Acute Kidney Injury in the Critically Ill

1. Acute Kidney Injury in the Critically Ill Stephanie Davidson, ACNP-BC Vanderbilt University Medical Center Medical Intensive Care Unit

2. Objectives • Brief pathophysiology review • Name the 3 types of acute kidney injury • Review contrast nephropathy and its treatments • Discuss necessary diagnostic tests • Discuss treatment modalities for the 3 types of acute kidney injury

3. Epidemiology • Acute Kidney Injury (AKI) – occurs in up to 20% of ICU patients • 25% will require RRT • 5% of general hospital population • AKI is usually multifactorial • Sepsis • Hypotension • Drugs • Mortality rate up to 80%

4. Pathophysiology • Blood flows from renal arteries and is delivered to the glomeruli • Glomeruli form ultrafiltrate  delivered to renal tubules • Nearly free of protein and blood elements • Tubules reabsorb and secrete solute and/or water from ultrafiltrate • Final tubular fluid (urine) leaves kidneys and drains into renal pelvis to ureters, bladder, then urethra

5. Pathophysiology • Urine volume indicated kidney perfusion • Urine specific gravity and osmolality (concentrating ability) indicate tubular function

8. Definition • Lack of consensus definition in the past • Acute Dialysis Quality Initiative (ADQI) created • RIFLE criteria • Graded risks of injury • Has been validated in variety of critically ill populations • Acute Kidney Injury Network (AKIN) • Modified RIFLE criteria • Diagnostic and staging criteria for injury • Acute Kidney Injury to describe all levels of injury

9. Bellomo et al.,Critical Care 2004, 8:R204-R212 

10. RIFLE Criteria OR

11. AKIN Criteria • Based on abrupt (48 hr) increases • ⬆ Cr of ≥ 0.3 mg/dl from baseline OR • ⬆ in Cr of ≥ 50% OR • Oliguria ( < 0.5mg/kg/hr x 6 hrs or more) ✴✴Exclude obstruction if UOP is basis for diagnosis ✴✴Optimize volume status, then apply criteria Mehta, R, et al. Crit Care, 2007; 11:R31

12. Risk Factors for AKI • age > 75 yrs • chronic kidney disease (CKD, eGFR < 60 mls/min/1.73m2) • Cardiac failure • Atherosclerotic peripheral vascular disease • Liver disease • Diabetes mellitus • Nephrotoxic medications

13. Complications of AKI Marini, J & Wheeler, A, Critical Care Medicine, 2010

14. Types of AKI • Pre-renal • Hypoperfusion (shock, cirrhosis, CHF) • Volume depletion (GI bleed, dehydration) • Intra-renal • Acute interstitial nephritis (drug induced) • Acute tubular necrosis • Tumor Lysis Syndrome • Post renal • obstruction

15. Tests and Formulas • FENa - fractional excretion of sodium • Can help differentiate prerenal from ATN • Measures percentage of filtered Na that is excreted • If <1%: prerenal, if >1%: ATN • Not accurate if pt has received diuretics • (PCr x UNa)/ (PNa x UCr) x 100% • Na = mEq/L Cr = mg/dl • Feurea – fractional excretion of urea • Better estimation if pt has had diuretics • (serumCr x urineUrea)/ (serumUrea x urineCr) x 100% • all units in mg/dl

16. Tests and Formulas • Urine to plasma creatinine ratio • Estimates tubular water resorption • Creatinine in filtrate is equal to that of plasma • Urine Cr increases as water, not Cr, is reabsorbed

18. Common Diagnostics • Urinalysis • Serum BUN/Cr • Urine Na+ • FENa or FEurea • Urine osmolality • Urine to plasma Cr ratio • Urine volume • Renal ultrasound • Gold standard • Will show obstructions, hydronephrosis, kidney size • Consider CT abd/pelvis • Consider 24 hr urine collection

19. Prerenal Failure • R/T hypoperfusion and incomplete compensatory mechanisms • Causes: • Hypovolemia: dehydration, hemorrhage, diuretics, GI losses • Edematous states: cirrhosis, CHF • Renal artery stenosis, hepatorenal syndrome, compartment syndrome with elevated intraabdominal pressures • Results: • Kidney is normal: glomeruli, tubules and interstitium intact • Untreated can lead to ischemia • Can occur is MAP <60 for >30minutes; worse if patient is hypoxic

20. Compensatory Mechanisms

21. Prerenal Treatment • Treat underlying problem • GI losses • CHF/cirrhosis (intravascularly dry) • Attempt to reverse oliguria • Fluid challenge • Over 20-30 min; repeat if needed  monitor UOP • Use crystalloid solution, 15-30ml/kg x1 • Avoid if pt has s/s volume overload • Lasix challenge: one dose of 1mg/kg • Consider invasive monitoring • CVP

