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Last updated: Lesson of the Month - October 2017…
on 17 Oct 2017

AKI in ICU

Introduction and Epidemiology

Yadullah Syed and Marlies Ostermann  -  Review Date June 2016

Introduction

Acute kidney Injury (AKI) is a term used to describe a variety of different diseases with heterogeneous aetiologies that lead to renal dysfunction with different prognostic outcomes. AKI has replaced the term 'acute renal failure' and describes a long list of conditions associated with acute renal dysfunction.­

History of AKI

William Heberden in 1802 described acute renal failure as 'Ischuria renalis', and in 1909 [1,2], William Osler’s textbook of medicine described it as acute Bright’s Disease. During the First World War, in 1917, Dr. F. Davies described it as 'war nephritis' in the Lancet [3]. The term acute renal failure was first used by Homer Smith in 1951 in his textbook The Kidney - Structure and Function in Health and Disease. The term 'AKI' was coined by the Acute Dialysis Quality Initiative (ADQI) in 2004 [4].

Definition

Acute kidney injury can be defined using RIFLE, AKIN ­or KDIGO criteria. The recent guideline by the UK's National Institute for Health and Care Excellence (NICE) recommends to define AKI in accordance with the AKIN, KDIGO and paediatric KDIGO classifications by any of the following: [5]

  • A rise in serum creatinine of ≥26 ­μmol/litre within 48­hours
  • A ≥ 50% rise in serum creatinine known or presumed to have occurred within the past 7­days
  • A fall in urine output to <0.5­ml/kg/hour for more than 6 ­hours in adults and more than 8 ­hours in children and young people
  • A ≥25% fall in estimated glomerular fitratlon rate (eGFR) in children and young people within the past 7­days

Note: The term ‘Adult’ refers to people who are aged ≥18 years, ‘Younger’ people to people 12-17 yrs of age, and 'Children' to subjects 11 years or younger (excluding neonates less than 1 month old). The reference creatinine is taken as the lowest creatinine level in the last 3 months. In the absence of previous blood results, admission creatinine is considered as the reference creatinine.

Pitfalls of various definition systems

  1. Creatinine is affected by non-renal variables , including muscle mass­, muscle dietary supplements, drugs that inhibit tubular creatinine secretion (eg H2 blockers) and laboratory techniques.
  2. Estimation of baseline renal function is difficult. In a patient with no previous serum creatinine result, the presentation creatinine acts as baseline. However, this approach is likely to lead to underdiagnosis of community acquired AKI.
  3. Small changes in serum creatinine may be blunted or exaggerated by changes in extracellular volume, and AKI may be missed or wrongly classified.
  4. Estimation of urine output is difficult without a urinary catheter in situ. Although this is not a major issue in ICU, it may be a problem in non-ICU settings.
  5. Serum creatinine rise can be delayed after definite renal injury. Patients may have acute tubular injury even if serum creatinine and urine output are still in the normal range.
  6. Pseudo AKI: Bilirubin, ascorbic acid, uric acid and certain drugs (eg cephalosporins, trimethoprim and cimetidine) may interfere with the creatinine assays. Therefore, it is important to be cautious and to interpret laboratory data in a clinical context.

Studies have used different classification systems to study the epidemiology of AKI. Not surprisingly, incidence and prevalence rates vary, depending on the classification system used, associated comorbid factors and subset of population studied. The same patient may be classified differently -­or may even not fulfil the AKI criteria - depending on the classification system. [6,7,8]

In developed countries, AKI is seen in 13-18% of all people admitted to hospital [5]. ­In critically ill patients AKI affects 20 - 60% of patients. [9,10,11,12,13,14,15] The high frequency of AKI amongst inpatients means that it has a major impact on patients and a­major economic impact. According to NHS Kidney Care, the cost of AKI to the NHS (excluding AKI in the community) is estimated to be between £434 million - £620 million per year. This­is more than the expenditure on breast cancer, lung and skin cancer combined [5]. Therefore any steps to prevent or treat AKI should have a positive outcome, at an individual patient level; and at the health care system level. AKI also carries increased short and long term morbidity and mortality, and a significant risk of ESRD.


