This document summarizes the pathogenesis and management of acute renal failure. It discusses the causes and stages of pre-renal, intrinsic renal, and post-renal acute kidney injury. Key factors in preventing acute renal failure in surgical patients include adequate hydration, maintaining renal perfusion pressure, avoiding nephrotoxins, and aggressive treatment of complications such as hyperkalemia. Treatment may involve renal replacement therapies like hemodialysis when criteria for initiation are met.

1. AETIOPATHOGENESIS & MANAGEMENT OF ACUTE RENAL FAILURE PRESENTER Dr Unnikrishnan P COORDINATOR Dr Sugandha MODERATORS Dr Sheela Rani Dr Suneesh DEPT OF ANESTHESIOLOGY, MCH-TVM

2. . Human beings are essentially big bags of water, the volume of which must be kept under tight control, to prevent us from either drying out or drowning…..

3. Highlights… FOLLOWING THE TRENDS…. CAPTURE THE KEYS TO OPEN THE DOOR HOW TO PREVENT ARF [Anesthetist Rested during Failure] NEVER ENDING CONTRAVERSIES REPLACING KIDNEY […very difficult]

4. ‘ ACUTE KIDNEY INJURY’ Abrupt reduction [<48 hrs] in kidney function, defined as an absolute increase in S creatinine of ≥0.3 mg/dL A percentage increase in S creatinine of ≥ 50% [1.5 fold from baseline] or a reduction in urine output-- documented oliguria of < 0.5 ml/kg/hr, for more than six hours.

5. STAGING SYSTEM FOR A.K.I. STAGE S.CREATININE CRITERIA URINE OUTPUT CRITERIA 1 INCREASE IN S.CREATININE ≥0.3mg/dL OR INCREASE TO ≥ 150-200% FROM BASELINE <0.5 ml/kg/hr FOR >6HRS 2 INCREASE IN S.CREATININE TO >200-300%[2-3 FOLD] FROM BASELINE <0.5 ml/kg/hr FOR >12 HRS 3 INCREASE IN S. CREATININE TO >300%[>3 FOLD] FROM BASELINE OR S.CREATININE OF ≥4mg/dL WITH AN ACUTE INCREASE OF ATLEAST 0.5 mg/dL <0.3ml/kg/hr FOR 24 HRS OR ANURIA FOR 12 HRS

6. RIFLE criteria

7. CLASSIFICATION

8. AETIOPATHOGENESIS .

9. PRERENAL ARF Most common Renal hypo perfusion Important form in perioperative period

10. . CAUSES-PRERENAL ARF HYPOVOLEMIA >HEMORRHAGE >G-I LOSSES >DECREASED INTAKE >URINARY LOSSES >SKIN LOSSES >OTHERS:BURNS,PANCREATITIS,SEVERE HYPOALBUMINEMIA ALTERED RENAL HEMODYNAMICS LOW CARDIAC OUTPUT STATES >CHF >VALVULAR HEART DISEASE >PPV > REDUCED VENOUS RETURN SYSTEMIC VASODILATION >SEPSIS >ANTIHYPERTENSIVES >VASODILATORS >ANAPHYLAXIS RENAL VASOCONSTRICTION >CATECHOLAMINES >HYPERCALCEMIA IMPAIREMENT OF RENAL AUTOREGULATION >NSAIDs >ACE-I >ARBs HEPATORENAL SYNDROME

11. HYPOVOLEMIA- extrinsic

12. HYPOVOLEMIA- intrinsic Tubuloglomerular feedback Afferent arteriolar vasodilatation Preferential efferent arteriolar vasoconstriction Aim is to utilize the existing filtration reserve maximally

13. In short…. EXTRINSIC  INCREASE MAP, IMPROVE INTRAVASCULAR VOLUME INTRINSIC  IMPROVE RENAL PLASMA FLOW, GFR & GLOMERULAR PRESSURE

14. When the insult cross the limits…. Compensatory mechanisms overwhelmed  renal perfusion decrease  GFR fall Decreased O2 delivery  needs to decrease its work  decrease filtration  oliguria Increased Na reabsorption = more work by medulla  blood flow towards medulla ,i.e. away from cortex  GFR decrease  oliguria “ acute renal success” Increase perfusion pressure If we wait …..ATN

15. Hepatorenal syndrome Unique form of prerenal ARF Structurally normal Profound renal vasoconstriction Correction of liver disease  resolution

