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Molecular abnormality of Tamm-Horsfall glycoprotein in calcium oxalate nephrolithiasis
B Hess1, Y Nakagawa, J H Parks
1Nephrology Program, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Insights
Tamm-Horsfall glycoprotein (THP) from kidney stone patients shows reduced ability to prevent calcium oxalate crystal aggregation. This impaired function is linked to abnormal self-aggregation of THP, potentially contributing to stone formation.
Area of Science:
- Nephrology
- Biochemistry
- Crystallography
Background:
- Tamm-Horsfall glycoprotein (THP) is a key urinary protein.
- THP naturally inhibits calcium oxalate monohydrate (COM) crystal aggregation.
- This inhibition is crucial for preventing kidney stones (nephrolithiasis) and nephrocalcinosis.
Purpose of the Study:
- To investigate the inhibitory function of THP in patients with severe nephrolithiasis.
- To determine if abnormalities in THP contribute to kidney stone formation.
Main Methods:
- Studied THP from six nephrolithiasis patients and compared its function to normal THP.
- Assessed THP's ability to inhibit COM crystal self-aggregation under simulated urine conditions (pH, NaCl, THP concentration).
- Evaluated THP self-aggregation properties.
Main Results:
- THP from nephrolithiasis patients exhibited significantly less inhibition of COM crystal aggregation compared to normal THP.
- Patient THP showed enhanced self-aggregation, reducing its availability for crystal interaction.
- Abnormal THP function was observed in a familial pattern, affecting a father and his oldest son.
Conclusions:
- Reduced THP inhibitory function, due to enhanced THP self-aggregation, may be a factor in severe nephrolithiasis.
- Familial aggregation of abnormal THP suggests a potential genetic component in THP dysfunction and kidney stone risk.
Abstract:
Tamm-Horsfall glycoprotein (THP) inhibits self-aggregation of calcium oxalate monohydrate (COM) crystals and may therefore be part of the natural defenses against deposition of COM in the kidney in the form of stones or nephrocalcinosis. We have studied THP from six patients with severe nephrolithiasis and have found that their THP inhibits COM self-aggregation less than normal THP under conditions of NaCl and THP concentration and pH similar to those of human urine. The reason for the reduced inhibition of COM crystal aggregation seems to be an enhanced self-aggregation of patient THP, which removes it from effective interactions with the COM crystals. In one family, the father and the oldest son both excreted THP that behaved abnormally and in similar ways, whereas THP from the other son and from the wife behaved normally.