Current Understanding of Pathophysiology

AKI is a syndrome and rarely has a distinct single pathophysiology. Many patients with AKI have a mixed aetiology where the presence of sepsis, ischaemia and nephrotoxicity co-exist.

Sepsis­­

There are a number of proposed mechanisms regarding the pathogenesis of septic AKI, including hypoperfusion at the systemic and/or microcirculatory level, apoptosis mediated by either the infective agents or cytokines released in response to infection (as well as renal mitochondrial hibernation). Inspite of normal or increased renal blood flow, microcirculatory flow may be impaired leading to medullary hypoxia and tubular cell dysfunction. Sepsis can also lead to damage of the endothelial glycocalyx which aggravates a breakdown of the vascular barrier and contributes to microcirculatory changes­ [16].

Drug-induced AKI

Certain drugs like NSAIDS/ACEi/ARB/renin receptor blockers/calcineurin inhibitors decrease renal perfusion by causing afferent arteriolar vasoconstriction. Other common nephrotoxic drugs are aminoglycosides. The epithelial cells along the proximal convoluted tubule (PCT) express receptors called megalin which are responsible for the uptake of aminoglycosides. These drugs become­concentrated in the PCT where they bind avidly to poly-anionic phospholipid-containing membranes, thereby Inducing myeloid body formation, impairing protein synthesis and degrading mitochondrial function. As a result, apoptosis and eventual necrosis of renal tubular epithelial cells occur. Direct glomerular injury is usually a secondary consequence of aminoglycoside-induced tubular impairment [17,18] ­

Contrast-induced Nephrotoxicity (CIN)

Contrast causes direct oxidant injury to proximal tubular cells. In addition, it affects vasomotor tone of afferent and efferent arterioles via its osmolality which reduces perfusion. [1,50]

Obstructive Uropathy

Typical histopathological changes due to urinary tract obstruction and back pressure include [54].

  • 1st week (1-7 days). Flattening of renal papillae and­ dilatation of distal nephron.
  • 2nd week (7-14 days). Atrophy and necrosis of collecting tubules.
  • 3rd & 4th (14-28 days). Progressive dilatation of distal and collecting tubules.
  • Beyond 4th week. Thinning of cortex, reduction in medulla by about 50%, proximal tubular atrophy and glomerular changes.

Unsurprisingly, outcomes becomes less favourable with increasing duration and severity of obstruction, pre-existing renal impairment and super-added infection.

Patients with partial obstruction may develop a form of nephrogenic diabetes insipidus as a result of a concentrating defect. This­may be mediated by direct effects of increased tubular pressure on distal tubular cells. These subset of patients will have polyuria.

Hepatorenal Syndrome (HRS)

Chronic liver disease or acute fulminant liver failure can lead to portal hypertension which will lead to peripheral or splanchnic arterial dilatation. As a result, effective volume is reduced which leads to activation of the renin angiotensin-aldosterone system, sympathetic nervous system and release of anti-diuretic hormone (ADH). Activation of renin angiotensin-aldosterone system will cause renal vasoconstriction and thereby reduce GFR and lead to HRS. The release of ADH mainly causes sodium and water retention and plasma volume expansion [19,20,21].

Intra-abdominal Hypertension

Intra-abdominal hypertension (IAH) increases renal vein pressure thereby decreasing glomerular perfusion pressure. The increase in renal parenchymal pressure can cause ureteric obstruction. There is also often a reduction in venous return and cardiac output which affects renal blood flow further. All changes ultimately lead to impairment of renal microcirculation [22].

