangiopathy, cholesterol emboli, renal artery stenosis, renal vein thrombosis, malignant hypertension
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- Recent studies have found an overall incidence of acute kidney injury (AKI) of almost 500 per million per year and the incidence of AKI needing dialysis being more than 200 per million per year.
- Prerenal AKI and ischaemic acute tubular necrosis (ATN) together account for 75% of the cases of AKI.
People with the following comorbid conditions are at a higher risk for developing AKI:
- Vascular disease
- Pre-existing renal impairment
- Congestive cardiac failure
- Chronic infection
- Myeloproliferative disorder
The presentation will depend on the underlying cause and severity of AKI. There may be no symptoms or signs, but oliguria (urine volume less than 400 mL/24 hours) is common. There is an accumulation of fluid and nitrogenous waste products demonstrated by a rise in blood urea and creatinine.
- Urine output:
- AKI is usually accompanied by oliguria or anuria, but polyuria may occur.
- Abrupt anuria suggests an acute obstruction, acute and severe glomerulonephritis, or acute renal artery occlusion.
- Gradual diminution of urine output may indicate a urethral stricture or bladder outlet obstruction, eg benign prostatic hyperplasia.
- Nausea, vomiting
- Abdomen: may reveal a large, painless bladder typical of chronic urinary retention
- Dehydration with postural hypotension and no oedema
- Fluid overload with raised JVP, pulmonary oedema and peripheral oedema
- Pallor, rash, bruising: petechiae, purpura, and nosebleeds may suggest inflammatory or vascular disease, emboli or disseminated intravascular coagulation
- Pericardial rub
- Distinguish acute and chronic kidney disease (CKD):
- Factors that suggest CKD include long duration of symptoms, nocturia, absence of acute illness, anaemia, hyperphosphataemia, hypocalcaemia.
- Previous creatinine measurements if available are very useful.
- Reduced renal size and cortical thickness on ultrasound is characteristic of CKD (renal size is typically preserved in patients with diabetes).
- Exclude urinary tract obstruction:
- History of previous stones or symptoms of bladder outflow obstruction
- Palpable bladder
- Complete anuria suggests renal tract obstruction
- Renal ultrasound is the best method to detect dilatation of the renal pelvis and calyces (obstruction may be present without dilatation, especially in patients with malignancy)
- Consider hypovolaemia:
- Low venous pressure and a postural fall in blood pressure
- Disproportionate rise in the plasma urea:creatinine ratio
- Low urinary sodium concentration (but use of diuretics makes urinary indices unhelpful)
- Evidence of renal parenchymal disease:
- Features of underlying systemic disease, eg rashes, arthralgia, myalgia
- Use of antibiotics and NSAIDs
- Urine dipstick and microscopy: dipstick blood or protein, or dysmorphic red cells, red cell casts (suggestive of glomerulonephritis), or eosinophils (suggestive of acute interstitial nephritis) on microscopy
- Consider major vascular occlusion:
- Occlusion of a normal renal artery results in loin pain and haematuria, occlusion of a previously stenosed renal artery may be asymptomatic; acute renal failure may be precipitated by occlusion (thrombotic or embolic) of the artery supplying the remaining kidney.
- Renal asymmetry on imaging is suggestive, especially in a patient with known vascular disease elsewhere.
- Risk factors include use of ACE inhibitors and diuretics in a patient with renal artery stenosis, hypotension or instrumentation of the renal artery or aorta.
- Complete anuria occurs.
- Occlusion of a previously normal renal artery is uncommon, mostly caused by embolisation from a central source.
- Chronic kidney disease: factors that suggest CKD include:
- Long duration of symptoms
- Absence of acute illness
- Hyperphosphataemia, hypocalcaemia (but similar laboratory findings may complicate acute kidney injury (AKI))
- Reduced renal size and cortical thickness on renal ultrasound (but renal size is typically preserved in patients with diabetes
- Acute on chronic renal failure
- Urinalysis: blood and/or protein suggests a renal inflammatory process; microscopy for cells, casts, crystals; red cell casts diagnostic in glomerulonephritis; tubular cells or casts suggest acute tubular necrosis (ATN)
- Urine osmolality: osmolality of urine is over 500 mmol/kg if the cause is pre-renal and 300 mmol/kg or less if it is renal; patients with ATN lose the ability to concentrate and dilute the urine and will pass a constant volume with inappropriate osmolality
- Biochemistry: Traditional blood (creatinine, blood urea nitrogen) and urine markers of kidney injury (epithelial cells, tubular casts, fractional excretion of Na+, urinary concentrating ability, etc.) are insensitive and nonspecific for the diagnosis of acute kidney injury (AKI). Work continues to find an appropriate biomarker, eg cystatin C (Cys-C).
