What is the management of renal failure in cirrhosis?

Pathophysiology and Management of Renal Failure in Cirrhosis

Core Pathophysiological Mechanism

The fundamental pathophysiology of renal failure in cirrhosis is splanchnic vasodilation leading to decreased effective arterial blood volume, which triggers compensatory mechanisms that ultimately cause renal vasoconstriction and impaired kidney function. 1

Primary Hemodynamic Cascade

• Splanchnic vasodilation reduces effective arterial blood volume and decreases mean arterial pressure, initiating the entire pathophysiological cascade 1, 2
• Compensatory activation of the renin-angiotensin-aldosterone system, sympathetic nervous system, and arginine vasopressin occurs in response to perceived hypovolemia 1
• Renal vasoconstriction results from these compensatory mechanisms, causing reduced kidney blood flow and impaired glomerular filtration rate 1
• Cirrhotic cardiomyopathy impairs the compensatory increase in cardiac output that would normally counteract vasodilation 1

Additional Contributing Factors

• Systemic inflammation, adrenal dysfunction, and intra-abdominal hypertension contribute to functional kidney injury beyond pure hemodynamic mechanisms 1, 2
• Increased synthesis of vasoactive mediators (cysteinyl leukotrienes, thromboxane A2, F2-isoprostanes, endothelin-1) may affect renal blood flow, though their exact role remains incompletely understood 1

Diagnostic Approach

Definition of AKI in Cirrhosis

AKI is defined by an increase in serum creatinine ≥0.3 mg/dL within 48 hours, OR an increase to ≥1.5 times baseline within 7 days, OR urine output <0.5 mL/kg/h for 6 hours. 1

Critical Diagnostic Limitations

• Serum creatinine underestimates renal dysfunction in cirrhosis due to impaired hepatic creatine production, reduced muscle mass, female sex, increased tubular secretion, and hyperbilirubinemia interference with assays 1
• Baseline creatinine should be the most recent value within 3 months when a value within 7 days is unavailable 1

Differential Diagnosis of AKI Types

Before diagnosing hepatorenal syndrome (HRS), exclude hypovolemia, shock, parenchymal renal disease, and nephrotoxic drug use. 1

• Hypovolemia from hemorrhage, gastrointestinal losses, or excessive diuresis 1
• Hepatorenal syndrome (HRS-AKI) characterized by intense renal vasoconstriction without structural kidney damage 1
• Acute tubular necrosis (ATN) from ischemic or toxic insults 1
• Parenchymal renal disease suspected with proteinuria >500 mg/day, hematuria >50 RBCs per high-power field, or abnormal renal ultrasound 1

HRS-AKI Diagnostic Criteria

HRS-AKI requires serum creatinine >1.5 mg/dL, absence of shock, no improvement after 2 days of diuretic withdrawal and albumin volume expansion, and absence of parenchymal disease. 1, 2

Management Algorithm

Stage 1 AKI (Creatinine increase >0.3 mg/dL but <2× baseline)

Immediately discontinue diuretics, beta-blockers, NSAIDs, ACE inhibitors, ARBs, and all nephrotoxic drugs. 1

• Screen and treat infections aggressively, particularly spontaneous bacterial peritonitis, as infection is the most important precipitant of HRS 1
• Volume expansion with crystalloids for diarrhea or excessive diuresis 1
• Packed red blood cells to maintain hemoglobin 7-9 g/dL for gastrointestinal bleeding 1
• Therapeutic paracentesis with albumin for tense ascites, as this improves renal function 1
• Albumin 1 g/kg (maximum 100 g) on day 1, then 20-40 g/day if no obvious cause identified and creatinine remains elevated after 2 days 1, 2

Stage 1b (Creatinine >1.5 mg/dL) or Stage 2-3 AKI (Creatinine ≥2× baseline)

Initiate vasoconstrictor therapy with terlipressin plus albumin if HRS criteria are met and creatinine remains elevated despite 2 days of risk factor management. 1

Terlipressin Dosing Protocol

• Start terlipressin 1 mg IV every 4-6 hours (equivalent to 0.85 mg terlipressin base) 1, 3
• Increase to 2 mg every 4-6 hours on day 4 if serum creatinine decreases <25-30% from baseline 1, 3
• Discontinue if creatinine is at or above baseline on day 4 3
• Continue treatment until creatinine decreases to <1.5 mg/dL (typically 1.0-1.2 mg/dL), usually requiring median 5-14 days 1, 3
• Response rate is 40-76% with complete response in 29-56% of patients 1, 3

Albumin Coadministration

• Albumin 1 g/kg (maximum 100 g) on day 1, then 20-40 g/day throughout terlipressin treatment 1, 3
• Monitor closely for pulmonary edema as albumin increases risk of fluid overload 1
• Central venous pressure monitoring may help prevent circulatory overload, though CVP is inaccurate for assessing cardiac output in cirrhosis 1

Renal Replacement Therapy

Consider RRT on an individualized basis for severe AKI (Stage 3), particularly when complicated by severe metabolic acidosis, hyperkalemia, or fluid overload refractory to medical management. 1

Definitive Treatment

Liver transplantation is the definitive treatment for HRS-AKI, as renal function typically normalizes post-transplant. 1, 2

• Simultaneous liver-kidney transplantation should be considered if measured GFR <30 mL/min persists despite treatment 1

Prognostic Considerations

• Median survival for all HRS patients is approximately 3 months 1, 2
• Untreated type 1 HRS has median survival of approximately 1 month 1, 2
• Even transient AKI episodes negatively impact mid-term survival regardless of reversibility 1
• Urine output <0.5 mL/kg for >6 hours is associated with higher mortality compared to creatinine-only criteria 1

Prevention Strategies

• Albumin with therapeutic paracentesis (8 g per liter removed) prevents post-paracentesis circulatory dysfunction and HRS 2
• Albumin plus antibiotics for spontaneous bacterial peritonitis reduces HRS incidence from 30% to lower rates 1, 2
• Avoid nephrotoxic medications including NSAIDs, aminoglycosides, and radiocontrast agents 1, 2
• Antibiotic prophylaxis in high-risk patients (prior SBP, low ascitic protein) reduces infection-related HRS 2

Critical Pitfalls to Avoid

• Do not delay treatment waiting for creatinine to reach 2.5 mg/dL, as earlier intervention with the new AKI criteria improves outcomes 1
• Do not rely solely on creatinine, as it significantly underestimates renal dysfunction in cirrhosis 1
• Do not continue diuretics or beta-blockers once AKI is identified, even if controversial for beta-blockers 1
• Do not administer albumin without monitoring for fluid overload, as pulmonary edema is a significant risk 1