Urinary Uric Acid Excretion Research Articles

Hyponatremia with Persistent Elevated Urinary Fractional Uric Acid Excretion: Evidence for Proximal Tubular Injury?

Background/Aims: Hyponatremia associated with high urinary fractional excretion of uric acid which persists after serum sodium is corrected is the cardinal feature of salt losing nephropathy (SLN). We hypothesize that low grade proximal tubular injury is present in SLN because the proximal tubule is the main site of uric acid and sodium transport. Methods: Five subjects with SLN were compared to four subjects with recurrent hyponatremia and three healthy individuals. Urinary NGAL (neutrophil gelatinase associated lipocalin, a marker of tubular injury) and fasting urinary fructose levels (a marker of proximal tubular injury) were measured. Results: Subjects with SLN (n=5) showed elevated fractional uric acid excretion (22 ± 6 vs 4 ± 2 percent, p<0.0001), elevated urinary NGAL levels (62 ± 37 vs 9 ± 7 ng/mg creatinine, p=0.001) and fasting urinary fructose levels compared with the 7 controls (383 ± 465 vs 60 ± 34µmole/µg creatinine, p <0.001). A strong correlation between urinary NGAL levels and urinary fructose levels was observed (r =0.87, p‹0.001). Conclusion: High urinary fractional excretion of uric acid in SLN is associated with elevated NGAL and fasting urinary fructose levels suggesting that SLN may involve tubular injury.

Metabolic Evaluation in Paediatric Urolithiasis: A 4-Year Open Prospective Study.

Children with urolithiasis are associated with considerable morbidity and commonly associated with metabolic abnormalities. By treating these abnormalities stone formation is prevented. To study the metabolic risk factors of urolithiasis in children and compare them with literature. In open, prospective and observational study, 75 children were evaluated from August 2010 to June 2014. In all patients' dietary history, water intake and results of laboratory findings were recorded. All urine samples obtained from patients were without dietary restrictions. Reference paediatric 24 hour urinary parameter was used according to western literature. We investigated 75 patients with urolithiasis. Low urine volume was found in 49 patients which is comparable with previous studies indicating simple intervention as to increase water intake. Low calcium intake was found in 44 patients suggesting that low calcium intake is associated with higher incidence of urolithiasis due to increased intestinal oxalate absorption. Hypocalcaemia was found in 32 patients and 24 hour urinary abnormality was found in only 16 patients'. Both these finding does not support previous literature. Stone analysis finding does not correlate with urinary finding. Low urine volume secondary to low water intake is predominant finding. Hypocalcaemia is major metabolic abnormality in contradiction to western literature. There are no nomograms for urinary excretion of Calcium, uric acid, oxalate and citrate in Indian children. Keeping the optimum blood calcium level & increased fluid intake can prevent stone formation in children.

Influence of non-alcoholic malt beverages on urinary excretions of calcium and uric acid

Background and objective: Malt beverage without alcohol (Barbican) is an energy beverage which is regularly consumed by Muslim countries and substantial quantities are exported to the Gulf States and Middle East countries. Barbican is used widely by people whom alcohol is forbidden either on medical grounds or on religious aspects. The aim of this study was to assess the effect of short-term drinking of Barbican on urinary excretion of calcium and uric acid in normal young males in Erbil city. Methods: Thirty healthy male volunteer subjects of 21-23 years age consumed 330 ml of Barbican® beverage per day for two successive days after cross design. The urinary calcium and urinary uric acid were evaluated before and after consumption. Results: There was no statistically significant increase in urinary uric acid before and after consumption of Barbican beverage (P = 0.071). Urinary calcium significantly decreased after consumption of Barbican drink (P = 0.037). Conclusion: Although many extrinsic and intrinsic factors influence formation of kidney stones and bone resorption, this study suggests that drinking of Barbican beverage may be helpful to prevent bone resorption and also to reduce risk of stone formation.

