1. Acute Kidney Injury Jeffrey Coughenour, MD, FACS Medical Director, Surgical Critical Care

3. Acute Kidney Injury More than 35 definitions exist in literature Based on: – Serum creatinine, urine output, BUN, renal replacement therapy RIFLE Criteria proposed in 2002 Acute kidney injury in the intensive care unit: An update and primer for the intensivist Dennen P Crit Care Med 2010 Jan;38(1):261-75

4. RIFLE Criteria

5. AKIN Diagnostic Criteria Abrupt onset (within 48 hours) including: – Absolute increase in SCr ≥ 0.3 mg/dL OR – Percentage increase in SCr ≥ 50% OR – Reduction in urine output (< 0.5 mL/kg/hr x6) Requires two SCr values within 48 hours AKIN Stage 1-3 correlates with RIFLE risk, injury, and failure

6. Incidence Approximately 7% of all hospitalized patients 65-70% of critically ill patients – RIFLE Stage F 10-20% of ICU admissions AKI requiring RRT: Mortality range 50-70% Sepsis most common cause

7. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis Hoste EA Crit Care 2006;10(3):R73. Epub 2006 May 12 5,383 admissions 67% of all ICU admissions met AKI criteria 45% developed AKI after ICU admission Mortality – No AKI 5.5%, maximal RIFLE stage increased to 8.8%, 11.4%, 26.3% respectively

8. Defining the contribution of renal dysfunction to outcome after traumatic injury Harbrecht BA Am Surg 2007 Aug;73(8):836-40 3,968 patients with ISS ≥ 14 167 (4%) developed SCr > 2 Mortality 2.9% vs. 34.1% Hospital LOS 10.9 vs. 29.1 Ventilator days 2.4 vs. 12.7

9. AKI and Mortality Independent risk factor “AKI appears to increase the risk of developing severe non-renal complications that lead to death” Respiratory failure 20.7% vs 57.4% ICU mortality 14% vs 42.8% In-hospital mortality 7% vs 34%

10. Causes of AKI Top 5 Sepsis Major surgery Low cardiac output Hypovolemia Medications Other common causes Cardiopulmonary bypass IAH-ACS Trauma Rhabdomyolysis Obstruction

11. Risk Factors Nephrotoxic medications Radiographic imaging dye Gadolinium Trauma: Age > 60, higher ISS, multiple transfusions, GCS 6 OR 20.7, hemoperitoneum OR 11.9

12. Prevention Primary prevention best, often unpredictable Contrast-induced nephropathy – Give fluid, NAC, low volume non-ionic or isoionic contrast agent Albumin after large-volume paracentesis or SBP (day 1 and 3) may decrease incidence of AKI

13. Secondary Prevention Recognize underlying risk factors Maintain renal perfusion Avoid hyperglycemia Avoid nephrotoxins

15. Acute Oliguria “Lack of urine output in the acutely hypovolemic patient is renal success, not renal failure”

16. Oliguria Urine output less than 400 mL/day Should be accompanied by: – Increase in serum Cr ≥ 0.5 mg/dL above baseline – Increase in serum Cr ≥ 50% above baseline – Reduction in creatinine clearance ≥ 50% – Severe renal dysfunction requiring some form of renal replacement therapy

17. Prerenal Disorders Represents 50% of acute oliguric renal failure UNa < 20 mEq/L, FENa < 1% Hypovolemia Severe cardiac dysfunction Loss of vascular tone Renal vasoconstriction agents (NSAIDs) Reduction in GFP (ACE-inhibitors)

18. Intrinsic Renal Disorders Impaired glomerular filtration, renal tubular dysfunction, or both UNa > 40 mEq/L, FENa > 2% Described as three entities: – Acute glomerulonephritis – Acute tubular necrosis (most common) – Acute interstitial nephritis

19. Acute Tubular Necrosis Ischemia and inflammatory cell injury Slough of tubular epithelial cells into lumen Obstructed proximal tubule creates back- pressure decreases filtration Tubules and adjacent parenchyma involved

20. Postrenal Disorders Obstruction of urinary flow – Collecting system – Ureters – Bladder outlet Acute—prerenal values (<20, <1%) Chronic—renal values (>40, >2%) Uncommon

22. Clinical Application “This too shall pass– just like a kidney stone”

23. Serum Creatinine Standard surrogate measure of GFR Affected by non-renal factors common in the ICU (variable secretion, volumes of distribution) Late marker of AKI – Rise in SCr = ~ 50% loss of function

24. Renal Ultrasound Confirm number of kidneys Rule out obstruction Evaluate degree of chronicity if baseline lab values are unknown Measure degree of volume depletion (IVC)

25. Urine Microscopy – Examination of sediment, easy, cost-effective Abundant tubular epithelial cells (ATN) White cell casts (interstitial nephritis) Pigmented casts (myoglobinuria) If unrevealing, urinary sodium determination may be helpful

