Approach to AKI
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Transcript Approach to AKI
Internal Medicine Resident Half-Day
Ahsan Alam, MD
Acute Renal Failure
Internal Medicine Resident Half-Day
Ahsan Alam, MD
Acute Kidney Injury
What is Acute Kidney Injury
Abrupt decline in GFR
Increase in serum creatinine
PUF = (PGC - PT) - (pGC - pT)
Varying definitions (RIFLE, AKIN, etc)
Rising Prevalence of AKI
Why do we care about AKI?
Mortality with hospital-acquired AKI
37.8
40
35
30.7
Mortality %
30
25
22
20
15
10.6
10
5
0
<1 mg/dL
1.1-2 mg/dL
2.1-3 mg/dL
>3 mg/dL
Nash K et al. Am J Kidney Dis 2002;39(5):930-936
Lassnigg, A. et al. J Am Soc Nephrol 2004;15:1597-1605
Mortality post cardiac surgery
Case #1
A 76 yr old female presents to ED with
abdominal pain and dyspnea
Serum creatinine is 135 mmol
Does she have AKI?
Diagnostic Approach
Time of onset – prior serum creatinine
Careful review of history and physical
exam
Comorbidities
Medications
Current illness (vomiting, diarrhea, blood
loss, etc)
BP, volume status, skin lesions,
flank/abdominal signs
Case #1
DM2, HTN, CAD (CABG 2004), CVA
2000 (right CEA 2009), hypothyroidism
Medications
telmistartan 80 mg, ramipril 10 mg,
furosemide 40/80 mg, metoprolol, clonidine,
atorvastatin, clopidogrel, insulin, thyroxine
If this is AKI, what are the most likely
diagnoses?
Causes of Hospital-Acquired
AKI and Mortality
160
4,622 consecutive patients
7.3% with AKI
140
120
N
100
80
60
40
20
0
Pre-renal
Medications
CIN
Sepsis
Episodes
147
61
43
25
7
7
Mortality
20
9
6
19
2
5
Nash K et al. Am J Kidney Dis 2002;39(5):930-936
Obstruction Hepatorenal
Case #1
The patient
undergoes
investigations for her
symptoms in
hospital…
Day
SCr
0
135
1
106
2
115
3
122
4
172
5
247
6
337
7
361
Case #1
Day
Procedure
Rx
0
SCr
135
1
Abdo U/S (ED)
CT Abdo/Pelvis (ED)
‘light’ hydration
106
2
CT Abdo/Pelvis/Ext r/o DVT +
PE study
NAC 600 mg bid
115
NAC 600 mg bid
122
3
4
172*
5
247
6
337
* CI-AKI
Case #1
Day
Procedure
Rx
0
SCr
135
1
Abdo U/S (ED)
CT Abdo/Pelvis (ED)
‘light’ hydration
106
2
CT Abdo/Pelvis/Ext r/o DVT +
PE study
NAC 600 mg bid
115
NAC 600 mg bid
122
3
4
172*
5
247
6
337
7
Nephrology consult
* CI-AKI
* Stage 2-3 AKI
361*
AKI Network (AKIN) Classification
Stage
SCr
UOP (ml/kg/hr)
1
>1.5-2X
or >27 mmol/L increase
<0.5 for >6 h
2
>2-3X
<0.5 for >12h
3
>3x
or >360 mmol/L
or RRT
<0.3 for 24h
or anuria for 12h
Lopes, J. A. et al. Crit Care 2008;12(4):R110
Risk Factors for AKI
Lameire et al. NDT. 2008;6:392
Consistent Risk Factors
Age
Hypovolemia
Hypotension
Sepsis
CKD
Hepatic dysfunction
Cardiac dysfunction
DM
Exposure to nephrotoxins
Differential Diagnosis of AKI
Pre-renal
Renal
Post-renal
Pre-renal
Hypovolemia
Diuretics, trauma, surgery, burns, hemorrhage,
pancreatitis, GI loss, etc.
Decreased effective circulating volume
Nephrotic sydrome, cirrhosis, CHF, tamponade,
massive PE, etc.
