(AKI) Acute Kidney Injury

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(AKI) Acute Kidney Injury

• Dr. Waleed Khairy, MD
• Ain Shams University

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Definition of AKI

• There are more than 35 definitions of AKI
  (formerly acute renal failure) in literature!

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Definition of Acute Kidney Injury (AKI) based on
Acute Kidney Injury Network
Stage Increase in Serum Creatinine Urine Output
1 1.5-2 times baseline OR 0.3 mg/dl increase from baseline lt0.5 ml/kg/h for gt6 h
2 2-3 times baseline lt0.5 ml/kg/h for gt12 h
3 3 times baseline OR 0.5 mg/dl increase if baselinegt4mg/dl OR Any RRT given lt0.3 ml/kg/h for gt24 h OR Anuria for gt12 h
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RIFLE criteria for diagnosis of AKI based on The
Acute Dialysis Quality Initiative
Increase in SCr Urine output
Risk of renal injury Injury to the kidney Failure of kidney function 0.3 mg/dl increase 2 X baseline 3 X baseline OR gt 0.5 mg/dl increase if SCr gt4 mg/dl lt 0.5 ml/kg/hr for gt 6 h lt 0.5 ml/kg/hr for gt12h Anuria for gt12 h
Loss of kidney function End-stage disease Persistent renal failure for gt 4 weeks Persistent renal failure for gt 3 months
Am J Kidney Dis. 2005 Dec46(6)1038-48
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Epidemiology

• AKI occurs in
• 7 of hospitalized patients.
• 36 67 of critically ill patients (depending on
  the definition).
• 5-6 of ICU patients with AKI require RRT.
• Nash K, Hafeez A, Hou S Hospital-acquired renal
  insufficiency. American Journal of Kidney
  Diseases 2002 39930-936.
• Hoste E, Clermont G, Kersten A, et al. RIFLE
  criteria for acute kidney injury are associated
  with hospital mortality in critically ill
  patients A cohort analysis. Critical Care 2006
  10R73.
• Osterman M, Chang R Acute Kidney Injury in the
  Intensive Care Unit according to RIFLE. Critical
  Care Medicine 2007 351837-1843.

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Mortality according to RIFLE

• Mortality increases proportionately with
  increasing severity of AKI (using RIFLE).
• AKI requiring RRT is an independent risk factor
  for in-hospital mortality.
• Mortality in pts with AKI requiring RRT 50-70.
• Even small changes in serum creatinine are
  associated with increased mortality.
• Hoste E, Clermont G, Kersten A, et al. RIFLE
  criteria for acute kidney injury are associated
  with hospital mortality in critically ill
  patients A cohort analysis. Critical Care 2006
  10R73.
• Chertow G, Levy E, Hammermeister K, et al.
  Independent association between acute renal
  failure and mortality following cardiac surgery.
  American Journal of Medicine 1998 104343-348.
• Uchino S, Kellum J, Bellomo R, et al. Acute
  renal failure in critically ill patients A
  multinational, multicenter study. JAMA 2005
  294813-818.
• Coca S, Peixoto A, Garg A, et al. The
  prognostic importance of a small acute decrement
  in kidney function in hospitalized patients a
  systematic review and meta-analysis. American
  Journal of Kidney Diseases 2007 50712-720.
• .

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Increase in Creatinine without AKI

• Inhibition of tubular creatinine secretion
• Trimethoprim, Cimetidine, Probenecid
• Interference with creatinine assays in the lab
  (false elevation)
• acetoacetate, ascorbic acid, cefoxitin
• flucytosine

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Increase in BUN without AKI

• Increased production
• GI Bleeding
• Catabolic states (Prolonged ICU stay)
• Corticosteroids
• Protein loads (TPN-Albumin infusion)

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New Biomarkers in AKIAlternatives to Serum
Creatinine

• Urinary Neutrophil Gelatinase-Associated
  Lipocalin (NGAL)
• Ann Intern Med 2008148810-819
• Urinary Interleukin 18
• Am J Kidney Dis 200443405-414
• Urinary Kidney Injury Molecule 1 (KIM-1)
• J Am Soc Nephrol 200718904-912

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• NGAL
• Expressed in proximal and distal nephron
• Binds and transports iron-carrying molecules
• Role in injury and repair
• Rises very early (hours) after injury in animals,
  confirmed in children having CPB
• IL-18
• Role in inflammation, activating macrophages and
  mediates ischemic renal injury
• IL-18 antiserum to animals protects against
  ischemic AKI
• Studied in several human models
• KIM-1
• Epithelial transmembrane protein, ?cell-cell
  interaction.
• Appears to have strong relationship with severity
  of renal injury

