Fractional Excretion Of Uric Acid Research Articles

Dynamics of Urine Electrolytes in Term Neonates during the 1st Week of Life

Abstract Background: Urine electrolyte assessment is vital for diagnosing and managing neonatal conditions. However, the challenge of urine collection in neonates has resulted in a lack of standardized urine electrolyte reference values. Aim: This study seeks to explore the reference levels and potential trends in serum and urine electrolytes to better understand how the kidneys handle these substances. Methods: Healthy neonates were prospectively enrolled following normal births. Using biochemical methods, blood and urine samples were collected and analyzed on the 1st and 5th postnatal days. Statistical analysis was performed using descriptive statistics and the Wilcoxon matched-pairs signed-rank test. Results: This prospective study enrolled 55 healthy neonates. Significant changes in serum electrolyte concentrations were observed between the 1st and 5th days after birth. Notably, sodium, creatinine, urea nitrogen, and uric acid levels decreased, whereas potassium, calcium, and phosphate levels increased. Urine analysis revealed significant increases in the tubular maximum phosphate reabsorption per glomerular filtration rate and decreases in the fractional excretion of potassium and uric acid by Day 5. Conclusion: This study challenges prevailing assumptions about the stability of neonatal urine electrolytes and highlights dynamic changes in the first postnatal week. These insights lay the groundwork for further research into electrolyte disorders in newborns and have potential implications for improving neonatal care practices.

Fractional Excretion of Urate is Positively Associated with Type 2 Diabetes in HUA Patients: A Cross-Sectional Study.

People with hyperuricemia (HUA) are often related to metabolic disorders such as diabetes, metabolic syndrome (MetS), and obesity. However, the correlation between excretion of uric acid and these diseases is unclear. Our study aimed to explore the relationship between uric acid excretion and type 2 diabetes (T2D). A total of 228 HUA patients from Tianjin Medical University General Hospital from 2022 to 2023 were included in this study. We collected demographic, biochemical, and anthropometric data on each subject. Urine uric acid excretion (UUAE) was calculated enzymatically from a single urine collection that lasted 24 hours. And fractional excretion of uric acid (FEUA) was calculated from serum uric acid and creatinine and uric acid and creatinine. Binary logistic regression modeling assessed the association between uric acid excretion and T2D. Of the 228 subjects, 13.4% had T2D and 48.7% had obesity. The obesity group had a lower FEUA (p<0.05) and a higher UUAE compared to the control group (p<0.05). And FEUA had a stronger correlation with the risk of T2D (p<0.001). Also, there was a negative association between BMI and FEUA and a positive link between BMI and UUAE in the outpatients. Increased FEUA levels were significantly associated with T2D in HUA patients. Therefore, routine calculating of FEUA is essential for proper diagnosis and appropriate treatment T2D of in HUA patients.

Association between urinary uric acid excretion and kidney outcome in patients with CKD

Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15–60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13–2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney.

Association between Regular Exercise and Urinary Uric Acid Excretion in Chinese Adults: A Cross-sectional Study

Abstract Regular exercise decreases the risk of hyperuricemia, which is related to reduced urinary uric acid excretion (UUA/UAE). However, few studies have assessed the association between regular exercise and UAE. We conducted this study to investigate their associations in the general population. This was a cross-sectional study that involved a total of 5513 Chinese community-dwellers, who reported data on physical exercise. Fasting morning spot urine was used to measure UUA and creatinine. UAE was primarily assessed by UUA to creatinine ratio (UCr) and secondly by excretion of uric acid per volume of glomerular filtration (EurGF) and fractional excretion of uric acid (FEua). Linear regression analysis was used to assess their associations. Of the included participants, their mean age was 55.1 ± 13.0 years, and 1984 (36.0%) undertook regular exercise. Compared with participants with regular exercise, those with irregular exercise or no exercise had higher UUA/UCr (0.36 ± 0.15 vs. 0.39 ± 0.15, P &lt; 0.001), EurGF (0.23 ± 0.10 vs. 0.24 ± 0.11 mg/dL, P &lt; 0.001), and FEua (0.07 ± 0.04 vs. 0.08 ± 0.04, P = 0.006). These associations remained significant after controlling for multivariable including serum uric acid (SUA) or upon the exclusion of participants with renal dysfunction or urinary tract infection. In conclusion, regular exercise might be associated with decreased UAE, independent of SUA, in Chinese community-dwellers.

