oxalates and Insulin-Resistance

Epidemiologically, there are many same characteristics among patients with urolithiasis, life-style related diseases and metabolic syndrome. In a comparison with the major urological diseases, the patients with stone disease have the largest amount of visceral fat on computerized tomography. The patients who finally had a diagnosis of metabolic syndrome in urolithiasis were 43% of men and female 31%. The clinical features of the patients include increased urinary oxalate excretion, abnormal uric acid metabolism, and acidic urine. The basic studies by the animal experiments suggest that there is a close relationship between urolithiasis and metabolic syndrome. After the treatment of the urinary stone, it is very important to make a long-term follow-up by not only the prevention of recurrent stone episode but also life style management and medical treatment for metabolic syndrome.

Topics: Animals; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Life Style; Male; Metabolic Syndrome; Oxalates; Uric Acid; Urinary Calculi

Ob/ob mice have recently emerged as a model for obesity-related hyperoxaluria as they are obese and excrete more urine oxalate compared to wild type mice. Ob/ob mice are deficient of leptin and develop obesity with hyperphagia and hyperinsulinemia. We hypothesized that insulin resistance and the gut microbiome contribute to hyperoxaluria in ob/ob mice. We developed a new liquid chromatography-mass spectrometry assay for urine oxalate and first compared urine oxalate excretion in ob/ob mice before and after ablation of intestinal bacteria with a standard antibiotic cocktail. We then compared urine oxalate excretion in ob/ob mice before and after leptin replacement or pioglitazone treatment, two maneuvers that reduce insulin resistance in ob/ob mice. Ob/ob mice excreted more oxalate into the urine in a 24-h period compared to wild type mice, but antibiotic, leptin, or pioglitazone treatment did not change urine oxalate excretion in ob/ob mice. Unexpectedly, we found that when food intake was carefully matched between ob/ob and wild type mice, the amount of 24-h urine oxalate excretion did not differ between the two mouse strains, suggesting that ob/ob mice excrete more urine oxalate because of hyperphagia. Since the level of urine oxalate excretion in wild type mice in our study was higher than those reported in prior studies, future work will be needed to standardize the measurement of urine oxalate and to define the range of urine oxalate excretion in wild type mice so that accurate and valid comparisons can be made between wild type mice and ob/ob mice or other mouse models.

Topics: Animals; Anti-Bacterial Agents; Gastrointestinal Microbiome; Hyperoxaluria; Hyperphagia; Insulin Resistance; Leptin; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Obese; Obesity; Oxalates; Pioglitazone

This study sought to explore the influence of different body weight statuses on 24-hour urine compositions in adults without urolithiasis based on a nationwide study of a Chinese Han population.. Twenty-four-hour urine samples from 584 Chinese Han adults without urolithiasis in six cities were analyzed. The participants were divided into four body weight status types according to their body mass indices (BMIs) according to WHO guidelines. The baseline characteristics and 24-hour urine compositions of the standard weight group were compared with those of the underweight, overweight and obese groups. The influences of different body weight statuses on the 24-hour urine compositions were explored using univariate and multivariate logistic regressions.. The numbers of participants in the underweight, standard weight, overweight and obese status groups were 24, 376, 149 and 35, respectively. The overweight and obese groups suffered significantly higher risks of hypertension and diabetes mellitus than the standard weight group. In the univariate analyses, compared with the standard weight group, the overweight group had significantly higher levels of urine citrate (mean difference [MD] = 0.51 mmol, 95% confidence interval [CI]: 0.15-0.87, P = 0.001), potassium (MD = 6.63 mmol, 95% CI: 1.13-12.14, P = 0.01) and magnesium (MD = 0.38 mmol, 95% CI: 0.08-0.69, P = 0.014). Significant increases in urine citrate (MD = 0.85 mmol, 95% CI: 0.01-1.68, P = 0.046), magnesium (MD = 0.69 mmol, 95% CI: 0.13-1.25, P = 0.016) and phosphate (MD = 2.28 mmol, 95% CI: 0.03-4.54, P = 0.047) were found in the obese group. No significant differences were detected between the standard weight and underweight groups. In the multivariate logistic regression analyses, we only observed significantly higher levels of urine potassium (odds ratio [OR] = 1.02, 95% CI: 1.00-1.04, P = 0.03) in the overweight group and phosphate (OR = 1.32, 95% CI: 1.05-1.66, P = 0.018) in the obese group when compared with the standard weight group.. Nonstone-forming adults with overweight or obese statuses were at higher risks of hypertension and diabetes mellitus. Obese nonstone-formers might have a greater risk of urinary stone formation due to increased urinary phosphate excretion. Additionally, underweight status had no influence on 24-hour urine composition.

