Acute kidney injury

Acute Kidney Injury

1. ACUTE KIDNEY INJURY ‘ BY DR SUMAN ROY MD PGT MMCH

2. ACUTE KIDNEY INJURY CLAUDE BERNERD (1878) Milieu exterieur Milieu interieur WALTER B. CANON Recognises that the constancy of internal state ( homeostatic state) ...To maintain minimum variability THE KIDNEY

3. 5-7% of acute care hospital admissions 30% of ICU admissions with mortality rates – 50% AKI worsens CKD Severe AKI requiring dialysis increases risk of developing dialysis-requiring-ESRD. Community-acquired AKI: Volume depletion, ADRs & obstruction of the urinary tract. Hospital-acquired AKI: Sepsis, major surgical procedures, heart or liver failure, IV iodinated contrast and nephrotoxic drugs Epidemiology

4. Diarrhoeal diseases Envenomations from snakes, spiders, caterpillars, and bees Malaria Leptospirosis Crush injuries from earthquakes and resultant rhabdomyolysis AKI in Tropics

5. Definition of AKI

6. KDIGO criteria (ungraded) Increase in SCr by ≥0.3 mg/dl (≥26.5 umol /l ) within 48 hours; or Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or Urine volume <0.5 ml/kg/h for 6 hours.

7. KDIGO- Staging of AKI

8. R isk I njury F ailure L oss of function E nd -Stage Renal disease RIFLE Criteria

9. In 2002, the Acute Dialysis Quality Initiative (ADQI) was created with the primary goal of developing consensus and evidence-based guidelines for the treatment and prevention of acute kidney injury (AKI). The first order of business was to create a uniform, accepted definition of AKI; hence, the RIFLE criteria were born. RIFLE is an acronym of Risk, Injury, and Failure; and Loss; and End-stage kidney disease RIFLE Criteria

10. R isk Increase in Cr of 1.5-2.0 X baseline or urine output < 0.5 mL /kg/hr for more than 6 hours

11. I njury increase in Cr 2-3 X baseline (loss of 50% of GFR) or urine output < 0.5 mL /kg/hr for more than 12 hours

12. F ailure increase in Cr rises > 3X baseline Cr (loss of 75% of GFR) or an increase in serum creatinine greater than 4 mg/ dL , or urine output < 0.3 mL /kg/hr for more than 24 hours or anuria for more than 12 hours .

13. L oss of function persistent renal failure (i.e. need for dialysis) for more than 4 weeks. E nd -Stage Renal disease persistent renal failure (i.e. need for dialysis) for more than 3 months

14. Etiologic Classification of AKI Acute kidney injury Pre-renal Intrinsic Post-renal Glomerular Interstitial Vascular Tubular

15. Pre-renal AKI

16. Etiology and Pathophysiology I. Hypovolemia • Hemorrhage, burns, dehydration • Gastrointestinal fluid loss: vomiting, surgical drainage , diarrhea

17. Renal fluid loss : diuretics, osmotic diuresis (e.g., diabetes mellitus ), hypoadrenalism Sequestration in extravascular space : pancreatitis , peritonitis , trauma, burns, S evere hypoalbuminemia

18. II. Low cardiac output • Diseases of - myocardium, valves, and pericardium; arrhythmias; tamponade • Other: pulmonary hypertension, massive pulmonary embolus

19. III. Altered renal systemic vascular resistance ratio • Systemic vasodilatation: sepsis, anaphylaxis IV. Renal hypoperfusion with impairment of renal autoregulatory responses

20. Pathophysiology : Hypovolemia leads to glomerular hypoperfusion , but filtration rate are preserved during mild hypoperfusion through several compensatory mechanisms . During states of more severe hypoperfusion , these compensatory responses are overwhelmed and GFR falls, leading to prerenal AKI.

21. NSAIDS - they reduce affarent renal vasodilation V. ACEIs and ARBs- limit renal efferent vasoconstriction

22. • Prerenal AKI can complicate any disease that induces : hypovolemia , low cardiac output, systemic vasodilatation , or selective renal vasoconstriction .

23. B. Intrinsic Renal AKI:

24. - accounts for nearly 40% of all AKI I.Renovascular obstruction bilateral or unilateral in the setting of one functioning kidney II.Disease of glomeruli or renal microvasculature Acute kidney injury Intrinsic Glomerular Interstitial Tubular Vascular Intrinsic Renal AKI

25. III. Acute tubular necrosis(ATN) Ischemia : as for prerenal AKI ( hypovolemia , low cardiac output, renal vasoconstriction, systemic vasodilatation )

26. Toxins Exogenous : radio contrast, cyclosporine, antibiotics ( e.g. aminoglycosides ), chemotherapy ( e.g. cisplatin ), organic solvents ( e.g. ethylene glycol), acetaminophen, illegal abortifacients Endogenous : Mb, Hb , uric acid, oxalate, plasma cell dyscrasia ( e.g. myeloma ) Postoperative AKI

27. C. Post renal AKI (OBSTRUCTION):

28. Pathophysiology of postrenal AKI It involves hemodynamic alterations triggered by an abrupt increase in intratubular pressures An initial period of hyperemia from afferent arteriolar dilation is followed by intrarenal vasoconstriction from the generation of angiotensin II, thromboxane A2, and vasopressin, and a reduction in NO production.