Renovascular obstruction
RAS/atherosclerosis/thrombosis/embolism,
dissecting aneurysm, vasculitis, compression
Impaired glomerular autoregulation
NSAIDs, ACEi/ARB, calcineurin inhibitors
Intrinsic Renal
Glomerular and small vessel diseases
Rapidly progressive GN, endocarditis, post-
strep GN, vasculitides, scleroderma/malignant
HTN, HUS, PET, DIC
Interstitial nephritis
Infection-related, inlammation, drug-induced,
infiltrative (lymphoma, leukemia, sarcoidosis)
Tubular Lesions
Post-ishemia, nephrotoxic (drugs, contrast,
anesthetics, heavy metals), pigment
nephropathy, light chain, hypercalcemia
Post-renal
Bladder flow obstruction
Urethral, bladder neck (BPH), neurogenic
bladder
Ureteral obstruction (bilateral or single
kidney)
Stones, clots, tumours, papillary necrosis,
retroperitoneal fibrosis, surgical ligation
Urine Output and AKI
Anuric
< 50 cc / 24 hrs
Oliguric
< 500 cc / 24 hrs
Non-olguric
Normal urine output, but inadequate
clearance
GFR 2 ml/min will produce ~3L of urine/day
if there is no tubular reabsorption
Diagnostic Approach
Urine dipstick
Specific gravity
pH
Leukocytes
Nitrites
Protein
Glucose
Ketones
Urine microscopy
Cellular elements
○ RBC, WBC, Renal
tubular epithelial cells
○ Other (squamous,
vaginal)
Casts
○ Hyaline, granular, waxy,
RBC, WBC, tubular cell
Organisms
○ Bacteria, yeast
Urobilinogen
Crystals
Bilirubin
Lipiduria
Blood
Urine Findings
WBC casts - pyelonephritis
WBC
Urine Findings
Crystalluria – uric acid
Crystalluria – calcium oxalate
(ethylene glycol toxicity)
Urine Findings
RBC casts - GN
Dysmorphic RBC - GN
Urine Findings
Muddy brown casts – acute tubular necrosis
Urine Findings
Specific gravity
pH
1.030
5.0
Leukocytes
Nitrites
Protein
Glucose
Ketones
+
Urobilinogen
Bilirubin
Blood
++++
80 yo female found on the floor of her apartment after 2 days, SCr 400
mmol/L, K 6.8 mmol/L, CK 54,000
Urine Indices
Perfusion-related
Una (mEq/L)
FeNa (%)
Urine Osm (mOsm/L)
BUN/PCr ratio
ATN
Urine Indices
Perfusion-related
ATN
Una (mEq/L)
<20
>40
FeNa (%)
<1
>1
Urine Osm (mOsm/L)
>500
300-350
BUN/PCr ratio
>20
10
FeNa
FeNa = UNa/PNa x 100
UCr/PCr
Limitations of FeNa
Diuretic use
Post-ischemic ATN who have less severe disease
AKI on chronic pre-renal disease (cirrhosis, CHF)
Contrast or pigment nephropathy
Acute GN or vasculitis
Alternatives
FE of urea, lithium, uric acid
Imaging
Assess kidney size/morphology
Hydronephrosis
Kidney Biopsy
Intrinsic renal AKI
Indications
Isolated glomerular
hematuria with proteinuria
Nephrotic syndrome
Acute nephritic syndrome
Unexplained acute or rapidly
progressive AKI
Kidney Biopsy
Crescentic GN
RPGN
Anti-GBM
disease
Anti-GBM Ab
Anti-GBM disease
Goodpasture’s
Pauci-immune
GN
Immune
complex GN
ANCA
Low C3
Normal C3
Wegener’s
Microscopic
polyarteritis
MPGN
Post-infectious
Lupus nephritis
Cryoglobulinemia
Endocarditis
Shunt nephritis
IgA Nephropathy
HSP
Fibrillary GN
Visceral abscess
Mimickers
Malignant HTN
HUS/TTP
Interstitial nephritis
Scleroderma
Pre-eclampsia
Atheroemboli
Principles of AKI Management
Identify AKI
Avoid further nephrotoxic injury
Optimize renal hemodynamics
Treat complications
Fluid balance, electrolytes, uremia
Nutritional support
Renal Support (RRT)
Monitoring after AKI
Medications
Pre-renal
Calcineurin inhibitors, radiocontrast, ACEi/
ARB, NSAIDS, amphotericin B
Intra-renal
aminoglycosides, amphotericin B, cisplatin,
cephalosporins, sulfa, rifampin, NSAIDS,
interferon
Post-renal
acyclovir, MTX, indinavir, sulfadiazine
Review renal dosing of medications
Fluid Management
Correct fluid deficit
Will not guarantee AKI prevention
Studies of PA catheters did not reduce AKI
High urine flow in specific conditions
Myoglobinuria, tumour lysis, contrast media, etc.
