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Acute kidney injury
ACUTE MEDICINE II
Acute kidney injury
Key points
Sian Finlay
C
The term ‘acute kidney injury’ has replaced ‘acute renal failure’
C
Small rises in serum creatinine are associated with adverse patient outcomes including increased mortality
C
A universal definition and staging system has been proposed to reflect the spectrum of illness severity and to facilitate standardized clinical research
C
Many patients with AKI can be effectively managed by simple prompt interventions by non-specialists
Michael C Jones
Abstract It is well established that acute renal failure is associated with a significant increase in mortality, but it has recently become apparent that even relatively small rises in serum creatinine are associated with adverse patient outcomes. The term ‘acute kidney injury’ (AKI) was developed to reflect this broader spectrum of renal injury, ranging from patients with small changes in blood chemistry to those with dialysis-dependent renal failure. A universal definition and staging system for AKI has been proposed by the international guideline group Kidney Diseases: Improving Global Outcomes International. This definition allows earlier recognition of patients with AKI and facilitates standardized clinical research. This article discusses a practical approach to managing a patient with AKI, with emphasis on optimizing physiological parameters and rapidly identifying patients who require specialist nephrology input.
that AKI is common in critical illness, with 4.9% of patients admitted to an intensive care unit requiring renal replacement therapy (RRT). Recent evidence shows that it is present in 18% to 22% of patients of the general hospital patient population.3 AKI is not simply a marker of severe illness but an independent risk factor for mortality. The mechanism unclear, but it may be due to an increased likelihood of complications, such as bleeding and sepsis. Mortality estimates range from 10% in patients with uncomplicated AKI to 80% in those with multiorgan failure.4
Keywords Acute kidney injury; KDIGO (Kidney Diseases: Improving Global Outcomes International); risk factors
Causes of AKI AKI is most frequently caused by renal hypoperfusion, sepsis or nephrotoxic drugs (Table 2). Urinary tract obstruction is common, especially in elderly men and patients with malignancy, and must always be excluded if the cause of AKI is unclear. In hospitalized patients, the cause is often multifactorial. A small proportion of patients with AKI have intrinsic renal disease, such as acute interstitial nephritis or glomerulonephritis that requires urgent specialist assessment and therapy. One of the key goals when assessing a patient with AKI is to rapidly identify this group and obtain prompt nephrology input.
Introduction It is now recognized that relatively small rises in serum creatinine are associated with adverse patient outcomes,1 including increased mortality and length of hospital stay. The term ‘acute kidney injury’ (AKI) was developed to reflect this spectrum of renal injury, ranging from patients with small changes in blood chemistry to those with dialysis-dependent renal failure. The Kidney Diseases: Improving Global Outcomes International (KDIGO)2 guideline group defines and stages AKI as in Table 1. Historically, it has been difficult to clarify the incidence of AKI because of the lack of consensus on its definition. It is known
Approach to the patient with AKI A focused history often provides clues to the cause. Patients should be asked specifically about: excessive fluid losses, e.g. diarrhoea or vomiting, highoutput stomas recent fluid intake urinary tract symptoms (suggestive of urinary tract infection or obstruction) history of malignancy, especially pelvic or prostatic detailed drug history including over-the-counter drugs and herbal remedies symptoms suggestive of sepsis features suggestive of a systemic disease: fever rash arthralgia or arthritis myalgia lethargy or malaise uveitis
Sian Finlay MB ChB BMSc(Hons) PhD FRCP(Ed) is an Acute Physician in the Department of Medicine, Dumfries and Galloway Royal Infirmary, Dumfries, and Clinical Director for Medicine at Dumfries and Galloway Royal Infirmary, Scotland, UK. She completed a PhD at the University of Aberdeen studying the genetic modification of macrophages. Her main clinical interests are acute kidney injury and sepsis, and she is author of the Acute Kidney Injury Competency Framework (Academy of Medical Royal Colleges, 2011). Competing interests: none declared. Michael C Jones BSc(Hons) MB ChB MD(Hons) FRCP(Ed) FRCP is an Acute Physician in the Department of Acute Medicine, University Hospital of North Durham, Durham, UK. He was previously a Consultant in Renal Medicine for 9 years. He was a Founder Member of the Society for Acute Medicine and served as Secretary, Vice President and President, and is also Director of Standards, Royal College of Physicians of Edinburgh. His main clinical interests lie in acute kidney injury and appropriate organization of unscheduled care. Competing interests: none declared.
