Generation of a GLO-2 deficient mouse reveals its effects on liver carbonyl and glutathione levels.

OBJECTIVE: Hydroxyacylglutathione hydrolase (aka as GLO-2) is a component of the glyoxalase pathway involved in the detoxification of the reactive oxoaldehydes, glyoxal and methylglyoxal. These reactive metabolites have been linked to a variety of pathological conditions, including diabetes, cancer and heart disease and may be involved in the aging process. The objective of this study was to generate a mouse model deficient in GLO-2 to provide insight into the function of GLO-2 and to determine if it is potentially linked to endogenous oxalate synthesis which could influence urinary oxalate excretion. METHODS: A GLO-2 knock out mouse was generated using CRISPR/Cas 9 techniques. Tissue and 24-h urine samples were collected under baseline conditions from adult male and female animals for biochemical analyses, including chromatographic measurement of glycolate, oxalate, glyoxal, methylglyoxal, D-lactate, ascorbic acid and glutathione levels. RESULTS: The GLO-2 KO animals developed normally and there were no changes in 24-h urinary oxalate excretion, liver levels of methylglyoxal, glyoxal, ascorbic acid and glutathione, or plasma d-lactate levels. GLO-2 deficient males had lower plasma glycolate levels than wild type males while this relationship was not observed in females. CONCLUSIONS: The lack of a unique phenotype in a GLO-2 KO mouse model under baseline conditions is consistent with recent evidence, suggesting a functional glyoxalase pathway is not required for optimal health. A lower plasma glycolate in male GLO-2 KO animals suggests glyoxal production may be a significant contributor to circulating glycolate levels, but not to endogenous oxalate synthesis.

Obesity and Its Impact on Kidney Stone Formation.

The prevalence of obesity is rising and places this cohort at risk for developing kidney stones. Some of the pathophysiologic responses that link obesity and kidney stone formation have been identified. Herein, we review the involved mechanisms driving this relationship and the impact of various weight loss strategies on kidney stone risk.

Obesity and Kidney Stone Procedures.

Obesity is a chronic disease that has increased in prevalence in the United States and is a risk factor for the development of nephrolithiasis. As with other medical conditions, obesity should be considered when optimizing surgical management and choosing kidney stone procedures for patients. In this review, we outline the various procedures available for treating stone disease and discuss any discrepancies in outcomes or complications for the obese cohort.

Impact of Demographic Factors and Systemic Disease on Urinary Stone Risk Parameters Amongst Stone Formers.

This article examines via multivariate analysis the associations between demographic factors and systemic diseases on stone risk parameters in a stone-forming population. A retrospective chart review of adult stone formers who completed 24-hour urine collections from April 2004 through August 2015 was performed. Data was collected on age, sex, race, body mass index (BMI), and diagnoses of diabetes and hypertension. CT imaging and renal/abdominal ultrasonography (within ± 66 mo) were reviewed for diagnosis of fatty liver disease. Statistical analysis included Pearson and Spearman correlation analysis, and linear and logistic regression analyses, both univariate and multivariate. Five hundred eighty-nine patients were included. Numerous urinary parameters were significant in association with demographic factors or systemic diseases in a multivariate analysis. Older age was associated with decreased calcium (Ca) excretion (P = 0.0214), supersaturation of calcium oxalate (SSCaOx; P = 0.0262), supersaturation of calcium phosphate (SSCaP; P < 0.0001), and urinary pH (P = 0.0201). Men excreted more Ca (P = 0.0015) and oxalate (Ox; P = 0.0010), had lower urine pH (P = 0.0269), and higher supersaturation of uric acid (SSUA; P < 0.0001) than women. Blacks had lower urine volume (P = 0.0023), less Ca excretion (P = 0.0142), less Ox excretion (P = 0.0074), and higher SSUA (P = 0.0049). Diabetes was associated with more Ox excretion (P < 0.0001), lower SSCaP (P = 0.0068), and lower urinary pH (P = 0.0153). There were positive correlations between BMI and Ca excretion (P = 0.0386), BMI and Ox excretion (P = 0.0177), and BMI and SSUA (P = 0.0045). These results demonstrate that demographic factors and systemic disease are independently associated with numerous risk factors for kidney stones. The mechanisms responsible for these associations and disparities (racial differences) need to be further elucidated.