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Urine analysis

• Unremarkable in pre and post renal causes
• Differentiates ATN vs. AIN. vs. AGN
• Muddy brown casts in ATN
• WBC casts in AIN
• RBC casts in AGN

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Major Disease Categories Causing AKI
Disease Category Incidence
Prerenal azotemia caused by acute renal hypoperfusion 55-60
Intrinsic renal azotemia caused by acute diseases of renal parenchyma -Large renal vessels dis. -Small renal vessels and glomerular dis. -ATN (ischemic and toxic) -Tubulo-interestitial dis. -Intratubular obstruccttion 35-40 gt90
Postrenal azotemia caused by acute obstruction of the urinary tract lt5
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Prerenal Azotemia

• Intravascular volume depletion
• bleeding, GI loss, Renal loss, Skin loss, Third
  space loss
• Decreased cardiac output
• CHF
• Renal vasoconstriction
• Liver Disease, Sepsis, Hypercalcemia
• Pharmacologic impairment of autoregulation and
  GFR in specific settings
• ACEi in bilateral RAS, NSAIDS in any renal
  hypoperfusion setting

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Intrinsic Renal Azotemia

• Large Renal Vessel Disease
• Thrombo-embolic disease
• Renal Microvasculature and Glomerular Disease
• Inflammatory glomerulonephritis, allograft
  rejection
• Vasospastic malignant hypertension, scleroderma
  crisis, pre-eclampsia, contrast
• Hematologic HUS-TTP, DIC
• Acute Tubular Necrosis (ATN)
• Ischemic
• Toxic
• Tubulo-interestitial Disease
• Acute Interestitial Nephritis (AIN), Acute
  cellular allograft rejection, viral (HIV, BK
  virus), infiltration (sarcoid)
• Intratubular Obstruction
• myoglobin, hemoglobin, myeloma light chains,
  uric acid, tumor lysis, drugs (indinavir,
  acyclovir, foscarnet, oxalate in ethylene glycol
  toxicity)

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Postrenal azotemia

• Stones
• Blood clots
• Papillary necrotic tissue
• Urethral disease
• anatomic posterior valve
• functional anticholinergics, L-DOPA
• Prostate disease
• Bladder disease
• anatomic cancer, schistosomiasis
• functional neurogenic bladder

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Initial diagnostic tools in AKI

• History and Physical exam
• Detailed review of the chart, drugs administered,
  procedures done, hemodynamics during the
  procedures.
• Urinalysis
• SG, PH, protein, blood, crystals, infection
• Urine microscopy
• casts, cells (eosinophils)
• Urine lytes
• Renal imaging
• US, Mag-3 scan, Retrograde Pyelogram
• Markers of CKD
• iPTH, sizelt9cm, anemia, high phosphate, low
  bicarb
• Renal biopsy

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5 Key Steps in Evaluating Acute Kidney Injury

• Obtain a thorough history and physical review
  the chart in detail
• Do everything you can to accurately assess volume
  status
• Always order a renal ultrasound
• Look at the urine
• Review urinary indices

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Prevention of AKI in ICU

• Recognition of underlying risk factors
• Diabetes
• CKD
• Age
• HTN
• Cardiac/liver dysfunction
• Maintenance of renal perfusion
• Avoidance of hyperglycemia
• Avoidance of nephrotoxins
• Dennen P, Douglas I, Anderson R, Acute Kidney
  Injury in the Intensive Care Unit An update and
  primer for the Intensivist. Critical Care
  Medicine 2010 38261-275.

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• Antibiotics
• Aminoglycosides (10-15 Incidence of Acute
  Tubular Necrosis)
• Occurs in 10-20 patients on 7 day course
• Results in non-oligurics increased Creatinine
• A single dose early in septic course is usually
  safe
• Sulfonamides
• Amphotericin B (Incidence 80-90)
• Levofloxacin
• Ciprofloxacin
• Rifampin
• Tetracycline
• Acyclovir (only nephrotoxic in intravenous form)
• Pentamidine
• Chemotherapy and Immunosuppressants
• Cisplatin
• Methotrexate
• Mitomycin
• Cyclosporine
• Heavy Metals

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Prevention of Contrast-Induced Nephropathy

• Avoid use of intravenous contrast in high risk
  patients if at all possible.
• Use pre-procedure volume expansion using isotonic
  saline (?bicarbonate).
• NAC
• Avoid concomitant use of nephrotoxic medications
  if possible.
• Use low volume low- or iso-osmolar contrast
• Dennen P, Douglas I, Anderson R, Acute Kidney
  Injury in the Intensive Care Unit An update and
  primer for the Intensivist. Critical Care
  Medicine 2010 38261-275.