­


Risk Groups and Aetiology

At Risk Groups

The KDIGO and NICE guldelines recommend that all patients should be stratified for risk of AKI according to their 'exposures' and 'susceptibilities'; and managed accordingly to reduce the risk of AKI. These risk factors may be patient- specific, disease-specific or intervention-specific. Below is a list of risk factors as outlined in the KDIGO guideline­­ ­[1]

This list is by no means complete. Interestingly, patients admitted to hospital during weekends compared to weekdays are more likely to have AKI [23]. Prognoisis is also worse at weekends [56].­Proteinuria has also been shown to be a risk factor for AKI in critically ill as well as non-ICU patients ­[24,25].

Scoring systems are available to identify and optimise patients at high risk of AKI; for instance, patients undergoing cardiac surgery, patients scheduled to have imaging with contrast and patients admitted via A+E.

Contrast nephropathy risk score­

Low risk cumulative risk <5 , high risk cumulitive score >16 [26] ­Abbreviations: CHF: congestive heart failure, IABP: intraaortic ballon pump, Scr: serum creatinine; eGFR: estimated glomerular filtration rate, CIN: contrast induced nephropathy (1)

­

Risk factors for Obstructive Uropathy

A high index of suspicion for obstructive uropathy should be maintained: in male patients with symptoms or history of benign prostatic hyperplasia and carcinoma of the prostate; in female patients with a history of carcinoma cervix, benign or malignant uterine masses, pelvic pathology (pelvic abscess, pelvic inflammatory disease), inadvertent ligation of the ureter during surgical procedure or pregnancy; and in both sexes, if known to have congenital urological issues, retroperitoneal malignancy, retroperitoneal fibrosis and/or vascular abnormalities (like aneurysmal dilatation of the aorta). Retroperitoneal fibrosis should be considered in patients known to have an inflammatory aortic aneurysm, trauma or granulomatous disease (TB, Crohns disease, sarcoidosis) or on certain drugs (eg methysergide, ß-blockers, bromocriptine) or after radiotherapy.

Causes of AKI

The traditional method of describing renal dysfunction is still very helpful in identifying the causes of AKI in ICU. Prerenal causes are most common (50-60%), followed by renal causes (30-45%) and post renal aetiologies (<5%).

Prerenal causes include:

(a) Decreased effective circulating volume as a result of fluid loss from gastrointestinal tract (diarrhoea, vomiting, high output stoma), renal tract, skin (burns, staphylococcal scalded skin syndrome, Steven Johnson Syndrome), bleeding, third space losses (pancreatitis, sepsis, cirrhosis), low cardiac output states and systemic vasodilation (sepsis, drugs).

(b) Decreased perfusion due to arterial stenosis or occlusion.

(c) Drugs causing afferent arteriolar vasoconstriction like NSAIDS/ACEi/AIIRB/renin receptor blockers/calcineurin inhibitors

(d) Hepatorenal syndrome.

(e) Intra-abdominal hypertension.

Renal causes include:

(a) Vascular involvement caused by vasculitis, thrombotic micrangiopathy or hypertensive emergencies.

(b) Glomerular involvement as in acute glomerulonephritis, nephrotic syndrome, thrombotic thrombocytopenic purpura/haemolytic uremic syndrome.

(c) Tubular damage as in acute tubulointerstitial nephritis or acute tubular injury (ATI). Acute tubular injury can be caused by a variety of insults including toxins and ischaemia. Nephrotoxins causing ATI may be exogenous (nephrotoxic drugs or radio contrast agents) or endogenous (haemoglobinuria, myoglobinuria, myeloma casts, intratubular crystals).