The Uricosuric Effect of SGLT2 Inhibitors Is Maintained in the Long Term in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.

(1) Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) increase uric acid excretion. The intensity of uricosuria is linked to glycosuria. (2) Methods: We aim to analyze the effect of SGLT2 inhibitors on urinary fractional excretion (FE) of uric acid and glucose in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in a single-center retrospective study with patients with T2DM and CKD who started on treatment with SGLT2is. Patients on renal replacement therapy or with glucagon-like peptide-1 (GLP1) analogs were excluded. Subgroup analysis was performed according to the estimated glomerular filtration rate (eGFR), the SGLT2i molecule, the main comorbidities, and concomitant treatment. As a secondary objective, the study analyzed the effect of SGLT2 inhibitors on uricemia levels. (3) Results: Seventy-three patients were analyzed, with a mean follow-up of 1.2 years. Uric acid and glucose FE significantly increased after the initiation of SGLT2is. This increase remained stable during the follow-up without differences among eGFR groups. No significant reduction in uricemia was observed. However, a trend towards a decrease was observed. (4) Conclusion: The use of SGLT2is in patients with CKD and T2DM is associated with an increase in uric acid FE, which maintains stability irrespective of glomerular filtration loss at least during 24 months of follow-up.

Effect of Dapagliflozin on Serum Uric Acid Levels in Patients with Advanced Chronic Kidney Disease.

Objective Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are hypoglycemic agents, have been shown to be cardioprotective through a variety of mechanisms, and the effect of lowering uric acid (UA) levels may be one of the mechanisms. In the present retrospective study, we investigated the changes in serum UA levels in patients with chronic kidney disease (CKD) treated with SGLT2 inhibitors. Methods We included 31 patients with CKD who were newly started on dapagliflozin for renal protection and evaluated trends in various parameters, including serum UA levels and UA excretion from urine. Results The patients' median age was 71 years old, 20 patients were men, 7 patients had diabetes, and the median estimated glomerular filtration rate was 33.9 mL/min/1.73 m2 (CKD stage 3: 21 cases, stage 4: 10 cases). The differences in UA and fractional excretion of UA after three weeks and three months of prescription showed significantly decreased UA values and an increased fractional excretion of UA. Conclusion Our findings suggest that dapagliflozin can lower serum UA levels via increased UA excretion, even in patients with advanced CKD.

Recurrent exercise-induced acute kidney injury associated with hypouricemia: a case report and literature review

BackgroundHereditary renal hypouricemia (RHUC) is a heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA. RHUC is an important cause of exercise-induced acute kidney injury (EIAKI), nephrolithiasis and posterior reversible encephalopathy syndrome (PRES). We present here an unusual case of a patient with RHUC who presented with recurrent EIAKI and had two heterozygous mutations in the SLC2A9 gene.Case presentationA 43-year old man was admitted to our clinic because of bilateral loin pain, nausea and sleeplessness for 3 days after strenuous exercise. The laboratory results revealed increased levels of blood urea nitrogen (BUN) (15 mmol/l) and serum creatinine (Scr) (450 μmol/l), while the UA level was extremely low at 0.54 mg/dl, and his fractional excretion of urate (FE-UA) was 108%. The patient had an episode of acute kidney injury after playing soccer approximately 20 years ago, and on routine physical examination, his UA was less than 0.50 mg/dl. In view of the marked hypouricemia and high FE-UA, a diagnosis of RHUC was suspected, which led us to perform mutational screening of the SLC22A12 and SLC2A9 genes. DNA sequencing revealed no mutation in SLC22A12 gene, but two heterozygous mutations in the SLC2A9 gene.ConclusionsThis is a rare report of a patient with RHUC2 due to the mutation of SLC2A9. And this unique symptom of EIAKI and decreased or normal serum concentrations of UA warrant more attention as an early cue of RHUC.

