Proximal Tubule Secretory Clearance, Injury, and Kidney Viability in Cirrhosis

Area of Science:

• Nephrology
• Hepatology
• Biomarker Discovery

Background:

• Cirrhosis impacts kidney structures, particularly tubules responsible for metabolite secretion and homeostasis.
• Standard kidney function assessments (e.g., GFR) may not fully capture tubular dysfunction in cirrhosis.
• Characterizing tubular function markers is crucial for understanding kidney health in cirrhotic patients.

Purpose of the Study:

• To investigate markers of kidney tubular function, injury, and viability in patients with cirrhosis compared to non-cirrhotic controls.
• To assess if glomerular filtration rate (GFR)-matched controls adequately represent kidney tubular health in cirrhosis.
• To identify specific tubular biomarkers altered in cirrhosis.

Main Methods:

• Recruited outpatients undergoing liver transplant evaluation and GFR-matched controls.
• Collected plasma and 24-hour urine samples for analysis.
• Measured urinary kidney injury molecule-1 (KIM-1), epidermal growth factor (EGF), and endogenous secreted metabolites.

Main Results:

• Patients with cirrhosis exhibited significantly higher urinary KIM-1 (4.4-fold) and EGF (7.41-fold) compared to controls.
• Despite similar GFR, 5 out of 8 measured solutes showed significantly greater kidney clearance in cirrhotic patients (1.3-2.1-fold).
• Specific solutes with increased clearance included indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine.

Conclusions:

• Cirrhosis is associated with molecular evidence of tubular injury and increased tubular viability in stable outpatients.
• Tubular secretory clearance appears largely preserved in cirrhosis, despite signs of injury.
• Findings suggest a phenotype of chronic ischemic kidney injury with initial preservation of tubular function in cirrhosis.