Evaluation of citraturia and calcium/citrate ratio in nephrolithiasis patients. The continuous versus interval saga

Introduction: Despite the progress in the pathogenesis of nephrolithiasis, the individual risk assessment of formation and recurrence of kidney stones by measuring risk factors in 24-hour urine is often difficult. Our objective was to evaluate urinary risk factors associated with nephrolithiasis, particularly citraturia and the calcium/citrate ratio in recurrent kidney stones formers and in subjects without nephrolithiasis. Methods: 103 kidney stone formers (30 men and 73 women) and 32 non-stone subjects (11 men and 21 women) were retrospective studied. Clinical and laboratory data were collected from every subject. Results: There was no difference in age between the groups (44.4±11.8 years and 43.3±17 years). In urine, volume, calcium (189.6±98.7 vs. 150.7±107.3, p=0.029), sodium and oxalate (33.7±28.2 vs. 22.2±15.3, p=0.041) were higher in kidney stones when compared to control subjects. Urinary excretion of uric acid and citrate was similar in both groups, with no significant differences. For the cohort of stone formers patients, but not for healthy subjects, there was a positive correlation between calcium and citrate excretion in urine (r=0.41, p<0.001). When utilizing the calcium/citrate ratio to differentiate stone and non-stone formers subjects, we could not find any difference. Conclusion: For the kidney stone formers, the assessment of risk factors by 24-hour urine needs to be categorized as continuous and not as interval variables. Prospective studies are necessary to determine the normal range of daily citraturia and to evaluate the role of isolated hypocitraturia in the incidence, prevalence and clinical course of kidney stone formation

Age and gender-associated metabolic characteristics of urinary stone patients

The aim of the present study was to investigate sex- and age-associated clinico-metabolic characteristics of urinary stone patients. A retrospective review was performed on data from 2,009 consecutive patients presenting with their first urinary stone episode between 2005 and 2013. Of the 2,009 patients, 1,426 (71.0%) satisfied the inclusion criteria and were enrolled in the study. Patients were grouped by age (<60, ≥60 years old) and sex. The medical history and 24 hr urinary chemistry results of each patient were obtained. The mean age of the 165 (11.6%) patients aged 60 or over was 65.5 ± 4.2 years. Body mass index was greater in elderly females than in younger females (p=0.031). After stratification by sex and age, lower urinary excretion of calcium and uric acid was a protective factor for both sexes among the elderly (p<0.05, each, respectively). Low urine pH was a common risk factor for both sexes among the elderly (p=0.013 in males, p=0.047 in females, respectively), whereas lower citrate excretion was a risk factor for only the elderly female group (p=0.004). With regard to urinary metabolic abnormalities, elderly females showed higher incidence of hypocitraturia compared to younger females (p=0.049). In conclusion, this study demonstrated the sex- and age-associated clinico-metabolic characteristics of urinary stone patients. Thus, it is important to tailor metabolic evaluation and medical prevention therapies for patient according to sex and gender characteristics.

Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3.

Emodinol, 1β,3β,23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our research group, has been demonstrated to exhibit uricosuric activity by our previous study. The aim of this study was to evaluate the uricosuric and nephroprotective effects of emodinol and explore its possible mechanisms in potassium oxonate-induced hyperuricemic mice with renal dysfunction. Mice were orally administrated 250 mg/kg of potassium oxonate once daily for 7 consecutive days to induce hyperuricemia with renal dysfunction. Emodinol was given at doses of 25, 50, and 100 mg/kg on the same day 1 h after oxonate treatment, and allopurinol (10 mg/kg) was given as a positive control. After 1 week, serum uric acid, serum creatinine, urine uric acid, urine creatinine, blood urea nitrogen, and hepatic xanthine oxidase activity were determined. The mRNA and protein levels of urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, oncoprotein-induced transcript 3, and organic cation/carnitine transporters in the kidney were detected by real-time polymerase chain reaction and Western blot analysis. In addition, urinary and renal Tamm-Horsfall glycoprotein concentrations were examined by ELISA assays. Emodinol significantly reduced serum urate levels, increased urinary urate levels and fractional excretion of uric acid, and inhibited hepatic xanthine oxidase activity in hyperuricemic mice. Moreover, potassium oxonate administration led to dys expressions of renal urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, and oncoprotein-induced transcript 3 as well as alternations of uromodulin concentrations, which could be reversed by emodinol. On the other hand, treatment of emodinol caused upregulated expressions of organic cation/carnitine transporters, resulting in an improvement of renal function characterized by decreased serum creatinine and blood urea nitrogen levels. Emodinol exhibited hypouricemic and nephroprotective actions by inhibiting xanthine oxidase activity and regulating renal ion transporters and oncoprotein-induced transcript 3, which may be a potential therapeutic agent in hyperuricemia and renal dysfunction.

Reduction of urinary uric acid excretion in patients with proteinuria.

