Write a short note on hepatorenal syndrome.

Definition

Hepatorenal syndrome (HRS) is a form of functional, potentially reversible acute kidney injury occurring in advanced liver disease with portal hypertension and ascites, in which the kidneys are structurally normal — a fact demonstrated by the observation that a kidney from a patient with HRS functions normally when transplanted into a recipient with normal liver function.

It is a diagnosis of exclusion, made only after other causes of renal failure have been ruled out.

PATHOPHYSIOLOGY — a logical chain worth reproducing in an answer

1. Portal hypertension → release of nitric oxide and other vasodilators → splanchnic arterial vasodilatation

2. → fall in effective arterial blood volume despite total body fluid overload

3. → activation of the renin–angiotensin–aldosterone system, sympathetic nervous system and ADH

4. → intense renal vasoconstriction with reduced renal blood flow and glomerular filtration

5. → sodium and water retention, worsening ascites, and progressive renal failure

Additionally, systemic inflammation and bacterial translocation (particularly with SBP) and cirrhotic cardiomyopathy (an inadequate cardiac output response) contribute — which is why infection is the commonest precipitant.

Classification

Diagnostic Criteria

1. Cirrhosis with ascites (or acute liver failure)

2. Acute kidney injury by standard criteria

3. No improvement after 2 days of diuretic withdrawal AND volume expansion with intravenous ALBUMIN — this step is both diagnostic and therapeutic, and is what distinguishes HRS from pre-renal azotaemia

4. Absence of shock

5. No current or recent nephrotoxic drugs (NSAIDs, aminoglycosides, contrast)

6. No structural kidney disease — proteinuria < 500 mg/day, no microhaematuria, normal renal ultrasound

Characteristic urinary findings — reflecting intense sodium avidity with intact tubules:

• Urine sodium very low (< 10 mEq/L)
• Fractional excretion of sodium < 1%
• Urine osmolality > plasma osmolality
• Bland urinary sediment — no casts, no significant proteinuria (in contrast to acute tubular necrosis, which shows muddy brown granular casts and a high urine sodium)

Differential Diagnosis of Renal Failure in Cirrhosis

Management

1. Prevention — far more effective than treatment

• Albumin infusion with large-volume paracentesis (for taps over about 5 litres).
• Albumin with antibiotics in spontaneous bacterial peritonitis — this specifically reduces the incidence of HRS and improves survival, and is one of the best-evidenced interventions in hepatology.
• Avoid nephrotoxins — NSAIDs, aminoglycosides, contrast; avoid ACE inhibitors and ARBs in advanced cirrhosis.
• Careful diuretic use with monitoring; avoid over-diuresis.
• Antibiotic prophylaxis in high-risk patients (low ascitic protein, previous SBP, gastrointestinal bleeding).

2. General measures on presentation

• Withdraw all diuretics and nephrotoxic drugs.
• Volume expansion with intravenous albumin — both diagnostic and therapeutic.
• Identify and treat precipitants — especially infection; perform a diagnostic ascitic tap and take cultures; treat gastrointestinal bleeding.
• Monitor fluid balance, weight, electrolytes and renal function closely.

3. Specific pharmacological therapy

• TERLIPRESSIN with intravenous ALBUMIN — the treatment of choice. Terlipressin is a splanchnic vasoconstrictor that reverses the splanchnic vasodilatation at the root of the syndrome, restoring effective arterial volume; albumin expands the volume and binds inflammatory mediators. Watch for ischaemic complications (digital, cardiac, mesenteric) and hyponatraemia.
• Alternatives where terlipressin is unavailable: noradrenaline with albumin (requiring intensive care), or midodrine with octreotide and albumin.

4. Renal replacement therapy — as a bridge to transplantation or where there is a reversible precipitant; it does not alter the natural history in the absence of transplantation.

5. TIPS — may improve renal function in selected patients with preserved liver function, but risks encephalopathy.

6. LIVER TRANSPLANTATION — the only definitive treatment. All patients with HRS should be assessed urgently for transplantation, since HRS reflects end-stage liver disease and carries a very poor prognosis without it. Combined liver–kidney transplantation is considered where renal failure has been prolonged.