- Serial urea, creatinine, electrolytes: important metabolic consequences of AKI include hyperkalaemia, metabolic acidosis, hypocalcaemia, hyperphosphataemia (serum urea is a poor marker of renal function because it varies significantly with hydration diet, it is not produced constantly and it is reabsorbed by the kidney).
- Serum creatinine has significant limitations. The level can remain within the normal range despite the loss of over 50% of renal function.
- Creatine kinase, myoglobinuria: markedly elevated creatine kinase and myoglobinuria suggest rhabdomyolysis.
- Cys-C: over the past decade serum Cys-C has been extensively studied and found to be a sensitive serum marker of GFR and a stronger predictor than serum creatinine of risk of death and cardiovascular events in older patients.
- C reactive protein: nonspecific marker of infection or inflammation.
- Serum immunoglobulins, serum protein electrophoresis, Bence Jones' proteinuria: immune paresis, monoclonal band on serum protein electrophoresis, and Bence Jones' proteinuria suggest myeloma.
- Antinuclear antibody (ANA): ANA positive in systemic lupus erythematosus (SLE) and other autoimmune disorders; anti-double stranded (anti-dsDNA) antibodies more specific for SLE; anti-dsDNA antibodies; antineutrophil cytoplasmic antibody (ANCA) (associated with systemic vasculitis; classical antineutrophil cytoplasmic antibodies (c-ANCA) and antiproteinase 3 (anti-PR3) antibodies associated with Wegener's granulomatosis; protoplasmic-staining antineutrophil cytoplasmic antibodies (p-ANCA) and antimyeloperoxidase (anti-MPO) antibodies present in microscopic polyangiitis), anti-PR3 antibodies, anti-MPO antibodies.
- Complement concentrations: low in SLE, acute postinfectious glomerulonephritis, cryoglobulinaemia.
- Antiglomerular basement membrane (anti-GBM) antibodies: present in Goodpasture's disease.
- Antistreptolysin O and anti-DNAse B titres: high after streptococcal infection.
- Renal ultrasonography: renal size, symmetry, evidence of obstruction
- Chest X-ray (pulmonary oedema); abdominal X-ray if renal calculi are suspected
- Contrast studies such as intravenous urogram (IVU) and renal angiography should be avoided because of the risk of contrast nephropathy
- Doppler ultrasound of the renal artery and veins: assessment of possible occlusion of the renal artery and veins
- Magnetic resonance angiography: for more accurate assessment of renal vascular occlusion
- ECG: recent myocardial infarction, tented T waves in hyperkalaemia
- Renal biopsy
Principles of management of acute kidney injury (AKI)
- Advice from a nephrologist should be sought for all cases of acute renal failure, as early consultation can improve outcomes.
- No drug treatment has been shown to limit the progression of, or speed up recovery from, AKI.
- Identify and correct prerenal and postrenal factors.
- Optimise cardiac output and renal blood flow.
- Review drugs: stop nephrotoxic agents; adjust doses and monitor concentrations where appropriate.
- Accurately monitor fluid balance and daily body weight.
- Identify and treat acute complications (hyperkalaemia, acidosis, pulmonary oedema).
- Optimise nutritional support: adequate calories, minimal nitrogenous waste production, potassium restriction.
- Identify and aggressively treat infection; minimise indwelling lines; remove bladder catheter if anuric.
- Identify and treat bleeding tendency: prophylaxis with proton pump inhibitor (PPI) or h2-receptor antagonist (H2RA), transfuse if required, avoid aspirin.
- Initiate dialysis before uraemic complications emerge.
- Renal specialists are not necessary for provision of renal replacement therapy, as this can be initiated promptly in most intensive treatment units (ITUs) by continuous venovenous haemofiltration.
Accurate control of fluid balance (avoid volume overload or depletion)
- Accurate measurement of urine output is essential to prevent volume overload or depletion.
