HISTORY • DEFINITION • EPIDEMIOLOGY • ETIOLOGY • SUBTYPE • PROGNOSIS • BIOMARKER • RISK FACTOR • EVALUATION • MANAGEMENT&GUIDELINE
Acute Kidney Injury 2nd Century AD: Galen surmises urine formed from kidneys 330-1453 AD: Byzantine physicians describe oliguria as symptom of AKI, as well as detailed urine findings in AKI; also, the transition to polyuric phase as late finding in AKI is recognized 330-1453 AD: likely precursors to ATN described: Aetius: “..the reasons for the destruction of the kidney are the toxic influence of remedies and poisons, and external pressure” Nonus: “…hematuria results from poisonous drugs and serpent venom…” (Eftychiadis AC, Am J Nephrol 1997)
Acute Kidney Injury 1827: English physician Richard Bright describes microscopic hematuria, oliguria, and edema in acute and chronic renal inflammatory states, gives eponymic definition for .acute/chronic GN
Acute Kidney Injury WWI & WWII: Post-traumatic oliguria seen in combatants, crush syndrome evolves as an AKI dx 1950-1960’s: AKI found retrospectively in ~20% of post-op open heart/aortic surgery
Acute Kidney Injury WW I: observations of thirst and oliguria in combat victims led to relationship between blunt trauma and AKI (Better, OS 1997) WWII: Spanish surgeon Joseph Trueta observes same in Spanish Civil War, WWII combatants Induces renal cortical vasospasm experimentally (Trueta, et al., 1947) WWII: Bywaters and Beall link myoglobin to AKI in crush syndrome during London Blitz (1940)
UK Renal Association 5th Edition, 2011 Acute kidney injury (AKI) has now replaced the term acute renal failure and an universal definition and staging system has been proposed to allow earlier detection and management of AKI. The new terminology enables healthcare professionals to consider the disease as a spectrum of injury. This spectrum extends from less severe forms of injury to more advanced injury when acute kidney failure may require renal replacement therapy (RRT)
Clinically AKI is characterised by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homoeostasis.
Definition of AKI There are more than 35 definitions of AKI (formerly acute renal failure) in literature! • Mehta R, Chertow G: Acute renal failure definitions and classification: Time for change? Journal of American Society of Nephrology 2003; 14:2178-2187.
Acute Kidney Injury 2001 : Acute Dialysis Quality Initiative (ADQI) Risk: 1.5x inc in SCr, GFR dec 25%, UOP<0.5 ml/kg/h x 6h Injury: 2x inc SCr, GFR dec 50%, UOP<0.5 ml/kg/h x 12h Failure: 3x inc SCr, GFR dec 75%, UOP<0.5/kg/h x 24h Also anuria x 12 hr Loss: complete loss (inc need for RRT) > 4 wks ESRD: complete loss (inc need for RRT) > 3 months 2007: Acute Kidney Injury Network (AKIN) Modified RIFLE to include ΔSCr o.3 mg/dL from baseline, within 48hr, based on 80% mortality risk
Definition of AKI As per the Acute Kidney Injury Network: An abrupt (within 48hrs) reduction in kidney function defined as an increase in serum creatinine level of 0.3mg/dl OR An increase in serum creatinine≥ 50% OR Urine output is < 0.5ml/kg/hr for >6 consecutive hours
Definition of AKI RIFLE classification AKIN classification
RIFLE classification Bellomo R, Ronco C, Kellum J, et al.: Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Initiative (ADQI) Group. Critical Care 2004; 8:R204-R212.
AKIN classification Modification of the RIFLE classification by Acute Kidney Injury Network (AKIN). Recognizes that small changes in serum creatinine(>0.3 mg/dl) adversely impact clinical outcome. Uses serum creatinine, urinary output and time. Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712-720.
AKIN classification *Patients needing RRT are classified stage 3 despite the stage they were before starting RRT Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes in Acute Kidney Injury. Critical Care 2007; 11: R31.
Epidemiology AKI occurs in ≈ 7% of hospitalized patients. 36 – 67% of critically ill patients (depending on the definition). 5-6% of ICU patients with AKI require RRT. Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. American Journal of Kidney Diseases 2002; 39:930-936. Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73. Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to RIFLE. Critical Care Medicine 2007; 35:1837-1843.
Data from the Intensive Care National Audit Research Centre (ICNARC) suggests that AKI accounts for nearly 10 percent of all .ICU bed days
Etiology Hemodynamic 30% Parenchymal65% Acute tubular necrosis 55% Acute glomerulonephritis5% Vasculopathy3% Acute interstitial nephritis 2% Obstruction 5%
Common causes of AKI in ICU • Sepsis • Major surgery • Low cardiac output • Hypovolemia • Medications (20%) Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294:813-818.
Nephrotoxins • NSAIDs • Aminoglycosides • Amphotericin • Penicillins • Acyclovir • Cytotoxics • Radiocontrast dye Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275.