MEDICINE --:-
1
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
ACUTE MEDICINE II
urinary protein quantification (protein:creatinine ratio, albumin:creatinine ratio) human immunodeficiency virus test and hepatitis serology blood and urine cultures.
KDIGO staging system for AKI Stage
SCr criteria
Urine output criteria
1
SCr increase 26 micromol/litre or SCr 1.5e1.9 baseline SCr 2e2.9 baseline
<0.5 ml/kg/hour for 6e12 consecutive hours <0.5 ml/kg/hour for >12 hours <0.3 ml/kg/hour for 24 hours, or anuria for 12 hours
2 3
SCr 3 baseline or SCr 354 micromol/litre or commenced on RRT, irrespective of stage
Management of AKI In many cases, AKI can be effectively treated by optimizing a patient’s haemodynamic status and discontinuing medication that is either directly nephrotoxic or likely to compromise renal perfusion. Underlying conditions, such as sepsis, must be treated simultaneously.
Which fluids and how much?
SCr, serum creatinine.
The choice of fluid depends on the clinical situation and type of fluid loss; crystalloids containing sodium in the range 130e154 mmol/litre are recommended for initial resuscitation.5 The use of colloids is more controversial. There have been reports of an increased risk of AKI associated with the use of high-molecularweight starches in patients with severe sepsis, and there may be an upper limit on the volume of starch solutions that can be safely used in resuscitation. Further controlled prospective studies are required to clarify this issue, but it is currently advisable to avoid hydroxyethyl starches in patients with, or at risk of, AKI. In rhabdomyolysis, renal injury can be minimized by achieving high urinary flow rates and alkalinizing the urine. In this context, 0.9% sodium chloride should be given at a rate of 10e15 ml/kg per hour, with the cautious addition of isotonic sodium bicarbonate to maintain urinary pH >6.5. Mannitol has been used in rhabdomyolysis as it acts as an osmotic diuretic and free radical scavenger, but there is little evidence of clinical efficacy. In patients with AKI, the volume of fluid required depends on the current fluid deficit and continuing losses. In the acutely ill patient, fluid replacement is often best achieved by the rapid infusion of repeated small volumes (500 ml of crystalloid), with frequent reassessment of the patient’s clinical condition, urine output and physiological parameters, especially blood pressure and pulse. Fluid replacement alone may not be sufficient to restore systemic blood pressure and renal perfusion. Patients whose condition is refractory to fluids may require vasopressors or inotropic support, which should be undertaken in a critical care environment. All patients with AKI require accurate charting of fluid intake and urine output. Severely ill patients should have a urinary catheter inserted to allow measurement of hourly urine volumes; this is not, however, essential for every patient with AKI, as many patients (especially those with stage 1 AKI) have a
Table 1
respiratory tract symptoms (sinusitis, nasal crusting, haemoptysis). A detailed clinical examination should be conducted, with an emphasis on: assessment of volume status heart rate and blood pressure peripheral perfusion (temperature, capillary refill) jugular venous pressure evidence of oedema signs of obstruction (palpable bladder, abdominal masses) evidence of vascular disease (audible bruits, enlarged pulsatile aorta, impalpable peripheral pulses).
Further investigation All patients with AKI require urea and electrolytes (at least daily until renal function improves), full blood count and urinalysis (looking for evidence of infection or glomerular disease). Other tests depend on the presentation and can be used to confirm or refute suspected causes of AKI: protein electrophoresis and serum immunoglobulins, especially in myeloma serum creatinine kinase to exclude rhabdomyolysis renal tract ultrasound (renal size, cortical thickness, evidence of obstruction) renal immunology including antinuclear antibody, antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody in patients with suspected vasculitis and primary renal immunological injury chest X-ray electrocardiogram urine electrolytes and osmolality
Causes of AKI Pre-renal (hypoperfusion)
Renal
Post-renal (obstruction)
Hypovolaemia (excessive fluid losses, reduced intake) Sepsis Drugs (e.g. diuretics) Cardiogenic shock Hepatorenal syndrome
Acute tubular necrosis (either due to ischaemia or tubular toxins) Rhabdomyolysis Acute glomerulonephritis (in isolation or as part of systemic vasculitis)
Bladder outflow obstruction (including benign prostatic hypertrophy or malignancy) Pelvic or intra-abdominal malignancy Calculi Retroperitoneal fibrosis
Table 2 MEDICINE --:-
2
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
ACUTE MEDICINE II
correctable pathology that will rapidly improve with simple interventions.
