Diagnosis and Management Consultant for Baxter of Acute Kidney - PDF document

Disclosures Diagnosis and Management  Consultant for Baxter of Acute Kidney Injury  Patent on 0.5% citrate anticoagulant solution for CRRT Ashita Tolwani, M.D., M.S. Professor of Medicine University of Alabama at Birmingham 2017 AKI Outline  Epidemiology Epidemiology of AKI  Definition  Pathophysiology and differential diagnosis  Overview of prevention and management 1

Acute Kidney Injury: Why Do We Care?  AKI is common (KDIGO definition)  21% of all hospital admissions  >50% of ICU patients  AKI is associated with increased risk of CKD, ESKD, CV disease, and death Worl rldwide, 2 dwide, 2,000,000 00,000  Dialysis‐requiring AKI ICU patients have the worst outcomes people will peopl will die this year die this year  11% of ICU patients with AKI require dialysis and 10‐30% survivors remain of AKI! of AKI! dialysis dependent at time of hospital discharge  AKI can be preventable, treatable, and reversible  Healthcare workers are not well informed about AKI and its consequences Mehta RL et al. Lancet 2015 Pannu et al. CJASN 2013 Cerda, et al. CJASN 2015 2

Definition  More than 30 different definitions exist with a variety of quoted incidence rates, risk factors, and morbidity and mortality rates  A staging system is needed to stratify patients so that both accurate identification and prognostication are possible Definition of AKI www.ADQI.net Using RIFLE, Patients with AKI Mortality Risk in Hospitalized Patients Have Poorer Outcomes Analysis of 71,000 pts/13 studies to validate RIFLE Criteria Mild AKI have poor outcomes > 0.3 > 0.5 > 1.0 > 2.0 ↑SCr ↑SCr mg/dL Source: Ricci Z. Kidney Int. 73: 538-546, 2008 Chertow et al, JASN 16: 3365-3370, 2005 Chertow et al, JASN 16: 3365-3370, 2005 3

KDIGO AKI Guidelines: Definition of AKI AKIN Criteria (Rifle V2.0) Increased SCr x1.5 UO < .5ml/kg/h OR > 0.3 mg/dL x 6 hr High R (I) Sensitivity UO < .5ml/kg/h Increased SCr x2 I (II) I (II) x 12 hr Increase SCr x3 UO < .3ml/kg/h or SCr  4mg/dl x 24 hr or High F (III) (Acute rise of  0.5 mg/dl) Anuria x 12 hrs Specificity RRT Started Criterion must be Modifications proposed by AKIN Amsterdam, 2005 reached within 48hr KDOQI Commentary AJKD 2013 Problems with Serum Creatinine Serum Creatinine and GFR in AKI  Creatinine is influenced by age, muscle mass, gender, and Muscle mass ethnicity Nutrition Infection  Creatinine does not reflect the presence or absence of structural injury and thus provides no guidance on AKI etiology or the Protein metabolism likelihood of response to various targeted therapies Edema  The rise is serum creatinine is delayed by 2‐3 days after the injury has occurred Serum creatinine Volume of  distribution Fluid therapy may dilute serum creatinine and therefore delay diagnosis Renal excretion  Inter‐laboratory variation in measuring creatinine, and bilirubin Drugs Nonlinear and other compounds interfere with the colorimetric modified Jaffe assay hence affect serum creatinine levels Filtration (GFR) Tubular excretion Star RA, Kidney Int, 1998 4

Relationship Between GFR and Creatinine Conceptual Model for AKI 120 80 GFR (mL/min) 40 Increased Increased Kidney Kidney 0  GFR  GFR Normal Normal Damage Damage Death Death risk risk failure failure 6 Serum 4 Creatinine (mg/dL) 2 Ideal Creatinine 0 Biomarker 0 7 14 21 28 Days Gill, N. et al. Chest 2005;128:2847-2863 What Can an Ideal AKI Biomarker Teach Us? Potential Biomarkers for AKI Proximal Tubule Injury •Urine IL-18 •Urine KIM-1 •Urine L-FABP  Predict and diagnose AKI early (before increase in serum Distal Tubule •Urine Cystatin C •Urine NGAL •α1-microglobulin creatinine) •Urine π-GST •β2-microglobulin •Urine α-GST  Identify the primary location of injury (proximal tubule, distal •Urine Netrin-1 •Urine NAG tubule, interstitium) Glomerular Injury  Pinpoint the type (pre‐renal, AKI, CKD), duration and severity • Urine albumin excretion Glomerular Filtration • Serum Creatinine of kidney injury • Blood urine Nitrogen • Serum Cystatin C  Identify the etiology of AKI (ischemic, septic, toxic, • Plasma NGAL combination) Loop of Henle Injury •Uromodulin  Predict clinical outcomes (dialysis, death, length of stay)  Monitor response to intervention and treatment Other Mechanisms / Sites of Adapted from Koyner  Expedite the drug development process (safety) Injury not specific to the and Parikh‐ Brenner and Nephron •Hepcidin – Iron trafficking Rector’s The Kidney •TIMP-2/ IGFBP7 – G1 cell cycle arrest Courtesy of J. Koyner Prasad Devarajan: Biomarkers in Acute Kidney Injury :Search for a Serum Creatinine Surrogate 5