Subtype Acute Kidney Injury AKI PRERENAL INTRINSIC POSTRENAL
Acute Kidney Injury PRERENAL Volume loss/Sequestration Impaired Cardiac Output Hypotension (and potentially hypo-oncotic states) Net result: glomerularhypoperfusion
Acute Kidney Injury RENAL/INTRINSIC Vascular disorders: small vessel large vessel Glomerulonephritis Interstitial disorders: Inflammation intercalative processes Tubular necrosis: Ischemia Toxin Pigmenturia
Acute Kidney Injury POSTRENAL Intrarenal Crystals Proteins Extrarenal Pelvis/Ureter Bladder/Urethra
Mortality according to RIFLE Mortality increases proportionately with increasing severity of AKI (using RIFLE). AKI requiring RRT is an independent risk factor for in-hospital mortality. Mortality in pts with AKI requiring RRT 50-70%. Even small changes in serum creatinine are associated with increased mortality. Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73. Chertow G, Levy E, Hammermeister K, et al.: Independent association between acute renal failure and mortality following cardiac surgery. American Journal of Medicine 1998; 104:343-348. Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294:813-818. Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712-720.
Acute kidney injury has a poor prognosis with the mortality ranging from 10%-80% Patients who present with uncomplicated AKI, have a mortality rate of up to 10%. In contrast, patients presenting with AKI and multiorgan failure have been reported to have mortality rates of over 50%. If renal replacement therapy is required the mortality rate rises further to as high as 80%
Non-Oliguric vs. Oliguric vs. Anuric Oliguric renal failure. Functionally, urine output less than that required to maintain solute balance (can’t excrete all solute taken in). Defined as urine output < 400ml/24hr. Anuric renal failure. Defined as urine output < 100ml/24hr. Less common – suggests complete obstruction, major vascular catastrophy, or more commonly severe ATN.
Non-Oliguric vs. Oliguric vs. Anuric Classifying by urine output may help establish a cause. Oliguria – more common with obstruction, prerenalazotemia Nonoliguric – intrarenal causes – nephrotoxic ATN, acute GN, AIN. More importantly, assists in prognosis. Significantly higher mortality with oliguric renal failure. 80% vs. 25% mortality in Oliguric vs. non-oliguric ARF Nonoliguric renal failure may also suggest greater liklihood of recovery of function.
BIOMARKER RESEARCH IN DEFINITIONS AND GOALS • a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention • a biomarker is “any substance, structure or process that can be measured in the body or its products and influence or predict the incidence or outcome of disease”
What is GFR? How is it Calculated? The Glomerular Filtration Rate (GFR) is the volume of fluid filtered from glomerularcapillaries into the Bowman’s capsule per unit time
Suspect AKI in a sick patient with a modest rise in their creatinine Large acute drop in GFR with oligoanuria GFR falls rapidly to near zero - only shown by oliguria Slow rise in Cr until eventually a new steady state is reached Only a small early rise in Cr: not easy to recognise as AKI
Limitations to Serum Creatinine as a Reflection of GFR The serum creatinineconcentration does not increase above the normal range until the GFR declines below 50 mL/min, and large declines in GFR may occur above this level without a concomitant increase in the serum .creatinine value
Limitations to Serum Creatinine as a Reflection of GFR In a cachectic patient with very low muscle mass, creatinine generation may be so feeble that the serum creatinine level remains “normal” (<0.9 mg/dL) even in the presence of a GFR less than 25 mL/min.
Serum creatinine is a useful marker of stable renal function, but it is unreliable when GFR is .rapidly changing
Because it may take up to 48 hours for GFR to return to baseline, in the postoperative period the serum creatinine value may still increase for a few days while GFR is actually recovering.
Urine flow rate is an unreliable marker of acute renal failure and may vary from anuric (zero flow), to oliguric (urinary flow rate <15 mL/hr), to nonoliguric (15-80 mL/hr), to polyuric (>80 mL/hr).
Indices of Tubular Injury • β2-Microglobulin • Urinary N-Acetyl-β-d-glucosaminidase • Neutrophilgelatinase-associated lipocalin (NGAL)
Risk Factors for AKI • Age > 75 yrs • Chronic kidney disease (CKD, eGFR < 60 mls/min/1.73m2) • Cardiac failure • Diabetes mellitus • Hypovolemia • Nephrotoxic medication • Atherosclerotic peripheral vascular disease • Liver disease • Sepsis
Risk Factors for Ischemic Tubular Injury • Volume depletion • Aminoglycosides • Radiocontrast • NSAIDs, Cox-2 inhibitors • Sepsis • Rhabdomyolysis • Preexisting renal disease • HTN • Diabetes mellitus • Age > 50 • Cirrhosis
Radiocontrast-Induced Acute Renal Failure • Induces renal vasoconstriction and direct cytotoxicity via oxygen free radical formation • Risk factors: • Renal insufficiency - Diabetes • Advanced age - > 125 ml contrast • Hypotension • Usually non-oliguric ARF; irreversible ARF rare