Renal Support in Hepatic Patient
By Mohammed Dabbour
Lecturer of Anesthesia
Ain shams University
Outline
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Introduction
Definition
Epidemiology
Pathophysiology
Precipitating factors
Diagnosis
Management (Prevention and treatment)
Conclusion
Introduction
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Renal dysfunction is a common and serious
problem in patients with advanced liver disease.
In particular, alterations in renal physiology in
acute liver failure or cirrhosis with ascites can
predispose patients to a specific functional form
of renal failure known as hepatorenal syndrome
The accurate assessment of the kidney function
and injury is currently affected by the reliance on
the measured concentration of serum
creatinine,which is significantly affected by the
degree of cirrhosis, hyperbilirubinemia and the
nutritional state of the patient.
Epidemiology
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The predictive factors for the development of
HRS include:
- a low serum sodium
- high plasma rennin
- absence of hepatomegaly
Co-existing liver and kidney
disease
■ Chronic liver disease and primary liver cancer
■ Obesity and metabolic syndrome are also
strongly associated with the development of
hypertension and diabetes
■ Hepatitis C has long been associated with
several glomerulopathies
Viral RNA, proteins and particles have been isolated from
kidney biopsy specimen, hepatitis C infection has been reported
to be associated with focal segmental glomerulosclerosis.
Hepatitis C also has been associated with an increased risk of
albuminuria, progression of diabetic nephropathy and
progression of kidney disease.
■ Hepatitis B virus (HBV) is associated with a
number of renal disease, including polyarteritis
nodosa, membranous and
membranoproliferative glomerulonephritis
■ Autosomal-dominant polycystic kidney is
associated with polycystic liver disease in up to
75-90% of cases
■ Familial amyloidosis is an autosomal dominant
disease
Renal diseases associated with major
types of liver disease
Hepatitis B
Membranous glomerulonephritis (GN),
membranoproliferative GN, IgA nephropathy, focal
segmental glomerulosclerosis
Hepatitis C
Membranoproliferative GN, membranous GN, cryoglobulinemia, fibrillary
GN, IgA nephropathy, tubulointerstitial nephritis
Alcoholic liver disease
IgA nephropathy
Obstructive jaundice
Prerenal azotemia/acute tubular necrosis from hypovolemia,
decreased cardiac output, sepsis; acute tubular necrosis
Primary biliary cirrhosis
Membranous GN, antineutrophil cytoplasmic autoantibodypositive vasculitis, antiglomerular basement membrane disease,
renal tubular acidosis, tubulointerstitial nephritis
Primary sclerosing cholangitis Membranous GN, membranoproliferative GN, antineutrophil
cytoplasmic autoantibody-positive vasculitis
Wilson’s disease
Renal tubular acidosis (Type 1) secondary to copper deposition
Alpha-1 antitrypsin deficiency Membranoproliferative GN, antiglomerular basement membrane
disease
Systemic diseases involving both
liver and kidney
Drug toxicity
Acetaminophen, ASA
Granulomatous diseases
Sarcoidosis
Infectious diseases
Malaria
Infiltrative diseases
Amyloidosis
Inflammatory
Lupus
Non alcoholic fatty liver disease
Pre-eclapmsia/HELLP
Hmeloysis,
elevated liver enzymes, low platelets
Polycystic kidney/liver disease
Autosomal dominant
Sickle cell disease
Shock states
Congestive heart failure, sepsis, hypovolemia
Serum creatinine concentration for the
assessment of kidney function in chronic liver
disease
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Kidney function is evaluated by assessing the GFR which can be
determined by measuring the volume of plasma that can be cleared
of a given substance over a timed unit of time
GFR has relied on the measurement of the concentration of serum
creatinine, which is associated with many problems:
- specific, but not sensitive
- measurement is affected by gender, age, ethnicity,
nutritional state, protein intake and importantly, liver
disease
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In chronic liver disease, the reduction in serum creatinine is due to a
50% decrease in hepatic production of creatinine and increase in
the volume distribution
Acute Kidney Injury Network Criteria for
staging Acute Kidney Injury
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In 2005, the Acute Kidney Injury Network
(AKIN) developed the RIFLE (Risk, Injury,
Failure, Loss, End stage renal disease) criteria
Acute kidney injury network(AKIN)acute kidney injury
staging criteria
Acute Kidney Injury Pathogenesis
A. Isolated ischemic injury → Inflammatory
response → Leucocyte release & tubular
damage → impaired Na reabsorption →
polymerization of Tamm-Horsfall proteins →
gel-like substance formation → tubular