16. INTRINSIC ARF CAUSES RENOVASCULAR >ATHEROEMBOLISM >MALIGNANT HTN > >HUS > DIC >PREECLAMPSIA GLOMERULAR >AGN TUBULES -ATN ISCHEMIA >MAJOR CARDIOVASCULAR Sx >TRAUMA >HEMORRHAGE >HYPOVOLEMIA TOXINS Exogenous: Radiocontrast dye,Antibiotics-Aminoglycosides,Chemotherapeutic agents-Cisplatin, Amphotericin-B, Ethylene glycol Endogenous: myoglobin,hemoglobin,calcium,bilirubin SEPSIS INTERSTITIUM Allergic: Antibiotics : b-lactam ,quinolone , rifampin NSAIDs B/L pyelonephritis INTRATUBULAR OBSTRUCTION acyclovir, methotrexate , indinavir , myeloma proteins

17. Ischemic ATN 4 PHASES INITIATION:GFR DECREASE , OBSTRUCTION BY DEBRIS , BACKLEAK EXTENSION : CONTINUED…. MAINTENANCE : GFR LOWEST , URINE O/P LOWEST, UREMIC COMPLICATIONS MAY OCCUR RECOVERY : EPITHELIAL CELL REGENERATION , GFR RETURNS

18. The so called diuretic phase… Recovery phase Filtration recovers early Recovery of epithelial function lags behind

19. Nephrotoxic ATN RISK FACTORS Advanced age Preexisting kidney disease Hypovolemia CCF Multiple myeloma

20. Toxins….

21. Contrast nephropathy FEATURES REVERSIBLE ACUTE ONSET [24-48 HRS] PEAK 3-5 DAYS RESOLUTION IN ONE WEEK B UREA & S CREATININE INCREASE

22. Atheroembolic ATN After manipulation of aorta or renal arteries during surgery / angiography / trauma In patients with atherosclerosis Frequently irreversible

23. POSTRENAL ARF Obstruction is always the most likely cause when there is anuria B/L ureteric U/L ureteric if single functioning kidney Bladder neck obstruction Urethral

24. Perioperative oliguria - pathophysiology Anesthetic agents: no renal vasodilation per se ; effects by reducing CO & BP EDB & high spinal anesthesia reduce sympathetic tone PPV decrease renal blood flow ACE-I cause significant reduction in perfusion pressure during anesthesia Narcotics can increase ADH response

25. Raised intra abdominal pressure Normal 0-17mm of Hg >20 mm of Hg  compression of pelvis  anuria Improvement occurs only after decompression May also cause false high CVP readings due to decreased venous return SITUATIONS EMERGENCY LAPAROTAMIES LEAKING ABD AORTIC ANEURISMS INTESTINAL DISTENSION PARALYTIC ILEUS ASCITES

26. Clinical features

27. Pre renal vomiting , diarrhoea Intestinal obstruction…. Carry over cases..NPOOOOOOO Look for Thirst Reduced JVP Decreased skin turgor Dry mucus membrane

28. Intrinsic renal oliguria,edema,hypertension  AGN Intake of nephrotoxic drugs h/o atrial fibrillation : renal artery thrombus h/o vascular surgeries : atheroembolic ARF Muscle trauma : rhabdomyolysis

29. Post renal Anuria Flank pain h/o prostatic disease

30. INVESTIGATIONS

31. URINE MICROSCOPY CONDITION FINDINGS PRERENAL TRANSPARENT HYALINE CAST POSTRENAL HYALINE CAST/PUS CELLS/HEMATURIA ATN MUDDY BROWN GRANULAR/EPITHELIAL CAST INTERSTITIAL NEPHRITIS WBCs, RBC CASTS, NON-PIGMENTED GRANULAR CAST,EOSINOPHILS, LYMPHOCYTES AGN RBC CASTS

32. Assessment of GFR

33. Blood urea 15-40mg/dL Increased in dehydration , post G-I bleed May be a better guide in timing dialysis to avoid uremic complications

34. Serum creatinine Normal: <1.5 mg/dL Overestimate GFR Lags behind renal injury & recovery Rise by 1-2 mg/dL in ARF,>2mg/dL in rhabdomyolysis Critically ill patient: a “normal” value may not be normal condition creatinine prerenal fluctuate ATN Peak by 7-10 days Contrast nephropathy Ischemic ATN Rise within 24-48hrs, peak in 3-5 days , reach baseline in 7-10 days AMINOGLYCOSIDE Rise delayed till 2 nd week