26. Urine Sodium In the setting of oliguria, urine sodium below 20 mEq/L usually indicates a prerenal disorder Elevated urine sodium can occur when a prerenal disorder is superimposed on intrinsic renal dysfunction (or diuretic therapy) One of the most reliable parameters to determine difference: FENa

27. FENa FENa < 1% = Prerenal disorder FENa > 2% = Intrinsic renal disorder

28. Optimize Central Hemodynamics CVP 6-8 mmHg CO low? Push CVP 10-12 mmHg Still low? Cardiac contractility measurement Consider inotropic support agent – Dopamine 5 mcg/kg/min – Dobutamine 5 mcg/kg/min – Goal CI above 3 L/min/m 2

30. Stroke Volume Variability Edwards Lifesciences, Irvine, CA

31. Stroke Volume Variability Correlation with “gold standard” of PAC debated Requires 100% mechanical ventilation Interference – Spontaneous respirations – Arrythmia

32. Avoid Fluid Overload SOAP study subset; 1,120 patients with AKI Association with positive fluid balance and increasing mortality Mean fluid balance differed between survivors and non-survivors Patients requiring RRT, increase in fluid balance 64.6% vs. 44.8% mortality Payen, Crit Care Med 2008

34. Maintain Perfusion To prevent or mitigate injury, especially with compromised autoregulation Volume Inotropic or vasopressor support Target MAP ≥ 65 generally accepted

35. Improving Perfusion If oliguria persists despite adequate filling pressure and flow… No evidence to support low-dose dopamine Mixed results with fenoldopam

36. Diuretics in AKI Studies conflicting re: affect on mortality No findings to support – Shortened duration of AKI – Reduced need for RRT – Improved outcomes Furosemide – Less than 10% of bolus dose reaches tubule lumen – Continuous infusion may be preferred method of delivery, 1-9 mg/hr rates reported

37. Hyperglycemia Decreased incidence of AKI and requirement for RRT with tight glucose control Tight blood glucose control is renoprotective in critically ill patients Schetz M, Vanhorebeek I, Wouters PJ, Wilmer A, Van den Berghe G J Am Soc Nephrol 2008 Mar;19(3):571-8 Epub 2008 Jan 30

38. Nutrition Malnutrition associated with increased mortality Prealbumin renally excreted, may falsely elevate in AKI AKI patients are hypercatabolic Consensus recommendation: 20-30 kcal/kg/day and 1.5 gm/kg/day protein

39. Treatment “Last week I would've given a kidney to anyone in this office. I would've reached right into my stomach and pulled it out for them. But now, no. I don't have the relationship with these people that I thought I did. I hope they ask, so they can hear me say, "Uh, no, I only give my organs to my real friends. Go get yourself a monkey kidney.“ --Michael Scott, The Office

40. Treatment CRRT Continuous renal replacement therapy SCUF Slow continuous ultrafiltration CVVH Continuous venovenous hemofiltration CVVHD Continuous venovenous hemodialysis

41. Classic Indications for RRT A—acidosis E—electrolyte disturbances I—intoxication O—overload U—uremia

42. Criteria for Initiation Non-obstructive oliguria Severe acidemia Hyperkalemia Uremic end-organ involvement Severe dysnatremia Hyper- or hyponatremia Overdose with dialyzable drug

43. Therapeutic GoalHemodynamicsPreferred Therapy Fluid removalStableIntermittent UF UnstableSCUF Urea clearanceStableIntermittent HD UnstableCRRT HyperkalemiaStableIntermittent HD UnstableIntermittent HD Metabolic acidosisStableIntermittent HD UnstableCRRT Cerebral edemaStableCRRT UnstableCRRT Adapted from Continuous Renal Replacement Therapy, John Kellum, Oxford Press 2009

44. Intermittent vs. Continuous Conflicting outcome data Recent meta-analysis demonstrated no difference in mortality What about renal recovery? – 2 studies—CRRT improved recovery – 4 studies—No difference – No definitive data

45. Continuous RRT Approximates “normal physiology” – Slow correction of metabolic disturbances – Volume removal better tolerated Goals – Maintain fluid, electrolyte balance, acid/base, prevent further renal damage, provide renal support pending recovery

46. Discontinuation of CRRT No consensus in nephrology or critical care literature UOP most important predictor of successful discontinuation – Greater than 400 mL/24 hrs without diuretics or > 2300 mL/24 hrs with diuretics, ≥ 80% chance of success Discontinuation of continuous renal replacement therapy: a post hoc analysis of a prospective multicenter observational study Uchino S Crit Care Med 2009 Sep;37(9):2576-82

47. Transition—CRRT to IHD No data – Hemodynamically stable – No vasopressor support – Need to mobilize patient ? – Need machine for more critically ill patient ?

48. Summary AKI is a common, complex condition Etiology often multifactorial Can be functional or structural “Acute kidney injury” replaces “acute renal failure” Small changes in SCr associated with adverse outcomes – Short and long-term increase in morbidity and mortality

49. Summary Diagnosis frequently delayed SCr poor marker of function in critically ill AKI increases risk of CKD AKI accelerates progression from CKD to ESRD Volume overload is associated with worse outcomes