Transcript Acute Renal Failure aka Acute Kidney Injury

Acute Renal Failure
aka Acute Kidney Injury
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
<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
RIFLE criteria for diagnosis of AKI based on The
“Acute Dialysis Quality Initiative”
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
Increase in Creatinine without AKI
• Inhibition of tubular creatinine secretion
Trimethoprim, Cimetidine, Probenecid
• Interference with creatinine assays in the lab
(false elevation)
glucose, acetoacetate, ascorbic acid, cefoxitin
flucytosine
Increase in BUN without AKI
• Increased production
GI Bleeding
Catabolic states (Prolonged ICU stay)
Corticosteroids
Protein loads (TPN-Albumin infusion)
New Biomarkers in AKI
Alternatives to Serum Creatinine
• Urinary Neutrophil Gelatinase-Associated
Lipocalin (NGAL)
– Ann Intern Med 2008;148:810-819
• Urinary Interleukin 18
– Am J Kidney Dis 2004;43:405-414
• Urinary Kidney Injury Molecule 1 (KIM-1)
– J Am Soc Nephrol 2007;18:904-912
AKI and Mortality(Brigham and Womens, 9210 adults)
Multivariable Odds Ratio for Death
• AKI (Δ in SCr >0.5)
•Age (per 10 yr)
•CKD
•CV dis.
•Respiratory dis
•GI dis.
•Cancer
•Infection
6.5
1.7
2.5
1.5
3
2.4
2.9
7.5
Chertow et al, JASN 16:3365-70;
2005
<0.0001
<0.0001
<0.0001
<0.04
<0.0001
<0.001
<0.0001
<0.0001
Major Disease Categories Causing AKI
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%
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
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)
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
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, size<9cm, anemia, high phosphate, low bicarb
• Renal biopsy
Likelihood ratio (LR) of ATN vs pre-renal azotemia on the
basis of the number of granular casts in urinary sediment
Granular
casts/hpf
LR for ATN
LR for prerenal
0
0.23
4.35
1-5
2.97
0.34
6-10
9.68
0.1
Clin J Am Soc Nephrol 4:691-693, 2009
RBC cast
Hyaline cast
Granular cast
Granular cast
Granular cast
WBC cast
Oval fat body
and Hyaline cast
WBC cast
Treatment of AKI
• Treatment is largely supportive in nature!
• Pharmacologic treatments under study:
– Dopamine: no benefit
– Atrial Natriuretic Peptide (ANP) or ANP-analogue
(Anaritide): promising
– Human Insulin like growth factor 1: no benefit
• Renal Replacement therapy remains the
cornerstone of management of minority of
patients with severe AKI
Nephron Clin Pract 2009;112:c222-c229
Is there a role for Dopamine in prevention or
treatment of AKI in ICU setting?
Clinical Outcomes:
• No effect on mortality
• No effect on the need for or incidence of Renal
Replacement Therapy (RRT)
Renal Physiologic Outcomes:
• Diuretic effect and increased creatinine clearance on the
first day which was not significant on the following days.
Adverse effect:
• on the immune, respiratory, and endocrine system.
Ann Intern Med. 2005;142:510-524
ANZICS Clinical Trial Group. Lancet 2000;356:2139-2143
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 Jun;32(6):1310-5
Is there a role for Fenoldepam 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 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
Is there a role for diuretics in the treatment of
AKI in ICU setting?
• PICARD Study:
Cohort study of 552 pts in 4 UC hospitals:
Odds Ratio
In-hospital Mortality
1.77
Non-recovery of renal function
1.68
• Improved urine output and shorter duration of RRT (none
has clinical relevance in ICU pts)
• But diuretics continue to be used for volume control in
AKI in ICU setting!