Biomarkers after AKI Early Detection New Paradigm for the Spectrum of AKI Idealized SCr Kim‐1 STRUCTURAL IL‐18 NO AKI (subclinical) AKI Creat (‐) Creat (‐) Biomarker (‐) Biomarker (+) NGAL INTRINSIC AKI FUNCTIONAL AKI (structural & functional) Creat (+) L‐FABP Creat (+) Biomarker (‐) Biomarker (+) Urinary Biomarkers Associated with Tubular Damage Classification of the Etiologies of AKI AKI Pathophysiology and Differential Diagnosis of AKI Prerenal Intrinsic Post-renal AKI AKI AKI Acute Acute Acute Acute Intratubular Tubular Interstitial Vascular GN Obstruction Necrosis Nephritis Syndromes 6

Evaluation of Cause of AKI Non ‐ICU ICU Form of AKI BUN:Cr U Na (mEq/L) FE Na Urine Sediment Prerenal >20:1 <10 < 1% Normal, hyaline casts Post‐renal >20:1 >20 variable Normal or RBC’s Intrinsic ATN <10:1 >20 > 2% Muddy brown casts; tubular epithelial cells, granular casts AIN <20:1 >20 >1% WBC’s WBC casts, RBC’s, eosinophils AGN variable <20 <1% Dysmorphic RBC’s, RBC casts Vascular variable >20 variable Normal or RBC’s Fractional Excretion of Na + (FENa) Fractional Excretion of Urea (FEurea) (Urine Na x Serum Cr) X 100 < 1% = pre‐renal (Urine UN x Serum Cr) X 100 < 35% = Pre‐renal (Serum Na x Urine Cr) > 2% = ATN (Serum UN x Urine Cr) > 50% = ATN  Normal renal function <1%  Most accurate with oliguric AKI  Better than FENa in patients on diuretics  Rationale: Urea reabsorbed in proximal tubule + inner  Caveat: medulla, not affected by loop and thiazide diuretics  < 1% without volume depletion  Contrast nephropathy  Acute GN  Rhabdomyolysis  Possibly > 2% with prerenal state:  Diuretics , severe CKD Steiner AJM 1984:77:699-702 7

Pre-renal AKI – Decreased Renal Blood Flow Pre-renal Urine Sediment Cause Examples Volume depletion Renal losses; GI fluid losses; hemorrhage; burns Decreased cardiac output Heart failure; massive pulmonary embolus; acute coronary syndrome Systemic vasodilation Sepsis; cirrhosis; anaphylaxis; anesthesia Intrarenal vasoconstriction Drugs (NSAIDs, COX‐2 inhibitors, amphotericin B, calcineurin inhibitors, contrast agents); hypercalcemia; hepatorenal syndrome Efferent arteriolar vasodilation Renin inhibitors; ACE inhibitors; ARBs Hyaline Casts A prolonged pre‐renal state can lead to ATN Impaired Autoregulation Can Lead to Pathogenesis of Pre-renal AKI “Normotensive AKI” Congestive Liver Heart Failure Volume Failure Depletion Sepsis Renal + Angiotensin II Vasoconstriction - + Nitric oxide Adrenergic nerves - + Prostaglandins Vasopressin Decreased GFR Abuelo JG. N Engl J Med 2007;357:797-805 8

Intrarenal Mechanisms for Autoregulation of the GFR Pre-renal Azotemia: Medications Angiotensin‐converting enzyme inhibitors Nonsteroidal anti‐inflammatory drugs NSAIDS ACEI/ARB Abuelo JG. N Engl J Med2007;357:797-805. Systemic Effects of Increased Abdominal Abdominal Compartment Syndrome Pressure  Intra‐abdominal hypertension:  Cardiac  GI  Intra‐abdominal pressure ≥12 mm Hg; or   venous return   splanchnic perfusion  Abdominal perfusion pressure <60 mm Hg   cardiac output  CNS   CVP, PCWP & SVR   intracranial pressure,  Abdominal compartment syndrome   perfusion pressure  Pulmonary  Intra‐abdominal pressure ≥20 mm Hg; and   intrathoracic &  Renal airway pressures  One or more new organ failures   renal perfusion   PaO2   GFR   PaCO2   urinary output 9