Serum uric acid (UA) concentration is positively associated with proteinuria. However, the relationship between proteinuria and urinary metabolites of purine metabolism remains unknown. This study developed a hydrophilic interaction chromatography (HILIC)-based HPLC method with ultraviolet detection (UV) to quantify creatinine (Cr), UA, xanthine, and hypoxanthine in human urine simultaneously. The urinary concentrations of UA and Cr obtained by our method are consistent with those measured by an autoanalyzer. The HPLC-HILIC-UV method was validated as selective and robust with simple sample preparation for measuring UA, xanthine, hypoxanthine and Cr, which is suitable for large clinical studies. The UA/Cr ratios in random urine samples were 5.5 times lower in proteinuria patients (0.077±0.008) than in healthy individuals (0.424±0.037). Moreover, the UA/hypoxanthine ratio in proteinuria patients was approximately 10 times lower than that in healthy individuals. Our findings revealed a reduced urinary UA excretion, which is one of the factors leading to increased serum UA in proteinuria patients.

Protective effect of standardized extract of Biophytum sensitivum against calcium oxalate urolithiasis in rats

ObjectiveThe present study investigated the antiurolithiatic effect of standardized methanolic extract of Biophytum sensitivum (MBS) against calcium oxalate urolithiasis in rats. MethodsThe MBS was standardized for amentoflavone content by HPLC method. Calcium oxalate urolithiasis was induced in rats by ethylene glycol–ammonium chloride feeding in drinking water. Antiurolithiatic activity of MBS was evaluated at three doses (100, 200 and 400mg/kg) in curative and preventive regimen by estimating histological changes in kidney and biochemical changes in urine, serum and kidney homogenate. Cystone (500mg/kg, p.o.) was used as reference standard drug. ResultsEthylene glycol–ammonium chloride feeding caused an increase in urinary volume, oxalate, total protein, phosphate and uric acid levels, along with a decrease in urinary excretion of calcium, magnesium and citrate. Supplementation with MBS significantly prevented change in the urinary excretion of calcium, oxalate, phosphate, total protein, uric acid, magnesium and citrate. The MBS supplementation prevented the elevation of serum creatinine, uric acid and blood urea nitrogen levels. The increased calcium, oxalate and phosphate levels in the kidney of lithiatic control rats were significantly reduced by the MBS supplementation. The MBS supplementation caused a significant decrease in the lipid peroxidation of kidney tissue. Histological study revealed minimum damage and less number of calcium oxalate deposits in the kidneys of MBS-treated rats. ConclusionsThese results indicated that the MBS reduced and prevented the growth of urinary stones. However, cystone (500mg/kg) is more effective than the MBS (400mg/kg) in alleviating the urolithiasis. This finding supports the traditional use of B. sensitivum for urolithiasis.

Effect of Antituberculous Drugs on Serum Uric Acid and Urine Uric Acid Excretion.

The aim of this study was to determine the effect of antituberculous drugs on serum uric acid (SUA), urine uric acid (UUA) excretion, and renal function. Patients with tuberculosis requiring a 6-month treatment course of antituberculous drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampicin for a further 4 months) were included in this study. Serum uric acid, 24-hour UUA excretion, uric acid clearance (UACl), serum creatinine, and creatinine clearance were determined at baseline and at the end of the second week, second month, and fourth month. Sixteen of 50 patients completed the study. Their mean ± SD baseline SUA and UACl was 4.44 ± 1.72 mg/dL and 8.77 ± 7.03 mL/min per 1.73 m, respectively. At the second week, a significant increase in SUA (9.78 ± 3.21 mg/dL, P < 0.001) and significant decrease in UACl (3.50 ± 2.50 mL/min per 1.73 m, P = 0.001) were noted. These changes persisted through the second month, but returned to baseline value at the fourth month. Thirteen patients (81.25%) had hyperuricemia. The 24-hour UUA followed the same pattern as that of UACl but showed no statistical significance. There were no changes in serum creatinine or creatinine clearance. One patient had arthralgia, and another developed tuberculous arthritis. The hyperuricemic effect of pyrazinamide and ethambutol was due primarily to a decrease in UACl, which was reversible, and had no negative effect on the renal function. Arthralgia was uncommon and required no specific treatment.

