Acute Kidney Injury

(Acute renal failure)

CPR Winter 2017 Day 34 Hour 1

Ashley Jefferson MD FRCP

Professor of Medicine
Division of Nephrology
University of Washington
 Why does this clown have AKI?

A.Pre-renal uremia
B.ATN 2nd
rhabdomyolysis
C.Dead (cardio-renal)
D.Obstruction
 Acute Kidney Injury

What is acute kidney injury?

– Definition: Abrupt (days-weeks) decrease in glomerular filtration
rate (climb in serum creatinine)

Why do we care?
– Accumulation of uremic toxins (GI symptoms, neurological
(seizures, encephalopathy)
– Volume overload
– Hyperkalemia (arrythmias)
– Progressive acidosis
– Accumulation of medications
 How much urine is enough….oliguria?

Daily osmolal load for excretion

= 600 mOsm (close to 10mOsm/kg)
Maximum urine concentration
= 1200 mOsm/L

 Minimum urine volume = 500mls/24hrs

Definitions
Oliguria: < 500mls/day
Anuria: < 50mls /day
 A. AKI
Team Question: Is this AKI?
B. CKD
43 year old Boeing engineer
presents to primary care
physician with fatigue.

Labs:
Na Cl BUN
136 100 78
K HCO3
5.3 18 8.0

– Hematocrit = 22% (nl 38-45%)

– Ca2+ normal, PO4 elevated

Ultrasound reveal bilateral 7cm

kidneys
 How to differentiate AKI from CKD

History & Exam

Urine output
– oliguria denotes AKI

Renal imaging (ultrasound or CT scan):

– Normal or large kidneys suggest acute
– Small kidneys (<9cm) suggest chronic
**Not all CKD has small kidneys (e.g., polycystic kidney disease,
diabetes, amyloid)

Other Labs (not as helpful)

– Anemia (many patients AKI are anemic)
– HyperK, metabolic acidosis, hyperphosphatemia (little benefit)
 How to differentiate AKI from CKD

Acute Kidney Chronic Kidney

Injury Disease

Days to weeks Months-years

May be oliguric Non-oliguric
Kidney size: normal (11-14cm) Kidney size may be reduced

Potentially reversible
 Clinical Case: AKI and acute pancreatitis

55yo woman is admitted with acute pancreatitis & develops

hypotension, respiratory distress and oliguria (20cc/hr).
Exam: unwell with acute abdomen, P112, BP 108/66, T38.2oC,
RR 28/min

Blood Urine Lytes

126 88 75 UNa 8 mEq/L
UK 27
4.8 16 2.1
UCl 12

Ucreat: 35 mg/dl
Uosm: 560 mOsm/kg
 Team Question: What is the most likely
diagnosis of her AKI?

A.Pre-renal uremia
B.Acute tubular
necrosis (ATN)
C.Acute interstitial
nephritis
D.Acute obstruction
Differential diagnosis of Acute Kidney Injury

Pre-Renal

Renal

Post-Renal
Post-Renal: Obstruction  Hydronephrosis
 Pre-renal uremia
“a good kidney looking at a bad world”

 EABV  RPF  GFR

How do we make the diagnosis?

– History and Exam
– BUN / Creatinine ratio
– Urine electrolytes
Raised serum BUN/Creatinine ratio (> 20:1):
an indicator of pre-renal uremia

Na, H2O
High BUN + urea

– Pre-renal (diuretics)
– Other Causes
• High protein intake/TPN
• Catabolism
• Drugs (steroids, tetracyclines)
• Gastro-intestinal hemorrhage

Low Creatinine
– Muscle mass
Urine electrolytes are the best marker for
impaired renal perfusion (pre-renal)
 Normal Sodium Reabsorption

65% 5-7%
18,000mmol 1000mmol

GFR 180L/d
25,000mmol
Na filtered 2-5%
450mmol

20-25%
6000mmol

1.5L urine containing

150mmol Na (FeNa 0.55%)
 Increased Na and H2O reabsorption in pre-renal uremia

Angiotensin II
SNS

↓GFR 14mls/min
= 20L/d
2800 mmol
Na filtered Aldosterone

ADH

< 500mls urine (oliguria)

Uosm > 500 (ADH)
UNa < 10 mmol/L, FENa < 1% (RAAS)
 Urinary Electrolytes
Hallmark of Pre-renal Uremia

RAAS
(aldo)

Low UNa (< 10 mmol/L)

High Uosm (> 500mOsm/kg)

ADH
 Low perfusion states leading to low UNa

Low renal perfusion

( EABV)

Peripheral
Hypovolemia Cardiogenic Renovascular
vasodilation

Cardiorenal: Sepsis Vasoconstriction

Heart failure Cirrhosis Drugs
(hepatorenal)
Anaphylaxis
 Hepato-renal syndrome

Clinical
• Oliguric AKI in setting advanced cirrhosis
• UNa < 10, benign urine sediment, no USS or pathological abnormalities
• Unresponsive to IV fluid challenge.

Mechanism
• Renal vasoconstriction
• Peripheral vasodilatation & shunting

Precipitating Factors
– GI bleed, XS diuresis, infection (SBP), paracentesis

Treatment
– IV Albumin
– Midodrine (α1 agonist) + octreotide (inhibits endogenous vasodilators)
– Liver transplant
 NSAID and ACEI are common causes of AKI
- in setting of decreased renal perfusion

PgE2 PgE2 Angiotensin II

Angiotensin II
NSAID ACEI
RPF

GFR maintained  GFR

 Treatment of pre-renal uremia:
Improve renal perfusion!