35. Creatinine clearance Volume of plasma cleared off creatinine per unit time Earlier warnings, 2hr samples [140-age] x body wt / S.Creatinine x 72 91-130 ml / min CrCl = U. Creatinine [mg/dL] x volume [mL/min] P Creatinine[mg/dL] S cystatin C

36. Assessment of tubular function Renal Failure Indices PRERENAL INTRINSIC FENa <1 >1 URINARY Na <20 >40 URINE OSM >400 250-300 URINE:PLASMA OSMOLALITY 1.4:1 1:1 Ur.Cr : P. Cr >50:1 <20:1 BUN/Cr >20 <10 SPECIFIC GRAVITY >1.018 <1.015

37. Assessment of tubular function Differentiate pre renal from intrinsic renal failure FeNa is the most useful Ratio of Na clearance to Creatinine clearance Prerenal  intact tubules  Na reabsorption avidly takes place  Cr Cl high  FENa <1 ATN  Na absorption impaired  FENa > 1 CKD & diuretics also FENa >1 Metabolic alkalosis  FECl better

38. Radiology Abdominal USG Small  Htve Nephrosclerosis , CRF Normal / large  DM , Amyloidosis Large kidneys with large dilated pelvis and ureters Pyelography : localization MRA/ Doppler US : arterial /venous obstruction

39. Others renal biopsy Increased potassium ,phosphorus , CK-MM, Uric Acid, decreased Calcium  rhabdomyolysis

40. Complications .

41. Complications .

42. Complications .

43. Also… hyperphosphatemia Infection Uremic syndrome Hypovolemia due to vigorous diuresis in recovery

44. Prevention of ARF- in perioperative period

45. Identify patients at risk PATIENT FACTORS TYPE OF SURGERY CKD CARDIOPULMONARY BYPASS ELDERLY AORTIC ANEURYSM SURGERY NEPHROTOXINS HEPATIC/RENAL TRANSPLANTATION HYPOVOLEMIA/HYPOTENSION SURGERY IN TRAUMA/BURNS SEPSIS HEMORRHAGE LIVER DISEASE/JAUNDICE DM,HTN MULTIPLE MYELOMA PREECLAMPSIA MASSIVE BLOOD TRANSFUSION ATHEROSCLEROTIC DISEASE CARDIAC DYSFUNCTION

46. Adequate pre-intra & post op hydration Large bore cannula Calculate for deficit correction ,maintenance,3 rd space losses Fluid challenge:250-500mL of NS over 10-15 mins If CVP monitoring established:  small elevation[1-2mm]= need more  large increase[5mm] = be slow Colloid Controversies  over use  in sepsis

47. Maintain renal perfusion pressure Maintain MAP at 70-100 mm of Hg Catecholamines may help if there is a cause for hypotension other than hypovolemia

48. Hemodynamic &urinary output monitoring Blood pressure CVP PAWP Urine output  ensure catheter is not compressed  ensure good urine flow from start  monitor output hourly  ensure output >1ml/kg/hr

49. Avoid nephrotoxins ACE-I & ARB NSAIDs AMINOGLYCOSIDES AMPHOTERICIN-B CISPLATIN ASPIRIN CYCLOSPORIN LMW-DEXTRAN ACYCLOVIR,INDINAVIR METHOTREXATE

50. Aggressive fluid loading Trauma Compartment syndrome Limb revascularization … .high chance for rhabdomyolysis

51. Adequate oxygenation

52. Pharmacologic strategies

53. Mannitol Improve urinary flow Plasma expansion Osmotic hemodilution Free radical scavenging Volume increase  volume depletion Increase O2 consumption Pulmonary edema, intra renal vasoconstriction

54. Mannitol 6.25-12.5g is given 15 mins prior to the defined insult / repeated 4-6 hrs 24 hr cumulative dose not >1.5 mg/kg Aortic surgeries Renal transplantation CABG rhabdomyolysis

55. Frusemide Inhibit Na-K ATPase in mTAL Renal vasodilation Clear debris oliguric to non oliguric conversion segmental blockade with thiazide e.g. metolazone 2.5-5.0mg po Ototoxicity, interstitial nephritis Shouldn’t be given if pt is not adequately fluid loaded

56. Frusemide Pigment nephropathy[ 2-3 times the normal dose with aggressive hydration] Contrast nephropathy [with saline] May reverse medullary hypoxia induced by toxins 2-10 mg/kg for converting oliguric to non oliguric renal failure Continuous infusion 1-10mg/hr after a LD of 10-20mg

