Hepatorenal Syndrome (HRS)
Summary
Hepatorenal Syndrome (HRS) is a form of functional renal failure occurring in advanced liver cirrhosis. The kidneys themselves are structurally normal, but severe renal vasoconstriction leads to hypoperfusion and failure. It carries a notoriously poor prognosis (mortality >50% without treatment). The terminology has recently shifted from Type 1/2 to HRS-AKI (Acute) and HRS-NAKI (Non-Acute). [1,2]
Clinical Pearls
The Vasodilation Paradox: Why do the kidneys clamp down? In cirrhosis, portal hypertension causes massive vasodilation in the gut (splanchnic circulation). Blood pools there, so the "Effective Arterial Blood Volume" (detected by baroreceptors) is LOW. The body thinks it is in shock, so it activates the RAAS system to clamp down peripheral vessels. The kidneys get caught in the crossfire—their vessels constrict to save BP, causing renal ischaemia.
Diagnosis of Exclusion: You cannot diagnose HRS until you have ruled out other causes. Specifically, you must demonstrate that the AKI does not improve after 2 days of volume expansion with Albumin. If it improves, it was just "Pre-Renal Dehydration".
Urine Sodium: In HRS, the kidneys are desperately trying to retain salt and water to fix the low BP. Therefore, Urine Sodium will be extremely low (less than 10 mmol/L). If Urine Sodium is high (>40), it suggests Acute Tubular Necrosis (ATN), not HRS.
Context
- Occurs in patients with Decompensated Cirrhosis and Ascites.
- 20% of hospitalized cirrhotic patients with AKI have HRS.
Precipitants
- SBP (Spontaneous Bacterial Peritonitis): Most common trigger.
- Large Volume Paracentesis (without albumin cover).
- Gastrointestinal Bleed.
- Over-diuresis.
The Splanchnic Vasodilation Hypothesis
- Portal Hypertension: Increases Nitric Oxide (NO) in the gut.
- Splanchnic Vasodilation: Massive pooling of blood in the abdominal veins.
- Low Effective Volume: Systemic arterial pressure drops.
- Compensatory Response: Sympathetic Nervous System + RAAS + ADH activation.
- Renal Vasoconstriction: Angiotensin II and Noradrenaline constrict renal afferent arterioles.
- Renal Hypoperfusion: GFR drops -> Oliguria / Azotemia.
New Terminology (ICA 2015)
Symptoms
- Volume Status: Usually intravascularly depleted (low BP, tachycardia) despite being overloaded with ascites/oedema.
- Stigmata: Spider naevi, Palmar erythema.
Diagnostic Criteria (ICA)
- Cirrhosis + Ascites.
- AKI (ICA stage 1 or higher).
- No response to 2 days of diuretic withdrawal and plasma volume expansion with Albumin (1g/kg).
- Absence of Shock.
- No Nephrotoxins (NSAIDs, Aminoglycosides).
- No Structural Kidney Disease (Proteinuria less than 500mg/day, microhaematuria, normal Renal US).
Urinary Indices
- Urine Na: < 10 mmol/L (Avid retention).
- FeNa: < 1%.
- Urine Sediment: Bland (no casts).
Management Algorithm
AKI IN CIRRHOSIS
(Creatinine rising)
↓
STOP NEPHROTOXINS & DIURETICS
TREAT INFECTION (SBP Screen)
↓
VOLUME EXPANSION TRIAL
IV Albumin (1g/kg/day) x 48hrs
↓
CREATININE IMPROVED?
┌─────────┴─────────┐
YES NO
↓ ↓
PRE-RENAL HRS-AKI DIAGNOSED
(Continue (Initiate Vasoconstrictors)
Albumin) ↓
TERLIPRESSIN + ALBUMIN
(Goal: Reduce Creatinine)
↓
RESPONSE?
┌───────┴───────┐
YES NO
↓ ↓
CONTINUE RRT / TIPS
TO TRANSPLANT PALLIATIVE
1. Pharmacotherapy (The Vasoconstrictor Cocktail)
- Terlipressin: Vasopressin analogue. Constricts splanchnic vessels, pushing blood back to systemic circulation.
- Dose: 1-2mg IV bolus q4-6h. OR Continuous Infusion (better tolerated).
- Goal: Reversal of HRS (Creatinine less than 1.5mg/dL).
- Albumin: 20-40g/day. Improves oncotic pressure and binds vasodilators.
- Alternative: Noradrenaline (if in ICU) or Midodrine + Octreotide (less effective).
2. TIPS (Transjugular Intrahepatic Portosystemic Shunt)
- Reduces portal hypertension directly. Can improve renal function in Type 2 (HRS-NAKI).
- Risk of precipitating Encephalopathy.
3. Definitive
- Liver Transplantation: Often combined Liver-Kidney (SLK) if renal failure is prolonged (>6 weeks) and unlikely to recover.
- Terlipressin Ischaemia: Peripheral gangrene (fingers/toes), myocardial ischaemia, intestinal ischaemia. (Check pulses daily!)
- Fluid Overload: Pulmonary oedema (from massive Albumin load).
- Untreated: HRS-AKI is almost uniformly fatal (>80% mortality at 3 months).
- With Treatment: Reversal in 40-50% of cases. Recurrence is common. Only transplant cures.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Decompensated Cirrhosis | EASL (2018) | Defined criteria for HRS-AKI. Terlipressin is Gold Standard. |
| Hepatorenal Syndrome | AASLD (2021) | Similar recommendations. |
Landmark Evidence
1. CONFIRM Study (NEJM 2021)
- Large RCT in North America confirming Terlipressin + Albumin is superior to Albumin alone (32% vs 17% reversal). Led to FDA approval.
What is Hepatorenal Syndrome?
It is kidney failure caused by severe liver disease. The kidneys themselves are actually healthy, but the liver disease messes up the blood flow signals. All the blood pools in the belly area, and the kidneys starve for blood.
Can we verify the kidneys are healthy?
Yes. If we took these kidneys out and put them in a healthy person, they would work perfectly. The problem is the environment they are in.
How do we treat it?
We give a drug (Terlipressin) that squeezes the blood vessels in the belly, forcing blood back out to the rest of the body (and the kidneys). We also give strong protein fluid (Albumin).
Does it assume the liver will recover?
Usually not. This complication generally means the liver is very sick and nearing the end. The main hope is often a liver transplant.
Primary Sources
- European Association for the Study of the Liver (EASL). Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018.
- Wong F, et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM Study). N Engl J Med. 2021.
Common Exam Questions
- Diagnosis: "AKI in cirrhosis unresponsive to fluid challenge?"
- Answer: Hepatorenal Syndrome.
- Treatment: "First line drug?"
- Answer: Terlipressin (+ Albumin).
- Investigaton: "Urine Sodium level?"
- Answer: Very low (less than 10).
- Contraindication: "When NOT to give Terlipressin?"
- Answer: Ischaemic heart disease / Peripheral vascular disease (Ischaemia risk).
Viva Points
- Terlipressin vs Noradrenaline: Trials show they are equally effective for HRS reversal, but Noradrenaline requires a central line/ICU. Terlipressin can be given on the ward.
- Albumin Limits: Stop albumin if the patient gets breathless (Pulmonary oedema). Fluid overload is a major risk.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.