Estimated excretion and clearance of uric acid as optimal surrogate indices for daily urinary uric acid excretion.

OBJECTIVES: Daily uric acid excretion is an essential index for patients with gout/hyperuricemias. We identified alternative indices most correlated with 24-hour uric acid clearance (Cua 24h) and 24-hour uric acid excretion (Eua 24h) using data from the reference interval of urinary clearance and excretion of urate study. METHODS: The subjects were indoor workers aged 20 to 65 who met the Clinical and Laboratory Standards Institute Guidelines C28-A3c. Alternative indices using spot urine were urine uric acid creatinine ratio, uric acid clearance - creatinine clearance ratio (Cua/Ccr), uric acid excretion - creatinine clearance ratio (Eua/Ccr), estimated uric acid clearance (eCua), and estimated uric acid excretion (eEua). eCua and eEua are the values obtained by multiplying Cua/Ccr and Eua/Ccr by the estimated glomerular filtration rate. RESULTS: The final number of subjects analyzed was 739. Among the indices using spot urine, eCua and eEua showed the highest correlation with Cua 24h and Eua 24h, respectively. Compared with Cua 60min and Eua 60min obtained from 60-minute urine collection, eCua and eEua showed lower root means squared error, lower bias, and significantly higher accuracy of within 30% and within 15%. CONCLUSIONS: The newly proposed eCua and eEua may be appropriate from a practical perspective.

The Association between Urinary Glucose and Renal Uric Acid Excretion in Non-diabetic Patients with Stage 1-2 Chronic Kidney Disease.

Aims: To test the hypothesis that in non-diabetic patients with early-stage chronic kidney disease (CKD), the renal excretion of urate and glucose transportation are coupled and interconnected. Methods: A cross-sectional study of 255 non-diabetic participants with stage 1-2 CKD recruited from our department was conducted. Spearman's correlation and multiple linear regression analyses were used to study the correlation between urinary glucose and renal uric acid excretion. ANOVA was used to compare urinary uric acid excretion among three tertiles of urinary glucose (UG; UG1: UG<0.24 mmol/24 h/1.73 m2, UG2: 0.24 mmol/24 h/1.73 m2≤ UG≤0.55 mmol/24 h/1.73 m2, and UG3: UG>0.55 mmol/24 h/1.73 m2), the fractional excretion of glucose (FEG; FEG1: FEG<0.04%, FEG2: 0.04%≤FEG≤0.09%, and FEG3: FEG>0.09%) and the excretion of glucose per volume of glomerular filtration (EgGF; EgGF1: EgGF<1.95 µmol/L, EgGF2: 1.95 µmol/L≤ EgGF≤3.99 µmol/L, and EgGF3: EgGF>3.99 µmol/L). Results: According to the multiple linear regression analysis, FEG and EgGF were positively correlated with the excretion of uric acid per volume of glomerular filtration (EurGF) after adjusting for confounding factors. The EurGF levels in the highest tertiles of UG, FEG and EgGF were higher than those in the lowest tertiles of UG, FEG and EgGF. Conclusion: Urinary glucose excretion is closely related to renal excretion of uric acid in non-diabetic patients with stage 1-2 CKD.

Circulating leptin is associated with serum uric acid level and its tubular reabsorption in a sample of adult middle-aged men.

PURPOSE: Leptin is associated with cardiovascular risk factors (e.g. hypertension, insulin resistance, kidney disease and excess body weight). Experimental studies showed that leptin might affect serum uric acid, by modulation of the uric acid excretion. However, there are few observational data on the relationship between leptin and uric acid in the general population. Therefore, the aim of the present study was to evaluate the relationship between leptin and uric acid and its excretion in a large middle-aged male general population. METHODS: A sample of 930 adult male individuals (mean age: 52 years) without therapy for high uric acid was included in the analysis (the Olivetti Heart Study). RESULTS: Uric acid was significantly and positively associated with blood pressure, BMI, waist circumference, insulin resistance, C-reactive protein and leptin (p < 0.01), while inversely with renal function (p = 0.01). The multivariate analysis confirmed the association between leptin and uric acid after adjustment for potential confounders (p < 0.01). After division for adiposity, this trend was confirmed separately for normal weight and excess body weight participants. Moreover, leptin was inversely associated with excretion of uric acid (p < 0.01), also in multivariate analysis (p = 0.03). CONCLUSION: The results of this study indicate a positive association between circulating leptin levels and uric acid, independently of potential confounders, both in normal and excess body weight men. Furthermore, an inverse association between leptin and uric acid excretion was detected.