Indications for RRT C
Medication
C C
Medication review is essential, and it is often necessary to discontinue specific drugs, either permanently or until renal function recovers. The term ‘nephrotoxic’ is often used to describe these medicines, although it is worth noting that many do not have direct renal toxicity but rather exert adverse effects by compromising renal perfusion in the setting of acute illness. Common drugs that can cause or worsen AKI include: angiotensin-converting enzyme inhibitors angiotensin II receptor blockers non-steroidal anti-inflammatory drugs aminoglycosides radiocontrast agents diuretics. Antihypertensive agents while not directly nephrotoxic, may need to be omitted during acute illness if the patient is haemodynamically compromised. Doses of medications should be reviewed, as dose reductions may be required in order to avoid drug toxicity or accumulation.
C C C
Table 3
Indications for renal replacement therapy Patients with established oligo-anuric AKI or those who do not respond to initial management may require RRT, usually haemodialysis or continuous veno-venous haemofiltration. The main indications for RRT are listed in Table 3.
Prevention of AKI Published data suggest that 30% of AKI cases may be preventable with simple measures such as correction of hypovolaemia and cessation of medications that can adversely affect renal perfusion during intercurrent illness. It is important to recognize patients at increased risk of AKI, and to manage them proactively rather than waiting for the serum creatinine to rise. Table 4 lists the major risk factors for AKI.
Renal tract obstruction and imaging Patients with suspected obstruction of the renal tract should have an ultrasound scan within 24 hours. This is important in patients with a history of urinary tract pathology, malignancy or a single kidney. Normal urine output does not exclude partial obstruction, and there may even be polyuria as a result of impaired concentrating ability in the renal tubules. If obstruction develops over a long period, it can be entirely asymptomatic and recognized only when the patient develops signs or symptoms of renal insufficiency. Patients with unexplained AKI or who fail to improve after fluid replacement and cessation of nephrotoxins should be imaged promptly. Unexplained haematuria (visible or nonvisible) requires imaging to exclude malignancy, especially in older patients.
Contrast-induced AKI Patients with pre-existing renal impairment and/or diabetes mellitus are at high risk of contrast-induced AKI. If contrast administration is essential for their management, these patients should be given volume expansion with intravenous crystalloid (isotonic saline, sodium bicarbonate) starting at least an hour before exposure and continuing for 3e6 hours afterwards. The addition of oral N-acetyl cysteine may offer some benefit, but the evidence for its efficacy remains inconclusive. A
Risk factors for AKI
Recognizing intrinsic renal disease
C
Although many cases of AKI are ‘pre-’ or ‘post-renal’ in origin, it is important not to miss intrinsic renal disease, which requires specialist investigation and treatment. There can be clues in the clinical history pointing towards systemic disease such as vasculitis (arthralgia, malaise, respiratory symptoms) or recent commencement of new drugs (acute interstitial nephritis). Alternatively, there may simply be no obvious explanation for the deterioration in renal function. Urinalysis is essential, as there is always evidence of microscopic haematuria and/or proteinuria in glomerulonephritis. Patients with unexplained AKI or suspected intrinsic renal disease should be referred promptly for nephrological advice. Further investigation might include a renal biopsy. Some forms of glomerulonephritis respond to immunosuppression with or without plasma exchange. Primary treatment of acute interstitial nephritis is withdrawal of any implicated drug, but it can also improve with corticosteroids.
