Acute renal failure


Published on

Published in: Health & Medicine
1 Comment
No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Acute renal failure

  1. 1. Acute Renal Failure Dr. Asif
  2. 2. Basic Renal Physiology <ul><li>nephron </li></ul><ul><li>the functional unit of the kidney </li></ul><ul><li>capable of forming urine </li></ul><ul><li>has two major components: </li></ul><ul><ul><li>glomerulus </li></ul></ul><ul><ul><li>tubule: </li></ul></ul><ul><ul><ul><li>proximal </li></ul></ul></ul><ul><ul><ul><li>loop of Henle </li></ul></ul></ul><ul><ul><ul><li>distal </li></ul></ul></ul><ul><ul><ul><li>collecting </li></ul></ul></ul>
  3. 3. structural organization <ul><li>renal parenchyma </li></ul><ul><li>cortex </li></ul><ul><li>medulla </li></ul><ul><li>nephrons </li></ul><ul><li>cortical </li></ul><ul><li>juxtamedullary </li></ul>
  4. 4. renal blood supply: <ul><li>the kidneys receive 20% of the cardiac output </li></ul><ul><li>vascular supply: </li></ul><ul><ul><ul><ul><ul><li>renal arteries </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>interlobar arteries </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>arcuate arteries </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>interlobular arteries </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>afferent arterioles </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>glomerular capillaries </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>efferent arterioles </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>peritubular capillaries </li></ul></ul></ul></ul></ul>
  5. 5. glomerular filtration rate (GFR) <ul><li>GFR depends on the interplay between hydrostatic and oncotic pressures within the nephron </li></ul><ul><li>hydrostatic pressure is usually higher in the glomerulus than within the tubule, forcing filtrate out of the capillary bed into the tubule </li></ul><ul><li>oncotic pressure is generated by non-filtered proteins: it helps to retain fluid in the intravascular space </li></ul><ul><li>GFR : Kf * (hydrostatic pressure - oncotic pressure) </li></ul><ul><li>Normal GFR : 100 ml/min/1.72m 2 </li></ul><ul><li>*Kf filtration coefficient in the glomerulus </li></ul>
  6. 6. <ul><li>Adjusting the resistances of the afferent and efferent arterioles, the kidneys can regulate both the hydrostatic pressures in the glomerular and peritubular capillaries, changing the rate of glomerular filtration and/or tubular reabsorption in response to homeostatic demands. </li></ul>
  7. 7. determinants of renal blood flow (RBF) <ul><li>RBF= </li></ul><ul><li>renal artery pressure - renal vein pressure </li></ul><ul><li>total renal vasculature resistance </li></ul>
  8. 8. ARF
  9. 9. Acute Renal Failure – Definitions, Facts and Figures <ul><li>ARF is an abrupt decline in glomerular and tubular function, resulting in the failure of the kidneys to excrete nitrogenous waste products and to maintain fluid and electrolyte homeostasis </li></ul><ul><li>ARF = a sudden reduction of GFR expressed clinically as elevations in blood BUN and creatinine </li></ul><ul><li>Generally elevation of BUN, creatinine occurred within 3 months </li></ul><ul><li>May heal partially or completely or progress to more severe renal insufficiency, including end-stage renal disease </li></ul><ul><li>Incidence of ARF varies on setting: </li></ul><ul><ul><li>Community <1% </li></ul></ul><ul><ul><li>Hospital 2-7%; ICU/postop 4-25% </li></ul></ul>
  10. 10. Acute Renal Failure– Definitions, Facts and Figures <ul><li>Significant mortality associated with AKI – 10-50% or higher depending on setting and risk factors </li></ul><ul><ul><li>ICU mortality with ARF 43-88% </li></ul></ul><ul><ul><li>Factors increasing mortality: multiorgan failure </li></ul></ul><ul><ul><li>Risk factors for developing ARF: age, IDDM, CKD, LV dysfunction </li></ul></ul>