Postrenal causes include:

Obstruction at the level of urethra, bladder outlet or ureters may be partial or complete due to intrinsic or extrinsic pathologies. A non-dilated system on ultrasound examination does not rule out obstruction, especially in patients with transitional cell carcinoma of bladder and patient with retroperitoneal fibrosis. Similarly, non-obstructed ureteric dilation can be seen in pregnancy in the first few months and also post renal transplantation.­

Typical­Aetiology

Sepsis

Sepsis-induced AKI accounts for approximately 50% of cases. This is by far the commonest cause of AKI in patients admitted to critical care.­

Drug/toxin exposure, including contrast

Nephrotoxic drugs account for 20-30% of cases of AKI. Contrast induced nephropathy (CIN) is defined as a rise in SCr of ≥0.5 mg/dl (≥44 mmol/l) or a 25% increase from baseline value at 48 hours after contrast exposure. It is the third most common cause of new AKI in hospitalised patients (after decreased renal perfusion and nephrotoxic medications) and accounts for around 10% of AKI cases. [27,28,29]

Cardiorenal syndrome

Cardiorenal syndrome (CRS) is a pathophysiological disorder of the heart and the kidneys in which acute or chronic dysfunction of one organ may induce acute or chronic dysfunction in the other organ. There are 5 types of CRS [30].

  • Type I: Acute cardiorenal syndrome: Abrupt worsening of cardiac function [eg acute decompensated congestive cardiac failure (CCF) or cardiogenic shock] leading to AKI.
  • Type II: Chronic cardiorenal syndrome: Chronic abnormalities in cardiac function (eg chronic CCF) resulting in progressive and potentially permanent CKD.
  • Type III: Acute renocardiac syndrome: abrupt worsening of renal function (AKI) causing acute cardiac disorder (eg heart failure, arrythmia)
  • Type IV: Chronic renocardiac syndrome: CKD contributing to decreased cardiac function, cardiac hypertrophy and or increased risk of cardiovascular events
  • Type V: Secondary cardiorenal syndrome due to systemic diseases giving rise to both chronic cardiac and renal failure (eg diabetes, hypertension)

Hepatorenal syndrome:

International club of ascites diagnostic criteria for hepatorenal syndrome (HRS). Revised Criteria (2007) [52,53].

  1. Presence of cirrhosis and ascites
  2. Serum creatinine >1.5 mg/dL (or 133 μmol/L)
  3. No improvement of serum creatinine (decrease equal to or less than 1.5 mg/dL) after at least 48 hours of diuretic withdrawal and volume expansion with albumin (recommended dose = 1 g/kg per day up to a maximum of 100 grams of albumin/day)
  4. Absence of shock
  5. No current or recent treatment with nephrotoxic drugs
  6. Absence of parenchymal kidney disease as indicated by proteinuria >500 mg/day, microhaematuria (>50 RBCs/high power field, and/or abnormal renal ultrasound scanning

HRS is classified into subtypes (Type 1 & 2). AKI is a dominant feature in type 1 HRS. Whereas ascites is a dominant feature of type 2 HRS. In type 1 HRS, there is a rapid fall in eGFR to <20 ml/min in less than 2 weeks or at least 2-fold increase in serum creatinine to a level >221µmol/L, progressive oligo-anuria and a median survival of about 2 weeks. In contrast, in HRS type 2, AKI is less severe with a protracted course and a median survival of around 6 months. However, it has potential to convert to type 1 HRS.

It has been acknowledged that patients with chronic liver disease often have lower muscle mass and lower baseline normal serum creatinine. By the time serum creatinine has risen to 132 µmols/L, advanced kidney injury has occurred. A recent working party developed a proposal for a revised classification system of renal dysfunction in patients with cirrhosis which includes criteria for AKI and CKD not meeting the traditional criteria of HRS type 1 and 2.

The new proposal defines AKI by an acute increase in serum creatinine of >50% from baseline or a rise in serum creatinine of ≥26.4 μmol/l (≥0.3 mg/dl) in <48 h.

Intra-abdominal hypertension

Normal intra-abdominal pressure (IAP) is 5-7mmHg. Intra-abdominal hypertension (IAH) is defined as sustained and repeated IAP >12 mmHg measured at end expiration in supine position in the absence of muscle contraction. Abdominal compartment syndrome is defined as IAP >20 and is associated with multiple organ failure.

