Acute Kidney Injury in the Hospitalized Patient Biff F. Palmer, - PDF document

10/25/14 ¡ Acute Kidney Injury in the Hospitalized Patient Biff F. Palmer, M.D. Professor of Internal Medicine University of Texas Southwestern Medical Center, Dallas Texas Classification of Acute Kidney Injury 1 ¡

10/25/14 ¡ RIFLE Classification for Acute Renal Failure Stage GFR criteria ( over 7d ) Urine output criteria Risk S Cr increased 1.5-2 times UO < 0.5 ml/kg/h <6h baseline or GFR decreased >25% Injury S Cr increased 2-3 times UO < 0.5 ml/kg/h >12h baseline or GFR decreased >50% Failure S Cr increased >3 times UO < 0.3 ml/kg/h 24h baseline or GFR decreased or anuria 12 h >75% or S Cr ≥ 4 mg/dl; acute rise ≥ 0.5 mg/dl Loss of Function Persistent acute renal failure: complete loss of kidney function >4 wks ESRD Complete loss of kidney function >3 months Crit Care. 2004; 8(4): R204–R212 Acute Kidney Injury Network • Introduces term acute kidney injury (AKI) • Classification into stage 1-3 (replaces R,I,F) – Abrupt (within 48 h) reduction in kidney function: increase S Cr of 0.3 mg/dL or more ( ≥ 26.4 µmol/L) or – A percentage increase in S Cr of >50% or more (1.5-fold from baseline) or – A reduction in urine output (documented oliguria of < 0.5 mL/kg/h for >6 h) • Differences from RIFLE – Changes within 48h vs 7d – Less severe injury – Avoids using GFR criteria Crit Care. 2007; 11(2): R31. 2 ¡

10/25/14 ¡ Kidney Disease Global Outocmes Acute Kidney Injury (KDIGO) Classification Stage S Cr Criteria Urine output criteria 1 1.5-1.9 times baseline or < 0.5 ml/kg/h for 6-12h ≥ 0.3 mg/dl above baseline 2 2.0-2.9 times baseline < 0.5 ml/kg/h >12h 3 ≥ 3 times baseline, ≥ 4.0 mg/ < 0.3 ml/kg/h for ≥ 24h or dl, or intiation of renal anuria for ≥ 12 h replacement therapy Kidney Intl 2:1-138, 2012 The Incidence of AKI is Increasing 3 ¡

10/25/14 ¡ Incidence of AKI is Increasing in Hospitalized Patients Data from Medicare beneficiaries, 1992-2001 J Am Soc Nephrol 17:1135-1142, 2006 Why is the incidence of AKI is increasing? Probably increasing as high-risk patients are exposed to diagnostic and interventional procedures and nephrotoxic agents and/or develop sepsis or other hemodynamic disturbances 4 ¡

10/25/14 ¡ Risk Factors For AKI • Advanced age • Diabetes mellitus • Black race • Preexisting chronic kidney disease – Up to 10 times the risk vs absence of CKD N Engl J Med 371:58-66, 2014 A Graded Relationship Exists Between the ↑ S Cr and Risk of CKD and Mortality Study of 29,388 VA patients undergoing cardiac surgery between 1999-2005 Incident CKD ∆ Cr severity % Mortality ∆ Cr severity % Years ¡A/er ¡Index ¡Surgery ¡ CKD progression ∆ Cr severity % Arch Intern Med 171:226-233, 2011 5 ¡

10/25/14 ¡ Post-op RF in Cardiac Surgical Patients Predicts In- Hospital Mortality and Long Term Survival • Cardiac surgery in 843 patients , 145 with post-op AKI • AKI (>25% change in S Cr ) associated with increased in hospital mortality and higher 5 year mortality • This long term effect persisted even if S Cr had returned to baseline at discharge J Am Soc Nephrol 16:195-200,2005 Post-op AKI in Cardiac Surgical Patients Predicts In- Hospital Mortality and Long Term Survival Stable ≥ 25% J Am Soc Nephrol 16:195-200,2005 6 ¡

10/25/14 ¡ Acute Kidney Injury Chronic Kidney Disease Increased cardiovascular events Increased risk of ESRD Increased mortality N Engl J Med 371:58-66, 2014 Case • 71 year old women with stage 3 CKD, hypertension, and coronary artery disease is admitted with urosepsis. On admission she is hypotensive and is resuscitated with 4.2 L of NS and low-dose norepinephrine and started on broad spectrum antibiotics. One day later she is noted to have trace pedal edema and basilar crackles. Hemodynamics have improved. Urine output ranges from 600-750 ml/day. Furosemide was withheld for fear of worsening renal function. 7 ¡

10/25/14 ¡ Hospital Course 1 2 3 4 5 6 Serum 1.17 1.02 1.10 1.17 1.24 1.3 creatinine (mg/dl) Hospital Course 1 2 3 4 5 6 Serum 1.17 1.02 1.10 1.17 1.24 1.3 creatinine (mg/dl) UA Nl 1+ protein, 1+ protein, 3-5 RTEC/hpf 5-8 RTEC/ hpf, 1-3 RTC casts/lpf Weight 52 kg 55.5 kg 57.5 kg 8 ¡

10/25/14 ¡ By the KDIGO, serum creatinine and urine output criteria do not qualify as clinically defined AKI. However, the proteinuria and renal tubular cells and casts suggest some degree of renal injury Continuum of Renal Injury At risk kidney Incipient AKI Clinical AKI P GC P GC P GC 9 ¡