29. POST RENAL Reduced GFR is due to underperfusion of glomeruli and, possibly, changes in the glomerular ultrafiltration coefficient

30. Approach to a patient with AKI

31. Diagnostic Evaluation History and Physical examination: Pre-renal : History: vomiting, diarrhoea , glycosuria causing polyuria, and several medications including diuretics, NSAIDs, ACE inhibitors, and ARBs. Examination: Physical signs of orthostatic hypotension, tachycardia, reduced jugular venous pressure, decreased skin turgor, and dry mucous membranes are often present in prerenal azotemia

32. Diagnostic Evaluation INTRINSIC RENAL: Review all medications Cause of AKI . Dose Adjustment. Systemic vasculitis with Glomerulonephritis: Palpable purpura Pulmonary hemorrhage , Sinusitis. Atheroembolic Livedo reticularis and other signs of emboli to the legs. Rhabdomyolysis . Signs of limb ischemia

33. Diagnostic Evaluation Post- Renal: Colicky flank pain radiating to the groin suggests acute ureteric obstruction. Nocturia and urinary frequency or hesitancy can be seen in prostatic disease. Abdominal fullness and suprapubic pain can accompany massive bladder enlargement. Definitive diagnosis of obstruction requires radiologic investigations.

34. Blood Tests CBC BUN/ creatinine Electrolytes Uric acid PT/ aPTT

35. Urine Analysis Volume Osmolality Proteinuri a Urinary Indices: FeNa & Urinary Sodium Sediments

36. Imaging Renal ultrasound (useful for obstructive forms) Doppler (to assess renal blood flow) CT Scan Pyelography Nuclear Medicine Scans : DMSA : anatomy. DTPA and MAG3: renal function, urinary excretion and upper tract outflow.

37. Cystatin -C Superior to serum creatinine , as a surrogate marker of early and subtle changes of kidney function. I dentifies kidney injury while creatinine levels remain normal Allows detection of AKI, 24-48 hours earlier than serum creatinine

38. Kidney Injury Molecule-1 (KIM-1) T ype 1 trans-membrane glycoprotein Served as a marker of severity of AKI Can be used to predict adverse outcomes in hospitalized patients better than conventionally used severity markers.

39. Neutrophil gelatinase - associated lipocalin (NGAL ) Highly upregulated after inflammation and kidney injury C an be detected in the plasma & urine within 2 hours of cardiopulmonary bypass–associated AKI. Considered equivalent to troponin in acute coronary syndrome.

40. Complications of AKI

41. Complications of AKI Intravascular overload: may be recognized by weight gain , hypertension , elevated central venous pressure ( raise JVP) , Pulmonary edema Electrolyte disturbance Hyperkalemia: (serum K+ >5.5 mEq /L ): decreased renal excretion combined with tissue necrosis or hemolysis. Hyponatremia : ( serum Na+ concentration < 135 mEq/L ): excessive water intake in the face of excretory failure

42. Hyperphosphatemia : ( serum Phosphate concentration of > 5.5 mg /dl ) failure of excretion or tissue necrosis Hypocalcemia : ( serum Ca++ < 8.5 mg/dl ) results from decreased Active Vit -D , hyperposhphatemia , or hypoalbuminemia Hypercalcemia : (serum Ca++ > 10.5 mg /dl) may occur during the recovery phase following rhabdomyolysis induced acute renal failure.

43. Metabolic acidosis :( arterial blood PH < 7.35 ) is associated with sepsis or severe heart failure Hyperuricemia : due to decreased uric acid excretion Bleeding tendency : may occur due to platelet dysfunction and coagulopathy associated with sepsis Seizure: may occur related to uremia

44. Treatment of AKI

45. General Issues   1. Optimization of systemic and renal hemodynamics through volume resuscitation and judicious use of vasopressors 2. Elimination of nephrotoxic agents (e.g., ACE inhibitors, ARBs, NSAIDs, aminoglycosides ) if possible 3. Initiation of renal replacement therapy when indicated

46. Pre-Renal AKI Prevention and treatment of prerenal azotemia requires optimization of renal perfusion. Severe acute blood loss should be treated with PRBC transfusion.