The Time-Feature of Uric Acid Excretion in Hyperuricemia Mice Induced by Potassium Oxonate and Adenine.

Hyperuricemia is an important risk factor of chronic kidney disease, metabolic syndrome and cardiovascular disease. We aimed to assess the time-feature relationship of hyperuricemia mouse model on uric acid excretion and renal function. A hyperuricemia mouse model was established by potassium oxonate (PO) and adenine for 21 days. Ultra Performance Liquid Chromatography was used to determine plasma uric acid level. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and Western blot was used to detect renal urate transporters' expression. In hyperuricemia mice, plasma uric acid level increased significantly from the 3rd day, and tended to be stable from the 7th day, and the clearance rate of uric acid decreased greatly from the 3rd day. Further study found that the renal organ of hyperuricemia mice showed slight damage from the 3rd day, and significantly deteriorated renal function from the 10th day. In addition, the expression levels of GLUT9 and URAT1 were upregulated from the 3rd day, while ABCG2 and OAT1 were downregulated from the 3rd day, and NPT1 were downregulated from the 7th day in hyperuricemia mice kidney. This paper presents a method suitable for experimental hyperuricemia mouse model, and shows the time-feature of each index in a hyperuricemia mice model.

[Inluence of osteoporosis and its causative factors on the prevention of recurrence of urinary stone disease].

INTRODUCTION: The aim of postoperative examination, treatment and follow-up of patients with urinary stone disease is a prevention of recurrence. A choice of method of prevention is based on the results of postoperative examination with consideration of etiological factors of urinary stone disease. An analysis of influence of osteoporosis and its causative factors on the recurrence of urinary stone disease is presented in the article. AIM: to clarify the influence of osteoporosis and its causative factors on excretion of calcium, uric acid and recurrence of urinary stone disease. MATERIALS AND METHODS: A total of 86 patients after surgical treatment of urinary stone disease were included in the study. A physicochemical analysis of stones and their fragments, excretion of calcium and uric acid were done postoperatively. The risk factors for osteoporosis were identified using specific questionnaire. Bone mineral density (BMD) was assessed by X-ray densitometry. After X-ray phasic analysis of the stones and studying of the daily excretion of calcium and uric acid, 10 and 7 patients were prescribed to thiazide diuretics and allopurinol, respectively. In 69 patients (80.2%) there were no indications to the treatment and all of them were included in control surveillance group. RESULTS: Calcium oxalate stones were predominated in patients who were under surveillance (=0,0254). A prevalence of risk factors for osteoporosis was similar in all groups (=0,2156), as well as rate of decrease in BMD (=0,64). In patients taking thiazide diuretics, a significant decrease in daily calcium excretion was found (=0,0054) without significant changes in excretion of uric acid and diuresis volume. Among patients receiving allopurinol there was a significant decrease in daily uric acid excretion (=0,021), without significant changes in excretion of calcium and diuresis volume. There were no significant changes of these values in the control group. A recurrence of urinary stone disease in treatment group was detected in 4 patients with a decrease of BMD after 381+/-61 days, while in control group there were 5 recurrences in patients with decreased BMD and I recurrence in patient with normal BMD after 836+/-64 days. CONCLUSION: Treatment aimed at prevention of recurrence of urinary stone disease allows to correct detected metabolic disturbances. However, such factor as the decrease in BMD can influence on the rate and frequency of recurrence of urinary stone disease. A clarifying of risk factors for osteoporosis and diagnosis of osteoporosis allow to give reliable recommendations for its treatment and to decrease risk of recurrence of urinary stone disease.

