Definitions of acute renal failure range from severe (i.e. requiring dialysis) to slight increases in serum creatinine concentration (e.g. of 44.2 micromol/L). In the absence of a universal definition, acute renal failure is often defined as a significant deterioration in renal function occurring over hours or days. There may be no symptoms or signs, but oliguria (urine volume less than 400 mL/24 h) is common. There is an accumulation of fluid and nitrogenous waste products demonstrated by a rise in blood urea and creatinine.
ARF may result from:
• Poor perfusion of the kidneys (prerenal)
• Intrinsic renal disease
• Urinary tract obstruction (postrenal)
Causes of acute renal failure
o Volume depletion (e.g. severe vomiting or diarrhoea, burns, inappropriate diuretics)
o Hypotension (e.g. trauma, gastrointestinal haemorrhage)
o Cardiovascular (e.g. severe cardiac failure, arrhythmias)
o Drugs affecting renal perfusion (e.g. NSAIDs, contrast media, ciclosporin, ACE inhibitors)
o Hepatorenal syndrome.
• Intrinsic ARF
o Acute tubular necrosis following prolonged ischaemia
o Nephrotoxins (e.g. aminoglycosides, myoglobin, cisplatin, heavy metals, light chains in myeloma kidney)
o Acute interstitial nephritis due to drugs, infection or autoimmune diseases
o Glomerular damage (e.g. crescentic glomerulonephritis, vasculitis, haemolytic uraemic syndrome)
o Vascular damage (e.g. renal artery occlusion, renal vein thrombosis, cholesterol emboli, scleroderma renal crisis, malignant hypertension).
o Ureteric obstruction (e.g. renal calculi, tumours, blood clots, retroperitoneal fibrosis)
o Bladder outlet obstruction (e.g. prostatic hypertrophy, bladder carcinoma).
• Acute renal failure is common, but the incidence depends on the definition used and the population studied. In a community-based study in the UK, there were 172 cases per million adults per year of severe acute renal failure (serum creatinine concentration greater than 500 micromol/L), with 22 per million receiving acute dialysis1.
• ARF is far more common in the elderly.
• Prerenal ARF and ischaemic acute tubular necrosis together account for 75% of the cases of acute renal failure1.
Risk Factors People with the following comorbid conditions are at a higher risk for developing ARF:
• Congestive cardiac failure
• Chronic infection
• Myeloproliferative disorder.
Presentation The presentation will depend on the underlying cause and severity of acute renal failure. The first indication may be a raised urea and creatinine on a blood test in a patient with non-specific symptoms and signs.
• Urine output:
o Abrupt anuria suggests an acute obstruction, acute and severe glomerulonephritis, or acute renal artery occlusion.
o Gradual diminution of urine output may indicate a urethral stricture or bladder outlet obstruction, e.g. 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 nose bleeds may suggest inflammatory or vascular disease, emboli or disseminated intravascular coagulation.
• Pericardial rub.
• Chronic renal failure:
o Anaemia, decreased calcium and raised phosphate may develop within days and so their presence does not necessarily help to distinguish ARF from CRF, but their absence suggests ARF.
o Making the distinction between acute renal failure and chronic renal failure can be very difficult. A history of chronic symptoms of fatigue, weight loss, anorexia, nocturia, and pruritus all suggest chronic renal failure. Previously abnormal blood tests may also give evidence for chronic renal failure.
o Renal ultrasound: in acute on chronic renal failure, renal abnormalities, such as small kidneys in chronic glomerulonephritis or large cystic kidneys in adult polycystic kidney disease, will almost always be present.
• Acute on chronic renal failure.
• Assessment of renal function
o Serum urea is poor marker of renal function, because it varies significantly with hydration diet, it is not produced constantly and it is reabsorbed by the kidney.
o Serum creatinine also has significant limitations. The level can remain within the normal range despite the loss of over 50% of renal function.
o A gold-standard measurement is an isotopic GFR, but this is expensive and not widely available.
o The GFR may be estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) equation2:
? GFR (ml/min/1.73 m2) = 186 x [(Serum Creatinine micromol/l/88.4)-1.154] x [age (years)-0.203] x 0.742 if female, and x 1.21 if African American.
o Prediction tables can be used to estimate GFR from serum creatinine, age, gender and ethnicity or by using an online GFR calculator based on this equation (see below for link).
• Urinanalysis and microscopy:
o Tubular cells or casts suggest acute tubular necrosis.
o Glomerulonephritis: suggested by brown urine with haemoglobin or myoglobin. Usually causes a nephritic picture, with red blood cells that may be dysmorphic, white blood cells and red cell casts.
o Proteinuria may also suggest acute interstitial nephritis, tubular necrosis and vascular diseases.
