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Decreased Tamm-Horsfall protein in lithiasic patients
M C Romero1, S Nocera, A B Nesse
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, República Argentina.
Insights
Recurrent kidney stone formers excrete significantly less Tamm-Horsfall glycoprotein (THP) than healthy individuals. This finding suggests THP may play a role in preventing urolithiasis.
Area of Science:
- Nephrology
- Urology
- Biochemistry
Background:
- Tamm-Horsfall glycoprotein (THP) is abundant in urine and may inhibit calcium oxalate crystal formation.
- The role of THP in kidney stone (urolithiasis) pathogenesis is not fully understood.
Purpose of the Study:
- To quantify urinary THP excretion in patients with a history of kidney stones.
- To compare THP levels in lithiasic patients with those in healthy control subjects.
Main Methods:
- Developed and validated an Enzyme-Linked Immunosorbent Assay (ELISA) for quantifying urinary THP.
- Measured THP levels in urine samples from recurrent kidney stone formers and control subjects, normalizing to creatinine.
Main Results:
- The ELISA demonstrated reliable quantification of urinary THP.
- Lithiasic patients excreted significantly lower levels of THP (124 IQR 82-171 µg THP/mmol creatinine) compared to controls (388 IQR 209-626 µg THP/mmol creatinine).
Conclusions:
- A specific antiserum against THP was successfully generated for ELISA use.
- Significantly reduced urinary THP excretion is associated with recurrent kidney stone formation, suggesting a potential role in urolithiasis pathogenesis.
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 micrograms THP/mmol creatinine for C (n = 85) and 124/82-171 micrograms 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.