Crystallization of Hierarchical Ammonium Urate: Insight into the Formation of Cetacean Renal Stones

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Among a wide variety of pathological crystalline materials in nephrolithiasis, uric acid and its salt form are the most abundant organic constituents. Even though rarely found in humans, ammonium urate (NH 4 HU) is the most prevalent kidney stone reported in managed bottlenose dolphins. In this study, we investigate the physicochemical properties of NH 4 HU crystals associated with dolphin kidney stones, which exhibit distinct hierarchical structures. We present a method of crystallizing NH 4 HU without common impurities, which allowed for the first measurement of NH 4 HU crystal solubility over a broad range of temperatures. Parametric evaluations of NH 4 HU crystallization are reported, wherein we assess the effects of supersaturation and solution alkalinity on crystal phase behavior, the kinetics of urate crystallization, and the size and morphology of synthetic NH 4 HU crystals. In vitro bulk crystallization assays from aqueous growth solutions containing supersaturated ionic species (NH 4+ and urate 1– ) were performed to prepare NH 4 HU crystals with characteristic spheroidal superstructures. Notably, synthesized samples adopt a morphology consisting of spicule-like NH 4 HU crystals protruding from the exterior surface of hierarchical structures, analogous to images of actual dolphin kidney stones. Moreover, the characterization of extracted tissues from dolphin kidneys reveals crystallites embedded within the membrane, which suggests the spicule-like morphology incurs an undesirable retention of stones. Collectively, these findings of ammonium urate crystallization may shed additional light onto the factors governing the pathological formation of cetacean renal stones.