occlusion → increased backpressure & leaking
B. Endothelial injury → affects afferent arteriolar
tonicity → clotting cascade activation &
endothelin release → VC → compromising the
microcirculation
Bacterial
infection
Large volume
paracentesis
GIt bleeding
Acute alcoholic
hepatitis
Renal vasoconstriction
Worsening
hyperdynamic
circulation
Cardiac dysfunction
(septic or cirrhotic(
Renal Vasoconstrictor
↑
↓Renal Vasodilator
Biomarkers of AKI
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Traditional markers:
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Serum creatinine
Serum urea
Urine markers
Fractional excretion of sodium
Urine casts on microscopy
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Novel kidney biomarkers:Two serum and three
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urine biomarkers
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Serum neutrophil gelatinase Lipocalin (sNGAL)
Cystatin C
Urinary Kidney Injury Molecule (KIM-1)
Interleukin-18 (IL-18)
NGAL (uNGAL)
Summary of studies evaluating the role of novel blood and
`
urine kidney injury biomarkers
Precipitating Factors
 Spontaneous
bacterial peritonitis
 Gastrointestinal bleeding
 Aggressive paracentesis
 Drugs
 Others
Spontaneous Bacterial Peritonitis
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Renal impairment is related to further
deterioration of systemic hemodynamics, mostly
by endotoxins and various cytokines induced in
SBP, causing further vasodilatation
Gastrointestinal bleeding
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Acute gastrointestinal bleeding leads to acute
blood volume contraction, with decreased renal
perfusion
Aggressive paracentesis
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It reduces the effective arterial blood volume
and further activates vasoconstrictor system
Drugs
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Diuretics
Aminoglycosides
Nonsteroidal anti-inflammatory drugs
ACE-inhibitors
Angiotensin II antagonists
Others:
- Surgery, acute alcoholic hepatitis and cholestasis
Definition of HRS
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HRS is defined as the development of renal
failure in patients with advanced liver failure
(acute or chronic) in the absence of any
identifiable causes of renal pathology
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In 1996, the International Ascites Club
subdivided HRS into 2 types;
Hepatorenal syndrome
Type I
■ characterized by a rapid decline in renal
function
■ defined as a doubling
of serum creatinine to a
level > 2.5 mg/dL or a
halving of the creatinine
clearance to < 20
mL/min within 2 weeks
■ clinical presentation is
that of acute renal
Type II
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■ renal function
deteriorates more slowly
■ serum creatinine
increases to > 1.5 mg/dL
or a creatinine clearance
of < 40 mL/min.
■ The clinical presentation
is that of stable renal
failure in a patient with
refractory ascites
Diagnosis of HRS
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Some patients with primary liver disease are at
higher risk for developing certain forms of
kidney disease while some systemic processes
can affect both liver and kidney
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Major criteria should be fulfilled to confirm
diagnosis
Hepatorenal syndrome:
Diagnostic criteria
 Major criteria (all must be present)
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Chronic or acute liver disease with advanced hepatic failure and
portal hypertension
Low GFR as indicated by a 24-hr creatinine clearance of < 40
mL/min or serum creatinine > 1.5 mg/dL
Absence of shock, sepsis, volume depletion, exposure to
nephrotoxins
No sustained improvement in renal function (to creatinine > 1.5
mg/dL or 24-hr CrCl to > 40 mL/min) following diuretic
withdrawal or plasma volume expansion with 1.5 L of normal saline
Proteinuria < 500 mg/dL
No ultrasonographic findings of obstructive uropathy or
parenchymal renal disease
Additional criteria (not
necessary but would support
diagnosis)
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Urine volume < 500 mL/day
Urine sodium < 10 mEq/L
Urine osmolality greater than plasma osmolality
Urine red blood cells < 50 per high-power field
Serum sodium < 130 mEq/L
Work-up for patients with suspected
HRS
 History
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Fluid losses -- vomiting, diarrhea, diuretic use
Gastrointestinal bleeding
Infection -- fever, cough, dysuria, abdominal discomfort
Exposure to nephrotoxins -- drugs (aminoglycosides, NSAIDs), radiocontrast
agents
Physical exam
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Heart rate, blood pressure (including orthostatic), temperature
Signs of infection (pulmonary, abdominal, cellulitis, etc.)
