Can CKD Cause Hepatorenal Syndrome?
No, chronic kidney disease (CKD) does not cause hepatorenal syndrome (HRS)—rather, advanced cirrhosis with portal hypertension causes HRS, and CKD can coexist as a separate comorbidity in patients with liver disease. 1
Understanding the Directional Relationship
HRS is fundamentally a complication of advanced liver disease, not kidney disease:
HRS develops from cirrhosis-induced hemodynamic changes: The primary pathophysiology involves splanchnic and systemic vasodilation from portal hypertension, leading to effective arterial underfilling, compensatory activation of vasoconstrictor systems (renin-angiotensin-aldosterone and sympathetic nervous systems), and ultimately severe renal vasoconstriction. 1, 2
The liver disease drives the kidney dysfunction: HRS occurs in the setting of preserved tubular function and absence of significant histologic kidney abnormalities—it is a functional, potentially reversible form of acute kidney injury triggered by the cirrhotic state. 3, 4
CKD is an independent comorbidity, not a cause: CKD is becoming increasingly prevalent in patients with cirrhosis, particularly those with metabolic syndrome, diabetes, and NASH, but this represents concurrent structural kidney disease rather than a causal pathway to HRS. 1
The Complex Overlap of CKD and HRS
The clinical challenge lies in distinguishing HRS-AKI superimposed on pre-existing CKD:
CKD affects nearly half of patients with cirrhosis, especially those with NASH, diabetes, and metabolic syndrome. 1
When HRS develops in a patient with underlying CKD, attributing further kidney injury becomes challenging—it's difficult to separate acute functional deterioration from HRS versus chronic progressive structural damage from the underlying CKD. 1
Management remains the same: If HRS is suspected in a patient with CKD, treatment should follow standard HRS algorithms with vasoconstrictors and albumin while awaiting better markers of tubular damage. 1
Key Diagnostic Criteria for HRS
HRS diagnosis requires all of the following, confirming it originates from liver disease, not kidney disease 2, 5:
- Cirrhosis with ascites
- AKI defined by International Club of Ascites criteria (Stage 1: creatinine increase ≥0.3 mg/dL or 1.5-2x baseline; Stage 2: 2-3x baseline; Stage 3: >3x baseline or >4 mg/dL with acute increase ≥0.3 mg/dL) 2
- No improvement after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin 1 g/kg body weight 2, 5
- Absence of shock 2
- No current or recent nephrotoxic drug use 2
- Absence of structural kidney injury (no proteinuria >500 mg/day, no microhematuria >50 RBCs/HPF, normal renal ultrasound) 2
Common Clinical Pitfalls
Do not confuse the direction of causality:
Patients with primary kidney disease (CKD) who later develop cirrhosis still develop HRS from the liver disease, not from their pre-existing CKD. 1
The presence of CKD does not prevent HRS from occurring—it simply makes diagnosis more complex and prognosis worse. 1
For liver transplant candidates with CKD: If measured GFR is below 30 ml/min, combined liver-kidney transplantation rather than liver transplantation alone should be considered. 1
Precipitating Factors for HRS (Not Causes)
HRS is precipitated by factors that worsen the hemodynamic derangements of cirrhosis 1, 2:
- Bacterial infections (especially spontaneous bacterial peritonitis)—HRS develops in approximately 30% of patients with SBP 2, 6
- Volume depletion from aggressive diuretics or large-volume paracentesis without albumin 2
- Gastrointestinal bleeding 2
- Any acute deterioration in liver function 2
These are triggers, not causes—the underlying cause remains the cirrhotic liver disease itself. 1, 2