Little evidence on fluid choice
Crystalloids
Hypooncotic colloids (4% albumin)
Hyperoncotic solutions (HES, dextrans) carry
risk of renal dysfunction
Renal Perfusion and
Vasoactive Agents
No support for
Loop diuretics
Dopamine
Selected use of
Mannitol (Rhabdomyolysis, post-cardiac
surgery)
Unclear support for
Natriuretic peptides (ANP, BNP)
Fenoldopam (DA agonist)
Theophylline (adenosine antagonist)
Renal Perfusion
Vasopressors
Inotropes to improve low cardiac
function
Target MAP needs to be individualized
Commonly 65 mmHg
Higher in elderly where autoregulation
impaired
Nutrition in AKI
AKI is a catabolic state
Inadequate nutritional support can delay renal
recovery
Cochrane review 2010:
“There is not enough evidence to support the
effectiveness of nutritional support for AKI…”
Adequate calorie delivery in anuric patient
will necessitate RRT
Treat Complications
Monitor and correct electrolytes,
acidosis
Renal replacement therapy
If indicated, do not withhold until patient is
anuric
Indications for Dialysis
AEIOU
Acidosis
Electrolyte disturbance
Ingestions
Overload (volume)
Uremia
New Paradigm for AKI
AKD
AKI
CKD
Natural history of AKI
Cerda et al. cJASN. 2008;
Follow up after AKI
Questions?
Case #1
Day
Procedure
Rx
0
SCr
135
1
Abdo U/S (ED)
CT Abdo/Pelvis (ED)
‘light’ hydration
106
2
CT Abdo/Pelvis/Ext r/o DVT +
PE study
NAC 600 mg bid
115
NAC 600 mg bid
122
3
4
172*
5
247
6
337
7
Nephrology consult
* CI-AKI
* Stage 2-3 AKI
361*
Fluids – Isotonic vs.
Hypotonic
Isotonic saline (0.9%) more protective
than half normal (0.45%)
1,620 pts undergoing cardiac catheterization
Goal is to achieve ‘good’ urine flow
Mueller C et al. Arch Intern Med. 162: 329-336, 2002
Fluids
Optimal rate and duration is not clear
IV rate >1-1.5 ml/kg/hr to achieve urine
flow >150 ml/hr
At least 1hr (3-12hr) prior and 3-6hr (612hr) after contrast
Bicarbonate vs Saline
Zoungas S et al. Ann Intern Med 2009;151:631-638
Bicarbonate vs Saline
Zoungas S et al. Ann Intern Med 2009;151:631-638
Bicarbonate vs Saline – Adverse
Events
Dialysis
(15/1552)
Mortality
CHF
Zoungas S et al. Ann Intern Med 2009;151:631-638
Bicarbonate
Effectiveness is uncertain
Evidence that it should be preferred over
isotonic saline is weak and inconsistent
N-Acetylcysteine – Rationale
Scavenger of free radicals
Vasodilatory properties; enhanced NO
availability
Attenuates ischemic injury in animals
N-Acetylcysteine
Kelly AM et al. Ann Intern Med 2008;148:284-294
Standard vs. High Dose NAC
N=354, <12h post STEMI
Standard: 600 mg IV pre,
600 mg PO bid post
High: 1200 mg IV pre,
1200 mg PO bid post
In-hopsital mortality:
11% placebo
4% low-dose
3% high dose
Marenzi G et al. N Engl J Med 2006;354:2773-2782
N-Acetylcysteine
Actual benefit is debatable, but safe*
and inexpensive
Appropriate to give IV or high-dose oral
Give in combination with IV isotonic
fluids
Contrast Medium
Limit ‘volume’ of iodine
grams iodine/GFR < 1
Iso-osmolar or low-osmolar contrast
preferred
IA: iso-osmolar
IV: low or iso-osmolar
MUHC CT Contrast
Iohexol (Omnipaque)
• Low-osmolar; Omni 300 ~ 650 mOsm/kg
Iodixanol (Visipaque)
• Iso-osmolar; Visi270 or 320 ~ 290 mOsm/kg
Both non-ionic
Concentration from 140-400 mg
iodine/ml
Hemodialysis/Hemofiltration
5 trials with conflicting results
RR for AKI 1.35 (95%CI 0.93-1.94)
Insufficient evidence to recommend
prophylactic hemodialysis or
hemofiltration
Case #2
58M with EtOH cirrhosis, admitted for SBP
4 months ago creatinine 68 , now 220
What may be the cause of his kidney
dysfunction, and how would you manage?
