Complement activation products in the urine from proteinuric patients

Area of Science:

• Nephrology
• Immunology
• Pathophysiology

Background:

• Plasma proteins in the tubular lumen can harm tubular cells.
• Complement system activation within the kidney tubules is implicated in tubulointerstitial injury.
• Understanding intratubular complement activation is crucial in proteinuric kidney diseases.

Purpose of the Study:

• To investigate the role of intratubular complement activation in patients with proteinuria.
• To measure complement activation products (CAP) in plasma and urine across various glomerular diseases.
• To assess the impact of metabolic acidosis on intratubular complement activation.

Main Methods:

• Measured urinary and plasma levels of complement activation products (iC3b, Bb, C9/membrane attack complex).
• Studied patients with minimal change nephrotic syndrome, focal glomerular sclerosis, IgA nephropathy, membranous nephropathy, and diabetic nephropathy.
• Assessed urinary CAP before and after sodium bicarbonate treatment in patients with renal insufficiency.

Main Results:

• Focal glomerular sclerosis and diabetic nephropathy showed the highest urinary CAP excretion; minimal change nephrotic syndrome did not.
• Membranous nephropathy exhibited isolated increase of membrane attack complex excretion.
• Urinary CAP excretion correlated with proteinuria levels (above nephrotic range), serum creatinine, and decreased after metabolic acidosis treatment.

Conclusions:

• Intratubular complement activation is associated with proteinuria level, glomerular disease type, and renal function impairment.
• Metabolic acidosis contributes to increased intratubular complement activation.
• Urinary CAP levels serve as a marker for the degree of intratubular complement activation in proteinuric kidney diseases.