Glomerular and tubular functions in children with different forms of beta thalassemia

Background: Although there are many available data about renal involvement in patients with beta thalassemia major (TM), the changes in renal functions of other types, such as thalassemia intermedia (TI) and thalassemia minor (TMin), were reported less. Therefore, we aimed to evaluate renal tubular and glomerular functions in patients with three types of beta thalassemia. Methods: This prospective case–control study was conducted on 118 beta-thalassemia patients (49 in TM, 18 in TI and 51 TMin) and 51 healthy controls. Glomerular functions [estimated glomerular filtration rate (GFR), serum cystatin C and urinary protein creatinine ratio] and tubular functions [fractioned sodium excretion (FENa), tubular reabsorption of phosphorus, urinary excretion of uric acid, levels of retinol-binding protein, alpha-1 macroglobulin (alpha-1M), and beta-2 microglobulin, calcium creatinine ratio] were assessed in all patients and controls. Results: The mean ages of the groups and controls at presentation were similar. Although GFR was similar in all patients and control groups, serum levels of cystatin C in patients with TM and TI were significantly higher compared to TMin and controls. Alpha-1M, FENa, urinary excretion of uric acid, and urine protein/creatinine ratio in TM and TI groups were significantly higher than the others. Mean cystatin C level was also higher in patients with TMin compared the controls. However, there were no significant differences according to all tubular and other glomerular functions between TMin and control groups. Conclusions: Although all types of beta thalassemia patients should be closely monitored to prevent further decrease in renal functions, the patients with TI should be considered to have a higher risk of glomerular and tubular deterioration as well as TM.

Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication".

The effects of tofisopam, a GABA-receptor agonist, following oral administration (300mg) with and without allopurinol pretreatment on the plasma concentration and renal transport of uric acid and oxypurinol were investigated in 5 healthy subjects. Fractional and urinary excretions of uric acid were both significantly increased at 2-3 hours after tofisopam administration (559% and 459%, respectively), while plasma uric acid concentration was significantly decreased (36%) at 2.5 hours, suggesting that tofisopam affects uric acid metabolism via the tubular transport system. The hypouricemic effect of tofisopam was comparable to or greater than that of losartan and/or fenofibrate, which also have uric acid-lowering activity. In addition, with prior administration of allopurinol, the fractional and urinary excretions of oxypurinol were increased at 2-3 hours after tofisopam administration (51% and 33%, respectively), while the plasma oxypurinol concentration was significantly decreased at 1.5 and 2.5 hours (15% and 21%, respectively). Accordingly, tofisopam may be an attractive compound for treatment of hyperuricemia and/or gout, especially in patients complicated with autonomic dysfunction symptoms, though it is possible that the uric acid-lowering effect of oxypurinol is attenuated by tofisopam.

Urinary uric acid excretion as an indicator of severe hypoxia and mortality in patients with obstructive sleep apnea and chronic obstructive pulmonary disease

ObjectiveUric acid (UA) is the end product of adenosine triphosphate degradation, and could increase due to hypoxia. We investigated the association of UA metabolites with nocturnal hypoxemia, apnea-hypopnea index (AHI), noninvasive mechanical ventilation (NIMV) usage and five-year mortality. Materials/subjects and methodsWe obtained urinary specimen before and after the night polysomnography in order to measure UA excretion and overnight change in urinary UA/creatinine ratio (ΔUA/Cr) in 75 subjects (14 controls, 15 chronic obstructive pulmonary disease (COPD) without nocturnal hypoxemia (NH), 15 COPD with NH, 16 obstructive sleep apnea syndrome (OSAS) without NH, 15 OSAS with NH). Percentage of time spent below SaO2 of 90% (T90%) for >10% of sleep time was considered as nocturnal hypoxemia. Patients were contacted after 5 years with a questionnaire including information on the use of NIMV treatment (n: 58) and urinary specimen analysis (n: 35). ResultsT90% was found to be significantly correlated with UA excretion (coefficient: 0.005, 95%CI: 0.003–0.007) and ΔUA/Cr (coefficient: 0.8, 95%CI: 0.3–1.2) after adjustments for age, gender, body mass index and apnea-hypopnea index. Median and IQR (interquartile range) of baseline UA excretion were 0.79 (0.51–0.89) and 0.41 (0.31–0.55) in 10 deceased and 58 surviving patients, respectively (p=0.001). UA excretion median and IQR of baseline and 5 years of NIMV treatment were 0.41 (0.36–0.57) and 0.29 (0.23–0.37), respectively (p=0.01). ConclusionUA excretion, as a marker of tissue hypoxia, may be useful in the management of OSA and COPD patients.

SLC2A9 Genotype Is Associated with SLC2A9 Gene Expression and Urinary Uric Acid Concentration.

