1. In the name of GOD 1

2. 2  ischuria renalis, was by William Heberden in 1802.  At the beginning of the twentieth century, Acute Bright’s disease, was well described in William Osler’s Textbook for Medicine (1909), as a consequence of toxic agents, pregnancy, burns, trauma, or operations on thekidneys.  During the First WorldWar the syndrome was named ‘‘war nephritis’’, and was reported in several publications.

3. 3  The syndrome was forgotten until the Second World War, when Bywaters and Beall published their classical paper on crush syndrome.  It is Homer W. Smith who is credited for the introduction of the term ‘‘acute renal failure’’, in a chapter on ‘‘Acute renal failure related to traumatic injuries’’ in his textbook The kidney-structure and function in health and disease (1951).

4. 4  A recent survey revealed the use of at least 35 definitions in the literature.  Kellum JA, Levin N, Bouman C, et al. Developing a consensus classification system for acute renal failure. Curr Opin Crit Care 2002; 8: 509–514.

5. 5  AKI is defined by an abrupt decrease in kidney function that includes, but is not limited to, ARF.

6. 6  Because the manifestations and clinical consequences of AKI can be quite similar (even indistinguishable) regardless of whether the etiology is predominantly within the kidney or predominantly from outside stresses on the kidney, the syndrome of AKI encompasses both direct injury to the kidney as well as acute impairment of function.

7. AKI Definition 7

8. 8 AKI is defined as any of the following :  Increase in SCr by >=0.3 mg/dl within 48 hours  Increase in SCr to>= X1.5 times baseline, which is known or presumed to have occurred within the prior 7 days  Urine volume of <0.5 ml/kg/h for 6 hours.

9. Staging of AKI 9 StageSerum creatinineUrine output 1 1.5–1.9 times baseline OR >=0.3 mg/dl increase <0.5 ml/kg/h for 6–12 hours 22.0–2.9 times baseline<0.5 ml/kg/h for >12 hours 33.0 times baseline OR Increase in serum creatinine to >4.0 mg/dl OR Initiation of renal replacement therapy OR, In patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m2 <0.3 ml/kg/h for >24 hours OR Anuria for >=12 hours

10. 10  The cause of AKI should be determined whenever possible.

11. 11

12. 12

13. 13 AKI stagingUrine outputClassRIFLE Stage 1 Increase of more than or equal to 0.3 mg/dl or increase to more than or equal to 150% to 200% (1.5- to 2-fold) from baseline Less than 0.5 ml/kg/h for more than 6 hours RiskIncrease in serum creatinine*1.5 or GFR ↓ >25%

14. 14 AKI stagingUrine outputClassRIFLE Stage 2 Increased to more than 200% to 300% (>2- to 3-fold) from baseline Less than 0.5 ml/kg per hour for more than 12 hours InjurySerum creatinine *2 or GFR ↓ >50%

15. 15 AKI stagingUrine outputClassRIFLE Stage 3 Increased to more than 300% (>3- fold) from baseline, or more than or equal to 4.0 mg/dl with an acute increase of at least 0.5 mg/dl or on RRT Less than 0.3 ml/kg/h for 24 hours or anuria for 12 hours Failure Loss ESRD Serum cr*3, or serum cr>4 mg/dl with an acute ↑ >0.5 mg/dl or GFR ↓ >75% Persistent acute renal failure=complete loss of kidney function >4 weeks ESRD >3 months

16. 16 Baseline GFRIncrease in SCr during 7 consecutive days GFR during next 3 months Diagnosis >60>1.5NAAKI >60<1.5<60AKD WITHOUT AKI >60<1.5>60NKD <60>1.5NAAKI+CKD <60<1.5<35% decrease AKD WITHOUT AKI AND CKD <60<1.5>35% decrease CKD

17. Risk assessment 17

18. 18  We recommend that patients be stratified for risk of AKI according to their susceptibilities and exposures.

19. 19

20. 20  Manage patients according to their susceptibilities and exposures to reduce the risk of AKI.

21. 21  Test patients at increased risk for AKI with measurements of SCr and urine output to detect AKI.  Individualize frequency and duration of monitoring based on patient risk and clinical course.