• Urine osmolality:
o Osmolarity of urine is over 500 mOsm/kg if the cause is pre-renal and 300 mOsm/kg or less if it is renal.
o Patients with acute tubular necrosis lose the ability to concentrate and dilute the urine, and will pass a constant volume with inappropriate osmolality.
• Urinary electrolytes:
o Can give an indication of activity of the renal tubules. In pre-renal failure, the urinary sodium tends to be below 20 mmol/L (tends to be above 40 mmol/L in acute tubular necrosis), urine osmolality tends to be above 500 mosm/L (tends to be below 350 in ATN), urine/plasma urea tends to be above 8 (below 3 in ATN) and urine/plasma creatinine tends to be above 40 (below 20 in ATN).
o Fractional excretion of sodium (FENa):
? The formula is: (Urine Na/ plasma Na)/ (urine creatinine/ plasma creatinine) x100.
? It can be misleading if diuretics are used or if there is not oliguria.
? The figure is usually under 1% if the cause is pre-renal and over 2% if it is renal3.
? However in nephropathy caused by radiological contrast medium and severe burns, the fractional excretion of sodium will usually be below 1%.
• Blood tests
o Full blood count and blood film: may show features suggestive of haemolytic anaemia or thrombocytopenia.
o Blood urea, electrolytes and creatinine
o Liver function tests: abnormal in hepatorenal syndrome
o Serum amylase
o Blood cultures
o Immunology: autoantibody tests for SLE including antinuclear antibody, antineutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane; antistreptolycin O titre (ASOT).
o Serum and urine electrophoresis.
o Recent myocardial infarction
o Tented T waves in hyperkalaemia.
• Renal ultrasound: quick and non-invasive study that can help detect obstruction.X-rays: chest x-ray (pulmonary oedema); abdominal x-ray if renal calculi are suspected. Contrast studies such as IVU and renal angiography should be avoided because of the risk of contrast nephropathy.
• Doppler ultrasound of the renal artery and veins: for assessment of possible occlusion of the renal artery and veins.
• Magnetic resonance angiography: for more accurate assessment of renal vascular occlusion.
• Renal biopsy.
Management The NSF lists a number of markers of good practice. With regard to acute renal failure these are largely prompt identification with rapid referral for appropriate treatment.
• Accurate control of fluid balance (avoid volume overload or depletion)
o Accurate measurement of urine output is essential to prevent volume overload or depletion.
o Most patients are oliguric and should generally be provided with a volume of fluid equal to the output on the previous day, plus at the very least an extra 500 mL if pyrexia is present.
o The situation may change rapidly and so daily clinical assessment, measurement of body weight and CVP monitoring are required.
o Diuretics do not alter the course or outcome of ARF4 but high dose diuretics may convert oliguric ARF to non-oliguric ARF, which is worthwhile if dialysis is not readily available. Doses of frusemide may have to be in hundreds of milligrams per day. There is an increased mortality rate in those who receive diuretics but this may reflect severity of illness rather than an adverse effect. The role of diuretics requires further evaluation.
o Pulmonary oedema: required high concentration oxygen, IV morphine, IV high doses (250 mg) frusemide given over 1 hour. May also require urgent haemodialysis or haemofiltration, continuous positive airways pressure ventilation and venesection (100-200 mL) if the patient is in extremis.
o If there is hypotension both noradrenaline and vasopressin may be beneficial5.
o There is no evidence for the use of low-dose dopamine infusions.
• Daily measurement of serum electrolytes, potassium and sodium restriction, nutritional support
o Potassium restriction is nearly always necessary and is typically limited to less than 50 mmol/day.
o Acute hyperkalemia may be managed with dextrose/insulin infusions and calcium gluconate.
o In the slightly longer term, potassium-binding resins can be used if dialysis is not immediately available.
o Sodium intake should be restricted to about 80 mmol/day, depending on losses.
o 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.
o It is important to maintain adequate nutrition, preferably via the enteral route, but using parenteral nutrition if necessary.
o Excretion of phosphate is impaired in renal failure and so dietary restriction is required. Renal failure with polyuria intravenous supplementation of fluid, potassium and phosphate.
o Nitrogen balance can be complex, especially with a hyper catabolic state and possible gastrointestinal bleeding, and diarrhoea.
o Sodium bicarbonate may be used to treat acidosis, but may worsen sodium overload.