  11. 11. Acute Renal Failure– Definitions, Facts and Figures <ul><li>Evidence of decreasing renal function (reduced GFR): </li></ul><ul><ul><li>Rising BUN (blood urea nitrogen) – nl about 10 mg/dL (nr = 7-25 mg/dL) </li></ul></ul><ul><ul><li>Rising creatinine – nl about 1 mg/dL (nr = 0.6 – 1.2 mg/dL) </li></ul></ul><ul><ul><li>Note normal BUN:creat ratio = 10-20:1 </li></ul></ul>
  12. 12. <ul><li>This slide depicts the inverse relationship between P Cr and GFR (measured by inulin clearance) in a large number of subjects with </li></ul><ul><li>varying degrees of renal function. The hyperbolic relationship </li></ul><ul><li>between P Cr and GFR complicates the use of </li></ul><ul><li>absolute increments in P Cr (e.g., > 0.5 or 1.0 mg/dl) </li></ul><ul><li>as yardsticks for defining acute renal failure. </li></ul>Serum Creatinine (mg/dl) Inulin Clearance (ml/min per 1.73m 2 ) 1.0 0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 40 60 80 100 120 140 160 180 20 0
  13. 13. Acute Renal failure– Definitions, Facts and Figures <ul><li>Oliguria = <400 cc/24 hours </li></ul><ul><li>Anuria = <75 cc/24 hrs (some references <100 cc/24 hrs) </li></ul><ul><li>DDx anuria: </li></ul><ul><ul><li>Obstruction </li></ul></ul><ul><ul><li>Acute tubular necrosis </li></ul></ul><ul><ul><li>Vascular event (e.g., renal vein thrombosis) </li></ul></ul><ul><ul><li>Cortical necrosis </li></ul></ul><ul><ul><li>(Some authorities say): </li></ul></ul><ul><ul><li>Azotemia is a consistent feature of acute renal failure (ARF), oliguria is not. </li></ul></ul>
  14. 14. <ul><li>acute renal failure: pathophysiology </li></ul><ul><li>Increase in NaCl delivered to macula densa. Damage to proximal tubule cells increases NaCl delivery to distal nephron,. This causes disruption of feedback mechanism. </li></ul><ul><li>Obstruction of tubular lumen. Casts (necrosis of tubular cells and sloughed basement membrane) clog the lumen. This will increase the tubular pressure and then GFR will fall. </li></ul><ul><li>Backleak of fluid through the tubular basement membrane. </li></ul>
  15. 15. Acute vs Chronic (ARF vs progression of chronic kidney disease) <ul><li>Distinction important (etiology, prognosis, therapy differ) </li></ul><ul><li>Past BUN, creatinine values; course of BUN, creatinine rise </li></ul><ul><li>Half and half nails </li></ul><ul><li>Kidney size and echogenicity by ultrasound (10 cm lower limit of normal; normal size usually 11-12 cm depending on height) </li></ul>
  16. 16. acute renal failure: common clinical features <ul><ul><li>azotemia </li></ul></ul><ul><ul><li>hypervolemia </li></ul></ul><ul><ul><li>electrolytes abnormalities: </li></ul></ul><ul><ul><li> K+  phosphate </li></ul></ul><ul><ul><li> Na+  calcium </li></ul></ul><ul><ul><li>metabolic acidosis </li></ul></ul><ul><ul><li>hypertension </li></ul></ul><ul><ul><li>oliguria - anuria </li></ul></ul>
  17. 17. Acute Renal Failure Classification <ul><li>Pre-renal (functional/hypoperfusion) </li></ul><ul><li>Renal (structural/intrinsic) </li></ul><ul><li>Post-renal (obstructive) </li></ul>
  18. 18. <ul><li>Classification based on clinical information </li></ul><ul><ul><li>History, PE, BUN:creat ratio, urine analysis </li></ul></ul><ul><ul><li>Urine electrolytes </li></ul></ul><ul><ul><li>Renal ultrasound </li></ul></ul><ul><ul><li>Occasionally special tests (e.g., kidney biopsy, CT scan, nuclear medicine scan, serologies) </li></ul></ul>
  19. 19. <ul><li>Classification provides: </li></ul><ul><ul><li>information on etiology of ARF </li></ul></ul><ul><ul><li>information on prognosis </li></ul></ul><ul><ul><li>directs appropriate therapy </li></ul></ul>
  20. 20. Acute Renal Failure Pre-renal Causes <ul><li>decreased effective perfusion without cellular injury </li></ul><ul><ul><li>Hemorrhage </li></ul></ul><ul><ul><li>Sodium depletion </li></ul></ul><ul><ul><li>Pump failure </li></ul></ul><ul><ul><li>Increased vascular capacity e.g., sepsis </li></ul></ul><ul><ul><li>Increased renal vascular resistance (hepatorenal, NSAIDs) </li></ul></ul><ul><ul><li>Vasoconstricting drugs (radiocontrast, cyclosporine, amphotericin B) </li></ul></ul><ul><ul><li>Decreased intraglomerular pressure (ACEI, ARB) </li></ul></ul><ul><li>Redistribution of ECF </li></ul><ul><ul><li>“ Third space” accumulation </li></ul></ul><ul><ul><li>Edematous disorders </li></ul></ul><ul><li>Drugs </li></ul><ul><li>renal tubular and glomerular functions are intact </li></ul><ul><li>reversible if underlying cause is corrected </li></ul>