HRS
Chronic or acute liver disease with advanced
hepatic failure and portal hypertension
SCr > 133 mg/dl or 24-hr CrCl < 40 ml/min
No improvement in SCr after diuretic withdrawal
and plasma volume expansion (saline 1.5 L) +/with albumin (1 g/kg to max of 100 g/day)
No nephrotoxin, shock, infection, GI loss
No parenchymal renal disease (no proteinuria
microhematuria and/or abnormal US)
Minor diagnostic criteria
Urine volume < 500 mL/d
UNa < 10 mEq/L
UOsm > POsm
Urine RBC < 50/hpf
Serum Na < 130 mEq/L
Treatment to Reverse HRS
Which of the following have been shown to
be effective?
1. Albumin
2. Combination Midodrine and Octreotide
3. Noradrenaline
4. Terlipressin
5. Dopamine
Albumin
Intravenous albumin in addition to antibiotics improves
survival in SBP
Sort et al. NEJM 1999;341:403
Albumin indicated when doing paracentesis
Improved outcomes when combined with pressors
Midodrine and Octreotide
Octreotide 100 ug sq TID increasing to 200 ug
sq TID
inhibitor of endogenous vasodilators and glucagon
Midodrine 7.5 mg po TID increasing to 12.5
mg po TID
peripheral vasoconstriction
Midodrine and Octreotide sometimes helpful
Response rate about 30-50%
Noradrenalin
Effects of Noradrenalin and albumin in patients
with Type I HRS: A Pilot Study. Hepatology
2002; 36:374
Noradrenaline started at 0.1 ug/kg/min and
increased every 4 hrs based on BP by 0.05
ug/kg/min to max of 0.7 ug/kg/min
Combined treatment lowered creatinine from 2.6
to 1.6 over 10 days
Overall 2-month survival in this group of 12
patients was 58%
Terlipressin
Numerous studies have shown a benefit in
treating patients with HRS benefit is generally
a 50% improvement in GFR.
Better when combined with albumin
Ischemic complications and worsening of
cerebral hyperemia
Effect is not long lasting
Terlipressin and Change in
Serum Creatinine
Case 3
68 year old female admitted with
worsening dyspnea, leg edema
Known CAD, CHF (LVEF 10%), DM2,
CKD (Cr 140), …
Meds: ACEi, BB, nitrate, loop diuretic,
aldactone, statin, ASA, insulin, etc.
Aggressively diuresed for 3 days, Cr 250
Cardio-Renal Conundrum
Cardiorenal syndrome
CRS Type 1
CRS Type 2
CRS Type 3
CRS Type 4
CRS Type 5
Cardio-Renal Syndrome
AT blockade interferes with autoregulation and
may need to be held if GFR deteriorates
Avoidance of agents which interfere with renal
sodium handling
NSAIDs, Coxibs, Thiazolidinediones
Nephrotoxic agents (e.g. contrast)
Serum potassium may also limit continued use
of RAS blockade or K-sparing diuretics