Renal Support in Hepatic Patient

1
Renal Support in Hepatic Patient

• By Mohammed Dabbour

Lecturer of Anesthesia Ain shams University
2
Outline

• Introduction
• Definition
• Epidemiology
• Pathophysiology
• Precipitating factors
• Diagnosis
• Management (Prevention and treatment)
• Conclusion

3
Introduction

• 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.

4
Epidemiology

• The predictive factors for the development of HRS
  include
• - a low serum sodium
• - high plasma rennin
• - absence of hepatomegaly

5
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.

6

• 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

7
Renal diseases associated with major types of
liver disease
8
Systemic diseases involving both liver and kidney
9
Serum creatinine concentration for the assessment
of kidney function in chronic liver disease

• 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
• 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

10
Acute Kidney Injury Network Criteria for staging
Acute Kidney Injury

• In 2005, the Acute Kidney Injury Network (AKIN)
  developed the RIFLE (Risk, Injury, Failure, Loss,
  End stage renal disease) criteria

11
Acute kidney injury network(AKIN)acute kidney
injury staging criteria
12
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

13
Bacterial infection
Large volume paracentesis
Acute alcoholic hepatitis
GIt bleeding
Renal vasoconstriction
Worsening hyperdynamic circulation
Cardiac dysfunction ((septic or cirrhotic
Renal Vasoconstrictor ?
Renal Vasodilator ?
14
Biomarkers of AKI

• Traditional markers
• Serum creatinine
• Serum urea
• Urine markers
• Fractional excretion of sodium
• Urine casts on microscopy
• Novel kidney biomarkersTwo serum and three urine
  biomarkers
• Serum neutrophil gelatinase Lipocalin (sNGAL)
• Cystatin C
• Urinary Kidney Injury Molecule (KIM-1)
• Interleukin-18 (IL-18)
• NGAL (uNGAL)

15

Summary of studies evaluating the role of novel
blood and urine kidney
injury biomarkers
16
Precipitating Factors

• Spontaneous bacterial peritonitis
• Gastrointestinal bleeding
• Aggressive paracentesis
• Drugs
• Others

17
Spontaneous Bacterial Peritonitis

• Renal impairment is related to further
  deterioration of systemic hemodynamics, mostly by
  endotoxins and various cytokines induced in SBP,
  causing further vasodilatation
• Gastrointestinal bleeding
• Acute gastrointestinal bleeding leads to acute
  blood volume contraction, with decreased renal
  perfusion

18
Aggressive paracentesis

• It reduces the effective arterial blood volume
  and further activates vasoconstrictor system
• Drugs
• Diuretics
• Aminoglycosides
• Nonsteroidal anti-inflammatory drugs
• ACE-inhibitors
• Angiotensin II antagonists
• Others
• - Surgery, acute alcoholic hepatitis and
  cholestasis

19
Definition of HRS

• 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
• In 1996, the International Ascites Club
  subdivided HRS into 2 types

20
Hepatorenal syndrome

• Type I

• Type II

• characterized by a rapid decline in renal
  function
• defined as a doubling of serum creatinine to a
  level gt 2.5 mg/dL or a halving of the creatinine
  clearance to lt 20 mL/min within 2 weeks
• clinical presentation is that of acute renal
  failure

• renal function deteriorates more slowly
• serum creatinine increases to gt 1.5 mg/dL or a
  creatinine clearance of lt 40 mL/min.
• The clinical presentation is that of stable
  renal failure in a patient with refractory ascites

21
Diagnosis of HRS

• 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
• Major criteria should be fulfilled to confirm
  diagnosis

22
Hepatorenal syndrome Diagnostic criteria

• Major criteria (all must be present)
• Chronic or acute liver disease with advanced
  hepatic failure and portal hypertension
• Low GFR as indicated by a 24-hr creatinine
  clearance of lt 40 mL/min or serum creatinine gt
  1.5 mg/dL
• Absence of shock, sepsis, volume depletion,
  exposure to nephrotoxins
• No sustained improvement in renal function (to
  creatinine gt 1.5 mg/dL or 24-hr CrCl to gt 40
  mL/min) following diuretic withdrawal or plasma
  volume expansion with 1.5 L of normal saline
• Proteinuria lt 500 mg/dL
• No ultrasonographic findings of obstructive
  uropathy or parenchymal renal disease

23

• Additional criteria (not necessary but would
  support diagnosis)
• Urine volume lt 500 mL/day
• Urine sodium lt 10 mEq/L
• Urine osmolality greater than plasma osmolality
• Urine red blood cells lt 50 per high-power field
• Serum sodium lt 130 mEq/L

24
Work-up for patients with suspected HRS

• History
• Fluid losses -- vomiting, diarrhea, diuretic use
• Gastrointestinal bleeding
• Infection -- fever, cough, dysuria, abdominal
  discomfort
• Exposure to nephrotoxins -- drugs
  (aminoglycosides, NSAIDs), radiocontrast agents
• Physical exam
• Heart rate, blood pressure (including
  orthostatic), temperature
• Signs of infection (pulmonary, abdominal,
  cellulitis, etc.)
• Other causes of renal failure -- purpuric rash
  may suggest cryoglobulinemia
• Investigations
• Complete blood count, electrolytes, creatinine
  level
• Urine sodium, osmolality
• Urinalysis for protein, cells, and casts
• Renal ultrasound

25
Assessment of Chronic kidney Disease in patients
with chronic Liver disease

• Timed urine creatinine clearance performs poor
  significance overestimating GFR in patients with
  chronic liver disease
• So why use estimated GFR if it performs so poorly
  ?????
• Because it is the most cost-effective method of
  assessing kidney function in chronic cases

26
Staging criteria for chronic kidney disease

27
Management of HRSPrevention treatment

• ? Prevention
• Prophylaxis against bacterial infection
• Volume expansion
• Strict use of diuretics
• Avoidance of nephrotoxic agents

28

• ? Treatment
• Initial management
• It requires exclusion of reversible or treatable
  conditions
• Pharmacologic therapy
• Renal support
• Transjugular Intrahepatic Portosystemic Shunt
• Liver transplantation

29
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

30

• ? 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

31

• ? 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

32
Renal support

• Dialysis
• The effectiveness of dialysis has not been
  proven
• 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

33

• Transjugular Intrahepatic Portosystemic Shunt
• Liver transplantation
• Endstage liver and kidney disease is a
  recognized indication for combined liver-kidney
  transplant

34
Conclusion

• 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

35

• 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.

36
THANK YOU