Recognising Acute Kidney Injury

CME Acute medicine Clinical Medicine 2012, Vol 12, No 3: 287–9

• Failure: GFR decrease above 75%, tri- blood vessels supplying the kidney – the Recognising acute pling of creatinine or creatinine greater latter include renal artery stenosis and than 355 µmol/l (or urine output below renal vein thrombosis. kidney injury 0.3 ml/kg/hr for 24 hr). • Loss: persistent AKI or complete loss of Renal Mike Jones, consultant acute physician, kidney function for more than Royal Infirmary of Edinburgh four weeks. Renal or intrinsic AKI can be due to damage • End-stage renal disease: complete loss to the glomeruli, renal tubules or intersti- While it is often possible to identify the sick of kidney function for more than tium. Common causes of each are glomer- patient who is clinically dehydrated, hypo- three months. ulonephritis, so-called acute tubular tensive or septic, a diagnosis of acute renal necrosis and acute interstitial nephritis. Subsequently, many of the original mem- failure (ARF) or acute kidney injury (AKI) bers of the ADQI group collaborated to form would often not be considered until the the Acute Kidney Injury Network (AKIN).3 Postrenal results of the urea and electrolytes were This group modified the RIFLE staging obtained. It was felt that seemingly small Postrenal AKI is a consequence of urinary system to reflect the clinical significance of changes in serum urea and creatinine were tract obstruction that may be related to relatively small rises in serum creatinine. unlikely to be associated with any signifi- benign prostatic hyperplasia, kidney stones, More recently, the international guideline cant changes in outcome, so there was less obstructed urinary catheter, bladder stone, group, Kidney Disease: Improving Global urgency in making a diagnosis and insti- or bladder, ureteral or renal malignancy. Outcomes (KDIGO), has produced a defini- tuting aggressive therapy. Within the last This term may also be applied to the intra- tion and staging system that harmonises the decade, however, it has been demonstrated renal obstruction associated with abnormal previous definitions and staging systems by that these seemingly small changes in protein deposition in the tubules, for both ADQI and AKIN. In this system, stage 1 serum creatinine are associated with sig- example as occurs with myeloma. (or ‘Risk’ stage) AKI is defined as: nificant increases in risk for the patient. Furthermore, it has become increasingly • serum creatinine increase by at least Practical application of apparent that the previous perception that 26 µmol/l within 48 hours or definitions of acute kidney injury patients who had ARF would usually • serum creatinine rise 1.5 fold or more recover completely is wrong. There is from the reference value (this should What do the above definitions and classifi- mounting evidence that patients who have be the lowest value recorded within cations mean in practice? A recent National suffered AKI are at far greater risk of pro- three months of the event), which is Confidential Enquiry into Patient Outcome gressing to chronic kidney disease (CKD). known or and Death (NCEPOD) report6 identified For this reason, greater emphasis is now • the change in renal function is pre- many deficiencies in the care of patients at placed on the rapid identification and sumed to have occurred within one risk of and suffering from AKI (the report’s amelioration of risks for AKI, with aggres- week or recommendations are shown in Table 1). sive treatment of the underlying cause.1 • urine output less than 0.5 ml/kg/hr for In assessing risk, it is important to realise more than six consecutive hours. that most AKI is associated with ischaemia, Definitions and staging sepsis or nephrotoxic insults. Studies have identified the risk factors most pertinent A collaborative network of international Causes of acute kidney injury for the development of AKI: experts representing nephrology and inten- AKI is common among hospitalised sive care societies established the Acute • age over 75 years patients.4,5 It affects at least 3–7% of patients Dialysis Quality Initiative (ADQI), and • CKD (eGFR (electronic glomerular fil- admitted to hospital and approximately 2 devised the RIFLE definition and staging tration rate) <60 ml/min/1.73 m ) 25–30% of patients in the intensive care unit system for AKI.2 In this classification AKI is • cardiac failure (ICU). Although the terminology for the categorised according to the criteria of • atherosclerotic peripheral vascular dis- acute decline of renal function has changed, Risk, Injury, Failure, Loss and End-stage ease the mechanisms underlying the deteriora- disease for kidneys. • liver disease tion have not. The old separation of prerenal, • diabetes mellitus • Risk: glomerular filtration rate (GFR) renal and postrenal causes remains relevant. • nephrotoxic medications, especially decrease greater than 25%, serum cre- angiotensin-converting enzyme inhibi- atinine increase 1.5 times or urine pro- Prerenal tors, non-steroidal anti-inflammatory duction less than 0.5 ml/kg/hr for drugs and certain antibiotics. six hours. Prerenal causes of AKI, which decrease • Injury: GFR decrease above 50%, dou- effective blood flow to the kidneys, include Patients with these risk factors should be bling of creatinine or urine production low blood volume, low blood pressure and actively assessed for AKI, including a review less than 0.5 ml/kg/hr for 12 hours. heart failure, as well as local changes to the of the physiological parameters routinely