- Most patients are oliguric and should be provided with a volume of fluid equal to the output on the previous day, plus an extra 500 mL for insensible losses (more if pyrexia is present). Twice daily clinical fluid balance assessment is required. Fluid-balance charts are frequently inaccurate and unthinking adherence to the output plus 500 mL rule may be inappropriate.
- The situation may change rapidly and so daily clinical assessment, measurement of body weight and central venous pressure (CVP) monitoring are required.
- Doses of furosemide may have to be in hundreds of milligrams per day. There is no evidence to suggest that the use of loop diuretics reduces mortality, reduces length of ITU/hospital stay, or increases the recovery of renal function.
- Pulmonary oedema: requires high concentration oxygen, IV morphine, IV high doses (250 mg) furosemide given over 1 hour, and IV nitrates. May also require haemodialysis or haemofiltration if not responding to these measures. Venesection and continuous positive airways pressure may be useful if the patient is in extremis.
- If there is hypotension both noradrenaline and vasopressin may be beneficial.
- There is no evidence for the use of low-dose dopamine infusions.
Daily measurement of serum electrolytes, potassium and sodium restriction, nutritional support
- Potassium restriction is nearly always necessary and is typically limited to less than 50 mmol/day.
- Acute hyperkalaemia may be managed with IV calcium gluconate and dextrose/insulin infusions.
- In the slightly longer term, potassium-binding resins can be used if dialysis is not immediately available.
- Sodium intake should be restricted to about 80 mmol/day, depending on losses.
- Acidosis may be limited by protein restriction, though a daily intake of at least approximately 1 g of high-quality protein per kilogram of body weight is necessary to maintain adequate nutrition.
- It is important to maintain adequate nutrition, preferably via the enteral route, but using parenteral nutrition if necessary.
- Excretion of phosphate is impaired in renal failure; hyperphosphataemia should be treated with calcium carbonate or other phosphate binders.
- Nitrogen balance can be complex, especially with a hypercatabolic state and possible gastrointestinal bleeding, and diarrhoea.
- Sodium bicarbonate may be used cautiously to treat acidosis, but may worsen sodium overload.
- Hyperglycaemia adversely affects the prognosis for patients with AKI; there has been shown to be a reduction in mortality and morbidity of critically ill patients with strict control of blood glucose concentration.
Prevention of infection
- Patients in renal failure are susceptible to infection.
- Infection is a significant cause of mortality. Therefore strict sepsis control is essential; avoidance of intravenous lines, bladder catheters, and respirators is recommended.
Active bleeding may require:
- Fresh frozen plasma and platelets
- Blood transfusion
- Intravenous desmopressin (increases factor VIII coagulant activity; shown in AKI to shorten prolonged bleeding time; repeated doses have a lesser effect)
Prevention of gastrointestinal haemorrhage
- Gastrointestinal haemorrhage is a potential cause of morbidity in AKI, and so prophylactic treatment to reduce gastric acid secretion is generally indicated.
Careful drug dosing and avoidance of nephrotoxic drugs
- Doses must be adjusted and drug levels monitored accordingly.
- Nephrotoxic drugs, such as NSAIDs and aminoglycosides, should be avoided.
Specific treatment of underlying intrinsic renal disease where appropriate
- Acute renal artery thrombosis (of a single functioning kidney) may be treated surgically, or by angioplasty and stenting.
- In rhabdomyolysis with myoglobulinuria, alkaline diuresis may prevent the development of severe renal failure, but must be undertaken with care in oliguric patients.
- Acute tubulointerstitial nephritis may respond to a short course of high-dose corticosteroids, though no controlled trials have been undertaken to support this approach.
- AKI due to crescentic glomerulonephritis may respond to treatment with prednisolone and cyclophosphamide, together with the addition of plasma exchange.
- Haemolytic uraemic syndrome may respond to plasma exchange with fresh frozen plasma.
Dialysis or haemofiltration
- In oliguric or anuric patients, the fluid intake required for feeding generally means that dialysis will be necessary.
- Peritoneal dialysis is usually only performed when haemodialysis is unavailable.
- In patients who are haemodynamically unstable, continuous dialysis techniques (eg haemodiafiltration) are better tolerated than intermittent haemodialysis and allow more effective control of fluid balance.
