Methods and composition for detecting and treating kidney diseases associated with adhesion of crystals to kidney cells
AssigneeArch Development Corporation
InventorsF. Gary Toback, John C. Lieske
Life of this patent
Estimating the term…
Abstract
An autocrine crystal adhesion inhibitor called CAI is an anionic, sialic acid-containing glycoprotein secreted by kidney epithelial cells that blocks adhesion of calcium oxalate monohydrate (COM) crystals to the cell surface. Novel amino acid sequences are shown for the amino-acid terminus and 6 interval fragments. Persons may be classified according to risk of developing kidney stones, by measuring the amount of CAI in a biological sample. Treatment efficacy is also monitored by this method. CAI is administered in vivo to prevent nephrolithiasis. A rapid, simple assay to detect agents that inhibit adhesion of COM crystals to the surface of kidney epithelial cells is characterized.
Claims5
A purified inhibitor of adhesion of calcium oxalate monohydrate (COM) crystals to kidney epithelial cells, said crystal adhesion inhibitor (CAI) having the following characteristics:
- (a) an estimated molecular weight of 39,000 daltons based on SDS-polyacrylamide gel electrophoresis;
- (b) an anionic glycoprotein containing sialic acid;
- and
- (c) an amino acid sequence selected from the group consisting of the seven sequences as follows:
- 1) (K/D)INGGGATLPQPLYQTSGVLTAGFAP YI (S) V (N) (A) (K) SEQ.ID. NO:
- 4;
- 2) (F) VVTTNFADSFGVPAGAVPAVTSQGVM D (S/A) (L) (N)SEQ.ID. NO:
- 5;
- 3) LIQVPSVATSVAIPFNK SEQ.ID. NO:
- 6;
- 4) LAFLNNDYSQFGTGTK SEQ.ID. NO:
- 7;
- 5) AAITSNFVTATSAL SEQ.ID. NO:
- 8;
- 6) LTSTELSTYASTK SEQ.ID. NO:
- 9;
- 7) NRFVPLPTAX(K) SEQ.ID. NO:
- 10.
A method of preventing further kidney stone formation in an individual with established nephrolithiasis, said method comprising administering a purified urinary crystal adhesion inhibitor (CAI), or a peptide having the crystal adhesion inhibiting activity of CAI, to the individual in a pharmaceutically effective amount and manner wherein said crystal adhesion inhibitor (CAI) has the following characteristics:
- (a) an estimated molecular weight of 39.000 daltons based on SDS-polvacrylamide gel electrophoresis;
- (b) an anionic glycoprotein containing sialic acid;
- and
- (c) an amino acid sequence selected from the group consisting of the seven sequences as follows:
- 1) (K/D) INGGGATLPQPLYQTSGVLTAGFAPYI(S)V(N(A) (K) (SEQ ID NO:
- 4):
- 2) (F) VVTTNFADSFGVPAGAVPAVTS GGVMD(S/A)(L)(N) (SEQ ID NO:
- 5):
- 3) LIOVPSVATSVAIPFNK (SEQ ID NO:
- 6);
- 4) LAFLNNDYSQFGTGTK (SEQ ID NO:
- 7);
- 5) AAITSNFVTATSAL (SEQ ID NO:
- 8);
- 6) LTSTELSTYASTK (SEQ ID NO:
- 9);
- 7) NRFVPLPTAX(K) (SEQ ID NO:10).
A method for isolating and purifying an inhibitor of COM crystal adhesion to kidney cells from a composition comprising the inhibitor, said method comprising:
- (a) exposing the composition to COM crystals to cause the inhibitor to bind to the crystals to form an inhibitor-COM crystal complex;
- (b) separating the inhibitor-COM crystal complex from other components of the composition;
- (c) separating the inhibitor from the COM crystals;
- and
- (d) further purifying the separated inhibitor.
Dependencies are inferred from the claim text.