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