MEDICINE --:-
Hyperkalaemia refractory to medical management Persisting anuria or oliguria despite adequate fluid resuscitation Fluid overload refractory to diuretics Metabolic acidosis Uraemic complications (encephalopathy, pericarditis, vomiting) Poisoning (e.g. lithium, salicylates)
C
C
C C
C C
C C C
Age >75 years Hypotension (systolic blood pressure <100 mmHg or drop of 40 mmHg from usual baseline) Sepsis (two or more systemic inflammatory response syndrome criteria due to suspected infection) Hypovolaemia (suggested by history or on clinical examination) Chronic kidney disease stage 3e5 (estimated glomerular filtration rate <60 ml/minute/1.73 m2) History of atherosclerotic vascular disease History of congestive cardiac failure or current presentation consistent with acute cardiac failure Diabetes mellitus Jaundice Nephrotoxic medication (including contrast agents)
Table 4
3
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
ACUTE MEDICINE II
KEY REFERENCES 1 Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005; 16: 3365e70. 2 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2: 1e138. 3 Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 2006; 34: 1913e7.
4 Shusterman N, Strom BL, Murray TG, Morrison G, West SL, Maislin G. Risk factors and outcome of hospital-acquired acute renal failure. Clinical epidemiology study. Am J Med 1987; 83: 65e71. 5 National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. Clinical Guideline no. 174. London: NICE, 2013.
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here. Investigations Serum sodium 143 mmol/litre (137e144) Serum potassium 5.4 mmol/litre (3.5e4.9) Serum bicarbonate 14 mmol/litre (20e28) Serum urea 38 mmol/litre (2.5e7.0) Serum creatinine 460 micromol/litre (60e110) C-reactive protein 302 mg/litre (<3 mg/litre)
Question 1 An 80-year-old man presented to the emergency department with a 3-day history of lethargy. He also complained of dribbling urinary incontinence. He had a past history of hypertension, urinary difficulty and chronic low back pain. He was taking ramipril 5 mg, aspirin 75 mg, tamsulosin 400 micrograms and cocodamol. On examination, he was obese. His temperature was 37 C, pulse 76 beats/minute, and blood pressure 140/85 mmHg. There were no other significant findings.
She was commenced on intravenous antibiotics, and her furosemide, lisinopril and metformin were withheld. A urinary catheter was inserted.
Investigations Haemoglobin 130 g/litre (130e180) Serum sodium 143 mmol/litre (137e144) Serum potassium 5.9 mmol/litre (3.5e4.9) Serum urea 35 mmol/litre (2.5e7.0) Serum creatinine 709 micrograms/litre (60e110) C-reactive protein 22 mg/litre (<3)
What is the most appropriate next step in her management? A. Dextrose and insulin infusion to correct hyperkalaemia B. Noradrenaline (norepinephrine) infusion to treat septic shock C. 500 ml intravenous 1.26% sodium bicarbonate over 15 minutes D. 500 ml intravenous colloid over 1 hour E. 500 ml intravenous isotonic saline over 15 minutes
Urinalysis 1þ leucocytes, 1þ blood, 1þ protein What is the most likely cause of his presentation? A. Bladder outlet obstruction B. Intrinsic renal disease C. Medication-induced acute kidney injury D. Multiple myeloma E. Sepsis
Question 3 A 44-year-old man is admitted to hospital after being found unconscious at home. He has a history of alcohol dependence and has not been seen for 2 days. Investigations Serum sodium 143 mmol/litre (137e144) Serum potassium 5.3 mmol/litre (3.5e4.9) Serum urea 35.6 mmol/litre (2.5e7.0) Serum creatinine 656 micromol/litre (60e110) Creatinine kinase 79,053 IU/litre
Question 2 A 69-year-old woman was admitted with a 1-day history of rigors and right-sided pleuritic chest pain. She had a past history of type 2 diabetes and heart failure. She was taking furosemide 40 mg once daily, lisinopril 5 mg once daily, metformin 500 mg twice a day, and aspirin 75 mg once a day. On examination, her pulse rate was 120 beats/minute, blood pressure 84/54 mmHg, temperature 38.5 C, respiratory rate 32 breaths/minute, and oxygen saturation 94% on 10 litres oxygen/ minute There was dullness to percussion and bronchial breathing at the right base.