  21. 21. Pre-Renal Azotemia Pathophysiology <ul><li>Renal hypoperfusion </li></ul><ul><ul><li>Decreased RBF and GFR </li></ul></ul><ul><ul><li>Increased filtration fraction (GFR/RBF) </li></ul></ul><ul><li>Increased Na and H 2 O reabsorption </li></ul><ul><ul><li>Oliguria, high U osm , low U Na </li></ul></ul><ul><ul><li>Elevated BUN/Cr ratio </li></ul></ul>
  22. 22. Renal Blood Flow <ul><li>F =  P/R </li></ul><ul><li>RBF = RAP – RVP </li></ul><ul><li>Raff + Reff </li></ul><ul><li>RBF ~ RAP </li></ul><ul><li>Raff + Reff </li></ul><ul><li>The determinants of renal blood flow (RBF) are summarized in this slide. In the absence of renal artery stenosis, renal arterial pressure (RAP) is the same as systemic mean arterial pressure (commonly referred to by nephrologists as “renal perfusion pressure”). Renal venous pressure (RVP) is usually, but not always, low and relatively constant. The glomerular afferent and efferent arterioles are the major sites of renal vascular resistance (R aff and R eff , respectively); changes in either will affect renal blood flow (RBF). </li></ul><ul><li>In the “universal pressure;flow relationship”, F = flow;  P = change in pressure; R = resistance. RBF = renal blood flow; RAP = renal arterial pressure; RVP = renal venous pressure; R aff = afferent arteriolar resistance; R eff = efferent arteriolar resistance </li></ul>
  23. 23. Pre-renal ARF <ul><li>History </li></ul><ul><li>-- blood or volume loss </li></ul><ul><li> -- cardiac failure, arrhythmia, (cardiogenic shock) </li></ul><ul><li> -- sepsis </li></ul><ul><li> -- exposure to drugs </li></ul><ul><li>(radiographic contrast, NSAID) </li></ul><ul><li>Sustained prerenal azotemia is the main factor that predisposes patients to ischemia- induced acute tubular necrosis (ATN) </li></ul>
  24. 24. Pre-renal ARF <ul><li>Physical exam – focus on volume status </li></ul><ul><ul><li>Vital signs – current and preceding the development of AKI </li></ul></ul><ul><ul><li>Neck veins, lungs, heart, mucous membranes </li></ul></ul><ul><ul><li>Edema – presacral and extremity </li></ul></ul>
  25. 25. Pre-renal ARF <ul><li>Laboratory studies </li></ul><ul><ul><li>BUN:creatinine ratio – elevated in pre-renal; >10-20:1 </li></ul></ul><ul><ul><li>Unremarkable urinary sediment, high specific gravity </li></ul></ul><ul><ul><li>May see hyaline casts </li></ul></ul><ul><ul><li>Urine dipstick negative (no blood or protein) </li></ul></ul>
  26. 26. Pre-renal ARF <ul><li>There is no intrinsic kidney damage in pre-renal ARF ; rising BUN and creat (ARF) occur because the kidneys are inadequately perfused. </li></ul><ul><li>Therefore, normal renal physiologic responses occur, manifested in urine electrolytes that reflect intact kidney tubular function. </li></ul>
  27. 27. Pre-renal ARF Urine Electrolytes <ul><li>Intact renal tubular function in the setting of impaired renal perfusion (due either to volume loss, pump failure, renal vasoconstriction , etc) results in avid tubular reabsorption of sodium. </li></ul><ul><li>Therefore, low urine Na (<20 mEq/L) and low fractional excretion of Na (<1%) and of urea (<35%) in pre-renal ARF. </li></ul>
  28. 28. Urine Electrolytes <ul><li>Fractional excretion: </li></ul><ul><li>urine/plasma x x 100 </li></ul><ul><li>urine/plasma x </li></ul><ul><li>X = Na or urea (or whatever is in question) </li></ul>
  29. 29. <ul><li>Prerenal azotemia and ischemic tubular necrosis represent a continuum. Azotemia progresses to necrosis when blood flow is sufficiently compromised to result in the death of tubular cells. </li></ul><ul><li>Most cases of ischemic ARF are reversible if the underlying cause is corrected. </li></ul>
