Cholesterol plus dietary tannins play a key role in formation of urinary stone

Abstract

The incidence of urolithiasis has been rising worldwide for several decades, but the main aetiological factors remain unknown. It was found that the prevalence of urolithiasis was correlated with intakes of high fat plus fruits rich in tannins through questionnaire-based dietary consumption surveys and epidemiological analysis. Cholesterol and polyphenols were also found in various renal stones of human. Cholesterol could co-precipitate with polyphenols extracted from various food materials in vitro, particularly condensed tannins. Therefore, prepared tannins from fruit were isolated by gel filtration column and characterized by high performance liquid chromatography. Mice gavaged with apple tannins and cholesterol caused remarkable cholesterol/tannins deposits, glomerular atrophy as well as increasing urine proteins, creatinine and electrolytes. Mice gavaged with ethylene glycol, tannins and cholesterol showed stronger nephrotoxicity, caused urine solute supersaturation in renal tubules, less urine and more deposits in urinary system, forming bladder stones (41.6% morbidity). Molecular dynamics simulation suggested that tannins and cholesterol formed complexes through van der Waals forces and hydrogen bonds. These findings indicated that interaction of cholesterol and tannins is a key factor in the formation of urinary stones, providing a clear explanation of urolithiasis formation. This study should help to design the strategies for prevention and control of various urinary stones as well as reveal the crucial reason for the increasing prevalence of urinary stones.