The spectrum of renal

disorders in liver disease

Dr. Chanya Padmaperuma
Medical Registrar
Causes of renal failure in chronic
liver disease
Acute Kidney Injury
The KDIGO guidelines define AKI as follows :

●Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L) within

48 hours, or

●Increase in serum creatinine to ≥1.5 times baseline, which is known or

presumed to have occurred within the prior seven days, or

●Urine volume <0.5 mL/kg/hour for six hours

Hepatorenal syndrome
• One of many potential causes of acute kidney injury in patients with acute or
chronic liver disease.
• Affected patients usually have
- portal hypertension due to cirrhosis
- severe alcoholic hepatitis
- (less often) metastatic tumors
- have fulminant hepatic failure from any cause
• Represents the end-stage of a sequence of reductions in renal perfusion
induced by increasingly severe hepatic injury
• Diagnosis of exclusion and is associated with a poor prognosis
Hepatorenal syndrome
pathogenesis
Main pathophysiological and clinical aspects of HRS
• HRS is a functional renal failure caused by intrarenal vasoconstriction which
occurs in patiens with end‐stage liver disease and circulatory dysfunction.
• Circulatory dysfunction is characterised by vasodilatation in the splanchnic
circulation with a relatively low and insufficient cardiac output, leading to
effective hypovolaemia.
• HRS may occur spontaneously with worsening liver function, or secondary to
a precipitating event such as bacterial infection (eg, SBP).
• HRS can be improved by the administration of vasoconstrictors and albumin,
or by TIPS.
Hepatorenal syndrome : pathogenesis
Heptorenal syndrome : Clinical
presentation
In a patient who has established or clinically evident acute or chronic liver disease:
●A progressive rise in serum creatinine

●An often normal urine sediment

●No or minimal proteinuria (less than 500 mg per day)

●A very low rate of sodium excretion (ie, urine sodium concentration less than 10 mEq/L)

●Oliguria
Hepato renal syndrome : types
 Diagnostic criteria (International
Ascites Club (IAC) 2007

When other causes pertaining to AKI, ATN, pre renal disease and Glomerulopathies are excluded.
Risk factors for HRS
HRS management principles
• The ideal therapy is improvement of liver function from
- Either recovery of alcoholic hepatitis
- Treatment of decompensated hepatitis B with effective antiviral
therapy
- Recovery from acute hepatic failure
- liver transplantation
Patients who do not respond to
initial medical therapy
• Transjugular intrahepatic portosystemic shunt — The transjugular
intrahepatic portosystemic shunt (TIPS) has been used in the
treatment of refractory ascites

• Dialysis

• Peritoneovenous shunt ( obsolete)

Bile cast nephropathy
• Bile cast nephropathy is a cause of acute kidney injury and is diagnosed via a kidney
biopsy.
• Promoted by associated kidney ischemia, but severe isolated cholestasis is sufficient
to induce its occurrence.
• Results from multiple concurrent insults to the kidney including direct toxicity from
bile acids, obstructive physiology from bile casts, and systemic hypoperfusion from
vasodilation.
• It likely represents a broad spectrum of clinical manifestations from initially
reversible nephropathy to later irreversible, intractable disease requiring liver and
kidney transplantation.
• The management of bile cast nephropathy is through normalization of bilirubinemia
and renal replacement therapy
Bile cast nephropathy;
pathophysiology

• During cholestasis, hepatocytes attempt to export bile acids to

prevent intracellular damage by inducing basolateral bile acid pumps
• The kidneys, similarly, undergo changes in the proximal tubule to
excrete excess bile.
• This excess bilirubin is believed to cause oxidative damages of the cell
membranes of the tubules and uncoupling of mitochondrial
phosphorylation at the cellular level
Bile cast nephropathy;
pathophysiology
• Inhibition of the Na-H, Na-K, Na-Cl pumps by sulfated bile salts in
proximal tubules and in the loop of Henle may result in pH changes
which may enhance bile cast deposition, tubular toxicity and injury
• It has been hypothesized that there is a limit to bilirubin transport in
the proximal tubules after which they become saturated, leading to
cast formation and tubular obstruction
• Lesions were more severe with coexisting ischemia
• Alcohol may exacerbate or be an etiologic factor with this entity
Investigations
• Renal dysfunction is exhibited
- Elevated creatinine levels
- Pigmented bile crystals on urinalysis
- Natriuresis
- B2 microglobinuria
- Usually occurs at bilirubin levels greater than 26 mg/dl (Sitprija et al)
(Evidence of decreased free water clearance, creatinine clearance, and mean arterial pressure)
(When the bilirubin level is greater than 40 mg/dl, renal perfusion was also decreased)
-Low serum albumin
- Glucosuria, phosphaturia, and microglobinuria
- Liver biopsy
Management: Bile cast nephropathy
• Owing to the rarity, there are currently no accepted treatment guidelines
• Interventions to reduce bilirubin burden
- Relief of biliary obstruction via ERCP with stent placement
• Extracorporeal treatment
- Hemodialysis
- Plasmapheresis
• Options aimed at reduction of inflammatory cytokines and reduction of bilirubin
have also emerged
- Molecular adsorbents recycling system (MARS)
- Coupled plasma filtration adsorption (CPFA)
- Plasma filtration adsorption dialysis
Management cont.
• Various medical therapies
- Steroids
- Cholestyramine
- Ursodeoxycholic acid
- Lactulose have been shown minimal benefit
- Later if severe liver –kidney transplantation
Glomerular lesions in liver disorders
• Cirrhosis and chronic active hepatitis
-IgA nephropathy
-Mostly in alcoholic hepatitis
- Also in chronic hepatitis associated with vira/cryptogenic/chronic
schistosomiasis
- Membranoproliferative pattern
Glomerular lesions in liver disorders
• Glomerulopathies associated with Hepatitis B virus
-Membranous nephropathy
-Membranoproliferative glomerulonephritis
-Poly arteritis nodosa ( ANCA negative)
• Management:
-Anitiviral therapy (Pegylated interferon [PegIFN] alfa) and nucleoside/nucleotide analogs)
-Immunosuppressive therapy with glucocorticoids or cytotoxic agents and plasmapheresis
are of little benefit and are potentially harmful
- In patients with rapidly progressive glomerulonephritis (RPGN) due to HBV infection,
immunosuppression in addition to antiviral medication
- In PAN : antiviral medication, and both glucocorticoids and plasmapheresis
Glomerular lesions in liver disorders
cont.
• Glomerulopathies associated with Hepatitis C
-Mixed cryoglobulinaemia
-Membranoproliferative glomerulonephritis
-Membranous nephropathy
Management
- Viral suppression
- Rituximab
- Plasmaparesis
- Immunosuppression
Summary
• Primary liver pathology can be associated in acute and chronic renal
injury
• Glomerular, tubular interstitial and vascular pathological
manifestations occur
• Management of each entity depends on individual factors
Thank you