MEDICINE --:-
Which of the following is the most appropriate management? A. Dextrose 5.0% and insulin infusion B. Sodium chloride 0.9% infusion C. Calcium resonium 15 g three times daily by mouth D. Sodium bicarbonate 1 g three times daily by mouth E. Urgent haemodialysis
4
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
Acute kidney injury
Key points
Sian Finlay
C
The term ‘acute kidney injury’ has replaced ‘acute renal failure’
C
Small rises in serum creatinine are associated with adverse patient outcomes including increased mortality
C
A universal definition and staging system has been proposed to reflect the spectrum of illness severity and to facilitate standardized clinical research
C
Many patients with AKI can be effectively managed by simple prompt interventions by non-specialists
Michael C Jones
Abstract It is well established that acute renal failure is associated with a significant increase in mortality, but it has recently become apparent that even relatively small rises in serum creatinine are associated with adverse patient outcomes. The term ‘acute kidney injury’ (AKI) was developed to reflect this broader spectrum of renal injury, ranging from patients with small changes in blood chemistry to those with dialysis-dependent renal failure. A universal definition and staging system for AKI has been proposed by the international guideline group Kidney Diseases: Improving Global Outcomes International. This definition allows earlier recognition of patients with AKI and facilitates standardized clinical research. This article discusses a practical approach to managing a patient with AKI, with emphasis on optimizing physiological parameters and rapidly identifying patients who require specialist nephrology input.
that AKI is common in critical illness, with 4.9% of patients admitted to an intensive care unit requiring renal replacement therapy (RRT). Recent evidence shows that it is present in 18% to 22% of patients of the general hospital patient population.3 AKI is not simply a marker of severe illness but an independent risk factor for mortality. The mechanism unclear, but it may be due to an increased likelihood of complications, such as bleeding and sepsis. Mortality estimates range from 10% in patients with uncomplicated AKI to 80% in those with multiorgan failure.4
Keywords Acute kidney injury; KDIGO (Kidney Diseases: Improving Global Outcomes International); risk factors
Causes of AKI AKI is most frequently caused by renal hypoperfusion, sepsis or nephrotoxic drugs (Table 2). Urinary tract obstruction is common, especially in elderly men and patients with malignancy, and must always be excluded if the cause of AKI is unclear. In hospitalized patients, the cause is often multifactorial. A small proportion of patients with AKI have intrinsic renal disease, such as acute interstitial nephritis or glomerulonephritis that requires urgent specialist assessment and therapy. One of the key goals when assessing a patient with AKI is to rapidly identify this group and obtain prompt nephrology input.
Introduction It is now recognized that relatively small rises in serum creatinine are associated with adverse patient outcomes,1 including increased mortality and length of hospital stay. The term ‘acute kidney injury’ (AKI) was developed to reflect this spectrum of renal injury, ranging from patients with small changes in blood chemistry to those with dialysis-dependent renal failure. The Kidney Diseases: Improving Global Outcomes International (KDIGO)2 guideline group defines and stages AKI as in Table 1. Historically, it has been difficult to clarify the incidence of AKI because of the lack of consensus on its definition. It is known
Approach to the patient with AKI A focused history often provides clues to the cause. Patients should be asked specifically about: excessive fluid losses, e.g. diarrhoea or vomiting, highoutput stomas recent fluid intake urinary tract symptoms (suggestive of urinary tract infection or obstruction) history of malignancy, especially pelvic or prostatic detailed drug history including over-the-counter drugs and herbal remedies symptoms suggestive of sepsis features suggestive of a systemic disease: fever rash arthralgia or arthritis myalgia lethargy or malaise uveitis
Sian Finlay MB ChB BMSc(Hons) PhD FRCP(Ed) is an Acute Physician in the Department of Medicine, Dumfries and Galloway Royal Infirmary, Dumfries, and Clinical Director for Medicine at Dumfries and Galloway Royal Infirmary, Scotland, UK. She completed a PhD at the University of Aberdeen studying the genetic modification of macrophages. Her main clinical interests are acute kidney injury and sepsis, and she is author of the Acute Kidney Injury Competency Framework (Academy of Medical Royal Colleges, 2011). Competing interests: none declared. Michael C Jones BSc(Hons) MB ChB MD(Hons) FRCP(Ed) FRCP is an Acute Physician in the Department of Acute Medicine, University Hospital of North Durham, Durham, UK. He was previously a Consultant in Renal Medicine for 9 years. He was a Founder Member of the Society for Acute Medicine and served as Secretary, Vice President and President, and is also Director of Standards, Royal College of Physicians of Edinburgh. His main clinical interests lie in acute kidney injury and appropriate organization of unscheduled care. Competing interests: none declared.