IAH is seen in clinical settings where there is:

  1. Decreased abdominal wall compliance (ARDS, abdominal or aortic surgery, trauma, high BMI)
  2. Increase in intraluminal contents (gastric retention, ileus)
  3. Increased abdominal contents (haematoma, ascites, trauma, pancreatitis, complicated abdominal surgery)
  4. Capillary leak with massive fluid resuscitation (sepsis, burns)

The degree of IAH often correlates with the severity of associated AKI.­


Clinical Approach

A detailed clinical history is very important but may be difficult if the patient is unwell and unable to give a history. History should focus on exploring relevant comorbid factors, especially any preexisting renal diseases and medications. The majority of critically ill patients with AKI have multiple reasons for AKI. Patients in whom the cause of AKI is unclear or a renal aetiology is suspected should be referred to a nephrologist.

Examination should focus on assessing volume and haemodynamic status and searching for stigmata of diseases causing AKI. Any patient presenting with anuria should have obstruction ruled out ASAP. This means inserting a urinary catheter and obtaining an ultrasound. Though it is important to remember that both non-dilated obstruction and a non-obstructed dilatation of the urinary tract can occur. If either of these scenarios are being considered, then further radiological investigation (CT abdomen, or ante/retrograde pyelography +/- nephrostomies) is indicated.

All patients should have a non-catheterised urine dipstick to look for haematuria and/or proteinuria which may by indicative of a renal cause of AKI in the absence of UTI or renal trauma. Spot urinary protein creatinine ratio (UPCR) should be done if urine dipstick positive for protein.

Management

General Principles

The recent KDIGO AKI guideline outlines best evidence management of patients with established AKI or at risk of AKI. (Figure below)

Patients with AKI or are at risk of developing AKI should have their haemodynamic­ status­ optimised. This may require treatment with fluids +/- vasopressors. The aim of fluid therapy should be to achieve a euvolaemic state without causing fluid overload. An early resuscitation goal is a mean arterial blood pressure of 65-90 mmHg. This target may need to be adjusted, ie depending on age, chronic blood pressure and associated comorbidities. Haemodynamic monitoring may be necessary to to judge whether treatment with fluids or catecholamines is necessary. If required, the patient should be admitted to HDU / ICU.

Fluid Management

The KDIGO guideline recommends that the expansion of intravascular volume in patients at risk of AKI (or with AKI) in the absence of haemorrhagic shock should initially be achieved using isotonic crystalloids rather than colloids. This recommendation is based on lack of evidence that colloids are superior to crystalloids; and some data showing that certain colloids (ie starches) may actually cause AKI. A meta-analysis published in JAMA reported an increased relative risk of renal failure of 1·27 (95%CI 1·09–1·47) with starches compared to crystalloids [31]. Similarly, a Cochrane review­including 25 studies with mortality data, reported an increased relative mortality risk of 1·10 (95%CI 1·02–1·19) for starches compared with crystalloids ­[32,33,34,35].

Certain colloids may be cautiously­chosen for early fluid resuscitation in specific patient cohorts; for instance, in patients with spontaneous bacterial peritonitis, albumin has been shown to reduce the incidence of AKI, hospital mortality and 3 month mortality [33,34,35,36,37,38]. ­Hypo- and hypertonic crystalloids may be used in patients with hyper- or hyponatraemia. Isotonic saline solution contains NaCl 154mmols/l and can cause hyperchloraemic metabolic acidosis when administered in large volumes [34]. Although direct proof of harm arising from saline induced hyperchloraemia is lacking, the use of balanced crystalloids is less likely to cause acid base disturbances. Balanced crystalloids have become the preferred fluids used for resuscitation in most ICUs [1].­­

Haemodynamic Management

The KDIGO guideline recommends applying protocol-based management of haemodynamic and oxygenation parameters in patients with septic shock (and high risk patients in perioperative settings) to prevent AKI. However, the exact target blood pressure and haemodynamic targets are unknown. Brienza et al showed that in the perioperative setting, protocolised therapies (irrespective of protocol) to achieve specific physiological targets significantly reduced the incidence of postoperative AKI ­[38].

