Decreased Tamm-Horsfall protein in lithiasic patients

Objectives: Tamm-Horsfall glycoprotein (THP) is the most abundant substance of renal origin appearing in urine. It seems to be one of the major inhibitors of calcium oxalate crystal nucleation and/or aggregation, but its role in the pathogenesis of stone formation has not yet been clarified. The present work was undertaken to quantify THP excretion in lithiasic (L) patients, so as to determine if these levels are different from those of control subjects (C). Design and Methods: THP was isolated from human urine by reprecipitation steps, rabbit antiTHP antibody was obtained and its specificity determined, an ELIsA was developed and technical conditions standardized, and quantitative measurements of urinary THP were performed on samples from L patients, who had suffered more than one lithiasic episode, and from C subjects. Microtiter plates coated with THP or diluted urine samples were subjected to successive incubation with antiTHP and alkaline phosphatase antirabbit IgG. Results: A good correlation between measured absorbance and THP concentration in standard and urine samples was observed. Data, expressed as Median and Interquartile Range, are 388/209-626 mu g THP/mmol creatinine for C (n = 85) and 124/82-171 mu g THP/mmol creatinine for L (n = 23). Conclusions: We have obtained an antiserum antiTHP that can be used in the ELIsA technique to determine reliable urinary THP values. The results show a significant decrease of THP excretion in recurrent stone formers compared to controls (p < 0.001) and may have interesting implications in the pathogenesis of urolithiasis.