  30. 30. Renal or Intrinsic ARF <ul><li>Classified according to primary site of injury: </li></ul><ul><li>Vascular </li></ul><ul><li>Glomerular (acute glomerulonephritis) </li></ul><ul><li>Tubular (acute tubular necrosis or ATN) </li></ul><ul><li>Interstitial (acute interstitial nephritis) </li></ul>
  31. 31. Renal or Intrinsic ARF <ul><li>In all types of intrinsic ARF, BUN:creat ratio preserved (10-20:1) </li></ul><ul><li>The history, PE, and especially, urine analysis will help to differentiate </li></ul>
  32. 32. Renal or Intrinsic ARF – Vascular Type <ul><li>Large vessels – must be bilateral </li></ul><ul><ul><li>Renal vein thrombosis </li></ul></ul><ul><ul><li>Renal artery stenosis </li></ul></ul><ul><li>Small vessels </li></ul><ul><ul><li>Vasculitis </li></ul></ul><ul><ul><li>Atheroembolic </li></ul></ul><ul><ul><li>Malignant hypertension </li></ul></ul><ul><ul><li>Thrombotic microangiopathies (HUS/TTP) </li></ul></ul>
  33. 33. Renal or Intrinsic AKI – Vascular Type <ul><li>Small vessels – atheroembolic </li></ul><ul><ul><li>Relatively common </li></ul></ul><ul><ul><li>Risk factors = catheter manipulation and anticoagulation in the setting of atherosclerosis </li></ul></ul><ul><ul><li>PE may reveal livedo reticularis </li></ul></ul><ul><ul><li>Progressive rise then stabilization of BUN, creatinine usually without significant recovery of kidney function </li></ul></ul><ul><ul><li>Cholesterol clefts occ seen on kidney biopsy but transient so bx not suggested; Dx clinically </li></ul></ul>
  34. 34. Atheroembolic ARF <ul><li>Urine eosinophils </li></ul><ul><li>Low C3 </li></ul><ul><li>DDX usually contrast vs atheroembolic </li></ul>
  35. 35. Renal or Intrinsic ARF – Glomerular <ul><li>History – systemic or primary kidney </li></ul><ul><li>-- edema </li></ul><ul><li>PE – BP (usually hypertensive) </li></ul><ul><li>-- edema </li></ul><ul><li>BUN:creat ratio preserved </li></ul><ul><li>Urine analysis: + protein, blood </li></ul><ul><li>RBCs, RBC casts </li></ul>RBC Casts
  36. 36. Renal or Intrinsic ARF – Glomerular <ul><li>Often will require kidney biopsy </li></ul>
  37. 37. Renal or Intrinsic ARF – Interstitial <ul><li>History – exposure to medications usually 7- 14 days earlier </li></ul><ul><li>-- penicillins, cephalosporins, dilantin </li></ul><ul><li>PE – maculopapular erythematous skin rash </li></ul><ul><li>-- 1/3 have fever, arthralgias </li></ul><ul><li>BUN:creat ratio 10-20:1 </li></ul><ul><li>Urine analysis -- + protein, blood </li></ul><ul><li>WBCs, WBC casts, eos </li></ul>
  38. 38. Renal or Intrinsic ATN – Acute Tubular Necrosis <ul><li>The most common type of hospital-acquired ARF </li></ul><ul><li>May be </li></ul><ul><li>1) ischemic or </li></ul><ul><li>2) nephrotoxic in etiology </li></ul><ul><li>Most common ATN is ischemic, most often due to a prolonged pre-renal state (prolonged reduced renal perfusion) </li></ul>
  39. 39. Renal or Intrinsic ATN – Acute Tubular Necrosis <ul><li>History – prolonged pre-renal state </li></ul><ul><li>-- exposure to nephrotoxin </li></ul><ul><li>aminoglycoside antibiotics </li></ul><ul><li>ethylene glycol </li></ul><ul><li>pigments (myoglobin, hemoglobin) </li></ul><ul><li>PE – volume status (to exclude pre-renal ARF) </li></ul>
  40. 40. Renal or Intrinsic ATN – Acute Tubular Necrosis <ul><li>BUN:creat ratio preserved (10-20:1) </li></ul><ul><li>Urine analysis – usually negative protein, blood </li></ul><ul><li>-- granular casts ( dirty </li></ul><ul><li>brown casts) </li></ul><ul><li>-- renal tubular epithelial cells </li></ul><ul><li>Urine chemistries – urine Na>40 meq/L </li></ul><ul><li>FxExNa >2% </li></ul><ul><li>FxExurea >40% </li></ul>
  41. 41. Granular casts
  42. 42. Acute Tubular Necrosis <ul><li>Acute tubular necrosis showing focal loss of tubular epithelial cells (arrows) and partial occlusion of tubular lumens by cellular debris (D) (H&E stain). </li></ul>