47. FLUIDS KDIGO advocates use of isotonic crystalloids rather than colloids (albumin or starches) . Colloids may be chosen to avoid excessive fluid administration requiring large volume resuscitation , or in specific patient subsets (e.g., a cirrhotic patient with spontaneous peritonitis, or in burns). Colloids- Albumin is renoprotective and Hyperoncotic starch shows nephro - toxicity.

48. Vasopressors A ppropriate use of vasoactive agents improve kidney perfusion in volume-resuscitated patients with vasomotor shock. D opamine associated with a greater number of adverse events than Nor-epinephrine.

49. Low Dose Dopamine Its use has been abandoned by most subsequent to negative results of various studies . KDIGO recommends not using low-dose dopamine to prevent or treat AKI. (1A)

50. Cirrhosis and Hepatorenal Syndrome Albumin may prevent AKI in those treated with antibiotics for SBP Bridge therapies [in combination with IV Inf albumin (25–50 mg/d)] include: terlipressin (a vasopressin analog), combination therapy with octreotide (a somatostatin analog) and midodrine (an α 1-adrenergic agonist), and norepinephrine

51. Cardio-Renal Syndrome Optimization of cardiac function . May require use of inotropic agents preload- and afterload-reducing agents, antiarrhythmic drugs, mechanical aids such as an intra-aortic balloon pump.

52. Treatment of Intrinsic AKI

53. Diuretic Renoprotective : Potentially lessening ischemic injury Can also be harmful, by worsening established AKI. No evidence of incidence reduction. KDIGO recommend not using diuretics to prevent AKI KDIGO suggest not using diuretics to treat AKI, except in the management of volume overload Indicated only for management of fluid balance, hyperkalemia , and hypercalcemia .

54. FENOLDOPAM Fenoldopam mesylate : pure dopamine type-1 receptor agonist Without systemic adrenergic stimulation. No conclusive studies available. For critically ill patients with impaired renal function, a continuous infusion of fenoldopam 0.1mg/kg/min improves renal function when compared to low dose dopamine.

55. Erythropoietin P otential clinical benefit of erythropoietin in AKI in animal studies. R enoprotective action of erythropoietin related to pleomorphic properties including anti-apoptotic & anti-oxidative effects, stimulation of cell proliferation, and stem-cell mobilization. Although one recent RCT in the prevention of human AKI was negative, the usefulness of erythropoietin in human AKI should be further tested in RCTs.

56. Growth factor intervention IGF-1 is a peptide with renal vasodilatory , mitogenic and anabolic properties. KDIGO Work Group recommends against its use in patients with AKI.

57. Rhabdomyolysis Aggressive volume repletion (may require 10 L of fluid/day) Alkaline fluids beneficial Diuretics may be used if fluid repletion is adequate & no urine output Dialysis Focus on calcium and phosphate status because of precipitation in damaged tissue

58. Glomerulonephritis or Vasculitis May respond to immunosuppressive agents and/or plasmapheresis Allergic interstitial nephritis due to medications requires discontinuation of the offending agent. Glucocorticoids have been used, but not tested in randomized trials. AKI due to scleroderma (scleroderma renal crisis) should be treated with ACE inhibitors.

59. Aminoglycoside Induced AKI KDIGO suggest not using aminoglycosides for the t/t of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available Avoid in high risk patients of age > 65 years, DM, septic shock S ingle dose daily rather than multiple-dose daily t/t regimens T opical or local applications of aminoglycosides (e.g., respiratory aerosols, instilled antibiotic beads), rather than I .V. application, when feasible

60. AMPHOTERICIN B NEPHROTOXICITY KDIGO suggest using lipid formulations of amphotericin B rather than conventional formulations Use azole antifungal agents and/or the echinocandins rather than conventional amphotericin B, if equal therapeutic efficacy can be assumed. Some studies indicate that the liposomal form of amphotericin B is less nephrotoxic than lipid complex or colloidal dispersion forms

61. Post-renal Prompt relief of urinary tract obstruction. Relief of obstruction is usually followed by an appropriate diuresis and may require continued administration of IVF & electrolytes for a period of time.

62. Indications for Dialysis A – Acidosis E – Electrolyte disturb, usually hyperkalemia I – Intoxications (lithium, ethylene glycol, etc) O – Overload (volume overload) U – Uremia (symptoms, signs )

63. Modes Of Dialysis Hemodynamically stable- IHD Hemodynamically unstable CRRT PD SLED

64. Prognosis Pre-renal and Post- renal better prognosis. Kidneys may recover even after dialysis requiring AKI. 10% of cases requiring dialysis develop CKD. Die early even after kidney function recovers completely.

65. Diagnose early – Biomarkers have great potential Look for etiology Prevent rather than treat No role of low dose dopamine, diuretics in prevention and treatment Initiate RRT when indicated