Lessons to be learned from real life data from 98 gout patients using benzbromarone

Aim: This study aims to analyze the efficacy and safety of benzbromarone as uricosuric, in a real-life clinical setting of a retrospective hospital-based gout cohort. Methods: Data from gout patients were retrieved from the digital hospital dossiers. Demographics, clinical variables, and laboratory parameters were collected at baseline and 6 months. Efficacy was measured by reaching a serum uric acid (sUA) target &lt; 0.30 mmol/L at 6 months, and the fractional excretion of uric acid (FeUA) was used as a parameter with a potential predictor value. Results: Data from 98 gout patients were analyzed. Patients were 70 (± 12) years of age, and 90% were male. After 6 months of treatment, 68 out of 98 patients (69%) reached a sUA level &lt; 0.30 mmol/L (5 mg/dL). In patients with a FeUA &lt; 4.5%, so-called low excretors, the FeUA increase was most impressive from 3.2% (± 1.0%) to 12.1% (± 6.9%) after 6 months of benzbromarone treatment (mean increase +8.9% [95% confidence interval (CI): +6.5 to +11.5%], P &lt; 0.001). In non-low excretors, FeUA was on average 7.3% (± 5.1%) and increased to 9.7% (± 6.1%): a mean +2.1% change (95% CI: –2.2 to +6.6%). The increase differed insignificantly in low versus non-low excretors: P &gt; 0.05. Four patients stopped benzbromarone treatment because of a progressive decline in renal function, a condition that was already present before benzbromarone was initiated. Remarkably 38% of patients still using benzbromarone after 3.8 (± 3.4) years of treatment. Conclusions: Using the uricosuric benzbromarone in real-life gout patients proved effectivity in lowering sUA levels within 6 months by increasing FeUA significantly. Particularly low excretors benefit from benzbromarone treatment manipulating this mode of action. Determining FeUA in gout patients may further help to find the patient profile benefiting the most from benzbromarone treatment.

Genetic and clinical characterization of familial renal glucosuria.

Familial renal glucosuria (FRG) is a hereditary disorder caused by variants in SLC5A2 encoding sodium-glucose cotransporter 2 (SGLT2). In this study, we aimed to characterize proximal tubule solute transport, glucagon secretion and the genotype-phenotype relationship in FRG patients. We sequenced SLC5A2 and PDZK1IP1 in 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients. We built an open-source online calculator of RTG, evaluated the proximal tubule transport of amino acid, uric acid and phosphate, and explored glucagon secretion after glucose ingestion in FRG patients. We identified 12 novel SLC5A2 variants (G484D, R564W, A212S, c.574+1G>C, W649*, S592Cfs*6, Q579*, Y339*, V39F, G491E, A464E and G360D) in our cohort and yielded 111 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2mmol/L. Patients with two SLC5A2 variants had lower RTG (3.9 vs 6.2mmol/L) and higher 24-h urinary glucose excretion (24hUG) than single-variant carriers (291.0 vs 40.0mmol/1.73 m2). Patients with homozygous missense or in-frame indels had mean 24hUG of 457.2mmol/1.73 m2, comparable to those with homozygous truncating variants (445.0mmol/1.73 m2) and significantly more than those with homozygous splicing variants (196.6mmol/1.73 m2). Patients with homozygous missense variants involving conservative residues (582.0mmol/1.73 m2) had more 24hUG than those with variants at non-conservative residues (257.6mmol/1.73 m2). Four out of 14 tested patients had mild aminoaciduria. The RTG of FRG patients had no significant correlation to phosphate reabsorption but a potential negative correlation to the fractional excretion of uric acid. Postprandial suppression of glucagon secretion was absent in most FRG patients. We built a comprehensive map showing the impact of SLC5A2 variant type and variant location on glucosuria severity. Our results highlighted the role of key residues in maintaining the transport function of SGLT2 and the functional link between glucosuria and reabsorption of amino acid and uric acid in FRG patients.

