AKI IN CIRRHOSIS

John Thomas
 WHY IS AKI IN CIRRHOSIS SIGNIFICANT?
• Incidence of AKI in Cirrhosis: ~20% of hospitalised cirrhotic patients
• AKI is a powerful predictor of death in decompensated liver disease
• AKI is one of the most important predictors of pre-transplant and post-
transplant mortality
• Pre-transplant creatinine is the most important predictor of survival post-
transplant
• MELD Score (Bilirubin, INR, Serum Creatinine) takes into account renal function in
determining 3-month mortality & need for transplantation
• AKI is potentially reversible if detected and treated early
 DEFINITION
• Acute Kidney Injury:
• Rapid decline in renal function over a period of hours – days (exact definition
depends on criteria used)
• Spectrum from mild impairment to severe renal failure
• Typically quantified by the decline in baseline eGFR/urine output or rise in
baseline serum creatinine
• Three major criteria: RIFLE, AKIN, KDIGO
• Risk, Injury, Failure, Loss of Kidney Function & End-stage Kidney disease (2004)
• Acute Kidney Injury Network (2007)
• Kidney Disease Improving Global Outcomes (2012)
 CAUSES OF AKI
• PRE-RENAL
• Hypovolemia
• Altered vascular
hemodynamics
• INTRA-RENAL
• Acute Tubular Necrosis
• Acute Interstitial Nephritis
• Acute Glomerulonephritis
• POST-RENAL
• Urinary tract obstruction
 CAUSES OF AKI IN CIRRHOSIS
AKI

Pre-renal Intra-renal Post-renal

(75%) (25%) (<1%)

Volume Volume Non-

ATN
Responsive (67%) responsive (33%)

Drugs e.g.
GI blood loss Diarrhoea Diuresis Sepsis Ischaemia Nephrotoxics
NSAIDs
 PATHOPHYSIOLOGY
• Cirrhotic patients are at a high risk of
developing AKI:
• Hyperdynamic circulatory state –
renal blood flow is very susceptible
to further decreases in effective
arterial blood volume
• Intravascular volume depletion – GI
bleeding/diarrhoea/diuretic use
• Sepsis – further decrease in
effective arterial blood volume
• Exposure to nephrotoxic agents
e.g. NSAIDs/Contrast agents/ABs
• Cirrhosis: Hyperdynamic circulatory
state
 PATHOPHYSIOLOGY
• Decreased clearance of bacterial DNA
from gut (f) reduced function of
mononuclear phagocyte system +
porto-systemic shunting of blood (f)
portal hypertension (thus bypassing
Kupffer cells in the Liver)  Increased
NO production
• Spectrum:
• Relative hypovolaemia  sodium &
water retention (ascites formation) +
increased intravascular volume +
increased cardiac output
• Progressive cirrhosis  worsening
vasodilatation  high-output cardiac
failure (heart becomes insufficient to
maintain perfusion pressure) +
decreased renal blood flow
 PATHOPHYSIOLOGY
• Precipitating events:
• Rapid fluid losses
• Sepsis

• Can cause both pre-renal AKI

and intrinsic renal AKI/ATN
 DIAGNOSIS OF AKI IN CIRRHOSIS
• Serum Creatinine
• Pros: Simple, inexpensive
• Cons:
• SCr alone is not helpful in distinguishing causes of AKI
• SCr lags behind actual renal injury - so it is a delayed marker of renal impairment
• SCr can remain within normal range despite significant renal damage due to renal reserve
• SCr is underestimated in cirrhotics – note: SCr is the end-product of muscle creatine, and
used as a marker of renal perfusion as it is freely filtered but no reabsorbed/secreted in the
renal tubules. In Cirrhotics, there is greatly reduced muscle mass  significantly reduced
creatinine from muscles  patients will appear to have a normal SCr despite a very low
glomerular filtration rate (less creatinine accumulates in serum).
• Severe hyperbilirubinemia can result in false measurements of SCr
• Other markers to do:
• Gold-standard:
• a
 DIFFERENTIATING CAUSES OF AKI –
NOT EASY
• Key principle: Tubular function (to reabsorb Na) maintained in pre-renal/HRS but not
in ATN
• Pre-renal/HRS
• Low urinary sodium (<20mEq/L)
• Low fractional excretion of sodium (<1%)
• Raised urine osmolality (>500mOsm/kg) i.e. concentrated urine
• Renal
• High urinary sodium (>40mEq/L)
• High fractional excretion of sodium (2%)
• Low urine osmolality (<350mOsm/kg)
• Granular/Epithelial casts in urine
• However, in Cirrhosis – the physiological changes result in a sodium avid state + often
many patients are on diuretics  this can make Urinary sodium and FENa an
unreliable marker to differentiate between Pre-renal and Renal.
 DIAGNOSIS OF HRS
• A diagnosis of exclusion
• Prerequisites:
• Ascites – the same mechanisms leading to ascites lead to formaiton of
HRS
• Advanced liver disease (median Child Pugh score is 11.2)
• Low Mean Arterial Pressure (median 74 mmHg)
• Low serum sodium (median 127 mEq/L)
• If these features are absent, the diagnosis of HRS is unlikely
• HRS Type 1:
• Abrupt deterioration in renal function that occurs mostly in an inpatient
setting and often develops after a precipitating event, particularly
spontaneous bacterial peritonitis
• Doubling of SCr to a level greater than 2.5 mg/dL (or a greater than
twofold to threefold increase in SCr) from baseline in < 2 weeks
• HRS Type 2:
• Steady or slowly progressive course that occurs mostly in an outpatient
setting in patients with refractory ascites.
• Of note, SCr levels in HRS are approximately 3.6 mg/dL and rarely
exceed 6 mg/dL, and urine output is usually approximately 600 mL/day
 TREATMENT
• Treatment of AKI depends on the cause
• Basic principle:
• Pre-renal AKI: Volume repletion
• ATN: Remove nephrotoxics, maintain renal perfusion, Renal replacement therapy (volume
overload/metabolic acidosis/hyperkalaemia)
• a
TREATMENT OF HRS