Recent advances on the mechanisms of kidney stone formation (Review).

Kidney stone disease is one of the oldest diseases known to medicine; however, the mechanisms of stone formation and development remain largely unclear. Over the past decades, a variety of theories and strategies have been developed and utilized in the surgical management of kidney stones, as a result of recent technological advances. Observations from the authors and other research groups suggest that there are five entirely different main mechanisms for kidney stone formation. Urinary supersaturation and crystallization are the driving force for intrarenal crystal precipitation. Randall's plaques are recognized as the origin of calcium oxalate stone formation. Sex hormones may be key players in the development of nephrolithiasis and may thus be potential targets for new drugs to suppress kidney stone formation. The microbiome, including urease­producing bacteria, nanobacteria and intestinal microbiota, is likely to have a profound effect on urological health, both positive and negative, owing to its metabolic output and other contributions. Lastly, the immune response, and particularly macrophage differentiation, play crucial roles in renal calcium oxalate crystal formation. In the present study, the current knowledge for each of these five aspects of kidney stone formation is reviewed. This knowledge may be used to explore novel research opportunities and improve the understanding of the initiation and development of kidney stones for urologists, nephrologists and primary care.

Effect of magnesium ammonium phosphate on the expression of adhesion molecules in sheep renal tubular epithelial cells.

Adhesion molecules play an important role in urinary calculus formation. The expressions of adhesion molecules in renal tubular has been reported in some animals. However, the role of adhesion molecules in the process of sheep urinary calculus formation is still unclear. The magnesium ammonium phosphate (MAP) is the main component of sheep urinary calculus. In this paper, the sheep renal tubular epithelial cells (RTECs) were isolated and treated with MAP, the expressions of osteopontin (OPN), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and apoptosis-related indicators caspase-3, Bcl-2 and Bax in RTECs were observed, the viability of RTECs was detected by Cell Counting Kit-8 (CCK-8). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and the expressions of inflammatory factors Interleukin-6 (IL-6), Interleukin-1 (IL-1), Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent (ELISA). The histopathological observation of kidney in urolithiasis sheep was made. The results showed that MAP could reduce the viability and SOD activity, enhance the activity of MDA significantly and promote the expressions of IL-1, IL-6, IL-17 and TNF-α of RTECs. By western blot and qPCR methods, the expressions of ICAM-1, VCAM-1 and OPN increased in 48 h. In addition, the expression of caspase-3 increased significantly and the ratio of Bcl-2/Bax reduced with exposure to MAP. The renal tissue structure was seriously damaged, the RTECs in urolithiasis sheep were degenerative and necrotic.

Factors associated with hematuric struvite crystalluria in cats.

OBJECTIVES: The aim of the study was to identify any dietary, signalment, geographic and clinical factors associated with hematuric struvite crystalluria (HSC) in a population of cats that visit general care veterinary hospitals in the USA. METHODS: In total, 4032 cats that had a first-time diagnosis of HSC and 8064 control cats with no history of hematuria or crystalluria were identified from medical records of all cats examined between 2007 and 2011 at 790 US veterinary hospitals. Extracted variables included age, sex, neuter status, breed, diet, urinalysis results and history of cystitis. Potential associations between these variables and HSC were estimated. RESULTS: Controlling for other factors, young cats fed a dry diet had an increased likelihood of HSC relative to young cats fed a non-dry diet. However, as age increased, the likelihood of HSC declined for cats fed a dry diet and increased for cats fed a non-dry diet. Moreover, the odds of HSC were significantly greater when cats were unneutered (vs neutered; odds ratio [OR] 45.52) or had a thin (vs heavy) body condition (OR 23.81), diagnosis of cystitis (OR 2.84), urine protein concentration >30 mg/dl (OR 4.72), alkaline (vs neutral) urine pH (OR 3.34), pyuria (OR 23.67) or bacteriuria (OR 2.24). CONCLUSIONS AND RELEVANCE: The present study provides estimates of the strengths of association between HSC and certain signalment and clinical characteristics of cats. This information could help clinicians to perform a more directed screening for struvite crystalluria in certain cat populations. Follow-up studies that build on the findings of this study could explore the clinical importance of HSC in cats.