THU268 Hyperuricemia In Insulin Resistance Is Associated With Increased Synthesis And Not Decreased Renal Excretion Of Uric Acid In Humans

Abstract Disclosure: R. Haykal: None. A. Kinzer: None. B. Abel: None. M. Lightbourne: None. M.S. Startzell: None. E. Cochran: None. R.J. Brown: None. Title: Hyperuricemia in insulin resistance is associated with increased synthesis and not decreased renal excretion of uric acid in humans. Background: In obesity and lipodystrophy (LD), insulin resistance (IR) is “selective”, with lack of insulin signaling causing hyperglycemia, but enhanced insulin signaling causing dyslipidemia. Rare human conditions exist in which there is extreme, non-selective IR impairing all insulin signaling pathways (e.g. mutations of the insulin receptor, INSR), resulting in hyperglycemia without dyslipidemia. We previously found that patients with non-selective IR do not have the hyperuricemia observed in selective IR. Potential mechanisms of hyperuricemia in selective IR include altered expression of renal uric acid transporters leading to impaired uric acid excretion, and increased activity of xanthine oxidoreductase (XOR), causing increased uric acid synthesis. We thus hypothesized that enhanced insulin signaling in selective IR would result in decreased fractional excretion of uric acid (FEUA) and/or increased biomarkers of XOR activity compared to non-selective IR. Method: We conducted 2 cross-sectional analyses of patients with severe IR that was either selective (due to LD) or non-selective (due to INSR mutation). Analysis 1 compared fasting insulin, fasting serum uric acid, and FEUA from 24-hr urine collection in 46 patients with LD and 13 with INSR. Analysis 2 compared products of purine nucleotide catabolism and salvage pathways by untargeted metabolomics in serum of 30 subjects each with LD and INSR. Results: In analysis 1, fasting insulin was lower in LD vs INSR (median 37.5 [25th-75th percentile 23.1-87.0] vs 88.7 [41.9-458.6] mcU/mL; P=0.0097). Serum uric acid was higher in LD vs INSR (5.3±1.6 vs 3.3±1.0 mg/dL; P=0.04). FEUA was comparable in the 2 groups (9.0±5 vs 8.5±3.5%; P=0.75). In analysis 2, uric acid was 1.6 fold higher (P&amp;lt;0.0001) in LD vs INSR. Xanthine, hypoxanthine, and xanthine to hypoxanthine ratio were comparable in both groups, but uric acid to xanthine ratio was 1.5 fold higher (P=0.01) and AMP was 0.8 fold lower in LD vs INSR (P=0.0029). Conclusion: Patients with selective IR due to LD had elevated serum uric acid, consistent with the hyperuricemia seen in selective IR due to obesity. By contrast, patients with non-selective IR due to INSR had lower serum uric acid despite higher fasting insulin. However, FEUA did not differ in these groups, thus hyperuricemia in non-selective IR might not be related to decreased renal excretion of uric acid. Elevated uric acid to xanthine ratio and lower AMP in selective IR suggest increased irreversible conversion of xanthine to uric acid by XOR, precluding salvage of purine nucleotides to AMP. Direct measurement of XOR activity in selective vs non-selective IR is needed to this potential mechanism by which insulin may lead to hyperuricemia. Presentation: Thursday, June 15, 2023

B-143 Distribution of Uricemia Levels in the Population of a Third-level Hospital. Study of the Prevalence of Hypouricemia

