Crystal-membrane interaction in kidney stone disease

Abstract

Urolithiasis is a multifaceted process that initiates with the formation of microcrystals in the urine and terminates with the formation of mature renal calculi. The attachment of crystals by the urothelium is a major event in the successful formation of the mature stone. The papillary tip is the primary site for crystal attachment and stone maturation, and the attachment process appears to be mediated by specific molecular interactions between molecular structures on the surfaces of stone crystals and molecular arrays on the surfaces of cell membranes. Animal models have demonstrated the interaction between cells and crystals, and they have suggested a correlation between cellular damage and crystal interaction, especially when crystals bind to and then break free from the tubular epithelium. Cell culture studies on inner medullary late collecting duct (IMCD) cells have demonstrated that calcium oxalate monohydrate, hydroxyapatite, and uric acid crystals bind to IMCD cells in primary culture. The attachment of these crystals to IMCD cells was crystal structure dependent, saturable, and competitively inhibitable if more than one crystal type was present at the same time. The crystals preferentially attach to cells that have lost partial or complete intercellular junctional integrity. These crystal-attaching cells appear to have altered membrane composition and/or structure. Recent studies on red blood cells and IMCD cells that have been enriched with cholesterol and selected phospholipids suggest that crystal-membrane phospholipid interactions play a major role in crystal attachment.(ABSTRACT TRUNCATED AT 250 WORDS)