Acute kidney injury definition, causes and pathophysiology Financial Disclosure Current support: Center for Sepsis and Critical Illness Award P50 GM-111152 from the National Institute of General Medical Sciences Azra Bihorac, MD MS FASN FCCM Associate Professor Anesthesiology, Medicine and Surgery University of Florida Previous Research Support: NIH, SCCM and Astute, Inc. Biases I am Nephrologist I am Intensivist 23-Jun-15 2 Some History Trivia Balkan nephropathy-1984-1986 Bosnian war-1992 ISN AKI Task Force in Crash Syndrome after earthquake in Turkey-1999 ISN fellowship at UF 2000 Key Points AKI is one of the most common hospital complications Kidney health must be assessed at hospital admission using history, estimated GFR and urine dipstick at the minimum AKI should be diagnosed and staged using consensus criteria Kidney can acutely suffer from many different causes Primary prevention is the key What is AKI Clinical syndrome Rapid (hours to days) decrease in renal excretory function Accumulation of waste nitrogen metabolism (creatinine, urea, unmeasured waste) metabolic acids potassium and phosphate Decreased urine output (not always) KDIGO-Kidney Disease: Improving Global Outcomes KDIGO- Or increase in scr 0.3 mg/dl 5 23-Jun-15 6 Bellomo et al, CC 2004 1
Diagnosis of AKI Incidence of AKI Rise in serum creatinine of 0.3 mg/dl or greater within 48 hours 50% or greater known or presumed to have occurred within the past 7days Fall in urine output to less than 0.5 ml/kg/hour for more than 6 hours in adults Monitor serum creatinine regularly in all people with or at risk of AKI 23-Jun-15 7 Non-dialysis-requiring AKI >5000 cases per million people per year Dialysis-requiring AKI 295 cases per million people per year Hospitalized patients 1.9% among all patients ICU (10-50%) > 36% on the day after ICU admission > 60% during ICU admission 8 Hsu Kidney Int 2007, Bagshaw Crit Care 2008, Hoste Crit Care 2006, Bihorac CCM 2013 Developing countries Late presentation, underreporting, lack of intensive care Kidney injury lead to up to 3% of admissions in general health-care facilities young, previously healthy individuals predisposing disease Developing Countries Malaria: 1-5% of cases HIV/AIDS: 50% Leptospirosis: 20 85% Dengue hemorrhagic fever: 3 11% Hantavirus hemorrhagic fever: 5% Pediatric AKI India 5-9% inpatient wards 25-36% in PICU Nigeria - 17.4 cases per 1000 children 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Prevalence of KDIGO-AKI for different surgery types No AKI AKI Failure vs no AKI Injury vs no AKI Risk vs no AKI The RIFLE and mortality in trauma patients 11% 8% 7% Bihorac et al, www.prisma-p.org Odds Ratio 1 2.5 2.7 4.6 10 23-Jun-15 Bihorac et al, Ann Surg 2010 12 2
Survival (%) Renal recovery Last measured Cr / mincr Survival (%) 23-6-2015 RIFLE and mortality AKI other complications Postoperative Complications 90-day mortality KDIGO-AKI (compared to no KDIGO-AKI) Percent change in creatinine (for every 10% change) Absolute Change in creatinine (per 0.1 mg/dl change) 2.9 (2.6, 3.3) 1.03 (1.03, 1.04) 1.06 (1.06, 1.07) Severe sepsis 30.8 (21.7, 43.8) 1.06 (1.05, 1.06) 1.10 (1.09, 1.10) MV > 14 days 6.2 (5.4, 6.9) 1.06 (1.05, 1.06) 1.08 (1.07, 1.08) Risk (RR=2.40; 58 073 participants in meta-analysis) Injury (RR=4.15; 55 351 participants in meta-analysis) Failure (RR=6.37; 53 758 participants in meta-analysis) 23-Jun-15 Ricci et al, 2008 13 Bihorac et al, Crit Care Med 2013. 100 Survival after perioperative AKI 100 90 Log-Rank p-value < 0.001 90 80 70 60 50 40 79% 71% 63% 55% No AKI Risk Injury Failure 50% 44% 38% Log-Rank p-value < 0.001 67% 30 Years after Hospital Discharge 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Bihorac and Segal, Ann Surg 2009. Hobson and Bihorac, Circulation 2009. 