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Prevention of AKI in hepatic dysfunction

• Intravenous albumin significantly reduces the
  incidence of AKI and mortality in patients with
  cirrhosis.
• Albumin decreases the incidence of AKI after
  large volume paracentesis.
• Albumin and terlipressin decrease mortality in
  HRS.
• Sort P, Navasa M, Arroyo V, et al. Effect of
  intravenous albumin on renal impairment and
  mortality in patients with cirrhosis and
  spontaneous bacterial peritonitis. New England
  Journal of Medicine 1999 341403-409.
• Gines P, Tito L, Arroyo V, et al. Randomised
  comparative study of therapeutic paracentesis
  with and without intravenous albumin in
  cirrhosis. Gastroenterology 1988 941493-1502.
• Gluud L, Kjaer M, Christensen E Terlipressin
  for hepatorenal syndrome. Cochrane Database
  Systematic Reviews 2006 CD005162.

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Management of AKI in ICU

• Treatment is largely supportive in nature
  Maintain renal perfusion
• Correct metabolic derangements
• Provide adequate nutrition
• ? Role of diuretics
• Renal Replacement therapy remains the cornerstone
  of management of minority of patients with severe
  AKI

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Maintaining renal perfusion

• Human kidney has a compromised ability to
  autoregulate in AKI.
• Maintaining haemodynamic stability and avoiding
  volume depletion are a priority in AKI.
• Kelleher S, Robinette J, Conger J Sympathetic
  nervous system in the loss of autoregulation in
  acute renal failure. American Journal of
  Physiology 1984 246 F379-386.

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Maintaining renal perfusion

• The individual BP target depends on age,
  co-morbidities (HTN) and the current acute
  illness.
• A generally accepted target remains MAP 65.
• Bourgoin A, Leone M, Delmas A, et al.
  Increasing mean arterial pressure in patients
  with septic shock Effects on oxygen variables
  and renal function. Critical Care Medicine 2005
  33780-786

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Volume resuscitation which fluid?

• no statistical difference between volume
  resuscitation with saline or albumin in survival
  rates or need for RRT.
• Finfer S, Bellomo R, Boyce N, et al. A
  comparison of albumin and saline for fluid
  resuscitation in the intensive care unit. New
  England Journal of Medicine 2004 350 2247-2256.

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Volume resuscitation how much fluid?

• Fluid conservative therapy decreased ventilator
  days and didnt increase the need for RRT in ARDS
  patients.
• Association between positive fluid balance and
  increased mortality in AKI patients.
• Wiedeman H, Wheeler A, Bernard G, et al.
  Comparison of two fluid management strategies in
  acute lung injury. New England Journal of
  Medicine 2006 3542564-2575.
• Payen D, de Pont A, Sakr Y, et al. A positive
  fluid balance is associated with worse outcome in
  patients with acute renal failure. Critical Care
  2008 12 R74

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Which inotrope/vasopressor?

• There is no evidence that from a renal protection
  standpoint, there is a vasopressor agent of
  choice to improve kidney outcome.
• Dennen P, Douglas I, Anderson R, Acute Kidney
  Injury in the Intensive Care Unit An update and
  primer for the Intensivist. Critical Care
  Medicine 2010 38261-275.

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Renal vasodilators?

• renal dose dopamine (lt5 µg/kg of body weight/min)
  increases RBF and, to a lesser extent, GFR.
  Dopamine is unable to prevent or alter the course
  of ischaemic or nephrotoxic AKI. Furthermore,
  dopamine, even at low doses, can induce
  tachy-arrhythmias, myocardial ischaemia, and
  extravasation out of the vein can cause severe
  necrosis .Thus, the routine administration of
  dopamine to patients for the prevention of AKI or
  incipient AKI is no longer justified.
• Lauschke A, Teichgraber U, Frei U, et al.
  Low-dose dopamine worsens renal perfusion in
  patients with acute renal failure. Kidney 2006
  691669-1674.
• Argalious M, Motta P, Khandwala F, et al.
  Renal dose dopamine is associated with the risk
  of new onset atrial fibrillation after cardiac
  surgery. Critical Care Medicine 2005
  331327-1332.