Pharmacological Management

Vasopressors

In AKI, kidneys lose renal auto-regulation. Appropriate use of vasoactive agents can preserve and improve kidney perfusion in volume-resuscitated patients with vasomotor shock. However, there is insufficient evidence to recommend one vasoactive agent over another [1]. The use of low dose dopamine, fenoldopam, atrial natriuretic peptide, recombinant human IGF-1 and theophylline is not recommended either to prevent or treat AKI [1].

Diuretics

Loop diuretics reduce oxygen consumption and thereby have potential to decrease ischaemic damage especially in the outer medullary segment [39]. However, studies have failed to show any benefit from diuretics in preventing or reversing AKI. In fact, in patients exposed to contrast, diuretics have been shown to increase the incidence of CIN. [40,41,42,43] The use of high dose diuretics (frusemide at >1g/d) is also associated with increased risk of ototoxicity [44]. ­­In AKI, diuretics should be reserved to correct or prevent fluid overload [1]. ­Mannitol stimulates osmotic diuresis. It has been suggested that Mannitol may be beneficial in patients with rhabdomyolyisis but these studies are either not randomised or underpowered.

In conclusion, diuretics are not recommended to prevent or treat AKI except for the management of fluid overload or oedema whilst awaiting RRT or recovery of renal function.

Supportive Measures

Nutrition

AKI is a pro-inflamatory state associated with metabolic derangements, especially in patients on RRT. There is often protein hypercatabolism driven by inflammation, stress and acidosis. Patients with AKI are at high risk of malnutrition and a total energy intake of 20–30 kcal/kg/d is recommended for any stage of AKI. [45,46]

Enteral feeding is associated with improved outcome/survival in ICU patients and is therefore recommended for patients with AKI in preference to parenteral nutrition. [47,48,49]

Prevention of CIN

All patients who need imaging with contrast should be assessed for risk of CIN [1]. ­Where ever possible, alternative imaging methods should be considered in patients at increased risk of CIN. When this is not possible, the lowest possible dose of contrast medium should be used. In patients with high risk of AKI, iso-osmolar or low osmolar iodinated contrast media should be used. Oral fluids alone cannot be recommended ­to prevent CIN in high risk patients. The KDIGO guideline recommends the­use oral N-Acetylcysteine (NAC) along with IV isotonic crystalloids to prevent CIN; whereas the recent NICE AKI guideline was unable to recommend NAC due to conflicting evidence from existing studies.

The use of theophylline and fenoldopam to prevent CIN is not recommended [1]. Prophylactic intermittent haemodialysis or haemofiltration for contrast-media removal in patients at increased risk for CIN is not recommended either.

Drug Dosing

The potential for inappropriate drug dosing in patients with, or at risk of developing AKI, is high. NICE recommends use of the electronic clinical decision support systems (CDSS) to support clinical decision-making and prescribing, but stresses that­it should not replace clinical judgement. ACE inhibitors and ARBs should be stopped in patients with diarrhoea, vomiting or sepsis until their clinical condition has improved and stabilised. They should be withheld for at least 24 hrs pre- and post-elective surgery, and in patients due to receive contrast (particularly if the patients eGFR is <40ml/min/1.73m2). Patients’ renal function should be reviewed before recommencing these drugs.

Referral to Nephrologist

NICE recommends the following referral criteria:

  1. AKI in a patient with renal transplant
  2. Patients with single organ AKI who meet the criteria for RRT. Patients who need inotropic support will also need critical care involvement.
  3. When the cause of AKI uncertain and specialist management of kidney injury might be needed (ie. vasculitis, glomerulonephritis, tubulointerstitial nephritis, myeloma)
  4. AKI with no clear cause
  5. Inadequate response to treatment
  6. Complications associated with AKI
  7. AKI stage 3 (according to RIFLE, AKIN or KDIGO criteria)
  8. AKI on background of CKD stage 4/5
  9. After resolution of an episode of AKI, where the patient has impaired renal function (eGFR is ≤30 ml/min/1.73 m2, hypertension), or 1+ or greater proteinuria on dipstick testing of an early morning urine sample.