The Association of Urinary Sodium and Potassium with Renal Uric Acid Excretion in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Hypertension and hyperuricemia are closely associated with an intermingled cause and effect relationship. Additionally, urinary sodium and potassium excretion is related to blood pressure. Whether or not it is associated with urinary uric acid excretion is not clear. Therefore, we aim to study the association of urinary sodium and potassium with renal uric acid excretion in patients with CKD. METHODS: A cross-sectional study of 428 patients with CKD recruited from our department was conducted. All patients were divided into hypertension and non-hypertension group. In these two groups, Spearman correlation and multiple linear regression analysis were used to study the correlation of urinary sodium and potassium with renal handling of uric acid. RESULTS: According to multiple linear regression analysis, in hypertension group, fractional excretion of sodium (FEna) was negatively correlated with 24 hour urinary uric acid (24-hUur) and uric acid clearance rate (Cur) (beta coefficients [B]=-0.066, -0.182, respectively; both P< 0.05), and positively correlated with fractional excretion of uric acid (FEur) (B=1.641, P< 0.001). Additionally, fractional excretion of potassium (FEk) was positively correlated with FEur (B=0.576, P< 0.001), but not related to 24-hUur and Cur (both P>0.05). And urinary sodium/potassium ratio (Una/k) was negatively related to 24-h Uur and Cur (B=-0.047, -0.159, both P< 0.05), and positively related to FEur (B=0.578, P< 0.05). Furthermore, FEna and FEk was still positively related to FEur in the lowest tertile of eGFR groups (both P< 0.05), but not related in the second and highest tertile of eGFR groups (all P> 0.05). In non-hypertension group, FEna was negatively correlated with 24-hUur (B=-0.589, P< 0.05), but not related to Cur and FEur (both P> 0.05). both FEk and Una/k was not related to 24-h Uur, Cur and FEur (all P> 0.05). Moreover, FEna and FEk was still not correlated with FEur in all tertiles of eGFR groups (all P> 0.05). CONCLUSION: We found that in patients with CKD, urinary sodium and potassium excretion is closely correlated to renal handling of uric acid, which was pronounced in hypertensive patients with low eGFR. This phenomenon may be one of the mechanisms of the relationship between hypertension and hyperuricemia. Further research is needed to confirm it. It is expected to manage hyperuricemia in terms of controlling the diet of sodium and potassium.

Urinary excretion of uric acid is negatively associated with albuminuria in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Increasing evidence has shown that albuminuria is related to serum uric acid. Little is known about whether this association may be interrelated via renal handling of uric acid. Therefore, we aim to study urinary uric acid excretion and its association with albuminuria in patients with chronic kidney disease (CKD). METHODS: A cross-sectional study of 200 Chinese CKD patients recruited from department of nephrology of Huadong hospital was conducted. Levels of 24 h urinary excretion of uric acid (24-h Uur), fractional excretion of uric acid (FEur) and uric acid clearance rate (Cur) according to gender, CKD stages, hypertension and albuminuria status were compared by a multivariate analysis. Pearson and Spearman correlation and multiple regression analyses were used to study the correlation of 24-h Uur, FEur and Cur with urinary albumin to creatinine ratio (UACR). RESULTS: The multivariate analysis showed that 24-h Uur and Cur were lower and FEur was higher in the hypertension group, stage 3-5 CKD and macro-albuminuria group (UACR> 30 mg/mmol) than those in the normotensive group, stage 1 CKD group and the normo-albuminuria group (UACR< 3 mg/mmol) (all P < 0.05). Moreover, males had higher 24-h Uur and lower FEur than females (both P < 0.05). Multiple linear regression analysis showed that UACR was negatively associated with 24-h Uur and Cur (P = 0.021, P = 0.007, respectively), but not with FEur (P = 0.759), after adjusting for multiple confounding factors. CONCLUSIONS: Our findings suggested that urinary excretion of uric acid is negatively associated with albuminuria in patients with CKD. This phenomenon may help to explain the association between albuminuria and serum uric acid.

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

BACKGROUND: A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. METHODS: We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. RESULTS: Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. CONCLUSIONS: Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia.

Intestine-Targeted Explosive Hydrogel Microsphere Promotes Uric Acid Excretion for Gout Therapy.

Uric acid metabolism disorder triggers metabolic diseases, especially gout. However, increasing uric acid excretion remains a challenge. Here, an accelerative uric acid excretion pathway via an oral intestine-explosive hydrogel microsphere merely containing uricase and dopamine is reported. After oral administration, uricase is exposed and immobilized on intestinal mucosa along with an in situ dopamine polymerization via a cascade reaction triggered by the intestinal specific environment. By this means, trace amount of uricase is required to in situ up-regulate uric acid transporter proteins of intestinal epithelial cells, causing accelerated intestinal uric acid excretion. From in vitro data, the uric acid in fecal samples from gout patients could be significantly reduced by up to 37% by the mimic mucosa-immobilized uricase on the isolated porcine tissues. Both hyperuricemia and acute gouty arthritis in vivo mouse models confirm the uric acid excretion efficacy of intestine-explosive hydrogel microspheres. Fecal uric acid excretion is increased around 30% and blood uric acid is reduced more than 70%. In addition, 16S ribosomal RNA sequencing showed that the microspheres optimized intestinal flora composition as well. In conclusion, a unique pathway via the intestine in situ regulation to realize an efficient uric acid intestinal excretion for gout therapy is developed.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.