N -Acetylneuraminic acids (nana): a potential key in renal calculogenesis

Abstract

N-Acetylneuraminic acids (NANA) promote binding of calcium ions to macromolecules and cells, increase the intrinsic viscosity of glycoproteins and facilitate gel formation in water. Since these properties are crucial in urinary calculogenesis, we evaluated NANA levels in urine and serum as well as their expression in kidney tissues. Using a modified thiobarbituric acid assay, the evaluation of free and bound NANA in 24-h urine samples revealed a ratio of 1.87 in 33 non-stone-formers but a reversed ratio of 0.84 in 41 recurrent calcium oxalate stone-formers. Time kinetics revealed a gradual rise in NANA expression until 48 h of culture and a significantly higher release into supernatants of papillary renal epithelial cells (REC) when compared with cortical REC. To examine NANA distribution in kidney tissues, paraffin-embedded biopsies from five normal and six stone-forming kidneys were labeled with the biotinylated NANA-specific lectins Maackia amurensis (MAA) and Sambucus nigra (SNA). Immunohistochemistry revealed intense luminal MAA reactivity of distal tubular REC and collecting ducts in 96.7% and 91.5% of normal and stone-forming kidneys respectively. By contrast, there was a marked difference between normal and stone-forming kidneys for SNA reactivity (17.7% vs 95%) at the same locations. Finally, the glycocalyx of recurrent stone-formers showed altered sialylglycoside linkages [α(2,6) instead of α(2,3)] that may indicate an altered REC function. Given the calcium-binding potential of NANA, their increased local concentration within the glycocalyx layer in the distal nephron may either initiate stone formation or facilitate attachment of microcrystals to REC.