Abstract Hypouricemia is a serum uric acid concentration ≤2.0 mg/dL. The causes may be congenital or acquired. Despite not being recognized as a relevant biomarker, the knowledge of the importance of uric acid in redox homeostasis and the hierarchization of hyperuricemia as an independent risk factor in metabolic diseases justifies a reassessment of the significance of the state of acquired hypouricemia. We aimed to study the prevalence of hypouricemia and its relationship with the referred patients’ ages, genders, and morbidities. A descriptive, quantitative study was carried out, through the survey and analysis of biochemical records and clinical records. We worked with the database of the laboratory’s system between January and October 2019, with the data groups of adult patients (≥16 years) that included serum uric acid dosage. The concomitant biochemical parameters (Urea, creatinine, white blood cell count, glucose) were evaluated, and the diagnoses and treatments were collected in the electronic medical record. To define the prevalence, we worked with the first analysis group of each patient. All statistical analyzes were carried out with the Statistix™ software version 7. The criteria for statistical significance were P &amp;lt; 0.05. We found that of the total 159 971 data groups from January to October 2019, 17 983 were selected. There were 234 patients with hypouricemia analyzed. The prevalence of patients with hypouricemia was 2.22%. In our population, postmenopausal women did not match the distribution of uricemia levels to that of men, nor did the mean values of each distribution. Men had higher levels of uric acid than women in any age situation. The prevalence of hypouricemia agrees with what is described in the literature. Of women with hypouricemia, 39% were in the process of pregnancy. Besides that, most patients had a pathology, less than 10% were present for health control, or did not have data in the clinical record. The prevalence of oncological pathology (46%) as a comorbidity in patients with hypouricemia (oncohaematological tumors more frequent than solid ones) and diabetes (22%) was striking. Hypouricemia values were more frequent in outpatients (70%) than in hospitalized patients, however, the last ones showed lower values (1.46 ± 0.4 mg/dL vs 1.52 ± 0.35 mg/dL). The white blood cell count values (0.1–26 * 103 cells/µL) and glucose (0.3–3.76 g/L) that accompany the hypouricemia situation behold pathological values, and the urea and creatinine values were normal. Because this is a retrospective work, we do not have studies of fractional excretion of uric acid, which could delve into the causal research of hypouricemia. Further studies are needed to elucidate the causes of hypouricemia and to clarify its value in diagnosing and treating diseases.

Analysis of Clinical Characteristics of Patients with Different Types of Primary Hyperuricemia

Objective: This paper aims to study the clinical characteristics of patients with different types of primary hyperuricemia (HUA). Methods: Using a retrospective research method, 200 patients with primary HUA in the hospital from June 2020 to January 2023 were selected as the research objects. Patients were grouped according to the detection results of 24-hour urinary uric acid excretion (UUE) and fractional excretion of uric acid (FEUA) (renal insufficiency type, renal overload type, mixed type, and other types). The general information of patients in the four groups (gender, age, body mass index, living habits, etc.), underlying diseases (hypertension, diabetes), blood test results [uric acid (UA), creatinine (Cre)], urine test results (24-hour urine UA, 24-hour urine Cre) were summarized and the differences between the groups were analyzed. Results: The 200 cases of HUA patients were divided into 54.00% with renal insufficiency type, 38.50% with mixed type, 6.00% with renal overload type, and 1.50% with other types. The age of patients with mixed HUA was younger than that of patients with other types, renal overload type, and renal insufficiency type, and the difference was statistically significant (P &lt; 0.05). The UA level of patients with other types of HUA was lower than that of patients with mixed type HUA, and there was statistical significance (P &lt; 0.05). The Cre level of patients with mixed type HUA was lower than that of patients with renal insufficiency type and renal overload type, and the difference was statistically significant (P &lt; 0.05). The 24-hour urinary UA level in patients with renal insufficiency type HUA was lower than that in patients with renal overload type and mixed type HUA, and the difference was statistically significant (P &lt; 0.05). The 24-hour urinary Cre level of patients with other types of HUA was lower than that of patients with renal overload type and mixed HUA, the difference was statistically significant (P &lt; 0.05). The estimated glomerular filtration rate (eGFR) level of patients with other types of HUA was lower than that of patients with mixed type HUA, and the difference was statistically significant (P &lt; 0.05). There was no significant difference in the proportions of hypertension, diabetes, coronary heart disease, and urinary calculi among patients with renal insufficiency type, renal overload type, mixed type, and other types of HUA (P &gt; 0.05). Conclusion: The primary HUA patients are mainly of renal insufficiency type, followed by mixed type. There are significant differences in the clinical characteristics of patients with different types of HUA. Among them, patients with other types of HUA are the oldest and have the lowest uric acid levels. Patients with mixed HUA had the best renal function but the highest 24-hour urine creatinine level. This study can be used as a basis for rational selection of urate-lowering drugs for different HUA patients.