22. Evaluation and general management of patients with and at risk for AKI 22

23. 23  Evaluate patients with AKI promptly to determine the cause, with special attention to reversible causes.

24. 24  Monitor patients with AKI with measurements of SCr and urine output to stage the severity.

25. 25  Manage patients with AKI according to the stage and cause.

26. 26

27. 27  Evaluate patients 3 months after AKI for resolution, new onset, or worsening of pre- existing CKD.  If patients have CKD, manage these patients as detailed in the KDOQI CKD Guideline.  If patients do not have CKD, consider them to be at increased risk for CKD and care for them as detailed in the KDOQI CKD Guideline 3 for patients at increased risk for CKD.

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29. 29

30. 30

31. Diagnostic approach to alterations in kidney function and structure 31

32. 32 Functional criteriaStructural criteria AKIIncrease in SCr by 50% within 7 days, OR Increase in SCr by 0.3 mg/dl within 2 days, OR Oliguria No criteria CKDGFR <60 ml/min per 1.73m2 for >3 months Kidney damage for >3 months

33. 33 Functional criteriaStructural criteria AKDAKI, OR GFR <60 ml/min per 1.73m2 for<3 months, OR Decrease in GFR by >35% or increase in SCr by 450% for3<months Kidney damage for <3 months NKDGFR >=60 ml/min per 1.73m2 Stable SCr No damage

34. 34

35. 35

36. Contrast-induced AKI 36

37. Contrast-induced AKI: definition, epidemiology, and prognosis 37

38. 38  Define and stage AKI after administration of intravascular contrast media as per Recommendations.  In individuals who develop changes in kidney function after administration of intravascular contrast media, evaluate for CI-AKI as well as for other possible causes of AKI.

39. 39  Many studies have now shown that patients who develop CI-AKI have a greater risk for death or prolonged hospitalization, as well as for other adverse outcomes, including early or late cardiovascular events.  when patients with CI-AKI require dialysis, the mortality is higher compared to those not requiring dialysis.

40. Assessment of the population at risk for CI-AKI 40

41. 41  Assess the risk for CI-AKI and, in particular, screen for pre-existing impairment of kidney function in all patients who are considered for a procedure that requires intravascular (i.v. or i.a.) administration of iodinated contrast medium.

42. 42

43. 43

44. 44  Consider alternative imaging methods in patients at increased risk for CI-AKI.

45. Nonpharmacological prevention strategies of CI-AKI 45

46. 46  Use the lowest possible dose of contrast medium in patients at risk for CI-AKI.

47. Additional radiological measures to reduce CI-AKI 47  Some CT strategies in patients at risk of CI-AKI  Perform CT, when possible, without contrast media.  Dosing per kilogram body weight to reduce the amount of contrast media is needed in thin patients.  Adapt injection duration to scan duration when performing CT-angiography, so that the injection is not still running when the scan is finished.  Use a saline chaser to decrease the amount of contrast media, by using the contrast medium that otherwise would remain in the dead space of the arm veins; this may save 10–20 ml of contrast media.

48. 48  …Some CT strategies in patients at risk of CI-AKI  Further reduction of contrast media may be instituted in patients with known decreased cardiac output (not unusual in patients with renal impairment) undergoing CT-angiographic studies.

49. 49  Some angiographic strategies in patients at risk of CI-AKI  Avoid test injections; the same amount may be enough for a diagnostic digital-subtraction angiography run.  Scrutinize each series before performing the next; avoid unnecessary projections.  Decrease kilovoltage in a thin patient; a lower iodine concentration may be used.

50. 50  Avoid ventriculography: echocardiography (and ‘‘echo contrast’’) is always a reasonable alternative.  Use plasma isotonic contrast-media concentrations for renal artery injections.  CO2 may be used as contrast medium in venous examinations and below the diaphragm for arterial examinations or alternatively use iodinated contrast media with the same contrast effect, i.e., about 40mg iodine per milliliter.

51. 51  We recommend using either iso-osmolar or low osmolar iodinated contrast media, rather than high-osmolar iodinated contrast media in patients at increased risk of CI-AKI.  Use selective or superselective catheterizations when appropriate, e.g., ‘‘single leg run-off’’.