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reviewed at the bedside using Early Warning fairly easy to predict in elderly patients may also indicate tumours, infection, Score systems such as the National Early presenting with sepsis and dehydration. calculi or severe renal ischaemia. High Warning Scoring System (NEWS). Good Investigations are very important, ranging numbers of white cells are indicative of assessment at an early stage with institution from simple bedside tests to the more infection, glomerulonephritis and intersti- of active measures can prevent the progres- resource-intensive. tial nephritis. sion of AKI. This should result in aggressive Serum and urinary biochemical estima- management of underlying potential pre- Reagent strip urinalysis tions remain the most important investiga- cipitating factors including: tion to reveal AKI. The classic laboratory Reagent strip urinalysis is a useful investi- findings are shown in Table 2 but, as dem- • reduced fluid intake gation, provided that the results are inter- onstrated above, a change in the serum • increased fluid losses preted carefully and simple abnormalities creatinine is among the most important • urinary tract infection (UTI) or are not assumed to indicate UTI. Protein criteria for the diagnosis of AKI. obstruction values of 3+ and 4+ suggest intrinsic • recent nephrotoxic drug ingestion glomerular disease. When positive for • sepsis. Ultrasound blood, such values suggest the presence of red blood cells (>5/high power field). The A critical investigation for the presence of Investigations observation of large numbers of red cells in an obstructive uropathy is ultrasound, The recognition of AKI is rarely made from the presence of proteinuria suggests a although in the early stages of obstruction, clinical examination alone, although it is glomerular aetiology for AKI. Haematuria or in the dehydrated patient, typical hydronephrosis/hydroureter may not be Table 1. Recommendations from the NCEPOD report.6 seen even when obstruction is present.

• All emergency admissions should have a risk assessment for AKI. • All emergency admissions should have electrolytes checked on admission and Treatment appropriately thereafter. Treatment of AKI is aimed at the underlying • Predictable, avoidable AKI should not occur. cause, but a mainstay is adequacy of fluid • All acute admissions should receive adequate senior review (consultant review within replacement. It is important that fluid resus- 12 hours). citation provides adequate filling of the • There should be sufficient critical care and renal beds to allow rapid step-up care. intravascular volume, although over-replace- • Undergraduate medical training should include the recognition of the acutely ill patient ment is also associated with an adverse out- and the prevention, diagnosis and management of AKI. come. Treatment of infection, removal of • Postgraduate training in all specialties should include training in the detection, nephrotoxins, relief of obstruction and spe- prevention and management of AKI. cific treatment of the renal insult (eg immu- AKI ϭ acute kidney injury; NCEPOD ϭ National Confidential Enquiry into Patient Outcome and Death. nosuppression for vasculitides) may all be pertinent. Adequacy of treatment in the Table 2. Classic laboratory findings in acute kidney injury (AKI). early stages of AKI means that most patients will not require active renal intervention in AKI type UOsm UNa FeNa(%) Urea/Cr Providing urea Ͼ10 the form of renal replacement therapy (RRT). Often there is more than one pre- Prerenal <500 <10 <1 >100 cipitating factor; therefore clinicians must < < > < Renal 350 20 2 40 adopt a holistic approach to the assessment Postrenal <350 >40 >4 40–100 and management of AKI. ϭ ϭ ϭ ϭ U urinary; Cr creatinine; UNa urinary sodium; FeNa fractional excretion of sodium Key points Outcomes Patients who develop AKI which requires Even small changes in serum creatinine are associated with poorer outcomes RRT in an ICU have a very high risk of Risk factors for acute kidney injury (AKI) should be recognised and modified rapidly mortality (50–90%), increasing with failure of each additional organ system. Studies Adequate physiological surveillance must be in place for all patients with AKI have shown however that an increase of The underlying condition should be treated to maximise the chance of improving the AKI serum creatinine of about 50 µmol/l is associated with a 6.5-fold increased risk of Investigations of a patient with AKI should include urinalysis and renal ultrasound mortality and with a prolonged hospital (when obstruction is a possibility) stay for the survivors. Other factors that KEYWORDS: acute kidney injury, AKI risk, AKI investigations affect outcome are:

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• older age Furthermore, the development of assays 4 Metcalfe W, Simpson KM, Khan IH et al. • multiorgan failure (ie with all AKI, the for more sensitive biomarkers has been Acute renal failure requiring renal replace- more organs that fail, the worse the proposed.7 One such marker, neutrophil ment therapy: incidence and outcome. QJM 2002;95:579–83. prognosis) gelatinase-associated lipocalin (NGAL), 5 Goldberg R, Dennen P. Long-term out- • oliguria has been demonstrated to be increased in comes of acute kidney injury. Adv Chronic • hypotension the serum of patients suffering from `renal Kidney Dis 2008;15:297–307. • vasopressor support stress', including AKI, before more conven- 6 National Confidential Enquiry into Patient • number of transfusions tional markers, including serum creatinine Outcome and Death. Acute Kidney Injury: Adding Insult to Injury, 2009. London: 8 • non-cavitary surgery. change. Such early recognition could allow NCEPOD, 2009. earlier intervention and thus improved This early identification and aggressive 7 Haase M, Bellomo R, Haase-Fielitz A. outcomes from AKI. Time for an eGFR equivalent in AKI recog- management of AKI should be a high pri- nition? Nephrol Dial Transplant 26: ority so that the patients’ condition can be 3075–76. improved without the use of RRT if at all References 8 Haase M, Haase-Fielitz A, Devarajan P et al. The outcome of neutrophil gelati- possible. 1 Schrier RW, Wang W, Poole B, Mitra A. nase-associated lipocalin (NGAL)-positive Acute renal failure: definitions, diagnosis, subclinical acute kidney injury: a multi- pathogenesis, and therapy. J Clin Invest center pooled analysis of prospective 2004;114:5–14. Developments studies. J Am Coll Cardiol 2011;57:1752–61. 2 Bellomo R, Ronco C, Kellum JA, Mehta RL, Recognition of AKI depends on measure- Palevsky P. Acute Dialysis Quality Initiative ment of the serum creatinine, as noted workgroup. Acute renal failure – definition, outcome measures, animal models, fluid above, but an increase in this marker is therapy and information technology needs: often a relatively late manifestation of AKI. the Second International Consensus To improve present systems, many hospi- Conference of the Acute Dialysis Quality tals are introducing electronic alerts that Initiative (ADQI) Group. Crit Care Address for correspondence: ensure clinicians are rapidly informed by 2004;8:R204–12. Dr M Jones, Consultant Acute 3 Mehta RL, Kellum JA, Shah SV et al. Acute the laboratory staff of changes in the serum kidney injury network: report of an Physician, Royal Infirmary of biochemistry, so that active intervention initiative to improve outcomes in acute Edinburgh, EH16 4SA. for the patient is not delayed. kidney injury. Crit Care 2007;11:R31. Email: [email protected]

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