Abstract
Urinary stone disease, particularly calcium oxalate, is common in both humans and cats. Calcifying nanoparticles (CNP) are spherical nanocrystallite material, and are composed of proteins (fetuin, albumin) and inorganic minerals. CNP are suggested to play a role in a wide array of pathologic mineralization syndromes including urolithiasis. We documented the development of a clinically relevant protocol to assess urinary CNP in 9 healthy cats consuming the same diet in a controlled environment using Nanoparticle Tracking Analysis (NTA®). NTA® is a novel method that allows for characterization of the CNP in an efficient, accurate method that can differentiate these particles from other urinary submicron particulates. The predominant nanoscale particles in feline urine are characteristic of CNP in terms of their size, their ability to spontaneously form under suitable conditions, and the presence of an outer layer that is rich in calcium and capable of binding to hydroxyapatite binders such as alendronate and osteopontin. The expansion of this particle population can be suppressed by the addition of citrate to urine samples. Further, compounds targeting exosomal surfaces do not label these particulates. As CNP have been associated with a number of significant urologic maladies, the method described herein may prove to be a useful adjunct in evaluating lithogenesis risk in mammals.
Highlights
Urinary tract stone formation is an ancient disease process with a recently reported prevalence of up to 20% in adults in developed nations [1]
The histogram is suggestive of a sample in which a subset of Calcifying nanoparticles (CNP) has undergone transition to larger forms and the size of the larger forms is consistent with prior reports[16]
Submicron particulate matter appears to be relatively abundant in feline urine as evidenced by NTA of the samples we analyzed
Summary
Urinary tract stone formation is an ancient disease process with a recently reported prevalence of up to 20% in adults in developed nations [1]. In many parts of the world, the prevalence of urolithiasis increased during the latter portion of the 20th century[2,3] and can result in numerous hospital visits, surgeries, and interventional procedures for the patient. Urolithiasis in cats is a frequently encountered disease, and the most common urolith type in both cats and humans is calcium oxalate (CaOx) [4,5]. Humans and cats are reported to have idiopathic hypercalciuria as a metabolic feature in this disease[8,9]. Pharmacologic management strategies for both species have yielded variable results[10,11,12,13]. High recurrence rates are problems in both species [14,15]
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