52. Pharmacological prevention strategies of CI-AKI 52

53. 53  We recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v. volume expansion, in patients at increased risk for CI-AKI.

54. 54  We recommend not using oral fluids alone in patients at increased risk of CI-AKI.

55. 55  We suggest using oral NAC, together with i.v. isotonic crystalloids, in patients at increased risk of CI-AKI.

56. 56  We suggest not using theophylline to prevent CI-AKI.

57. Effects of hemodialysis or hemofiltration 57

58. 58  We suggest not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at increased risk for CI-AKI.

59. Dialysis Interventions for Treatment of AKI 59

60. Timing of renal replacement therapy in AKI 60

61. 61  Initiate RRT emergently when life- threatening changes in fluid, electrolyte, and acid-base balance exist.

62. 62  Consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests—rather than single BUN and creatinine thresholds alone—when making the decision to start RRT.

63. Potential applications for RRT 63  Renal support  This approach is based on the utilization of RRT techniques as an adjunct to enhance kidney function, modify fluid balance, and control solute levels.

64. 64  Volume control Recent studies have shown potential benefits from extracorporeal fluid removal in CHF. Intraoperative fluid removal using modified ultrafiltration has been shown to improve outcomes in pediatric cardiac surgery patients.

65. Potential applications for RRT 65  Nutrition Restricting volume administration in the setting of oliguric AKI may result in limited nutritional support and RRT allows better nutritional supplementation.  Drug delivery RRT support can enhances the ability to administer drugs without concerns about concurrent fluid accumulation.

66. 66  Regulation of acid-base and electrolyte status Permissive hypercapnic acidosis in patients with lung injury can be corrected with RRT, without inducing fluid overload and hypernatremia.  Solute modulation Changes in solute burden should be anticipated :tumor lysis syndrome. Although current evidence is unclear,studies are ongoing to assess the efficacy of RRT for cytokine manipulation in sepsis.

67. Criteria for stopping renal replacement therapy in AKI 67

68. 68  Discontinue RRT when it is no longer required, either because intrinsic kidney function has recovered to the point that it is adequate to meet patient needs, or because RRT is no longer consistent with the goals of care.

69. 69  We suggest not using diuretics to enhance kidney function recovery, or to reduce the duration or frequency of RRT.

70. Anticoagulation 70

71. 71  In a patient with AKI requiring RRT, base the decision to use anticoagulation for RRT on assessment of the patient’s potential risks and benefits from anticoagulation.

72. 72  For patients without an increased bleeding risk or impaired coagulation and not already receiving effective systemic anticoagulation, we suggest the following:  For anticoagulation in intermittent RRT, we recommend using either unfractionated or low-molecular-weight heparin, rather than other anticoagulants.

73. 73  For patients with increased bleeding risk who are not receiving anticoagulation, we suggest the following for anticoagulation during RRT:  We suggest using regional citrate anticoagulation, rather than no anticoagulation, during CRRT in a patient without contraindications for citrate.

74. 74  In a patient with HIT, all heparin must be stopped and we recommend using direct thrombin inhibitors (such as argatroban) or Factor Xa inhibitors (such as danaparoid or fondaparinux) rather than other or no anticoagulation during RRT.  In a patient with HIT who does not have severe liver failure, we suggest using argatroban rather than other thrombin or Factor Xa inhibitors during RRT.

75. Overview of the advantages and disadvantages of different anticoagulants in AKI patients 75 Heparin (unfractionated) Wide availability Large experience Short half-life Antagonist available Monitoring with routine tests(aPTT or ACT) Low costs Narrow therapeutic index – risk of bleeding Unpredictable kinetics – monitoring required HIT Heparin resistance

76. Overview of the advantages and disadvantages of different anticoagulants in AKI patients 76 Low-molecular-weight heparin More predictable kinetics– Weight-based dosing possible More reliable anticoagulant response– No monitoring required Single predialysis dose may be sufficient in IHD Reduced risk of HIT Risk of accumulation in kidney failure Monitoring requires nonroutine test (anti–Factor Xa) Different drugs not interchangeable Incomplete reversal by protamine In most countries more expensive than unfractionated heparin