- Indications for dialysis in AKI:
- Urea >25-30 mmol/L and creatinine >500-700 micromol/L, unless there is clear evidence that recovery is underway
- Refractory hyperkalaemia
- Intractable fluid overload
- Acidosis producing circulatory compromise
- Overt uraemia manifesting as encephalopathy, pericarditis, or uraemic bleeding
- Oliguria with urine output less than 200 mL/12 hours
- Acidaemia (pH<7.0)
- Toxicity with drugs that can be dialysed
Life-threatening complications include:
- Volume overload (severe pulmonary oedema)
- Metabolic acidosis
- Spontaneous haemorrhage, eg gastrointestinal
- When AKI is severe enough to need dialysis, in-hospital mortality is around 50%, and it may exceed 75% in the context of sepsis or in critically ill patients.
- The prognosis is closely related to the underlying cause. In prerenal failure, correction of volume depletion, using central venous pressure monitoring when necessary, should result in rapid recovery of renal function. However, once acute tubular necrosis (ATN) has developed, and in other causes of acute kidney injury (AKI), the patient will often be oliguric for several days or weeks.
- If there is not a significant return of renal function within 6 to 8 weeks this usually means that there is end-stage renal failure (ESRF) but, rarely, late recovery can occur.
- Prognosis is improved by rapid and aggressive treatment. This includes correcting prerenal causes like hypovolaemia or inserting stents to bypass obstruction in postrenal causes.
- Patients who need dialysis have a higher mortality but this is a reflection of the condition rather than a result of the treatment.
- Within an intensive care setting, mortality varies from 7.5% to 40% and outside of intensive care from zero to 17%.
- The Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system indicates prognosis. In those who have a score between 10 and 19 the mortality rate is 60% but with a score above 40 it approaches 100%.
- Another system to help indicate prognosis and to aid classification for research purposes is called RIFLE and was developed by the Acute Dialysis Quality Initiative Workgroup. The first 3 items are Risk, Injury and Failure. The last two are outcomes or Loss and End-stage renal failure.
- Indicators of poor prognosis include older age, multiple organ failure, oliguria, hypotension, number of transfusions and acute on chronic renal failure.
- Identification of patients at risk.
- Maintain adequate blood pressure and volume status.
- Avoid potentially nephrotoxic agents, especially NSAIDs, ACE inhibitors or angiotensin-II receptor blockers.
- Acetylcysteine plus volume expansion may be used for prevention of contrast nephropathy.
Further reading & references
- Lameire N, Van Biesen W, Vanholder R; Acute kidney injury. Lancet. 2008 Nov 29;372(9653):1863-5.
- Hilton R; Acute renal failure. BMJ. 2006 Oct 14;333(7572):786-90.
- Lameire N, Van Biesen W, Vanholder R; Acute renal failure. Lancet. 2005 Jan 29-Feb 4;365(9457):417-30.
- Vaidya VS, Ferguson MA, Bonventre JV; Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008;48:463-93.
- Clinical practice guidelines - acute kidney injury, Renal Association (April 2008)
- Oxford Textbook of Medicine 4th edition; Section 20.6, Acute Renal Failure.
- Davis A, Gooch I; Best evidence topic report. The use of loop diuretics in acute renal failure in critically ill patients to reduce mortality, maintain renal function, or avoid the requirements for renal support. Emerg Med J. 2006 Jul;23(7):569-70.
- Bagshaw SM, Delaney A, Haase M, et al; Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Crit Care Resusc. 2007 Mar;9(1):60-8.
- Lameire NH, De Vriese AS, Vanholder R; Prevention and nondialytic treatment of acute renal failure. Curr Opin Crit Care. 2003 Dec;9(6):481-90.
- Vigano GL, Mannucci PM, Lattuada A, et al; Subcutaneous desmopressin (DDAVP) shortens the bleeding time in uremia. Am J Hematol. 1989 May;31(1):32-5.
- Agraharkar M; Acute renal failure, eMedicine, Aug 2009.
- Bellomo R, Ronco C, Kellum JA, et al; 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. Epub 2004 May 24.
|Original Author: Dr Colin Tidy||Current Version: Dr Hayley Willacy|
|Last Checked: 21/05/2010||Document ID: 1772 Version: 22||© EMIS|
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