10/25/14 ¡ Need For Biomarkers in AKI • Lack of early biomarkers has impaired ability to initiate timely preventive and therapeutic measures Neutrophil Gelatinase-Associated Lipocalin (NGAL): A Novel Early Biomarker of Renal Injury • NGAL is one of the maximally induced genes and proteins immediately after injury • NGAL is easily detected in the urine very early after injury Am J Nephrol 24:307-15,2004 10 ¡

10/25/14 ¡ Urine NGAL is Increased 2 Hours After CPB In Patients Who Later Develop AKI 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Post CPB Time (hours) Lancet 365:1231-38,2005 Do increased NGAL levels predict adverse outcomes in the setting of a normal serum creatinine concentration? 11 ¡

10/25/14 ¡ In Absence of Increased S Cr NGAL Predicts Increased Risk for Adverse Outcomes Pooled data from 2,322 patients with predominately cardiorenal syndrome from 10 prospective observational studies of NGAL J Am Coll Cardiol 57:1752-61, 2011 Outcome of NGAL Positive Patients with Subclinical AKI J Am Coll Cardiol 57:1752-61, 2011 12 ¡

10/25/14 ¡ Urinary Biomarkers of Nephron Injury Are Predictive of Adverse Outcomes During Hospitalization Multicenter prospective cohort study in of 1635 ER patients at time of admission (Event rates: Dialysis initiation or death during hospitalization) J Am Coll Cardiol 59:246-55, 2012 Need For Biomarkers in AKI • Availability of biomarkers can facilitate early identification of AKI and allow initiation of preventive and or therapeutic measures: – Avoid nephrotoxins – Ensure hemodynamic stability, maintain MAP of at least 65 mmHg – Closely monitor fluids, urine output, CVP – Reno-protective agents 13 ¡

10/25/14 ¡ Continuum of Renal Injury At risk kidney Incipient AKI Clinical AKI P GC P GC P GC Early recognition and rapid renal recovery Feasible Strategies to Minimize Further Kidney Injury • Preferential use of balanced physiologic solutions for patients requiring fluid resuscitation 14 ¡

10/25/14 ¡ Types of Crystalloid Solutions • Balanced – A physiologic mixture of electrolytes and buffers designed to approximate makeup of plasma • Unbalanced – Typically contains NaCl and no other electrolytes or buffers Crystalloid Solutions Na + K + Ca 2+ Mg 2+ Cl - Buffer Glucose pH pOsm (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mg/dl) (mOsm/L) (mEq/L) Plasma 141 4.5 5 2 103 HCO 3 70-110 7.4 290 15 ¡

10/25/14 ¡ Crystalloid Solutions Na + K + Ca 2+ Mg 2+ Cl - Buffer Glucose pH pOsm (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mg/dl) (mOsm/L) (mEq/L) Plasma 141 4.5 5 2 103 HCO 3 70-110 7.4 290 Normal 154 - - - 154 - - 6.0 308 Saline Crystalloid Solutions Na + K + Ca 2+ Mg 2+ Cl - Buffer Glucose pH pOsm (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mg/dl) (mOsm/L) (mEq/L) Plasma 141 4.5 5 2 103 HCO 3 70-110 7.4 290 Normal 154 - - - 154 - - 6.0 308 Saline Lactated 130 4 4 - 109 Lactate - 6.5 274 28 (mEq/ Ringer’s L) solution 16 ¡

10/25/14 ¡ Crystalloid Solutions Na + K + Ca 2+ Mg 2+ Cl - Buffer Glucose pH pOsm (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mg/dl) (mOsm/L) (mEq/L) Plasma 141 4.5 5 2 103 HCO 3 70-110 7.4 290 Normal 154 - - - 154 - - 6.0 308 Saline Lactated 130 4 4 - 109 Lactate - 6.5 274 28 (mEq/ Ringer’s L) solution Plasma- 140 5 - 3 98 Acetate 27 7.4 294 mEq/L, Lyte gluconate 23 Normal Saline • Most commonly used crystalloid • The term “normal saline” comes from in vitro study of RBC lysis performed by Dutch physiologist Hartog Hamburger in 1890’s • His studies suggested 0.9% was concentration of salt in blood rather than true value of 0.6% 17 ¡

10/25/14 ¡ Potential Consequences of High Cl - Concentration in Normal Saline • Hyperchloremic metabolic acidosis – Dilution of extracellular fluid HCO 3 concentration – Volume expansion leading to decreased proximal HCO 3 reabsorption – Increased Cl - /HCO 3 exchange in β -intercalated cell (pendrin) – Plasma Cl - increases to greater extent than Na + narrowing strong ion difference thus causing increased H + generation to aid in restoring charge equilibrium Comparison of Rapidly Infused Crystalloids on Acid-base Status in Dehydrated Patients in ED 7.44 • Prospective DB Plasamalyte randomized trial in 90 7.42 patients with diagnosis 7.4 of dehydration of Lactated Ringer’s varying causes 7.38 • Blindly allocated to 7.36 Normal Saline receive either normal 7.34 saline, lactated Ringer’s, or Plasmalyte at 20 ml/ 7.32 kg/h for 2 hours 0 Hr 1 Hr 2 Hr Int J Med Sci 9: 59-64, 2012 18 ¡