JAMA. 2002 Nov 27;288(20):2547-53
Crit Care Resusc. 2007 Mar;9(1):60-8
Results of individual RCTs comparing CRRT to IHD in AKI
in ICU
Study
n
n
CRRT
IHD
Mehta et al
KI 2001
84
82
Augustine et
al
AJKD 2004
40
Uehlinger et
al
NDT 2005
Primary
endpoint
Mortality
Mortality
Persisten
t RRT
requirem
ent
CRRT
IHD
CRRT
IHD
ICU mortality
59.5
41.5
14
7
40
In-hospital
mortality
67.5
70
61.5
66.7
70
55
In-hospital
mortality
47
51
2.7
3.7
Vinsonneau
et al
Lancet 2006
175
184
60-day mortality
67.4
68.5
1.8
0
Lins et al
NDT 2009
172
144
In-hospital
mortality
58.1
62.5
16.9
25.5
CRRT vs SLED (Sustained low efficiency
dialysis)
• SLED became popular because of CRRT
disadvantages:
– Expensive, continuous pt immobilization, need for specialized machines
and pre-mixed commercial solutions, and anticoagulation
• Only 2 small studies compared these 2 in
hemodynamically unstable pts with AKI
• They did not see significant differences in hemodynamic
parameters and solute clearance
• They did not look at any patient-relevant outcomes, so
the jury is still out there
Am J Kidney Dis 2004;43:342-349
J Artif Organs 2007;30:1083-1089
Am J Kidney Dis 2008;51:804-810
Results of RCTs comparing benefits of the intensity of RRT
(high vs low dose dialysis)
Study
n
Low dose
modality
High dose
modality
Endpoint
Results
for low
dose
Results
for high
dose
P
Schiffl et al
NEJM 2002
146
Thrice-weekly
IHD
Daily IHD
1-Mortality
2-Time to renal
recovery
46%
16 days
28%
9 days
Sig
Ronco et al
Lancet 2000
425
CVVH dose of 20
ml/kg/h
CVVHDF
dose of 35 or
45 ml/kg/h
90-day survival
34%
59%
Sig
Palvesky et al
NEJM 2008*
1100
High dose:
CRRT 35 ml/kg/h or
SLED X 6/wk or IHD
X 6/wk
Low dose:
CRRT 20
ml/kg/h or
SLED X 3/wk or
IHD X 3/wk
60-day mortality
51.8%
53.6%
NS
RENAL
Clinical Trial
(not published)
1500
CVVHDF 25
ml/kg/h
CVVHDF 40
ml/kg/h
90-day Survival
*Veterans Administration/National Institute of Health Acute Renal Failure Trial Network Study
NS
Overall conclusion on RRT modality benefit in AKI
• CRRT does not confer a survival advantage as
compared to IHD
• SLED may replace CRRT although there is no outcome
benefit study up to this date
• There is limited data regarding the ideal timing of RRT
initiation and the preferred mode of solute clearance
• No evidence to support a more intensive strategy of RRT
in the setting of AKI
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 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?
• 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.
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
prilosec. 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)
Hepatorenal Syndrome
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
Case 3
• 52 yo F underwent matched allo-Hematopoietic Stem
cell transplant (HSTC) for AML. Between days 3-7 she
gradually gained 8 Kg and edema developed. Since
day#7 her Bili rose daily and peaked at 8 with jaundice,
RUQ tenderness, and ascites. Liver US showed reversal
of flow in the portal vein. Since day#8 SCr rose slowly
from baseline of 1.0 to 3.5 mg/dl, with 400 cc/day UOP
on day#10. Her FeNa was 0.05% despite of 1.5L fluid
challenge. Her urine sediment was blend.
What is the most likely cause of her AKI?
• She required HD for volume control, and
remained HD dependent.
• Dx: Portal/Hepatic Veno-Occlusive
Disease (VOD)
• VOD is responsible for 90% of hepatorenal
syndromes in HSCT
Case 4
• 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?
• 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.
Case 5
• 68 yo F with CAD, DM, HTN, PVD, CKD with baseline
SCr of 1.4 mg/dl underwent elective cardiac angio and
stent placement. No new meds. She has been
hemodynamically stable throughout the procedure and
afterward. Since day#2 post procedure, her SCr has been
gradually rising to 2.5 mg/dl with 500-600 cc/day UOP.
UA showed SG 1.025, 1+ protein. Urine eosinophils (+).
Serology tests showed low complements. She was
discharged and in her f/u visit in 3 weeks she had SCr of
2.7.
What could be the cause of her AKI?
• She never required RRT, but her SCr
continued to rise slowly to 3.1 mg/dl. She
died 7 months later.
• Dx: Cholesterol emboli
Case 6
• 18 yo F with no PMH admitted with projectile
vomitting, fatigue, and low PO intake. Her
BP=200/110, normal UOP with dry mucosa,
trace edema, and otherwise normal exam.
BUN=120 mg/dl, Creat=10 mg/dl which
continued to rise on the following days, Hct=25%
without schistocytes on PBS, UA: 3+ protein, 3+
blood, >50 RBC, many RBC casts. FeNa 1%.
US showed normal sized kidneys.
What other tests do you order?
What may be the cause of her AKI?
• ANA (-), normal complements, cryo (-), serology for
hepatitis B, and C (-), P-ANCA (+), C-ANCA (-), antiGBM (-), ASO (-), UPEP and SPEP without M spike,
ESR 80.
• Her renal Bx showed crescentic glomerulonephritis,
minimal non-specific immune complex deposits, without
chronic changes.
• She remained dialysis dependent despite of steroid,
cytoxan, and 10 plasmapheresis treatments.
• Dx: Pauci-immune Crescentic Glomerulonephritis
due to Wegner’s granulomatosis
Case 7
• 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?
• Her CPK=57,700
• She was treated with IV NaHCO3 gtt to alkalinize
urine to PH>6.5 .
• Her UOP remained normal but she required HD
for uremia.