Urinary Catheter

Transurethral catheterisation should be considered in all oliguric or anuric patients, if there is a clinical suspicion of bladder outlet obstruction. This should not be attempted in trauma patients in whom there is a suspicion of ruptured urethra. Presence of blood at the external urethral meatus on the background of pelvic trauma should raise suspicion of urethral injury. In trauma patients who have urethral injury, or in patients in whom transurethral catheterisation has been unsuccessful, suprapubic catheterisation should be considered. In patients with ureteric obstruction, percutaneous antegrade ultrasound-guided nephrostomy (+/- subsequent antegrade stent insertion by interventional radiologist under local anaesthesia or a retrograde stent insertion by a urologist under general anaesthesia) is indicated. An infected obstructed system is an emergency that requires emergency nephrostomy insertion.­

Criteria for Referral to Urologist

  1. Pyonephrosis
  2. An obstructed solitary kidney
  3. Bilateral upper urinary tract obstruction
  4. Complications of AKI caused by urological obstruction
  5. Traumatic AKI­

Management of Complications

Medical Management

Medical management refers to non-dialytic therapy and aims to correct complications so that renal replacement therapy can be avoided or until renal replacement can be provided. The following advice is based on detailed guidance in the Oxford Handbook of Nephrology and Hypertension [55].

Hyperkalaemia

Significant hyperkalaemia is defined as serum potassium >6 mmol/L. Hyperkalaemia can cause neuromuscular depression and cardiac dysrhythmias. ECG changes seen with hyperkalemia vary from normal ECG to ventricular fibrillation and asystole.

Acute hyperkalemia is less well tolerated by older patients, patients with underlying cardiac disease and oliguric patients (who cannot excrete potassium). Patients with chronic hyperkalaemia may tolerate potassium levels of 6-7 mmol/L (but K >6.5mmol/L should definitely be treated). Treatment options inlcude:

(i) Calcium

Calcium is cardio-protective but has no effect on serum K levels. 10% calcium gluconate or calcium chloride can be used to treat hyperkalaemia.

10 ml of 10% calcium chloride contains 1360 µmols Ca²+/ml whereas 10 ml of 10% calcium gluconate only contains 220Ca²+/ml. The onset of action is within minutes and lasts for <1 hour. If ECG changes do not improve after 5 min, the dose can be repeated (up to 40 ml of calcium gluconate) [55].

(ii) Insulin and glucose ­

If ­K≥ 6.5, or there are ECG changes, administer 50 ml of 20% dextrose with 10 units of short acting insulin. Insulin binds to cellular receptors and increases Na-K-ATPase activity which results in a K shift into cells. The effect starts within 15-30 minutes (peak ~ one hour) and lasts for about 2-4 hours.

(iii) Sodium bicarbonate

NaHCO3 1.26% or 1.4% solution can be administered if the patient has acidosis in association with hyperkalemia and volume depletion. The onset of action is within hours.

(iv) ß2-agonists

Nebulised salbutamol has the potential to decrease potassium approximately by up to 1mmol/L. It acts via Na-K-ATPase channels but the onset of action is slower.

The required dose (10-20mg) can precipitate arrhythmias in patients with underlying cardiac disease. ­

(v) Diuretics

Diuretics can be used to aid in removal of potassium. The commonest diuretic used is furosemide either as iv bolus (40-120 mg) or as an infusion 10-40 mg/hr. 1mg of bumetanide is approximately equivalent to 40 mg of oral furosemide.

(vi) Calcium resonium

Calcium resonium -­either orally or rectally - can be given to prevent enteric potassium absorption. The rectal preparation is more effective but may cause colonic ulceration­ and necrosis. Laxatives (lactulose) should be prescribed along with calcium resonium. It takes 1-2 days for an effect to be seen.

