Urinary Citrate and Citrate Metabolism

Abstract

Citrate is the most abundant organic anion in human urine. Its urinary excretion rate mainly depends on acid–base status: Alkalosis induces an increase in urinary citrate excretion, whereas acidosis has the opposite effect. It is important to note that citrate utilization by renal cells and urinary citrate excretion are mainly affected by intracellular changes in acid base homeostasis of proximal tubular cells. Even small acid loads such as meat protein-rich meals decrease urinary excretion of citrate. Low urinary citrate (hypocitraturia) is defined as daily urinary citrate excretion rates below 1.70 mmol (320 mg) in men and 1.90 mmol (350 mg) in women. Hypocitraturia occurs in 20–60% of calcium stone formers. Sufficient citrate in urine is important because citrate retards the crystallization of stone-forming calcium salts, mediates inhibitory effects of macromolecular modulators of calcium oxalate crystallization and – due to its alkalinizing effect – reduces rates of uric acid stone formation. Treatment with alkali citrate, usually in the form of potassium citrate or magnesium potassium citrate, is widely used to increase urinary citrate and reduce rates of stone formation in patients with hypocitraturic calcium nephrolithiasis as well as uric acid stone disease.