57. Dopamine Non specific DA1+DA2 agonist “ subpressor dopamine has proved ineffective in clinical trials , may trigger arrhythmias and should not be used as a renoprotective agent in this setting” S/E: increased myocardial O2 consumption, decrease hypoxic drive, intestinal ischemia

58. Others Fenoldapam Nor adrenaline Dopexamine CCBs PGE1 ANP ADENOSINE AMINOSTEROIDS

59. ALSO NOTE… FORCED ALKALINE DIURESIS IN RHABDOMYOLYSIS N-ACETYL CYSTINE IN ACETAMINOPHEN INDUCED INJURY CONTRAST NEPHROPATHY  hydration , n-acetyl cystiene , theophylline/aminophyllin, bicarbonate containing IVFs[rather than saline]

60. Treatment of complications of ARF

61. Hyperkalemia regular insulin 10 u + glucose [50 mL 50% dextrose Ca gluconate 105 10 mliv Inhaled salbutamol 5 mg nebulised Kayexelate,Na polystyrene sulfonate NaHCO3 50-100 mEq iv dialysis

62. others Metabolic acidosis: NaHCO3 to keep its level >15mmol/L or pH >7.2 Hyperphosphatemia :Ca carbonate, Al(OH)3 Hypocalcemia :Ca gluconate , CaCl2 Nutrition Anemia Rx of CHF

63. Renal replacement therapy

64. Criteria for initiation of RRT Anuria Oliguria Pulmonary edema Hyperkalemia >6.5mmol/L Severe acidemia <7.2 Uremic encephalopathy Uremic pericarditis Drug overdose with dialyzable toxins

65. Dialysis dialyser,dialysate,blood delivery system Vascular access Diffusion technique  heparinized blood and dialysate flows in opp direction through a synthetic membrane down a conc. gradient Convection technique  similar to what happens in glomeruli. Blood passes across a filter which has pores of different sizes so as to filter various molecules

66. hemodialysis ADVANTAGES Efficient solute removal in short period of time Lower cost more suitable in severe hyperkalemia more effective than PD in ARF

67. hemodialysis DISADVANTAGES Need for large bore venous access Need for anticoagulation No removal of cytokines Unsuitable if hemodynamically unstable

68. Complications Hypotension: poor tolerance to fluid removal or due to acetate component. Treatment  decrease blood flow rate , IVFs Hypoxemia : loss of CO2 via dialyzer , bronchospasm ,Treatment:Adr / b-agonist / aminophylline Hemorrhage : 1mg of protamine  100iu of heparin Arrhythmias Dialysis disequilibrium syndrome: headache, nausea, delirium, seizures

69. hemodialysis Intermittent HD: 3-4hrs per day,3-4 times per week Slow Low Efficiency Dialysis ^-12 hrs per day

70. Continuous RRT When intermittent HD fails When patient is not tolerating intermittent HD due to hemodynamic instability

71. Types Arteriovenous Venovenous

72. Venovenous Continuous venovenous hemodialysis Continuous venovenous hemofiltration Continuous venovenous hemodiafiltration

73. Advantages .better hemodynamic stability Less arryhthmias Improved nutritional support Better pulmonary gas exchange Better fluid control

74. Disadvantages High risk of bleeding Immobilization prolonged Costly Difficult vascular access Filter problems

75. peritoneal dialysis Less effective than HD Useful if HD not available Bleeding diathesis Impossible to attain vascular access Hemodynamically unstable No anticoagulation is needed

76. disadvantages Impaired drainage Peritonitis Protein loss Compromised lung function Abnormal blood sugar & electrolyte values Very slow and ineffective when rapid correction is needed

77. Peritoneal dialysis Access via a peritoneal catheter 1.5-3L of a dextrose containing solution infused Allowed to dwell for a short period of time[2-4hrs] Convective + diffusive clearance

78. . “ Recent evidence suggest that more intensive hemodialysis [e.g. daily rather than alternative day intermittent dialysis] may be clinically superior and confers improved survival in ARF , once dialysis is required.”

79. References Harrisons principles of internal medicine,17 th e Acute kidney injury network , akinet.org Principles of critical care,2 nd e Farokh Erach Udwadia Acute renal failure, Dr Rebecca Jacob, IJA 2003;47(5) Anesthesia and coexisting disease,4 th e ccmtutorials.com Perioperative acute renal failure and its management, Dr D Mallikarjuna [isacon-2007

80. THANK YOU