  43. 43. Acute Renal Failure Nephrotoxic ATN <ul><li>Endogenous Toxins </li></ul><ul><ul><li>Heme pigments (myoglobin, hemoglobin) </li></ul></ul><ul><ul><li>Myeloma light chains </li></ul></ul><ul><li>Exogenous Toxins </li></ul><ul><ul><li>Antibiotics (e.g., aminoglycosides, amphotericin B) </li></ul></ul><ul><ul><li>Radiocontrast agents </li></ul></ul><ul><ul><li>Heavy metals (e.g., cis-platinum, mercury) </li></ul></ul><ul><ul><li>Poisons (e.g., ethylene glycol) </li></ul></ul>
  44. 44. Acute Tubular Necrosis <ul><li>Tubular epithelial degeneration and hyaline amphophilic casts (positive with immunologic stains for myoglobin) in a patient with rhabdomyolysis and myoglobinuric acute tubular necrosis. </li></ul>
  45. 45. Acute Interstitial Nephritis Causes <ul><li>Allergic interstitial nephritis </li></ul><ul><ul><li>Drugs </li></ul></ul><ul><li>Infections </li></ul><ul><ul><li>Bacterial </li></ul></ul><ul><ul><li>Viral </li></ul></ul><ul><li>Sarcoidosis </li></ul>
  46. 46. Allergic Interstitial Nephritis Clinical Characteristics <ul><li>Fever </li></ul><ul><li>Rash </li></ul><ul><li>Arthralgias </li></ul><ul><li>Eosinophilia </li></ul><ul><li>Urinalysis </li></ul><ul><ul><li>Microscopic hematuria </li></ul></ul><ul><ul><li>Sterile pyuria </li></ul></ul><ul><ul><li>Eosinophiluria </li></ul></ul>
  47. 47. Acute Interstitial Nephritis <ul><li>Drug-induced allergic interstitial nephritis (H&E stain). Note the diffuse interstitial infiltrate, many red-staining eosinophils, and sparing of the glomerulus (on the left). </li></ul>
  48. 48. Cholesterol Embolization <ul><li>Cholesterol embolization may occur after a “sentinel” procedure (e.g., cardiac catherization) or be associated with slowly progressive renal failure over a period of months or years. Whatever the time course, it is generally irreversible. Cholesterol emboli usually lodge in vessels 100 to 200 microns in diameter, and are visualized as clear spaces where the cholesterol crystals have been dissolved by routine processing. The early response of platelets and occasional mononuclear cells is seen in the medium size artery occluded by acute cholesterol emboli in the left panel (Jones Silver stain). In later stages of organization the lumen may have more fibrous reorganization surrounding the cholesterol clefts, as shown in the right lower diagram (PAS stain). </li></ul>
  49. 49. Contrast-Induced ARF Prevalence <ul><li>Less than 1% in patients with normal renal function </li></ul><ul><li>Increases significantly with renal insufficiency </li></ul>
  50. 50. Contrast-Induced ARF Risk Factors <ul><li>Renal insufficiency </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Multiple myeloma </li></ul><ul><li>High osmolar (ionic) contrast media </li></ul><ul><li>Contrast medium volume </li></ul>
  51. 51. Contrast-induced ARF Clinical Characteristics <ul><li>Onset - 24 to 48 hrs after exposure </li></ul><ul><li>Duration - 5 to 7 days </li></ul><ul><li>Non-oliguric (majority) </li></ul><ul><li>Dialysis - rarely needed </li></ul><ul><li>Urinary sediment - variable </li></ul><ul><li>Low fractional excretion of Na </li></ul>
  52. 52. Contrast-induced ARF Prophylactic Strategies <ul><li>Use I.V. contrast only when necessary </li></ul><ul><li>Hydration </li></ul><ul><li>Minimize contrast volume </li></ul><ul><li>Low-osmolar (nonionic) contrast media </li></ul><ul><li>N-acetylcysteine, fenoldopam </li></ul>
  53. 53. Acute Renal Failure Post-renal Causes <ul><li>Intra-renal Obstruction </li></ul><ul><ul><li>Acute uric acid nephropathy </li></ul></ul><ul><ul><li>Drugs (e.g., acyclovir) </li></ul></ul><ul><li>Extra-renal Obstruction </li></ul><ul><ul><li>Renal pelvis or ureter ;must be bilateral unless solitary kidney (e.g., stones, clots, tumors, papillary necrosis, retroperitoneal fibrosis) </li></ul></ul><ul><ul><li>Bladder (e.g., BPH, neuropathic bladder) </li></ul></ul><ul><ul><li>Urethra (e.g., stricture) </li></ul></ul>