Objectives SLC2A9 gene variants have been associated with urinary uric acid (UA) concentration, but little is known about the functional mechanism linking these gene variants with UA. SLC2A9 encodes a UA transporter present in the proximal tubule of the kidney, and gene expression levels of SLC2A9 and other genes in the uricosuric pathway (ABCG2, SLC17A1, SLC17A3, and SLC22A12) could potentially mediate the relationship between SLC2A9 gene variants and urinary UA excretion.MethodsThe association between urinary UA concentrations and single nucleotide polymorphisms (SNPs) within the SLC2A9 gene region, expression levels of genes in the uricosuric pathway, and dietary protein intake were analyzed for a sample of non-Hispanic white participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort. The SLC2A9 SNP most significantly associated with urinary UA concentration was then tested for associations with gene expression levels from uric acid absorption/secretion associated genes. Models including interactions between dietary protein (total, animal, and vegetable) and genetic factors were also assessed.ResultsThe most significant SLC2A9 SNP associated with urinary UA (rs12509955, corrected p = 0.001) was also associated with SLC2A9 gene expression levels (corrected p = 0.0084); however, SLC2A9 gene expression levels were not significantly associated with urinary UA concentrations (p = 0.509). The interactions between rs12509955 and total dietary protein, and SLC2A9 gene-level gene expression and dietary vegetable protein on the outcome of urinary UA were marginally significant (p = 0.11 and p = 0.07, respectively). Gene expression level of one SLC2A9 transcript had a significant interaction with dietary animal protein (SLC2A9-001 ENST00000506583, p = 0.01) and a marginally significant interaction with total dietary protein (p = 0.07) on urinary UA.ConclusionOur results illustrate that SNPs in the SLC2A9 gene influence SLC2A9 gene expression as well as urinary UA excretion. Evidence is also suggestive that gene-by-diet interactions may disproportionately increase urinary UA in genetically susceptible individuals that consume higher amounts of protein.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

High urinary homoarginine excretion is associated with low rates of all-cause mortality and graft failure in renal transplant recipients

Renal transplant recipients (RTR) have an increased cardiovascular risk profile. Low levels of circulating homoarginine (hArg) are a novel risk factor for mortality and the progression of atherosclerosis. The kidney is known as a major source of hArg, suggesting that urinary excretion of hArg (UhArg) might be associated with mortality and graft failure in RTR. hArg was quantified by mass spectrometry in 24-h urine samples of 704 RTR (functioning graft ≥1 year) and 103 healthy subjects. UhArg determinants were identified with multivariable linear regression models. Associations of UhArg with all-cause mortality and graft failure were assessed using multivariable Cox regression analyses. UhArg excretion was significantly lower in RTR compared to healthy controls [1.62 (1.09-2.61) vs. 2.46 (1.65-4.06) µmol/24 h, P < 0.001]. In multivariable linear regression models, body surface area, diastolic blood pressure, eGFR, pre-emptive transplantation, serum albumin, albuminuria, urinary excretion of urea and uric acid and use of sirolimus were positively associated with UhArg, while donor age and serum phosphate were inversely associated (model R (2) = 0.43). During follow-up for 3.1 (2.7-3.9) years, 83 (12 %) patients died and 45 (7 %) developed graft failure. UhArg was inversely associated with all-cause mortality [hazard risk (HR) 0.52 (95 % CI 0.40-0.66), P < 0.001] and graft failure [HR 0.58 (0.42-0.81), P = 0.001]. These associations remained independent of potential confounders. High UhArg levels are associated with reduced all-cause mortality and graft failure in RTR. Kidney-derived hArg is likely to be of particular importance for proper maintenance of cardiovascular and renal systems.

Post-streptococcal acute glomerulonephritis complicated by gouty arthritis: a case report

Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients.

EFFECT OF LOSARTAN ON SERUM INTERLEUKIN-6 (IL-6) LEVELS IN HYPERTENSIVE PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA AT DR. MOHAMMAD HOESIN HOSPITAL PALEMBANG

