Analysis of the soluble organic matrix of five morphologically different kidney stones

Abstract

Our aims were to analyze the protein composition of the organic matrix of urinary stones and to investigate the role of albumin in its constitution. Five different morphological types of stones were studied. Proteins extracted from the stone were submitted to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by immunoblotting with antibodies to 13 urinary proteins. Nine of the 13 proteins were found in all types of stone: human serum albumin (HSA), alpha 1-acid glycoprotein (alpha 1-GP), alpha 1-microglobulin (alpha 1-M), immunoglobulins (Igs), apolipoprotein A1 (apo-A1), transferrin (Tr), alpha 1-antitrypsin (alpha 1-T), retinol-binding protein (RBP) and renal lithostathine (RL). The beta 2-microglobulin (beta 2-M) was present only in calcium oxalate and uric acid stones. In contrast, ceruloplasmin, haptoglobin and Tamm-Horsfall protein (THP) were detected in none of them. Because HSA appeared as the major protein component in all stones, we wondered whether it might play a specific role in the constitution of the stone matrix. Association of HSA with urinary proteins that were present in stones was demonstrated by showing that proteins present in the matrix comigrated with HSA on gel filtration, whereas proteins that were absent did not. Moreover, HSA induced the binding of stone matrix proteins to an albumin-specific affinity column. Finally, we evidenced HSA binding to calcium oxalate monohydrate (COM) crystals in a solution similar to urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between Stone-Forming Calcific Crystals and Macromolecules

“…Its amino acid sequence is, however, different from other proteins of the S-100 family. Human serum albumin has also been found in the matrices of kidney stones and CaOx crystals induced in human urine [12,32]. It has high affinity for Electron micrographs of COM crystals.…”

“…ASP = Aspartic acid; GLA = g-carboxyglutamic acid; RGD = arginine-glycine-aspartic acid; PT = proximal tubule; TAL = thin ascending limb of the loop of Hcnle; TDL = thick descending limb of the loop of Henle. 60 Urollnt 1997;59:59- 71 Khan CaOx crystals, but has no influence on their growth and very little effect on their aggregation [105], A protein simi lar to pancreatic lithostathine has also been detected in stone matrix [32]. The other major proteins involved in crystallization and stone formation are discussed in the following paragraphs.…”

Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers

“…Such proteins include TammHorsfall protein (THP) (20), osteopontin (uropontin) (2), prothrombin fragment 1 (PF1) (38), inter-␣-trypsin inhibitor (ITI) (9), and bikunin (BK), a portion of ITI (3), calgranulin (34), CD59 (7), and albumin (10). Although some reports suggest defects, deficiencies, or variations of these molecules among SF vs. normal subjects (13,14,26,27,43), it remains unclear whether any of these is a cause or a consequence of stones; no research thus far has translated molecular knowledge into clinical practice.…”

Effects of Allopurinol on Renal Stone Formation and Osteopontin Expression in a Rat Urolithiasis Model

“…Certain noncollagenous and plasma proteins, including OPN, sialoproteins, albumin and α 2 HS-glycoprotein [16, 17]known to accumulate in bone and other mineralized tissues are also found in human renal stones. Of these, OPN is the major constituent of calcium oxalate-associated crystal ‘ghosts’ observed in the nuclei, lamellae, and striations of organic matrix material in deposits within epithelial cells [18].…”