  54. 54. Acute Renal Failure Post-renal <ul><li>Elevated pressure in urinary conduits results in renal parenchymal destruction if unrelieved </li></ul><ul><li>important to rule out quickly : </li></ul><ul><ul><li>potential for recovery of renal function is often inversely related to the duration of the obstruction </li></ul></ul>
  55. 55. Post-Renal ARF Obstructive ARF <ul><li>History – symptoms ( frequency, hesitancy, etc) </li></ul><ul><li> -- carcinoma, DM, stones, medications </li></ul><ul><li>PE – distended bladder, prostatic enlargement, pelvic masses, lymph nodes </li></ul><ul><li>Laboratory studies </li></ul><ul><li>-- elevated BUN:creat ratio </li></ul><ul><li>-- unremarkable urine sediment </li></ul><ul><li>-- variable urine chemistries </li></ul>
  56. 56. Post-Renal ARF Obstructive ARF <ul><li>Bladder catheterization </li></ul><ul><li>Renal ultrasound – hydronephrosis </li></ul><ul><li>Treatment is to relieve the obstruction </li></ul><ul><ul><li>Bladder catheterization </li></ul></ul><ul><ul><li>Nephrostomy tubes </li></ul></ul>
  57. 57. Normal kidney on ultrasound
  58. 58. Hydronephrosis on ultrasound
  59. 59. Acute Renal Failure Diagnostic Tools <ul><li>History and Physical examination </li></ul><ul><li>Blood tests : CBC, BUN/creatinine, electrolytes, uric acid, PT/PTT, CK </li></ul><ul><li>Urinary sediment </li></ul><ul><li>Urinary indices </li></ul><ul><ul><li>Urine volume </li></ul></ul><ul><ul><li>Urine electrolytes </li></ul></ul><ul><li>Radiologic studies </li></ul><ul><li>Renal ultrasound (useful for obstructive forms) </li></ul><ul><li>Doppler (to assess renal blood flow) </li></ul><ul><li>Nuclear Medicine Scans </li></ul><ul><ul><li>DMSA: anatomy </li></ul></ul><ul><ul><li>DTPA and MAG3: renal function, urinary </li></ul></ul><ul><ul><li>excretion and upper tract outflow </li></ul></ul>
  60. 60. Distinguishing tubulo-interstitial disease from Pre-Renal ARF <ul><li>Most difficult classification of ARF </li></ul><ul><ul><li>Urine sediment helpful </li></ul></ul><ul><li>(i) Bland </li></ul><ul><ul><li>Pre-renal azotemia </li></ul></ul><ul><ul><li>Urinary outlet obstruction </li></ul></ul><ul><li>(ii) RBC casts or dysmorphic RBCs </li></ul><ul><ul><li>Acute glomerulonephritis </li></ul></ul><ul><ul><li>Small vessel vasculitis </li></ul></ul><ul><li>(iii) WBC Cells and WBC Casts </li></ul><ul><ul><li>Acute interstitial nephritis </li></ul></ul><ul><ul><li>Acute pyelonephritis </li></ul></ul><ul><ul><li>(iv) RTE cells, RTE cell casts, pigmented granular (“muddy brown”) casts </li></ul></ul><ul><ul><li>Acute tubular necrosis </li></ul></ul><ul><ul><li>Urine chemistries helpful </li></ul></ul><ul><li>1) ATN = tubular necrosis; tubular function is impaired, thus high urine Na </li></ul><ul><ul><li>(Reabsorption of water and sodium impaired in tubulo-interstitial disease and ATN) </li></ul></ul><ul><li>2) Pre-renal = intact tubular function, thus urine Na is low </li></ul><ul><li>(Reabsorption of water and sodium intact in pre-renal failure) </li></ul>
  61. 61. Red Blood Cell Cast <ul><li>Two examples of red blood cell casts, typical of glomerular bleeding. </li></ul>
  62. 62. Red Blood Cells <ul><li>Monomorphic (non-dysmorphic) RBC suggest non-glomerular source of bleeding – i.e., bleeding from the calyces, pelvis, ureter(s), bladder, prostate or urethra. Dysmorphic red blood cells suggest glomerular injury. </li></ul><ul><li>Dysmorphic </li></ul><ul><li>monomorphic </li></ul>
  63. 63. White Blood Cells
  64. 64. White Blood Cell Cast
  65. 65. Renal Tubular Epithelial Cell Cast
  66. 66. Pigmented Granular Casts <ul><li>Pigmented granular (“muddy brown”) casts are characteristic of acute tubular necrosis </li></ul>
