The retention of crystals in the kidney is considered to be a crucial step in the development of a renal stone. This study demonstrates the time-dependent alterations in the extent of calcium oxalate (CaOx) monohydrate (COM) crystal binding to Madin-Darby canine kidney (MDCK) cells during their growth to confluence and during the healing of wounds made in confluent monolayers. As determined by radiolabeled COM crystal binding studies and confirmed by confocal-scanning laser microscopy, relatively large amounts of crystals (10.4 ± 0.4 μg/cm2) bound to subconfluent cultures that still exhibited a low transepithelial electrical resistance (TER < 400 Ω ⋅ cm2). The development of junctional integrity, indicated by a high resistance (TER > 1,500 Ω ⋅ cm2), was followed by a decrease of the crystal binding capacity to almost undetectable low levels (0.13 ± 0.03 μg/cm2). Epithelial injury resulted in increased crystal adherence. The highest level of crystal binding was observed 2 days postinjury when the wounds were already morphologically closed but TER was still low. Confocal images showed that during the repair process, crystals selectively adhered to migrating cells at the wound border and to stacked cells at sites were the wounds were closed. After the barrier integrity was restored, crystal binding decreased again to the same low levels as in undamaged controls. These results indicate that, whereas functional MDCK monolayers are largely protected against COM crystal adherence, epithelial injury and the subsequent process of wound healing lead to increased crystal binding.

There are at least two models that may explain these results. First, sialic acids are presented at the surface of immature cells in an orientation that specifically matches crystal surface characteristics favoring crystal-cell interactions. Second, sialic acid molecules are not directly associated with the crystals, but may be involved in the exposure of another crystal binding molecule at the cell surface.

These results show that the prevention of crystal binding is cell type specific and expressed only by differentiated MDCK cells. The anti-adherence properties acquired by MDCK cells may mirror a specific functional characteristic of its in situ equivalent, the renal distal tubule/collecting ducts.

These results identify HA as binding molecule for COM crystals at the surface of migrating and proliferating MDCK cells.

While the physical chemistry of stone formation has been intensively studied during the last decade, it has become clear that the pathophysiology of renal stone disease cannot be explained by crystallization processes only. In recent years, evidence has emerged that the cells lining the renal tubules can have an active role in creating the conditions under which stones may develop. Since it is difficult to study these mechanisms in vivo, cultured renal tubular cells have become increasingly popular for the study of physiological and cell biological processes that are possibly linked to stone disease. In this paper, we discuss the possible contribution of cellular processes such as transepithelial oxalate transport and crystal--cell interaction to the formation of renal stones. Experimental studies that have been performed with cultured renal cells to elucidate the mechanisms involved in these processes will be summarized.