Rx underlying cause
– Volume expansion (normal saline)
– Cardiac support etc.

Often readily reversible

*Prompt treatment is required as prolonged renal

hypoperfusion can progress to tubular injury (acute
tubular necrosis (ATN))
Differential diagnosis of Acute Kidney Injury

Pre-Renal

Renal

Post-Renal
 Causes of Acute Kidney Injury

Arterial injury
Vascular Atheroembolism
Vasculitis

Pre-Renal
Glomerular Glomerulonephritis

Renal
Tubular ATN
Post-Renal

Acute interstitial
Interstitial nephritis
Frequency of Hospital acquired AKI

50%

40%

30%

20%

10%

0%
l n ar
TN a it o l N IN
A ren cu PG A
e - ruc s R
r t Va
P bs
O

Liano F et al, Kidney Int 1996

 Acute tubular necrosis

Commonest cause of hospital acquired AKI

Tubular Injury 2nd:

– Ischemia (cellular ATP depletion)
– Toxins (toxic injury to tubular cells)
 Causes of ATN

Ischemic injury (hypotension /  renal perfusion)

Toxic Injury
Exogenous
– Drugs (gentamicin, amphotericin, NSAID, cisplatin, others)
– Toxins (heavy metals, herbs, radiocontrast, solvents)

Endogenous
– Heme pigments (rhabdomyolysis)
– Uric acid (tumor lysis syndrome)
 Radiocontrast induced nephropathy

Risk Factors
– Renal impairment (eGFR < 30)
– Diabetes
– CHF
– Volume depletion

Prevention
– Avoid procedure (if possible)
– Limit amount of IV contrast
– IV fluids (saline / NaHCO3)
– N-acetylcysteine Only IV, Not oral contrast as above!
 ATN: Rhabdomyolysis

Heme pigment nephropathy

– Muscle injury leads to fluid sequestration
& myoglobinuria (endogenous toxin)
– Creatine kinase (CK) > 10,000

Causes
– Trauma / crush injury (“found down”)
– Seizures
– Drugs (statins, cocaine, others)
– Electrolytes (hypoK, hypoPO4)

Therapy
– Aggressive volume resuscitation
– ?alkaline diuresis
– Rx electrolyte abnormalities
How do we differentiate ATN from Pre-renal
Uremia
 How do we differentiate ATN from Pre-renal
Uremia

History and Examination

BUN / creatinine ratio
Urine sediment (muddy brown casts)
Urine electrolytes

Acute Tubular
Pre-Renal Uremia
Necrosis
Urine Sodium (mEq/L) <10 >20
(Urine Chloride) (<15) (>20)

Fractional Excretion
<1% >2%
Sodium (FeNa)

Urine Osmolality >500mOsm/kg ~300mOsm/kg

 Treatment of ATN

Treatment of the underlying condition!!

Prevent complications
– Volume control
– Dosing medications appropriately
– Avoiding further nephrotoxic agents (e.g contrast, antibiotics)

Supportive Care

Acute Dialysis
– Hyperkalemia
– Symptomatic Uremia
– Volume Overload
– Metabolic Acidosis
– Pericardial Rub
 Causes of Acute Kidney Injury

Arterial injury
Vascular Atheroembolism
Vasculitis

Pre-Renal
Glomerular Glomerulonephritis

Renal
Tubular ATN
Post-Renal

Acute interstitial
Interstitial nephritis
 Renal Atheroembolism

Clinical Features
– AKI
– Digital infarcts
– Livedo reticularis
– Hypocomplementemia
– Peripheral eosinophilia

Management
– ACEI
– Statins
– Avoidance of
anticoagulation
 Acute (Allergic) Interstitial Nephritis (AIN)

Drugs
– Antibiotics (penicillins; rifampin;
ciprofloxacin; sulfonamides)
– Others (NSAID; omeprazole;
allopurinol…..)

Clinical Features
– Fever, rash, eosinophilia (< 50%)
– Oliguria, microhematuria, UTP<1g
– Urine eos (low predictive value)

Therapy
– Stop offending agent
– + / - steroids
How much pee is in a swimming pool?

Methods
Measure concentration of artificial sweetener
acesulfame potassium (ACE K) in 31 pools
in two Canadian Cities (Univ of Alberta)

Results
Estimate that a 110,000 gallon pool would
contain 7 gallons of urine

Li X-F, Environmental Science & Technology Letters 2017

 Why does tubular injury (ATN) lead to a
decrease in GFR?

1. Intraluminal cast obstruction

Injured proximal tubular cells detach and form
obstructing casts

Muddy brown casts

 Why does tubular injury lead to a decrease in
GFR

1. Intraluminal cast obstruction

Injured proximal tubular cells detach and form
obstructing casts

2. Tubuloglomerular feedback
Failure to reabsorb NaCl in PCT
 activation of TGF and  GFR
 Why does tubular injury lead to a decrease in
GFR

1. Intraluminal cast obstruction

Injured proximal tubular cells detach and form
obstructing casts

2. Tubuloglomerular feedback
Failure to reabsorb NaCl in PCT  activation of TGF
and  GFR

3. Backleak of tubular fluid

Loss of cell integrity allows tubular fluid to leak back into
peritubular capillary
 Answers to Questions

1. Clown: Dead
2. CKD
3. Pre-renal uremia