Background: Hypertension and hyperuricemia are factors related to cardiovascular disease risk. Hyperuricemia is found in approximately 25% patients with hypertension while hypertension is found in 30% patients with hyperuricemia or gout. The link between hypertension and hyperuricemia theoretically explained by the effect of uric acid on renal and vascular smooth muscle cells. Hyperuricemia leads to inflammation and endothelial dysfunction. Losartan is an angiotensin renin blocker that has other effects as an anti-inflammatory and uricosuric agent. Objective: This study to determine the effect of losartan on serum IL-6 levels in hypertensive patients with asymptomatic hyperuricemia in DR. Mohammad Hoesin Hospital Palembang. Method: This study is a clinical trial before and after design. This research was conducted in the Internal Medicine Dr. Mohammad Hoesin (RSMH) Hospital Palembang began from March to August 2013. Result: Research subjects were 30 patients with 53.3% men and 46.7% women. Effect of losartan on reduction in systolic and diastolic blood pressure (146.00 ± 4.98/88.67 ± 3.45 to 126.67 ± 7.39/79.00 ± 4.02 mmHg, p = 0.000), uric acid serum (8.57 ± 1.26 to 5.94 ± 1.57 mg/dl, p = 0.000), 24-hour urinary uric acid (369.03 ± 146.49 to 510, 67 ± 231.70 mg/24 hours, p = 0.001), IL-6 serum levels is 3.27(0.48–19.8) to 2.66(0.3–17.83) pg/ ml (p = 0.015) by administration losartan potassium tablet 50 mg once daily for eight weeks. Conclusion: Losartan decreased interleukin-6, blood pressure, serum uric acid levels and increased urinary excretion of uric acid 24 hours in hypertensive patients with asymptomatic hyperuricemia significantly.

Decreased urine uric acid excretion is an independent risk factor for chronic kidney disease but not for carotid atherosclerosis in hospital-based patients with type 2 diabetes: a cross-sectional study.

BackgroundThe associations between urine uric acid excretion (UUAE) and chronic kidney disease (CKD)/atherosclerosis have not been investigated. Our aims were to investigate the relationships between UUAE and CKD and carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes.MethodsThis was a cross-sectional study that was conducted with 2627 Chinese inpatients with type 2 diabetes. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartiles according to their UUAE levels. Carotid atherosclerotic lesions, including carotid intima-media thickness (CIMT), plaque and stenosis, were assessed by Doppler ultrasound. Both CKD and carotid atherosclerotic lesions were compared between the UUAE quartile groups.ResultsAfter adjustment for confounding factors, there was a significant decrease in the prevalence of CKD in the patients with type 2 diabetes across the UUAE quartiles (16.9%, 8.5%, 5.9%, and 4.9%; p < 0.001). Multiple logistic regression analyses revealed that the UUAE quartiles were significantly and inversely associated with the presence of CKD (p < 0.001). Compared with the diabetics in the highest UUAE quartile, those in the lowest quartile exhibited a nearly 4.2-fold increase in the risk of CKD (95% CI: 2.272-7.568; p < 0.001). The CIMT value (0.91 ± 0.22 mm for the diabetics with CKD and 0.82 ± 0.20 mm for the diabetics without CKD, p = 0.001) and the prevalence of carotid plaques (62.1% for the diabetics with CKD and 41.8% for the diabetics without CKD, p = 0.025) were significantly higher in the diabetics with CKD than in those without CKD. However, there was no obvious difference in carotid atherosclerotic lesions across the UUAE quartiles after controlling for the confounding factors.ConclusionsDecreased UUAE was closely associated with the presence of CKD but not with carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. Our results suggest that UUAE is an independent risk factor for CKD in type 2 diabetes. In selected populations, such as patient with type 2 diabetes, the role of uric acid in atherosclerosis might be the result of other concomitant atherosclerotic risk factors, such as CKD.

Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice.

Hyperuricemia has been considered to be a key risk factor for kidney disease. The formation of uric acid crystals in the kidney further stimulates an intensive inflammatory response. Rhein possesses various pharmacological activities, including anti-inflammatory, antioxidative, antitumor, purgative effects, and so on. To our knowledge, no previous work has been reported about the therapeutic effect of rhein on urate nephropathy. In this study, a model of hyperuricemia and nephropathy induced by adenine and ethambutol in mice was established. Meanwhile, the potential beneficial effects and mechanisms of rhein on hyperuricemia and nephropathy were also investigated. The results demonstrated that rhein significantly decreased the serum uric acid level by inhibiting the xanthine oxidase activity and increasing the excretion of urinary uric acid. In addition, rhein also markedly improved kidney damage related to hyperuricemia. Further investigation indicated that rhein improved the symptoms of nephropathy through decreasing the production of proinflammatory cytokines, including interleukin 1β, prostaglandin E2, and tumor necrosis factor-α and inhibiting the expression of transforming growth factor-β1. The present study suggests that rhein may have a considerable potential for development as an anti-hyperuricemic and nephroprotective agent for clinical application.

Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease.

Purpose. To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method. Materials and Methods. 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. Results. Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P < 0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P < 0.05). Conclusion. Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.