  67. 67. Urine Chemistries Fractional Excretion of Na and Urea <ul><li>Since urinary indices depend on urine sodium concentration, they should be interpreted cautiously if the patient has received diuretic </li></ul><ul><li>Spot urine Na may be affected (raised) by diuretic use and baseline impaired kidney function (CKD where maximum urine Na reabsorption is impaired) </li></ul><ul><li>Fractional excretion of Na accounts for this by including creatinine: </li></ul><ul><li>FxExNa = urine [Na] ÷ plasma [Na] X 100 </li></ul><ul><li>urine creatinine ÷ plasma creatinine </li></ul><ul><li>FxExurea – substitute urine urea nitrogen for Na </li></ul><ul><li>useful if patient receiving diuretics </li></ul>
  68. 68. renal indices <ul><li>Renal Failure Index (RFI) </li></ul><ul><li>RFI = urine [Na] </li></ul><ul><li>urine creatinine / serum creatinine </li></ul>
  69. 69. Prerenal azotemia: <ul><ul><li>Urine sediment : hyaline and fine granular casts </li></ul></ul><ul><ul><li>Urinary to plasma creatinine ratio : high </li></ul></ul><ul><ul><li>Urinary Na : low </li></ul></ul><ul><ul><li>FENa : low </li></ul></ul><ul><ul><li>Increased urine output in response to hydration </li></ul></ul>
  70. 70. Renal azotemia: <ul><ul><li>Urine sediment: brown granular casts and tubular epithelial cells </li></ul></ul><ul><ul><li>Urinary to plasma creatinine ratio : low </li></ul></ul><ul><ul><li>Urinary Na: high </li></ul></ul><ul><ul><li>FENa: high </li></ul></ul>
  71. 71. Acute Renal Failure Urine Volume <ul><li>Anuria (< 100 ml/24h) </li></ul><ul><ul><li>Acute bilateral arterial or venous occlusion </li></ul></ul><ul><ul><li>Bilateral cortical necrosis </li></ul></ul><ul><ul><li>Acute necrotizing glomerulonephritis </li></ul></ul><ul><ul><li>Obstruction (complete) </li></ul></ul><ul><ul><li>ATN (very rare) </li></ul></ul><ul><li>Oliguria (100-500 ml/24h) </li></ul><ul><ul><li>Pre-renal azotemia </li></ul></ul><ul><ul><li>ATN </li></ul></ul><ul><li>Non-Oliguria (> 500 ml/24h) </li></ul><ul><ul><li>ATN </li></ul></ul><ul><ul><li>Obstruction (partial) </li></ul></ul>
  72. 72. urine and serum laboratory values
  73. 73. Acute Tubular Necrosis Clinical Characteristics 25% 50% Mortality 26% 84% Dialysis required 3.1 + 0.5 6.8 + 1.4 FE Na (%) 50 + 5 68 + 6 U Na (mEq/L) 1,280 + 75 < 400 UV (ml/24h) 30% 8% Toxin-induced 59% 41% Incidence Non-Oliguric ATN Oliguric ATN Characteristic
  74. 74. <ul><li>Prior to the article by Anderson (reference below), it was believed that most cases of ATN were oliguric. Today, we know that ATN can present with oliguria or non-oliguria and that both presentations are common. Any cause of ATN can present with nonoliguria ; non-oliguria is more likely with nephrotoxic causes of ATN such as aminoglycosides, contrast media, cis-platinum, and amphotericin. The increased incidence of non-oliguric ATN during the past 25 years is most likely due to the increased usage of nephrotoxins, more frequent chemical testing, and more aggressive use of fluids, potent diuretics, and vasodilators in the management of ATN. The reduced mortality of non-oliguric compared to oliguric ATN is probably not because of the increased urine volume but rather due to a lower associated mortality of the conditions causing non-oliguric compared to oliguric ATN. (Data from Anderson et al: Non-oliguric Acute Renal Failure. New Engl J Med 296:134, 1977.) </li></ul>
  75. 75. acute renal failure: prevention <ul><li>recognize patients at risk (postoperative states, cardiac surgery, septic shock) </li></ul><ul><li>prevent progression from prerenal to renal </li></ul><ul><li>preserve renal perfusion </li></ul><ul><ul><li>isovolemia, cardiac output, normal blood pressure </li></ul></ul><ul><ul><li>avoid nephrotoxins (aminoglycosides, NSAIDS, amphotericin) </li></ul></ul>
  76. 76. Treatment of ARF <ul><li>Based on type/etiology of AKI (acute kidney injury) i.e., pre-renal, post-renal, or intrinsic renal initially </li></ul><ul><ul><li>Pre-renal – volume, improve renal perfusion </li></ul></ul><ul><ul><li>Post-renal – relieve obstruction </li></ul></ul><ul><ul><li>Intrinsic – glomerular, tubular, interstitial, vascular </li></ul></ul><ul><ul><li>depends on type </li></ul></ul><ul><li>Follow clinically; attention to volume status, avoid additional insults; treat complications of ARF </li></ul>
