Download Acute Kidney Injury

Dr. Waleed Khairy, MD
Ain Shams University
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There are more than 35 definitions of AKI
(formerly acute renal failure) in literature!
Stage
Increase in Serum
Creatinine
Urine Output
1
1.5-2 times baseline
OR
0.3 mg/dl increase
from baseline
<0.5 ml/kg/h for >6 h
2
2-3 times baseline
<0.5 ml/kg/h for >12
h
3
3 times baseline
OR
0.5 mg/dl increase if
baseline>4mg/dl
OR
Any RRT given
<0.3 ml/kg/h for >24
h
OR
Anuria for >12 h
Increase in SCr
Urine output
Risk of renal injury
0.3 mg/dl increase
< 0.5 ml/kg/hr for > 6 h
Injury to the kidney
2 X baseline
< 0.5 ml/kg/hr for >12h
Failure of kidney
function
3 X baseline OR
> 0.5 mg/dl increase if
SCr >=4 mg/dl
Anuria for >12 h
Loss of kidney
function
End-stage disease
Persistent renal failure
for > 4 weeks
Persistent renal failure
for > 3 months
Am J Kidney Dis. 2005 Dec;46(6):1038-48
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; 39:930-936.
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; 10:R73.
Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to
RIFLE. Critical Care Medicine 2007; 35:1837-1843.
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; 10:R73.
Chertow G, Levy E, Hammermeister K, et al.: Independent association between acute renal failure and
mortality following cardiac surgery. American Journal of Medicine 1998; 104:343-348.
Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter
study. JAMA 2005; 294:813-818.
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; 50:712-720.
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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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Increased production
GI Bleeding
Catabolic states (Prolonged ICU stay)
Corticosteroids
Protein loads (TPN-Albumin infusion)
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Urinary Neutrophil Gelatinase-Associated
Lipocalin (NGAL)
◦ Ann Intern Med 2008;148:810-819
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Urinary Interleukin 18
◦ Am J Kidney Dis 2004;43:405-414
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Urinary Kidney Injury Molecule 1 (KIM-1)
◦ J Am Soc Nephrol 2007;18:904-912
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NGAL:
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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
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KIM-1:
◦ Epithelial transmembrane protein, ?cell-cell interaction.
◦ Appears to have strong relationship with severity of renal injury
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
Disease Category
Prerenal azotemia caused by acute renal
hypoperfusion
Incidence
Intrinsic renal azotemia caused by acute
diseases of renal parenchyma:
35-40%
-Large renal vessels dis.
-Small renal vessels and glomerular dis.
-ATN (ischemic and toxic)
-Tubulo-interestitial dis.
-Intratubular obstruccttion
Postrenal azotemia caused by acute
obstruction of the urinary tract
55-60%
*>90%*
<5%
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Intravascular volume depletion
bleeding, GI loss, Renal loss, Skin loss, Third space
loss
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Decreased cardiac output
CHF
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Renal vasoconstriction
Liver Disease, Sepsis, Hypercalcemia
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Pharmacologic impairment of
autoregulation and GFR in specific settings
ACEi in bilateral RAS, NSAIDS in any renal
hypoperfusion setting
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Large Renal Vessel Disease
Thrombo-embolic disease
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Renal Microvasculature and Glomerular Disease
Inflammatory: glomerulonephritis, allograft rejection
Vasospastic: malignant hypertension, scleroderma crisis, preeclampsia, contrast
Hematologic: HUS-TTP, DIC
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Acute Tubular Necrosis (ATN)
Ischemic
Toxic
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Tubulo-interestitial Disease
Acute Interestitial Nephritis (AIN), Acute cellular allograft rejection,
viral (HIV, BK virus), infiltration (sarcoid)
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Intratubular Obstruction
myoglobin, hemoglobin, myeloma light chains, uric acid, tumor
lysis, drugs (indinavir, acyclovir, foscarnet, oxalate in ethylene glycol
toxicity)
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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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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, size<9cm, anemia, high phosphate, low
bicarb
Renal biopsy
1)
2)
3)
4)
5)
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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Recognition of underlying risk factors
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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; 38:261-275.