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Role of ANP analogues in AKI?

• 61 patients in 2 cardiothoracic ICU with post-op
  AKI assigned to receive recombinent ANP
  (50ng/kg/min) or placebo
• The need for RRT before day 21 after development
  of AKI was significantly lower in ANP group (21
  vs 47)
• The need for RRT or death after day 21 was
  significantly lower in ANP group (28 vs 57)

Crit Care Med. 2004 Jun32(6)1310-5
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Is there a role for Fenoldopam in prevention or
treatment of AKI in ICU setting?

• Dopamine-1 receptor agonist, lack of Dopamine-2,
  and alpha-1 receptor effect, make it a
  potentially safer drug than Dopamine!
• Reduces in hospital mortality and the need for
  RRT in AKI
• Reverses renal hypoperfusion more effectively
  than renal dose Dopamine
• So far so good specially in cardiothoracic ICU
  patients, awaiting more powered trials in other
  groups!

J Cardiothorac Vasc Anesth. 2008 Feb22(1)23-6.
J Cardiothorac Vasc Anesth. 2007
Dec21(6)847-50 Am J Kidney Dis. 2007
Jan40(1)56-68 Crit Care Med. 2006
Mar34(3)707-14
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Is there a role for diuretics in the treatment of
AKI in ICU setting?

• Loop diuretics may convert an oliguric into a
  non-oliguric form of AKI that may allow easier
  fluid and/or nutritional support of the patient.
  Volume overload in AKI patients is common and
  diuretics may provide symptomatic benefit in that
  situation. However, loop diuretics are neither
  associated with improved survival, nor with
  better recovery of renal function in AKI.

JAMA. 2002 Nov 27288(20)2547-53 Crit Care
Resusc. 2007 Mar9(1)60-8
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NAC

• The most recent trials seem to confirm a
  potential positive preventive effect of
  N-acetylcysteine (NAC), particularly in
  contrast-induced nephropathy (CIN), NAC alone
  should never take the place of IV hydration in
  patients at risk for CIN fluids likely have a
  more substantiated benefit. (150 mg/kg in 500 mL
  saline (0.9) over 30 min immediately before
  contrast exposure and followed by 50 mg/kg in 500
  mL saline (0.9) over the subsequent 4 h )

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EPO

• Erythropoietin (EPO) has tissue-protective
  effects and prevents tissue damage during
  ischaemia and inflammation, and currently trials
  are performed with EPO in the prevention of AKI
  post-cardiac surgery, CIN and post-kidney
  transplantation.

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Case 1

• 26 yo F is involved in a MVA, with multiple
  fractures, blunt chest and abdominal trauma. She
  was briefly hypotensive on arrival to ED,
  received 6L NS and normalized BP. Non contrast CT
  showed small retroperitoneal hematoma. On day2
  her SCr is 0.9 mg/dl, lipase is elevated and
  tense abdominal distension is noted. US showed
  massive ascites. UOP drops to lt20 cc/hr despite
  of 10 L total IV intake. On day3, SCr is
  2.1mg/dl, CVP is 17, UNa is 10 meq/L, with a
  bland sediment.
• What is the cause of her AKI?
• What bedside diagnostic test and therapeutic
  intervention is indicated?

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• Bladder pressure was 29 mmHg
• UOP and SCr improved with emergent paracenthesis.
• Dx Abdominal Compartment Syndrome causing
  decreased renal perfusion from increased renal
  vein pressure.

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Case 2

• 59 yo M, s/p liver transplant in 2001 and acute
  on chronic rejection, now decompensated ESLD, is
  admitted with worsening ascites, hepatic
  encephalopathy and GI bleed (which is now
  controlled). The only medications he has been
  receiving are Lactulose and omeprazole. He has
  been hemodynamically stable with average
  BP100/70 mmHg.He had a 3.5 L paracenthesis on
  day 2. His SCr has been slowly rising from 1.2 to
  4.7 mg/dl within the 2nd to 4th day of admission
  and his UOP has dropped to 150 cc/day. His daily
  FeNa is lt1 despite of 2 L fluid challenge. His
  Urine sediment is blend. His renal US is normal.
• What is the cause of his AKI?