Topics: Adult; Body Mass Index; Body Weight; Calcium; China; Citric Acid; Humans; Insulin Resistance; Logistic Models; Middle Aged; Multivariate Analysis; Obesity; Overweight; Oxalates; Sodium; Uric Acid; Urolithiasis

Urinary excretion of oxalate is one of risk factors in urinary stone formation. Prevention of undesirable overflow into the production of oxalate definitely leads to a decrease of urolithiasis. The activity of serine : pyruvate/alanine : glyoxylate aminotransferase (SPT/AGT) or glyoxylate reductase/hydroxypyruvate reductase (GRHPR), the key enzyme of primary hyperoxlauria type 1 and 2, respectively, and their subcellular distribution highly affects the oxalate production. On the other hand, urolithiasis is tightly related to lifestyle disease, such as diabetes mellitus and insulin resistance. The hypothesis that insulin resistance induces mitochondria dysfunction, resulting in the decrease of mitochondria-related enzyme activity is a very attractive new treatment strategy of urolithiasis. Namely, the improvement of insulin resistance might prevent stone formation.

Topics: Humans; Insulin Resistance; Life Style; Oxalates; Urolithiasis

Recent epidemiological studies revealed an association of obesity, diabetes mellitus, hypertension and metabolic syndrome (MetS) with kidney stone disease. We examined how these disorders cause kidney stones. A clinical study on 467 patients with nephrolithiasis at our institution revealed that clustering of MetS traits increased the risk of uric acid stone formation by decreasing urinary pH. A subsequent study analyzing detailed data from 30,448 patients enrolled in the 6th Nationwide Survey on Urolithiasis in Japan showed that clustering of MetS traits were associated with an increased severity of the kidney stone disease and elevated urinary excretion of calcium, uric acid and oxalate. Finally, the OLETF rats, an animal model of MetS, showed lower urinary pH, decreased citrate excretion, and increased uric acid and calcium excretion. In addition, the administration of pioglitazone, an agent that improves insulin resistance, significantly increased the urinary pH. These results indicate that MetS causes changes in urinary constituents, leading to an increased risk of both uric acid and calcium oxalate stone formation. We suggest that kidney stone disease should be considered as a component of MetS and that the improvement in insulin resistance by means of diet and lifestyle changes and medical therapy might help to prevent this disorder.

Topics: Animals; Calcium; Humans; Hydrogen-Ion Concentration; Insulin Resistance; Metabolic Syndrome; Nephrolithiasis; Oxalates; Rats; Uric Acid; Urine

Fructose consumption has markedly increased over the past decades. This intake may increase the urinary excretion of calcium, oxalate, uric acid, and other factors associated with kidney stone risk. We prospectively examined the relationship between fructose intake and incident kidney stones in the Nurses' Health Study I (NHS I) (93,730 older women), the Nurses' Health Study II (NHS II) (101,824 younger women), and the Health Professionals Follow-up Study (45,984 men). Food frequency questionnaires were used to assess free fructose and sucrose intake every 4 years. Total-fructose intake was calculated as free fructose plus half the intake of sucrose, and expressed as percentage of total energy. Cox proportional hazard regressions were adjusted for age, body mass index (BMI), thiazide use, caloric intake, and other dietary factors. We documented 4902 incident kidney stones during a combined 48 years of follow-up. The multivariate relative risks of kidney stones significantly increased for participants in the highest compared to the lowest quintile of total-fructose intake for all three study groups. Free-fructose intake was also associated with increased risk. Non-fructose carbohydrates were not associated with increased risk in any cohort. Our study suggests that fructose intake is independently associated with an increased risk of incident kidney stones.

Topics: Adult; Diet; Female; Fructose; Humans; Insulin Resistance; Kidney Calculi; Magnesium; Middle Aged; Oxalates; Prospective Studies; Risk Factors