  77. 77. GENERAL PROTOCOL FOR MANAGEMENT <ul><li>treat the underlying disease </li></ul><ul><li>strictly monitor intake and output (weight, urine output, insensible losses, IVF) </li></ul><ul><li>monitor serum electrolytes </li></ul><ul><li>adjust medication dosages according to GFR </li></ul><ul><li>avoid highly nephrotoxic drugs </li></ul><ul><li>attempt to convert oliguric to non-oliguric renal failure (furosemide x 3) </li></ul>
  78. 78. <ul><li>hemoglobinuria + myoglobinuria </li></ul><ul><li>hemoglobinuria: </li></ul><ul><li>transfusion reactions, HUS (hemolytic uremic syndrome), ECMO (extra-corporeal membrane oxygenation) </li></ul><ul><li>myoglobinuria: </li></ul><ul><li>crush injuries, rhabdomyolysis </li></ul><ul><li>urine (+) blood but (-) red blood cells </li></ul><ul><li> CPK  K+ </li></ul><ul><li>treatment </li></ul><ul><li>aggressive hydration + urine alkalinization </li></ul><ul><li>mannitol / furosemide </li></ul>
  79. 79. acute renal failure: fluid therapy <ul><li>If patient is fluid overloaded </li></ul><ul><ul><ul><li>fluid restriction (insensible losses) </li></ul></ul></ul><ul><ul><ul><li>attempt furosemide 1-2 mg/kg </li></ul></ul></ul><ul><ul><ul><li>Renal replacement therapy (see later) </li></ul></ul></ul><ul><li>If patient is dehydrated: </li></ul><ul><ul><ul><li>restore intravascular volume first </li></ul></ul></ul><ul><ul><ul><li>then treat as euvolemic (below) </li></ul></ul></ul><ul><li>If patient is euvolemic: </li></ul><ul><ul><ul><li>restrict to insensible losses (30-35 ml/100kcal/24 hours) + other losses (urine, chest tubes, etc) </li></ul></ul></ul>
  80. 80. sodium <ul><li>most patients have dilutional hyponatremia which should be treated with fluid restriction </li></ul><ul><li>severe hyponatremia (Na< 125 mEq/L) or hypernatremia (Na> 150 mEq/L): dialysis or hemofiltration </li></ul>
  81. 81. potassium <ul><li>Oliguric renal failure is often complicated by hyperkalemia, increasing the risk in cardiac arrhythmias </li></ul><ul><li>Treatment of hyperkalemia: </li></ul><ul><ul><li>sodium bicarbonate (1-2 mEq/kg) </li></ul></ul><ul><ul><li>insulin + hypertonic dextrose: 1 unit of insulin/4 g glucose </li></ul></ul><ul><ul><li>sodium polystyrene (Kayexalate): 1 gm/kg . Can be repeated qh. (Hypernatremia and hypertension are potential complications) </li></ul></ul><ul><ul><li>dialysis </li></ul></ul>
  82. 82. nutrition <ul><li>provide adequate caloric intake </li></ul><ul><li>limit protein intake to control increases in BUN </li></ul><ul><li>minimize potassium and phosphorus intake </li></ul><ul><li>limit fluid intake </li></ul><ul><li>If adequate caloric intake can not be achieved due to fluid limitations, some form of dialysis should be considered </li></ul>
  83. 83. Treatment of ARF – Indications for Dialysis <ul><li>A – acidosis </li></ul><ul><li>E – electrolyte disturb., usually hyperkalemia </li></ul><ul><li>I – intoxications (lithium, ethylene glycol, etc) </li></ul><ul><li>O – overload (volume overload) </li></ul><ul><li>U – uremia (symptoms, signs) </li></ul>
  84. 84. ARF -- Summary <ul><li>Dx AKI by falling GFR [rising BUN and creatinine] </li></ul><ul><li>Classify into pre-renal, renal, or post-renal by history, PE, BUN:creat ratio, urine analysis </li></ul>
  85. 85. ARF – Summary (cont…) <ul><li>Sometimes also need urine chemistries [urine Na, FxExNa and/or FxExurea] to distinguish pre-renal from ATN </li></ul><ul><li>Sometimes need renal ultrasound to verify obstruction [post-renal ARF] </li></ul><ul><li>Rarely need other studies, esp to dx type of intrinsic ARF [e.g., kidney biopsy: GN vs interstitial nephritis vs ATN] </li></ul>
  86. 86. ARF – Summary (cont…) <ul><li>Distinguishing the types of intrinsic ARF usually depends on history, PE, urine analysis </li></ul><ul><ul><li>Vascular – large or small vessels </li></ul></ul><ul><ul><li>Tubular = ATN </li></ul></ul><ul><ul><li>Interstitial = AIN </li></ul></ul><ul><ul><li>Glomerular = acute GN </li></ul></ul>