77. Overview of the advantages and disadvantages of different anticoagulants in AKI patients 77 Citrate Strict regional anticoagulation– reduced bleeding risk Risk of accidental overdose with potentially fatal consequences Insufficient citrate metabolism in patients with ↓ liver function and shock states resulting in accumulation with metabolic acidosis and hypocalcemia Other metabolic complication (acidosis, alkalosis, hypernatremia, hypocalcemia, hypercalcemia) Increased complexity Requires strict protocol

78. Vascular access for renal replacemen therapy in AKI 78

79. 79  We suggest initiating RRT in patients with AKI via an uncuffed nontunneled dialysis catheter, rather than a tunneled catheter.

80. 80  When choosing a vein for insertion of a dialysis catheter in patients with AKI, consider these preferences (Not Graded):  First choice: right jugular vein;  Second choice: femoral vein;  Third choice: left jugular vein;  Last choice: subclavian vein with preference for the dominant side.

81. 81  We recommend using ultrasound guidance for dialysis catheter insertion.

82. 82  We recommend obtaining a chest radiograph promptly after placement and before first use of an internal jugular or subclavian dialysis catheter.

83. 83  We suggest not using topical antibiotics over the skin insertion site of a nontunneled dialysis catheter in ICU patients with AKI requiring RRT.

84. 84  We suggest not using antibiotic locks for prevention of catheter-related infections of nontunneled dialysis catheters in AKI requiring RRT.

85. 85

86. Prevention and Treatment of AKI Kidney International 86

87. Hemodynamic monitoring and support for prevention and management of AKI 87

88. 88  In the absence of hemorrhagic shock, we suggest using isotonic crystalloids rather than colloids (albumin or starches) as initial management for expansion of intravascular volume in patients at risk for AKI or with AKI.

89. 89  We recommend the use of vasopressors in conjunction with fluids in patients with vasomotor shock with, or at risk for, AKI.

90. Glycemic control and nutritional support 90

91. 91  In critically ill patients, we suggest insulin therapy targeting plasma glucose 110– 149 mg/dl.

92. 92  We suggest achieving a total energy intake of 20–30 kcal/kg/d in patients with any stage of AKI.

93. 93  We suggest to avoid restriction of protein intake with the aim of preventing or delaying initiation of RRT.  We suggest administering 0.8–1.0 g/kg/d of protein in noncatabolic AKI patients without need for dialysis,1.0– 1.5 g/kg/d in patients with AKI on RRT.

94. 94  We suggest providing nutrition preferentially via the enteral route in patients with AKI.

95. The use of diuretics in AKI 95

96. 96  We recommend not using diuretics to prevent AKI.  We suggest not using diuretics to treat AKI, except in the management of volume overload.

97. Vasodilator therapy: dopamine, fenoldopam, and natriuretic peptides 97

98. 98  We recommend not using low-dose dopamine to prevent or treat AKI.

99. 99  We suggest not using fenoldopam to prevent or treat AKI.

100. Prevention of aminoglycoside- and amphotericin-related AKI 100

101. 101  We suggest not using aminoglycosides for the treatment of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available.

102. 102  We suggest that, in patients with normal kidney function in steady state, aminoglycosides are administered as a single dose daily rather than multiple- dose daily treatment regimens.

103. 103  We recommend monitoring aminoglycoside drug levels when treatment with multiple daily dosing is used for more than 24 hours.

104. 104  We suggest monitoring aminoglycoside drug levels when treatment with single- daily dosing is used for more than 48 hours.

105. 105  We suggest using topical or local applications of aminoglycosides (e.g., respiratory aerosols, instilled antibiotic beads), rather than i.v. application, when feasible and suitable.

106. 106  We suggest using lipid formulations of amphotericin B rather than conventional formulations of amphotericin B.

107. 107  In the treatment of systemic mycoses or parasitic infections, we recommend using azole antifungal agents and/or the echinocandins rather than conventional amphotericin B, if equal therapeutic efficacy can be assumed.

108. Other methods of prevention of AKI in the critically ill 108

109. 109  We suggest not using NAC to prevent AKI in critically ill patients with hypotension.

110. Thank you 110