15 80 70 60 50 40 30 No AKI Complete recovery (CR) Partial recovery (PR) No recovery (NR) 20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years after Hospital Discharge Renal Recovery AHR Complete recovery 1.24 (1.14 1.35) Partial recovery 1.46 (1.33 1.59) No recovery 2.46 (1.91 3.17) Adjusted for age, sex, race, LOS, ICU LOS, DM, A fib, CHF, CPD, MV, Sepsis, type of surgery, discharge site Bihorac and Segal, Ann Surg 2009. Serum creatinine and 90-day mortality Cardiovascular mortality and perioperative kidney disease Odds ratio for dying given specific values for continuous risk factors. Severity of AKI Bihorac A, www.prisma-p.org Ann Surgery 2015 (in press) 51,457 adult surgical patients after major surgery Bihorac A, www.prismap.org 3
$1000 23-6-2015 Cardiovascular mortality and kidney disease Variable Adjusted Hazard Ratios AKI no CKD 2.11 (1.95, 2.27) AKI and CKD 3.95 (3.54, 4.41) CKD no AKI 2.12 (1.82, 2.47) ESRD 5.38 (4.74, 6.10) Age 1.04 (1.04, 1.04) Male 1.04 (0.98, 1.11) African-Americans 1.10 (1.01, 1.21) Charlson Comorbidity Index > 3 2.48 (2.22, 2.77) Admission Hemoglobin<10 g/dl 1.11 (1.01, 1.21) Admission Hemoglobin [10,12) g/dl 1.13 (1.04, 1.23) Cost of AKI 50,314 adult surgical patients. Adjusted Relative Cost Ratio (95% CI) Patients with no acute kidney injury 1 (Reference) Patients with any acute kidney injury 1.53 (1.52, 1.55) Acute kidney injury, Stage RIFLE-R 1.36 (1.34, 1.38) Acute kidney injury, Stage RIFLE-I 1.70 (1.67, 1.73) Acute kidney injury, Stage RIFLE-F 2.09 (2.05, 2.13) Incremental cost for AKI between $9000 and $26,000. 51,457 adult surgical patients after major surgery Hobson and Bihorac, Ann Surg 2014 AKI magnifies the cost of other complications Causes of AKI 120 100 80 60 40 20 No AKI AKI Hospital Sepsis and infection Major Surgery Heart failure Nephrotoxic drugs IV Radiocontrast Hepato-renal syndrome Community Dehydration Infection Obstruction Glomerular diseases Malignant hypertension 0 No PC MV CV/pressors Severe Sepsis Hobson and Bihorac, Ann Surg 2014 23-Jun-15 22 Nephrotoxic Drugs Toxic when not properly dosed Be aware of renal clearance and lack of it! Opioids Benzodiazepines Vancomycin 4
Developing Countries Community-acquired AKI Young and healthy Diarrhea, Tropical infections HUS, Post-infectious GN Snake bites, Medications HIV/AIDS Drug-induced hemolysis in G6PD deficiency Hurricane, earthquake-rhabdomyolysis Developing Countries Obstetric AKI 7-52% of AKI cases First trimester Sepsis Hemorrhage Abortion Third trimester Puerperal sepsis Eclampsia Post-partum hemorrhage Old Concepts Prerenal, Intrinsic or Postrenal Acute Kidney Injury Prerenal Uosm > 500 mosm/kg Una < 20meq/L FEna < 1% Microscopy - bland Intrinsic Renal Diseases Postrenal Uosm: variable Una: low early, high late FEna: variable Microscopy - bland Ischemic / Toxic ATN Uosm ~ 300 mosm/kg Una > 40meq/L FEna > 2% Microscopy dark pigment cast Acute Interstitial Nephritis Uosm: variable, ~300 mosm.kg Una > 40 meq/l FEna > 2% Microscopy leukocytes, erythrocyts, leukocyte casts Acute Glomerulonephritis Uosm: variable (>400 in early GN) Una: variable (<20meq/l in early GN) FEna: variable, <1% in early GN Microscopy hematuria, proteinuria Erythrocyte casts (dysmorphic) Bellomo, Lancet 2012 A perfect blood scrubber How to guarantee removal of any substance from the blood: Filter all the plasma. This is what the kidney does. Why the Kidney Kidney produces 100-200 L of ultrafiltrate daily The entire plasma volume is filtered every 30 min. 99% of the renal filtrate is reabsorbed. Proximal tubular epithelial cells are exposed to toxins and mediators coming from remote tissues or exogenously 29 30 5
Acknowledgment www.prisma-p.org Twitter @azrabihorac E-mail azra.bihorac@gmail.com 23-Jun-15 31 6