Protein regulation of intrarenal crystallization

In this review we discuss the key role renal proteins appear to play during initiation and growth of renal stones.

Specific macromolecules have been identified in urine that can regulate crystal nucleation, growth, aggregation, and adhesion to renal cells. Many are incorporated into the matrix of crystals while they grow, including urinary prothrombin fragment 1, thereby increasing crystal susceptibility to degradation by cellular proteases. None of these macromolecular inhibitors appears to be quantitatively decreased in the urine of stone formers, although functional deficiencies thought due to abnormal glycosylation have been implicated, especially in the case of Tamm Horsfall protein. Increasing information is available on the nature and expression of crystal binding molecules on the renal cell surface, and they appear to be maximally expressed in response to stressful stimuli. Studies that employ atomic force microscopy and knockout mice are now being used to further clarify macromolecule-crystal interactions.

The exact series of events that transform supersaturation to crystal formation and renal stones are poorly defined. Multiple anchored and soluble renal proteins potentially modulate or even regulate these events. A combination of proteomics and molecular biology seems likely to unravel these critical mediators in the coming years.