Whey protein peptides PEW and LLW synergistically ameliorate hyperuricemia and modulate gut microbiota in potassium oxonate and hypoxanthine-induced hyperuricemic rats

PEW and LLW are peptides derived from whey protein digestive products; both peptides exhibit xanthine oxidase inhibitory activity in vitro. However, it remains unclear whether these peptides can alleviate hyperuricemia (HUA) in vivo. In this study, we investigated the roles of PEW and LLW, both individually and in combination, in alleviating HUA induced by potassium oxonate and hypoxanthine. Together, PEW and LLW exhibited synergistic effects in reducing the serum levels of uric acid (UA), creatinine, and blood urea nitrogen, as well as increasing the fractional excretion of UA. The combined treatment with PEW and LLW inhibited UA synthesis, promoted UA excretion, and restored renal oxidative stress and mitochondrial damage. Moreover, the combined treatment alleviated dysbiosis of the gut microbiota, characterized by increased helpful microbial abundance, decreased harmful bacterial abundance, and increased production of short-chain fatty acids. Taken together, these results indicate that the combination of PEW and LLW mitigate HUA and kidney injury by rebalancing UA synthesis and excretion, modulating gut microbiota composition, and improving oxidative stress.

#3594 CHANGES IN ALBUMINURIA AND KIDNEY FUNCTION AFTER 8 WEEK HIGH-INTENSITY INTERVAL TRAINING PROGRAM IN 2ND AND 3RD TRIMESTER OF PHYSIOLOGICAL PREGNANCY

Abstract Background and Aims Physical exercise is the best prophylaxis of many disorders and should be continued during uncomplicated pregnancy. Several studies suggested that most pregnant women had no contraindications to perform intensive exercises. In recently published studies the beneficial effect of high-intensity interval training (HIIT) on both mental health and reduction of excessive weight gain during pregnancy has been demonstrated. The knowledge regarding kidney function after exercise in pregnancy is very scarce and only few studies concerning this topic were published. The aim of this study was to estimate changes in markers of kidney function in healthy pregnant exercising women. Changes after single intensive exercise and after 8 week training program were analyzed. Method The group of 36 women in 2nd and 3rd trimester of pregnancy were recruited to the study. At the beginning of the study all participants had normal kidney function (serum creatinine level below 0.6 mg/dl) and albuminuria (uACR below 30 mg/g) in rest. 19 women participated in 8-week HIIT program and 17 women in 8-week educational program (EDU group). Before and after 8 week training and education programs a progressive maximal exercise test on cyclometer was performed. Several biochemical measurements were performed. Results Women from both groups revealed mild changes concerning kidney function in rest, typical for physiological pregnancy (e.g. low sodium, creatinine and uric acid levels). After progressive maximal exercise test some unexpected findings were found: the fractional excretion of urea and uric acid increased (FeUrea from 41.25 to 50.05%; FeUA from 7.18 to 8.04%) and serum uric acid decreased significantly (sUA from 3.35 to 3.28mg/dL). Other changes after short exercise were typical: significant increase of uACR (from 5.12 to 9.43mg/g), serum creatinine (from 0.52 to 0.56mg/dL) and urea (from 16.45 to 21.65 mg/dL), among others. The 8-week HIIT training program did not change kidney function in rest. In both groups a significant increase of eCrCl and sUA were observed. The interesting observation was that uACR increased significantly only in EDU group. Conclusion Changes in kidney function after short intensive exercise in pregnancy were typical for healthy subjects, but there was no negative impact on markers of renal hypoperfusion. It was probably related to increased renal blood flow occurring in healthy pregnancy. The supervised 8-week HIIT training program had no negative impact on kidney function. The possible positive impact of this training on albuminuria was suggested.

Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia.

The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague-Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.

