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Renal Failure in Hepato-Pancreato-Biliary (HPB) Diseases

Introduction

Renal failure is a significant complication in patients with HPB diseases, particularly those associated with obstructive jaundice and liver dysfunction. Understanding the factors contributing to renal failure and effective management strategies is crucial for improving patient outcomes.

Incidence and Mortality

  • Postoperative Acute Kidney Injury (AKI):
    • The reported incidence of postoperative AKI in patients with jaundice is as high as 10%, varying with the nature of the procedure.
    • Mortality rates in jaundiced patients who develop renal failure can reach up to 70%.
  • AKI in Liver Resection:
    • AKI occurs in approximately 15% of patients undergoing liver resection.
    • In acute liver failure (ALF), 40% to 80% of patients develop AKI.
    • AKI is a frequent complication in chronic liver disease, occurring in up to 50% of hospitalized patients.

Factors Contributing to Renal Failure in HPB Diseases

Depressed Cardiac Function

  • Obstructive jaundice is associated with decreased cardiac function, leading to reduced renal perfusion.
  • Decreased cardiac output may result in:
    • Increased production of atrial natriuretic peptide (ANP):
      • Causes natriuresis.
      • Counters water- and sodium-retaining hormones.
      • Inhibits thirst mechanism.
      • Produces peripheral vasodilation.
    • Plasma levels of ANP are increased in patients with extrahepatic biliary obstruction.

Hypovolemia

  • Bile acids have a direct diuretic and natriuretic effect on the kidneys, causing extracellular volume depletion and hypovolemia.
  • Infusion of bile into the renal artery increases urine flow, natriuresis, and kaliuresis.
  • This diuretic effect may be mediated by:
    • Increased prostaglandin E2 production by the kidneys.
    • Effects on FXR and TGR5 receptors.

Effects of Bile Salts on Renal Function

  • Bile Salt–Mediated Effects on Renal FXR and TGR5 Receptors:
    • Bile salts interact with these receptors, influencing renal function.
  • Diuretic and Natriuretic Effects of Bile Acids:
    • Lead to significant extracellular volume depletion.
    • Result in hypovolemia and decreased renal perfusion.

Endotoxemia

  • Approximately 50% of patients with obstructive jaundice have endotoxin in their peripheral blood.
  • Causes include:
    • Decreased hepatic clearance of endotoxin by Kupffer cells.
    • Lack of bile salts in the gut lumen, allowing absorption of endotoxins and anaerobic bacterial growth.
  • Effects of Endotoxin:
    • Causes renal vasoconstriction.
    • Redistributes renal blood flow away from the cortex.
    • Disturbs coagulation, activating complement, macrophages, leukocytes, and platelets.
    • Results in glomerular and peritubular fibrin deposition.
    • Combined with reduced cortical blood flow, leads to tubular and cortical necrosis.

Acute Kidney Injury (AKI) in HPB Procedures

Incidence and Risk Factors

  • AKI correlates with:
    • Preexisting cardiovascular disease.
    • Preoperative serum alanine aminotransferase elevation.
    • Underlying renal disease.
    • Diabetes mellitus.

Intraoperative Oliguria and Urine Output

  • Oliguria (urine output less than 0.5 mL/kg/hr) is common intraoperatively and is often a neurohormonal response to surgical stress.
  • Low urine output is an unreliable marker of volume status during surgery.
  • Retrospective Analysis Findings:
    • 85% of postoperative patients not developing AKI had urine output less than 0.5 mL/kg/hr.
    • More patients without AKI had low urine output compared to those who developed AKI (75%).

AKI in Liver Resection with Low Central Venous Pressure (LCVP)

  • Clinically relevant AKI was rare (≤1%) following LCVP-assisted liver resection and resolved in half of these patients during a short follow-up period.
  • Biochemically defined renal dysfunction was relatively common (16%) but was transient with limited clinical significance.
  • Some permissive, clinically nonrelevant renal dysfunction is common in this patient population.

Role of Epidural Anesthesia (EDA)

  • A retrospective review of 1,153 liver resections found that:
    • EDA and/or EDA LCVP-assisted liver surgery significantly increases the incidence of AKI (defined by the Acute Kidney Injury Network [AKIN] criteria) following major resections.
    • No significant increase in AKI incidence was observed in minor liver resections.