22. Intrarenal Failure Tubular Disorders Interstitial Nephritis Glomerulonephritis and small vessel vasculitis

23. ATN • Sudden decline in GFR, accumulation of nitrogenous wastes, and dysregulation of electrolytes and acid-base balance • Causes: • Prerenal if delayed treatment • Hypotension • Sepsis • Tumor lysis syndrome • Nephrotoxic substances • Drugs: aminoglycosides, amphotericin, cyclosporine, ACEi, NSAIDs • Ethylene glycol/methanol

25. ATN Treatment • Treat underlying cause • Sepsis, hypotension, ischemia, drugs • Avoid volume overload • Nonoliguric renal failure has better outcomes than oliguric • Monitor for hyperkalemia and treat • Monitor acid-base status (BMP)

26. ATN Treatment • Consult nephrology • Courtesy and evaluate for possible RRT • Monitor for AEIOU of HD • A = acidosis/alkalosis • E = electrolyte disturbances • I = Intoxications (methanol, ethylene glycol, salicylate) • O = overload (volume) • U = uremia • If any of these exist or are refractory, pt may need dialysis

27. -Decision when to start hemodialysis is difficult and cannot be guided by a single objective measure -Delaying until patient is symptomatic could increase risk of harm and/or death Tattersall, J., et al, Neph. Dial. Transplant (2011). 26(7):2082-2086

28. Contrast-Induced Nephropathy • Evaluate risk vs. benefit of test • Occurs within 72 hrs of contrast given • Can resolve within 5 days • Prevent with fluid • 0.9% saline: 1mL/kg x 12 hrs pre and post procedure • Isotonic bicarb: same dosing • No consensus on which is better • No evidence for NAC (mucomyst) • Consider holding ACE-I/ARB and metformin prior to contrast

29. AIN • Drug induced allergic reaction in the renal interstitium • Common drugs: PCN, cephalosporins, sulfonamides, quinolones, rifampin, thiazides, furosemide, NSAIDs, allopurinol, cimetidine • Oliguria and rising serum creatinine often only indicators • ¼ of patients will have eosinophilia • ⅔ of patients will have eosinophiluria • Discontinue offending drug, consider steroids Marini, J & Wheeler, A, Critical Care Medicine, 2010

31. Post Renal Failure • Less than 10% of AKI cases • High suspicion if abrupt stop in flow or decreased UOP • Causes: • Renal calculi/clots • Prostatic hypertrophy • Ureteral stone • Rhabdomyolysis • Check renal ultrasound- hydronephrosis, renal obstruction • Consider CT of abd/pelvis • Treat underlying cause

33. Outcomes and Prognosis • AKI patients associated with • Increased hospital and long term mortality • Longer hospital LOS • Increased costs • AKI patients requiring HD • Extremely high risk for CKD • 10% may go on to develop ESRD **Importance to have post-discharge follow up with nephrologist Waikar, S. & Bonventre, J., Harrison’s Principles of Internal Medicine, 2012.

34. References Bellomo, R, et al. Acute renal failure-definition, outcome measures, aminal models fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8:R 204. Erdbruegger, U. and Okusa, M. (2012). Etiology and diagnosis of acute tubular necrosis and prerenal disease. Retrieved from www.uptodate.com. Esson, M. and Schrier, R. (2002). Diagnosis and Treatment of Acute Tubular Necrosis. Annals of Internal Medicine, 137: 744-752 Fink, M., Abraham, E., Vincent, J.L., and Kochanek, P. (2005). Textbook of Critical Care (5th ed.). Philadelphia, PA: Elsevier Saunders. Levin, A, et al. Improving outcomes from acute kidney injury: report of an initiative. Am J Kidney Dis. 2007; 50:1.

35. References Lewington, A. and Kanagasundaram, S. (2011). Summary of clinical practice guidelines for acute kidney injury. Retrieved from www.renal.org/Clinical/GuidelinesSection/AcuteKidneyInjury.aspx McPhee, SJ and Papadakis M. (2008). Current Medical Diagnosis and Treatment. Tierney Jr, Lawrence (Ed.). New York, NY: McGraw Hill Medical. Neesh, P., Nadim, M., An overview of drug-induced acute kidney injury. Critical Care Medicine, 2008; 36: No 4 (suppl). Palevsky, P. (2012). Definition of acute kidney injury (acute renal failure). Retrieved from www.uptodate.com. Post, T. and Rose, B. (2012). Diagnostic approach to the patient with acute or chronic kidney disease. Retrieved from www.uptodate.com. Ricci, A., Cruz, D., and Ronco, C. (2008). The RIFLE criteria and mortality in acute kidney injury: A systematic review. Kidney International, 73, 538- 546

36. References Tattersall, J., et al. When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) Study. Nephrol. Dial. Transplant (2011) 26(7). 2082-2086. Waikar S.S., Bonventre J.V. (2012). Chapter 279. Acute Kidney Injury. In Longo D.L., Fauci A.S., Kasper D.L., Hauser S.L., Jameson J, Loscalzo J (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved August 16, 2014 fromhttp://accessmedicine.mhmedical.com/content.aspx?bookid=331&S ectio nid=40727068.