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• Patient required HD.
• He had a second liver transplant and came off HD
  after the surgery with stable SCr of 1.4 mg/dl.
• Dx Hepatorenal Syndrome (HRS)

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Hepatorenal Syndrome

• Major diagnostic criteria
• No improvement with at least 1.5 L fluid
  challenge
• SCr gt1.5 mg/dl or GFRlt 40 cc/min
• Absence of proteinuria (lt500 mg/d)
• Other causes are rouled out (obstruction, ATN,
  etc.)
• Minor diagnostic criteria
• Urine volume lt 400 cc/day
• UNa lt 10 meq/L
• SNa lt 130 meq/L
• Urine RBC lt 50/hpf

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Case 3

• 45 yo M with CHF and Bipolar Disorder on Lithium
  for 10 years, admitted for abdominal pain after a
  heavy meal, which turned out to be due to acute
  cholecyctitis. He was kept NPO on D5 1/2NS 50
  cc/hr. Next morning he felt well but thirsty and
  hungry, BP120/80, I/O1200/4500. His SCr rose
  from 1.2 to 1.9 mg/dl. SNa 149 meq/L. UNa 10
  meq/L. UOsm 190 mOsm/Kg.
• What is the cause of his AKI?

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• Patients IVF was changed to ½ NS, replacing 80
  of UOP per hour. SCr and SNa improved to baseline
  in 2 days.
• Dx Prerenal azotemia secondary to renal free
  water loss in DI.

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Case 4

• 54 yo F with CAD, on statin, started a new
  exercise program with intense weight training.
  She was brought to ED with neck pain, and LE
  weakness. VS stable, normal UOP, with dry mucosa.
  LE muscle strength 2/5 bilaterally. BUN 40 mg/dl,
  creatinine8 mg/dl. FeNa 1.5. Renal US normal.
  UA 1.010, 3 blood, few RBCs, few granular
  casts.
• What would be the next test to order?
• What may be the cause of her AKI?

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• Her CPK57,700
• She was treated with IV NaHCO3 to alkalinize
  urine to PHgt6.5 .
• Her UOP remained normal but she required HD for
  uremia.
• Dx ATN due to Rhabdomyolysis

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Case 5

• 72 yo M with DM, and prostate cancer metastatic
  to the bone, s/p radiotherapy, on hormonal
  therapy. He is admitted with weakness,
  progressive weight loss, and persistent nausea.
  His med list also includes Diclofenac sodium
  daily for hip pain. BP150/90, 350cc of urine
  collection immediately after foley placement, and
  normal exam. BUN107 mg/dl, creatinine9.8 mg/dl
  (2.0 almost for 6 months), which remained
  unchanged with hydration. Uric acid8.2 mg/dl.
  UA 1.010, 1 protein, 1 blood, few RBCs, no
  cast, no WBC. US showed 10-11 cm kidneys, no
  hydronephrosis.
• What seems to be the cause for his AKI?

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• Patient was initiated on HD for uremia and
  remained HD dependent for his symptomatic uremia.
• Patient and his family were concerned about his
  renal recovery (outcome), so a renal Bx was done
  showing severe chronic interstitial nephritis,
  with fibrosis and glomerulosclerosis.
• Dx ESRD due to chronic tubulo-interstitial
  disease secondary to NSAIDs

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Case 6

• 38 yo M with post ERCP pancreatitis, is admitted
  to ICU, intubated for hypoxic respiratory
  distress, is anuric, febrile, and hypotensive,
  requiring massive volume resuscitation, on two
  vasopressors. He has received 11 L of NS and
  other IV meds within the last 8 hours and
  currently his CVP12, has coarse crackles, and 2
  edema. His Creatinine rose from 1.2 to 3.5 the
  morning after the above event, FeNa gt 1, UNa 45
  meq/L, UA 1.010, no protein, no blood, moderate
  epithelial cells, many muddy brown granular cell
  casts, moderate epithelial cell casts. US showed
  normal sized kidneys with no hydronephrosis.
• What is the cause of his AKI?

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• He was started on CVVH (continuous veno-venous
  hemofiltration )for volume control. Has had a
  long hospital stay complicated with polymicrobial
  bacteremia and VAP (Ventilator-associated
  pneumonia).
• Dx ATN secondary to renal ischemia and sepsis

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Natural Clinical Course of ATN

• Initiation Phase (hours to days)
• Continuous ischemic or toxic insult
• Evolving renal injury
• ATN is potentially preventable at this time
• Maintenance Phase (typically 1-2 wks)
• Maybe prolonged to 1-12 months
• Established renal injury
• GFR lt 10 cc/min, The lowest UOP
• Recovery Phase
• Gradual increase in UOP toward post-ATN diuresis
• Gradual fall in SCr (may lag behind the onset of
  diuresis by several days)

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Thank you!