MEDICINE --:-
1
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
ACUTE MEDICINE II
urinary protein quantification (protein:creatinine ratio, albumin:creatinine ratio) human immunodeficiency virus test and hepatitis serology blood and urine cultures.
KDIGO staging system for AKI Stage
SCr criteria
Urine output criteria
1
SCr increase 26 micromol/litre or SCr 1.5e1.9 baseline SCr 2e2.9 baseline
<0.5 ml/kg/hour for 6e12 consecutive hours <0.5 ml/kg/hour for >12 hours <0.3 ml/kg/hour for 24 hours, or anuria for 12 hours
2 3
SCr 3 baseline or SCr 354 micromol/litre or commenced on RRT, irrespective of stage
Management of AKI In many cases, AKI can be effectively treated by optimizing a patient’s haemodynamic status and discontinuing medication that is either directly nephrotoxic or likely to compromise renal perfusion. Underlying conditions, such as sepsis, must be treated simultaneously.
Which fluids and how much?
SCr, serum creatinine.
The choice of fluid depends on the clinical situation and type of fluid loss; crystalloids containing sodium in the range 130e154 mmol/litre are recommended for initial resuscitation.5 The use of colloids is more controversial. There have been reports of an increased risk of AKI associated with the use of high-molecularweight starches in patients with severe sepsis, and there may be an upper limit on the volume of starch solutions that can be safely used in resuscitation. Further controlled prospective studies are required to clarify this issue, but it is currently advisable to avoid hydroxyethyl starches in patients with, or at risk of, AKI. In rhabdomyolysis, renal injury can be minimized by achieving high urinary flow rates and alkalinizing the urine. In this context, 0.9% sodium chloride should be given at a rate of 10e15 ml/kg per hour, with the cautious addition of isotonic sodium bicarbonate to maintain urinary pH >6.5. Mannitol has been used in rhabdomyolysis as it acts as an osmotic diuretic and free radical scavenger, but there is little evidence of clinical efficacy. In patients with AKI, the volume of fluid required depends on the current fluid deficit and continuing losses. In the acutely ill patient, fluid replacement is often best achieved by the rapid infusion of repeated small volumes (500 ml of crystalloid), with frequent reassessment of the patient’s clinical condition, urine output and physiological parameters, especially blood pressure and pulse. Fluid replacement alone may not be sufficient to restore systemic blood pressure and renal perfusion. Patients whose condition is refractory to fluids may require vasopressors or inotropic support, which should be undertaken in a critical care environment. All patients with AKI require accurate charting of fluid intake and urine output. Severely ill patients should have a urinary catheter inserted to allow measurement of hourly urine volumes; this is not, however, essential for every patient with AKI, as many patients (especially those with stage 1 AKI) have a
Table 1
respiratory tract symptoms (sinusitis, nasal crusting, haemoptysis). A detailed clinical examination should be conducted, with an emphasis on: assessment of volume status heart rate and blood pressure peripheral perfusion (temperature, capillary refill) jugular venous pressure evidence of oedema signs of obstruction (palpable bladder, abdominal masses) evidence of vascular disease (audible bruits, enlarged pulsatile aorta, impalpable peripheral pulses).
Further investigation All patients with AKI require urea and electrolytes (at least daily until renal function improves), full blood count and urinalysis (looking for evidence of infection or glomerular disease). Other tests depend on the presentation and can be used to confirm or refute suspected causes of AKI: protein electrophoresis and serum immunoglobulins, especially in myeloma serum creatinine kinase to exclude rhabdomyolysis renal tract ultrasound (renal size, cortical thickness, evidence of obstruction) renal immunology including antinuclear antibody, antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody in patients with suspected vasculitis and primary renal immunological injury chest X-ray electrocardiogram urine electrolytes and osmolality
Causes of AKI Pre-renal (hypoperfusion)
Renal
Post-renal (obstruction)
Hypovolaemia (excessive fluid losses, reduced intake) Sepsis Drugs (e.g. diuretics) Cardiogenic shock Hepatorenal syndrome
Acute tubular necrosis (either due to ischaemia or tubular toxins) Rhabdomyolysis Acute glomerulonephritis (in isolation or as part of systemic vasculitis)
Bladder outflow obstruction (including benign prostatic hypertrophy or malignancy) Pelvic or intra-abdominal malignancy Calculi Retroperitoneal fibrosis
Table 2 MEDICINE --:-
2
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
ACUTE MEDICINE II
correctable pathology that will rapidly improve with simple interventions.