(vii) Other measures

  • Low potassium diet should be advised and dietician input should be sought.
  • Blood transfusion should be avoided in oligo-anuric patients with hyperkalemia
  • All drugs that increase serum potassium (ie. ACEi, ARBs, renin receptor blockers, NSAIDS, potassium sparing diuretics) should be stopped / avoided.
  • The underlying cause of AKI should be treated.

Note: Hyperkalemia resistant to medical management requires RRT.

Acidosis

Acidosis should be treated with fluids and/or sodium bicarbonate either oral or iv. Severe acidosis is an indication for RRT.

Fluid overload

Patient should be sat in an­upright position and high flow oxygen should be administered. Diamorphine 1.25-2.5 mg should be administered as an anxiolytic and vasodilator along with an anti-emetic. Intravenous GTN infusion should be considered unless there is a contraindication. Diuretics (bolus or infusion) should be commenced. Respiratory support may be necessary in patient who are hypoxic or tiring despite above treatment. In exceptional circumstances venesection can be considered.

In case patients do not respond to above medical management, RRT or ultrafiltration should be considered.

Bleeding

Apart from routine measures, consider giving DDAVP (0.3 µg/kg) in patients with severe AKI provided there is no history of ischaemic heart disease or hyponatraemia. DDAVP leads to release of von Willebrand factor, boosts factor VIII levels and improves platelet function.

Criteria for RRT

The decision to start on RRT is based on patient’s condition rather than an isolated blood result (urea, creatinine, potassium or pH). Absolute indications for RRT are:

  • Hyperkalaemia not responding to medical management
  • Worsening metabolic acidosis not responding to medical management
  • Life threatening complications of uraemia (ie pericarditis or encephalopathy)
  • Life threatening fluid overload not responding to medical management

Management of Intra-abdominal hypertension

The World Society of Abdominal Compartment Syndrome (WSACS) has published the following guidance for the management of intraabdominal hypertension. (www.wsacs.org)

Abdominal wall compliance can be improved by sedation, analgesia and muscle relaxation Intraluminal decompression can also be achieved by using nasogastric and rectal tubes and the use of prokinetic agents like metoclopramide and erythromycin. Abdominal fluid contents can be evacuated by paracentesis or percutaneous drainage. Positive fluid balance should be avoided, and use of diuretics or ultrafiltration may be necessary. The abdominal perfusion pressure should be maintained >60 mmHg with vasopressors. Ventilation and alveolar recruitment should be optimised.

Note: Decompressive laparotomy may be indicated in abdominal compartment syndrome with multi-organ dysfunction.­


Outcomes

Despite the widespread use of RRT in the ICU, AKI is associated with an associated mortality risk of 40 – 90% depending on patient population. There is increasing evidence that survivors of AKI have an increased risk of CKD, end-stage renal failure and premature death, even if renal function recovers [51]. More work is necessary to determine how to follow up patients who survived an episode of AKI.­


References, Guidelines and Other Resources

References

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  2. Eknovan G. Emegence of the concept of acute renal failure. Am J Nephrol 2002; 22: 225-230
  3. Davies F, Weldon R. A contribution to the study of ‘‘war nephritis’’. Lancet 1917; ii: 118–120
  4. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31
  5. NICE clinical guidelines- CG169. Acute kidney injury: Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy
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Guidelines

International:

KDIGO : Clinical practice guidelines for Acute kidney injury, http://www.kidney-international.org , VOLUME 2 | ISSUE 1 | MARCH 2012

UK:

NICE. CG24 : Acute kidney injury: prevention, detection and management of acute kidney injury up to the point of renal replacement therapy. August 2013.

Renal association: Acute kidney Injury.

Important websites

www.kdigo.org

www.nice.org.uk

www.renal.org.uk

www.esicm.org

www.wsacs.org

www.adqi.net

www.akinet.org

www.icascites.org