Molecular abnormality of Tamm-Horsfall glycoprotein in calcium oxalate nephrolithiasis.
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.
Hess
B
B
Nephrology Program, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Nakagawa
Y
Y
Parks
J H
JH
Coe
F L
FL
D000328:Adult; D000596:Amino Acids / Q000032:analysis; D002129:Calcium Oxalate; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003460:Crystallization; D004563:Electrochemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007669:Kidney Calculi / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009088:Mucoproteins / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology; D058949:Uromodulin; D014783:Viscosity
D000596:Amino Acids; D046911:Macromolecular Substances; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D002129:Calcium Oxalate; D012965:Sodium Chloride