Indications for RRT C
Medication
C C
Medication review is essential, and it is often necessary to discontinue specific drugs, either permanently or until renal function recovers. The term ‘nephrotoxic’ is often used to describe these medicines, although it is worth noting that many do not have direct renal toxicity but rather exert adverse effects by compromising renal perfusion in the setting of acute illness. Common drugs that can cause or worsen AKI include: angiotensin-converting enzyme inhibitors angiotensin II receptor blockers non-steroidal anti-inflammatory drugs aminoglycosides radiocontrast agents diuretics. Antihypertensive agents while not directly nephrotoxic, may need to be omitted during acute illness if the patient is haemodynamically compromised. Doses of medications should be reviewed, as dose reductions may be required in order to avoid drug toxicity or accumulation.
C C C
Table 3
Indications for renal replacement therapy Patients with established oligo-anuric AKI or those who do not respond to initial management may require RRT, usually haemodialysis or continuous veno-venous haemofiltration. The main indications for RRT are listed in Table 3.
Prevention of AKI Published data suggest that 30% of AKI cases may be preventable with simple measures such as correction of hypovolaemia and cessation of medications that can adversely affect renal perfusion during intercurrent illness. It is important to recognize patients at increased risk of AKI, and to manage them proactively rather than waiting for the serum creatinine to rise. Table 4 lists the major risk factors for AKI.
Renal tract obstruction and imaging Patients with suspected obstruction of the renal tract should have an ultrasound scan within 24 hours. This is important in patients with a history of urinary tract pathology, malignancy or a single kidney. Normal urine output does not exclude partial obstruction, and there may even be polyuria as a result of impaired concentrating ability in the renal tubules. If obstruction develops over a long period, it can be entirely asymptomatic and recognized only when the patient develops signs or symptoms of renal insufficiency. Patients with unexplained AKI or who fail to improve after fluid replacement and cessation of nephrotoxins should be imaged promptly. Unexplained haematuria (visible or nonvisible) requires imaging to exclude malignancy, especially in older patients.
Contrast-induced AKI Patients with pre-existing renal impairment and/or diabetes mellitus are at high risk of contrast-induced AKI. If contrast administration is essential for their management, these patients should be given volume expansion with intravenous crystalloid (isotonic saline, sodium bicarbonate) starting at least an hour before exposure and continuing for 3e6 hours afterwards. The addition of oral N-acetyl cysteine may offer some benefit, but the evidence for its efficacy remains inconclusive. A
Risk factors for AKI
Recognizing intrinsic renal disease
C
Although many cases of AKI are ‘pre-’ or ‘post-renal’ in origin, it is important not to miss intrinsic renal disease, which requires specialist investigation and treatment. There can be clues in the clinical history pointing towards systemic disease such as vasculitis (arthralgia, malaise, respiratory symptoms) or recent commencement of new drugs (acute interstitial nephritis). Alternatively, there may simply be no obvious explanation for the deterioration in renal function. Urinalysis is essential, as there is always evidence of microscopic haematuria and/or proteinuria in glomerulonephritis. Patients with unexplained AKI or suspected intrinsic renal disease should be referred promptly for nephrological advice. Further investigation might include a renal biopsy. Some forms of glomerulonephritis respond to immunosuppression with or without plasma exchange. Primary treatment of acute interstitial nephritis is withdrawal of any implicated drug, but it can also improve with corticosteroids.