Hepatorenal Syndrome (HRS)

Types of HRS

  • Type 1 HRS (HRS-AKI):
    • Rapidly progressive, resulting in oliguric renal failure within 2 weeks.
    • Often associated with rapid deterioration of renal and liver function.
  • Type 2 HRS (HRS-NAKI):
    • Slowly progressive renal impairment.
    • Associated with refractory ascites.
    • Further subdivided into:
      • HRS-AKD (Subacute Kidney Disease)
      • HRS-CKD (Chronic Kidney Disease)

Pathophysiology

  • Functional renal failure caused by:
    • Intrarenal vasoconstriction
    • Splanchnic vasodilation
  • May be precipitated by:
    • Infection
    • Intravascular volume depletion
  • Represents the extreme end of the spectrum of renal dysfunction in cirrhosis.

Precipitating Factors

  • Worsening systemic vasodilation (e.g., infection).
  • Decreased effective arteriolar volume (e.g., hypovolemia, gastrointestinal hemorrhage).
  • Use of nephrotoxic drugs.
  • Intraoperative hypotension or hemorrhage.

Revised Nomenclature and KDIGO Classification

  • Aligns with the Kidney Disease Improving Global Outcomes (KDIGO) classification system.
  • HRS-AKI replaces HRS type 1.
  • HRS-NAKI replaces HRS type 2.

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Management of AKI and HRS in HPB Diseases

Initial Management

  • Volume Expansion:
    • Administration of albumin infusions.
  • Withdrawal of Diuretic Therapy:
    • If being used.
  • Search for Nephrotoxic Drugs:
    • Identification and discontinuation.

Vasoconstrictor Therapies

  • Terlipressin:
    • A synthetic peptide with vasoconstrictive activity on the vasopressin (V1) receptor.
    • May be more effective for HRS related to sepsis or systemic inflammatory conditions.
    • FDA approval pending (early 2020) for use in type 1 HRS.
  • Midodrine and Octreotide:
    • Used in combination.
  • Noradrenaline:
    • Compared with terlipressin without significant outcome difference in randomized trials.

Renal Replacement Therapies

  • Continuous or Intermittent Renal Replacement Therapy:
    • Offered to patients not responding to vasoconstrictors or TIPS.
    • Especially for prospective liver transplantation candidates.
    • Recovery of renal function achieved in up to 50% of patients.
  • Continuous Hemofiltration Systems:
    • Less hemodynamic instability.
    • Lower risk of aggravating cerebral edema compared to intermittent hemodialysis.
    • Associated with improved survival in ALF.

Liver Transplantation

  • Most effective treatment for kidney injury in the context of liver failure.
  • Renal replacement therapy serves as a bridge to transplantation.

Renal Failure in Acute and Chronic Liver Failure

AKI in Acute Liver Failure (ALF)

  • AKI occurs in 40% to 80% of ALF patients.
  • Associated with:
    • Increasing age.
    • Acetaminophen etiology.
    • Development of infection.
  • Multifactorial Etiology:
    • Early renal dysfunction may result from direct drug toxicity (e.g., acetaminophen overdose).
    • Also seen in Wilson disease and pregnancy-related syndromes.
  • Monitoring Renal Function:
    • Urea synthesis is impaired in ALF.
    • Serum creatinine levels are preferred for monitoring.

AKI in Chronic Liver Disease

  • Occurs in up to 50% of hospitalized patients with chronic liver disease.
  • Strong predictor of poor survival in both short and long term.
  • Encompasses subtypes:
    • HRS-AKI
    • Non-HRS-AKI
  • Overlap Between HRS-AKI and Non-HRS-AKI:
    • Particularly in acute-on-chronic liver failure (ACLF) and multiorgan failure (MOF).

Role of Renal Support Therapies

  • Optimization of Intravascular Filling:
    • Essential in patients with deteriorating renal function.
  • Terlipressin and Albumin Infusions:
    • Improve renal function and survival rates.
  • Early Intervention with Renal Replacement Therapy:
    • Prudent in ALF due to metabolic complexity.
  • Less Defined Role in ACLF:
    • Use is most clear-cut when liver failure is limited and transplantation is an option.

Conclusion

Renal failure in HPB diseases is a multifaceted complication with significant impact on patient outcomes. Understanding the underlying mechanisms, risk factors, and effective management strategies, including volume optimization, vasoconstrictor therapies, and renal replacement therapies, is essential. Early recognition and intervention can improve renal function and survival rates, particularly in patients eligible for liver transplantation.