Other causes of renal failure -- purpuric rash may suggest cryoglobulinemia
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Investigations
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Complete blood count, electrolytes, creatinine level
Urine sodium, osmolality
Urinalysis for protein, cells, and casts
Renal ultrasound
Assessment of Chronic kidney
Disease in patients with chronic
Liver disease
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Timed urine creatinine clearance performs poor
significance overestimating GFR in patients with
chronic liver disease
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So why use estimated GFR if it performs
so poorly
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Because it is the most cost-effective method of
assessing kidney function in chronic cases
Staging criteria for chronic kidney
disease
Management of HRS
Prevention & treatment
♣ Prevention:
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Prophylaxis against bacterial infection
Volume expansion
Strict use of diuretics
Avoidance of nephrotoxic agents
♣ Treatment:
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Initial management:
It requires exclusion of reversible or treatable
conditions
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Pharmacologic therapy
Renal support
Transjugular Intrahepatic Portosystemic
Shunt
 Liver transplantation
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Pharmacologic therapy
● Dopamine
Has renal vasodilator effect when given in subpressor doses,
but no studies have shown convincing benifit
● Noradrenaline
was used with albumin and frusemide in management of
patients with type I HRS
● Midodrine & Octreotide
Midodrine is an oral alpha adrenergic agent and
sympathomimetic drug
Octreotide is a long acting analog of somatostatin
Combined long term administration of oral midodrine and subcutaneous
octreotide lead to improvement in renal function compared with
nonpressor doses of dopamine
● Misoprostol
It is a synthetic analogue of prostaglandin E1, acts as a
renal vasodilator
● Ornipressin
It is a nonselective agonist of V1 vasopressin receptors
that causes VC of the splanchnic vasculature, thus
increasing systemic pressure and renal perfusion
pressure
● Terlipressin
It is a synthetic analogue of vasopressin with VC
activity
. Lowers incidence of ischemic complications
. Longer half life than vasopressin
● Endothelin anatgonists
Enothelin is a potent endogenous vasoconstrictor, so
renal failure was prevented by an endothelin anatgonist,
e.g., Bosentan
● N-acetylcysteine
It is a drug with antioxidant properties
● Pentoxifyllin
It inhibits the tumor necrosis factor
Renal support
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Dialysis:
The effectiveness of dialysis has not been proven
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Molecular Adsorbent Recirculating System
This system is a modified form of dialysis using
albumin-containing dialysate that is recirculated
and perfused online through charcoal and anion
exchanger columns.
It enables the removal of water and albumin
bound substances
 Transjugular
Intrahepatic
Portosystemic Shunt
 Liver
transplantation
Endstage liver and kidney disease is a
recognized indication for combined
liver-kidney transplant
Conclusion
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Chronic liver disease is associated with primary
and secondary kidney disease
Evaluation of kidney function relies on the
measurement of serum creatinine, which is
affected by the degree of liver disease
Hepatologists should use exogenous measures
of kidney functions & biomarkers like cystatin C
Kidney Injury Biomarkers need further
evaluation in the chronic liver disease population
Early diagnosis potentially increases the survival
outcomes
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Numerous studies have shown the benefit of
terlipressin with fewer side effects
The combination of midodrine and octreotide
can be used in absence of terlipressin
Intravenous albumin should be considered.
Orthotopic liver transplantation is the most
effective strategy for the treatment of
hepatorenal syndrome.