MEDICINE --:-
Hyperkalaemia refractory to medical management Persisting anuria or oliguria despite adequate fluid resuscitation Fluid overload refractory to diuretics Metabolic acidosis Uraemic complications (encephalopathy, pericarditis, vomiting) Poisoning (e.g. lithium, salicylates)
C
C
C C
C C
C C C
Age >75 years Hypotension (systolic blood pressure <100 mmHg or drop of 40 mmHg from usual baseline) Sepsis (two or more systemic inflammatory response syndrome criteria due to suspected infection) Hypovolaemia (suggested by history or on clinical examination) Chronic kidney disease stage 3e5 (estimated glomerular filtration rate <60 ml/minute/1.73 m2) History of atherosclerotic vascular disease History of congestive cardiac failure or current presentation consistent with acute cardiac failure Diabetes mellitus Jaundice Nephrotoxic medication (including contrast agents)
Table 4
3
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010
ACUTE MEDICINE II
KEY REFERENCES 1 Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005; 16: 3365e70. 2 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2: 1e138. 3 Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 2006; 34: 1913e7.
4 Shusterman N, Strom BL, Murray TG, Morrison G, West SL, Maislin G. Risk factors and outcome of hospital-acquired acute renal failure. Clinical epidemiology study. Am J Med 1987; 83: 65e71. 5 National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. Clinical Guideline no. 174. London: NICE, 2013.
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here. Investigations Serum sodium 143 mmol/litre (137e144) Serum potassium 5.4 mmol/litre (3.5e4.9) Serum bicarbonate 14 mmol/litre (20e28) Serum urea 38 mmol/litre (2.5e7.0) Serum creatinine 460 micromol/litre (60e110) C-reactive protein 302 mg/litre (<3 mg/litre)
Question 1 An 80-year-old man presented to the emergency department with a 3-day history of lethargy. He also complained of dribbling urinary incontinence. He had a past history of hypertension, urinary difficulty and chronic low back pain. He was taking ramipril 5 mg, aspirin 75 mg, tamsulosin 400 micrograms and cocodamol. On examination, he was obese. His temperature was 37 C, pulse 76 beats/minute, and blood pressure 140/85 mmHg. There were no other significant findings.
She was commenced on intravenous antibiotics, and her furosemide, lisinopril and metformin were withheld. A urinary catheter was inserted.
Investigations Haemoglobin 130 g/litre (130e180) Serum sodium 143 mmol/litre (137e144) Serum potassium 5.9 mmol/litre (3.5e4.9) Serum urea 35 mmol/litre (2.5e7.0) Serum creatinine 709 micrograms/litre (60e110) C-reactive protein 22 mg/litre (<3)
What is the most appropriate next step in her management? A. Dextrose and insulin infusion to correct hyperkalaemia B. Noradrenaline (norepinephrine) infusion to treat septic shock C. 500 ml intravenous 1.26% sodium bicarbonate over 15 minutes D. 500 ml intravenous colloid over 1 hour E. 500 ml intravenous isotonic saline over 15 minutes
Urinalysis 1þ leucocytes, 1þ blood, 1þ protein What is the most likely cause of his presentation? A. Bladder outlet obstruction B. Intrinsic renal disease C. Medication-induced acute kidney injury D. Multiple myeloma E. Sepsis
Question 3 A 44-year-old man is admitted to hospital after being found unconscious at home. He has a history of alcohol dependence and has not been seen for 2 days. Investigations Serum sodium 143 mmol/litre (137e144) Serum potassium 5.3 mmol/litre (3.5e4.9) Serum urea 35.6 mmol/litre (2.5e7.0) Serum creatinine 656 micromol/litre (60e110) Creatinine kinase 79,053 IU/litre
Question 2 A 69-year-old woman was admitted with a 1-day history of rigors and right-sided pleuritic chest pain. She had a past history of type 2 diabetes and heart failure. She was taking furosemide 40 mg once daily, lisinopril 5 mg once daily, metformin 500 mg twice a day, and aspirin 75 mg once a day. On examination, her pulse rate was 120 beats/minute, blood pressure 84/54 mmHg, temperature 38.5 C, respiratory rate 32 breaths/minute, and oxygen saturation 94% on 10 litres oxygen/ minute There was dullness to percussion and bronchial breathing at the right base.
MEDICINE --:-
Which of the following is the most appropriate management? A. Dextrose 5.0% and insulin infusion B. Sodium chloride 0.9% infusion C. Calcium resonium 15 g three times daily by mouth D. Sodium bicarbonate 1 g three times daily by mouth E. Urgent haemodialysis
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Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Finlay S, Jones MC, Acute kidney injury, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.12.010