• Dx: ATN due to Rhabdomyolysis
Case 8
• 47 yo M with CAD, and CHF, admitted with LE cellulitis,
started on Zosyn. On day#4 of admission BP=90/60,
HR=68, normal UOP. LE edema(+), few pruritic purpuric
rash on the shins. SCr rose from 1.1 to 3.5 mg/dl.
BUN=96 mg/dl. UA: trace protein, small blood, few
RBCs, moderate WBC, with few WBC casts. FeNa>1%,
Urine eosinophil (+). Renal US showed 13 cm kidneys.
What may be the cause of his AKI?
What would be your next step?
• Zosyn was stopped.
• Patient required two HD treatment for uremia.
• Renal biopsy showed Acute Interestitial
Nephritis.
• Subsequently he was started on Prednisone for
one month and remained HD independent with
stable SCr of 1.8-2 mg/dl.
• Dx: AIN secondary to Zosyn
Case 9
• 72 yo M with DM, and prostate cancer metastatic to the
bone, s/p XRT, 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 6
months PTA), 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?
• 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
Case 10
• 32 yo M s/p Cadaveric Renal Transplant (CRT)
in 2006 for adult PCKD, on prograf, prednisone,
and cellcept, and history of BK viruria is admitted
for increased Creatinine=1.9 mg/dl, Hct=27%,
WBC 2,500, Plt 90,000. He seems well
hydrated, with stable VS, and normal exam. UA:
1.015, no protein, no blood, few granular casts.
FeNa 1%. (-) BK virus PCR in the blood.
What would be your next step?
What seems to be the cause for his allograft
failure?
• Renal Bx showed acute cellular rejection BANFF
IIb. No BK viral inclusions were identified.
• He received IV Solumedrol and Thymoglobulin
and his creatinine dropped to a stable level of
1.3-1.4 mg/dl.
• Dx: Acute cellular rejection
Case 11
• 59 yo F with prolonged HTN, s/p OLT in 2000, on
norvasc, prograf and prednisone was brought in for
AMS. T=39, BP=95/60, HR=104, UOP=20 cc/hr,
intubated for airway protection, otherwise normal exam.
BUN=80 mg/dl, creatinine=6 mg/dl (normal baseline),
K=6.5 meq/L, Hct=20%, Plt=20000, FeNa 1%, urine
eosinophil (-), UA: 2+ blood, no protein, RBC > 50/hpf,
no WBC, no cast.
What would be your next step?
What could be the reason for her AKI?
• Her PBS showed many schistocytes and
fragmented RBCs.
• Her Prograf was replaced with Sirolimus
• She underwent plasmapheresis, and required
HD for anuria, and persistent hyperkalemia. She
came off HD after 2.5 months with stable
creatinine=1.2 mg/dl.
• Dx: TTP secondary to Prograf
Case 12
• 72 yo F with depression and hypothyroidism, was found
by neighbors on the floor, unconscious, in respiratory
distress. Intubated for airway protection. VS stable,
anuric, Lungs CTA. BUN 50 mg/dl, Creatinine=4 mg/dl,
with high anion gap metabolic acidosis, and an osmolar
gap of > 10. Lactic acid=1.8, FeNa 1%, urine eosinophil
(-), UA: 1.020, 1+ blood, no protein, few RBCs, many
oxalate crystals, few granular casts. US showed normal
sized kidneys with no hydronephrosis.
What is your next step?
What seems to be the cause for her AKI?
• Her ethylene Glycol level came back after 2
days to be 40 mg/dl.
• Pt was given Fomepizole and initiated on HD for
persistent acidemia. She remained HD
dependent, eventually extubated, started
therapy for depression and discharged to NH.
• Dx: Ethylene Glycol toxicity
Case 13
• 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?
• He was started on CVVH for volume control.
Has had a long hospital stay complicated with
polymicrobial bacteremia and VAP.
• Dx: ATN secondary to renal ischemia and
sepsis
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 < 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)
When to do renal biopsy in AKI ?
• Any evidence of glomerular disease
-nephrotic range proteinuria
-sub-nephrotic range proteinuria with hematuria
-RBC cast
• AKI in renal allograft
• Determine the prognosis and chance of recovery of renal
function in dialysis dependent AKI.
• Whenever potential Bx result can change the
management or prognosis.
When to initiate RRT in a patient with AKI ?
1) Renal Replacement Therapy:
Electrolytes imbalances
Acid-base disturbances
Uremic complications
-Encephalopathy
-Pericarditis
-Persistant nausea, and food
intolerance
2) Renal/Multiorgan Support Therapy
-Protects other organs by improving overall
body milieu (balance of inflammatory
mediators)
-Allowing therapies for other organs that pt
could not otherwise tolerate
-volume resuscitation
-aggressive nutrition
3) Removal of toxic agents in overdose
-Ethylene Glycol
-Methanol
-Salicylates
-Lithium
-Theophylline
-Isopropanol
Thank you!