• Prevention of infection
o Patients in renal failure are susceptible to infection.
o Sepsis causes 30% to 70% of deaths in patients with acute tubular necrosis. Therefore strict sepsis control is essential., avoidance of intravenous lines, bladder catheters, and respirators is recommended.
• Impaired haemostasis: Active bleeding may require:
o Fresh frozen plasma and platelets
o Blood transfusion
o Intravenous desmopressin: increases factor VIII coagulant activity. Shown in acute renal failure to shorten prolonged bleeding time. Repeated doses have a lesser effect.
• Prevention of gastrointestinal haemorrhage
o Gastrointestinal haemorrhage is a potential cause of morbidity in ARF, prophylactic treatment to reduce acid secretion is generally indicated.
• Careful drug dosing and avoidance of nephrotoxic drugs
o Doses must be adjusted and drug levels monitored accordingly.
o Nephrotoxic drugs, such as NSAIDs and aminoglycosides, should be avoided.
• Specific treatment of underlying intrinsic renal disease where appropriate
o Acute renal artery thrombosis (of a single functioning kidney) may be treated surgically, or by angioplasty and stenting.
o In rhabdomyolysis with myoglobulinuria, alkaline diuresis may prevent the development of severe renal failure, but must be undertaken with care in oliguric patients.
o Acute tubulointerstitial nephritis may respond to a short course of high-dose corticosteroids, though no controlled trials have been undertaken to support this approach.
o ARF due to crescentic glomerulonephritis may respond to treatment with prednisolone and cyclophosphamide, together with the addition of plasma exchange.
o Haemolytic uremic syndrome may respond to plasma exchange with fresh frozen plasma.
• Dialysis or haemofiltration
o In oliguric or anuric patients, the fluid intake required for feeding generally means that dialysis will be necessary.
o Peritoneal dialysis is usually only performed when haemodialysis is unavailable.
o In patients who are haemodynamically unstable, continuous dialysis techniques (e.g. haemodiafiltration) are better tolerated than intermittent haemodialysis and allow more effective control of fluid balance.
o Indications for dialysis in acute renal failure
? Presence of clinical features of uraemia (e.g. pericarditis gastritis, hypothermia, fits or encephalopathy)
? Fluid retention leading to pulmonary oedema: inability to reduce excess volume with diuretics with urine volume under 200ml in 12 hours
? Severe hyperkalaemia (potassium above 6.5mmol/L) unresponsive to medical management
? Serum sodium above 155mmol/L or below 120 mmol/L
? Severe acid-base disturbance (pH under 7.0) that cannot be controlled by sodium bicarbonate
? Severe renal failure (urea greater than 30 mmol/L, creatinine greater than 500 micromol/L.
? Toxicity with drugs that can be dialysed.
• 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 ATN has developed, and in other causes of ARF, 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 but rarely late recovery can occur.
• Survival in ARF depends on the cause, and mortality remains high (40-80%) in patients with multiple organ failure. Death is likely if ARF is associated with failure of more than three other organ systems6.
• In patients acquiring ARF in the community, mortality is much lower (10-30%).
• Prognosis is improved by rapid and aggressive treatment. This includes correcting pre-renal causes like hypovolaemia or inserting stents to bypass obstruction in post-renal causes.
• Patients who need dialysis have a higher mortality but this is a reflection of the condition rather than a result of the treatment.
• Recovery from glomerulonephritis is variable. Patients usually recover if treated early, but are likely to remain dependent on dialysis if treated late or inadequately.
• 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%7.
• 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 failure8.
• Indicators of poor prognosis include older age, multiple organ failure, oliguria, hypotension, number of transfusions and acute on chronic renal failure.
1. Lameire N et al; Acute renal failure. Lancet 2005 Jan 29-Feb 4;365(9457):417-30.
2. Levey AS et al; Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999; 130:461-70.
3. Schrier RW et al; Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest; 2004 Aug;114(4):598.
4. Uchino S, Doig GS, Bellomo R, et al; Diuretics and mortality in acute renal failure.;Crit Care Med 2004 Aug;32(8):1669-77.
5. Lameire NH, De Vriese AS, Vanholder R; Prevention and non-dialytic treatment of acute renal failure.;Curr Opin Crit Care 2003 Dec;9(6):481-90.
6. Chertow GM, Christiansen CL, Cleary PD, et al; Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.;Arch Intern Med 1995 Jul 24;155(14):1505-11.
7. Knaus WA, Harrell FE Jr, Lynn J, et al; The SUPPORT prognostic model. Objective estimates of survival for seriously ill hospitalized adults. Study to understand prognoses and preferences for outcomes and risks of treatments.;Ann Intern Med 1995 Feb 1;122(3):191-203.