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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
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Sulfonamides
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Amphotericin B (Incidence 80-90%)
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Levofloxacin
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Ciprofloxacin
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Rifampin
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Tetracycline
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Acyclovir (only nephrotoxic in
intravenous form)
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AntiHyperlipidemics
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Sulfonamides
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Statins
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Vasculitis reaction
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Gemfibrozil
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NSAIDs
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Nephrotic Syndrome type reaction
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Rifampin
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Diuretics (Thiazides and furosemide)
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Allopurinol
Serum Creatinine rise is reversible on
stopping Fenofibrate
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Cimetidine
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Ciprofloxacin
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Chemotherapy
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Dilantin
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Cisplatin
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Ifosphamide
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Causes Fanconi's Syndrome
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Miscellaneous Drugs
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Chronic Stimulant Laxative use
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Associated with Acute Renal Failure due
to Rhabdomyolysis
Fenofibrate (Tricor)
Increases Serum Creatinine without
significant decrease in GFR
Resulting chronic volume depletion and
Hypokalemia causes nephropathy
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Pentamidine
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Chemotherapy and Immunosuppressants
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Cisplatin
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Methotrexate
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Mitomycin
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Cyclosporine
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NSAIDs
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Heavy Metals
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Aspirin
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Mercury Poisoning
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Lead Poisoning
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Arsenic Poisoning
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Bismuth
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Lithium related kidney disorders
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Polydipsia and Nephrogenic Diabetes
Insipidus
Radiographic contrast
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ACE Inhibitors
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Dialysis indications: Creatinine >2.5
or Seizures, ALOC, Rhabdomyolysis
Chronic kidney disease with fibrosis
Expect an increase of Serum Creatinine
in Chronic kidney disease
Low dose Aspirin reduces Renal function
in elderly
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Decreased Creatinine Clearance after
2 weeks of use
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Changes persisted for at least 3
weeks off Aspirin
Mesalamine (Asacol, Pentasa)
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Acute Renal Failure
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Mesalamine is an NSAID analog and
has systemic absorption from the
bowel
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Penicillins and Cephalosporins
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Hypersensitivity (fever, rash, arthralgia)
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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; 38:261-275.
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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; 341:403-409.
Gines P, Tito L, Arroyo V, et al.: Randomised comparative study of therapeutic paracentesis with
and without intravenous albumin in cirrhosis. Gastroenterology 1988; 94:1493-1502.
Gluud L, Kjaer M, Christensen E: Terlipressin for hepatorenal syndrome. Cochrane Database
Systematic Reviews 2006; CD005162.
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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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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The individual BP target depends on age, comorbidities (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; 33:780-786
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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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Fluid conservative therapy decreased
ventilator days and didn’t 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; 354:2564-2575.
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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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; 38:261-275.
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renal dose dopamine (<5 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 tachyarrhythmia’s,
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;
69:1669-1674.
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; 33:1327-1332.
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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 Jun;32(6):1310-5
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Dopamine-1 receptor agonist, lack of Dopamine-2,
and alpha-1 receptor effect, make it a potentially
safer drug than Dopamine!
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Reduces in hospital mortality and the need for RRT
in AKI
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Reverses renal hypoperfusion more effectively than
renal dose Dopamine
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So far so good specially in cardiothoracic ICU
patients, awaiting more powered trials in other
groups!
J Cardiothorac Vasc Anesth. 2008 Feb;22(1):23-6.
J Cardiothorac Vasc Anesth. 2007 Dec;21(6):847-50
Am J Kidney Dis. 2007 Jan;40(1):56-68
Crit Care Med. 2006 Mar;34(3):707-14
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Loop diuretics may convert an oliguric into a nonoliguric 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 27;288(20):2547-53
Crit Care Resusc. 2007 Mar;9(1):60-8
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The most recent trials seem to confirm a
potential positive preventive effect of Nacetylcysteine (NAC), particularly in contrastinduced 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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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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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 day#2 her SCr
is 0.9 mg/dl, lipase is elevated and tense
abdominal distension is noted. US showed massive
ascites. UOP drops to <20 cc/hr despite of 10 L
total IV intake. On day#3, 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
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UOP and SCr improved with emergent
paracenthesis.
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Dx: Abdominal Compartment Syndrome causing
decreased renal perfusion from increased renal
vein pressure.
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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 BP~100/70
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 <1% despite of 2 L fluid
challenge. His Urine sediment is blend. His renal US is
normal.
What is the cause of his AKI?
 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)
Major diagnostic criteria:
No improvement with at least 1.5 L fluid
challenge
SCr >1.5 mg/dl or GFR< 40 cc/min
Absence of proteinuria (<500 mg/d)
Other causes are rouled out (obstruction, ATN,
etc.)
Minor diagnostic criteria:
Urine volume < 400 cc/day
UNa < 10 meq/L
SNa < 130 meq/L
Urine RBC < 50/hpf
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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, BP=120/80, I/O=1200/4500. 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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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, creatinine=8
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 CPK=57,700
She was treated with IV NaHCO3 to
alkalinize urine to PH>6.5 .
Her UOP remained normal but she required
HD for uremia.
Dx: ATN due to Rhabdomyolysis
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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.
BP=150/90, 350cc of urine collection immediately
after foley placement, and normal exam. BUN=107
mg/dl, creatinine=9.8 mg/dl (2.0 almost for 6
months), which remained unchanged with
hydration. Uric acid=8.2 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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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 CVP~12, has coarse crackles, and 2+
edema. His Creatinine rose from 1.2 to 3.5 the morning
after the above event, FeNa > 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 venovenous 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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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 < 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)