Raising Awareness Towards Underdiagnosed Renal Hypouricemia: A Case Report

Renal hypouricemia (RHUC) is an autosomal recessive disease caused by the dysfunction of uric acid (UA) transporters in the proximal tubule causing increased fractional excretion of uric acid (FEUA). It is associated with mutations of SLC22A12 that codifies for URAT1, involved in RHUC type 1, or SLC2A9 which codifies for GLUT9 and is involved in RHUC type 2. We present the case of a man diagnosed with RHUC type 2 following hospitalization for acute kidney injury (AKI). A 43-year-old was hospitalized due to AKI after a 20 km walk at an outdoor temperature of 30°C. On the objective examination, he was dehydrated. Blood tests presented severe azotemia (creatininemia 16.43 mg/dL, uremia 254 mg/dL), UA 3.6 mg/dL, fosfatemia 6 mg/dL, Na 138 mEq/L, K 4.2 mEq/L, Cl 102 mEq/l, arterial gasometry with pH 7.35, pCO2 36 mmHg, HCO3 20 mmol/L, lactates 1.4 mmol/L. Urine test with proteinuria and unremarkable sediment. His kidneys had foci of microlithiasis. He started vigorous fluid therapy and sustained improvement in renal function was seen, with no need for renal function replacement therapy. The subsequent evaluation showed hypouricemia &lt;1.5 mg/dL and FEUA of 32.5% (normal range 5.5%-8.5%). The molecular study identified the variant c.1221del p.(His407Glnfs*8) in the SLC2A9 gene in homozygosis, which established the diagnosis of RHUC type 2. This case highlights the importance of recognizing hereditary RHUC to prevent its manifestations, including exercise-induced AKI, nephrolithiasis, nephrocalcinosis, and more rarely, progression to stage 5 CKD. Its diagnosis should be considered in individuals with serum UA &lt;2 mg/dL and elevated FEUA. Additionally, it should be confirmed by the identification of mutations in homozygous or compound heterozygous in SLC22A12 or SCL2A9. Treatment includes xanthine oxidoreductase inhibitors and adequacy of physical activity. The use of uricosuric antihypertensive drugs whose mechanism of action involves blocking the URAT1 transporter should be avoided.

The effect of dapagliflozin on uric acid excretion and serum uric acid level in advanced CKD

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) exhibit renoprotective effect in patients with chronic kidney disease (CKD) and reduce serum uric acid (UA) in patients with diabetes mellitus. However, it is not clarified whether SGLT2i reduce serum UA levels in patients with advanced CKD. This study aimed to investigate the impact of SGLT2i on change in serum UA levels in patients with advanced CKD. Data of 121 Japanese patients with CKD who were newly administered 10 mg dapagliflozin in our department between August 2021 and August 2022 were analyzed. Changes in UA and fractional excretion of UA (FEUA) were analyzed using multiple regression analysis. Of 75 patients, 21 (28.0%) patients, 24 (32.0%) patients, 29 (38.7%) patients, and 1 (1.3%) patient were categorized as having CKD stage 3a, 3b, 4, and 5, respectively. The median age was 67 years, and 72.0% were male. 23 (30.7%) of patients had diabetes mellitus. The median estimated glomerular filtration rate, serum UA, and FEUA were 35.7 mL/min/1.73 m2, 6.4 mg/dL, and 6.76%, respectively, at the time of dapagliflozin administration. After administration, serum UA decreased to 5.6 mg/dL and FEUA increased to 9.22%. Dapagliflozin increases FEUA and reduces serum UA levels in patients with advanced CKD.

Chloride and Potassium Assessment are a helpful tool for Differential Diagnosis of Thiazide Associated Hyponatremia.

Differential diagnosis of thiazide associated hyponatremia (TAH) is challenging. Patients can eitherhave volume depletion or a syndrome of inappropriate antidiuresis (SIAD)-like presentation. To evaluate the impact of the simplified apparent strong ion difference in serum (aSID), sodium + potassium-chloride) as well as the urine chloride and potassium score (ChU, chloride-potassium in urine) in the differential diagnosis of TAH, in addition to assessment of fractional uric acid excretion (FUA). Post-hoc analysis of prospectively collected data from June 2011 to August 2013. Hospitalized patients enrolled at University Hospital Basel and University Medical Clinic Aarau, Switzerland. 98 patients with TAH < 125 mmol/l were included, divided according to treatment response in volume-depleted TAH requiring volume substitution or SIAD-like TAH requiring fluid restriction. We computed sensitivity analyses with ROC curves. positive predictive value (ppv) and negative predictive value (npv) of aSID, ChU, and FUA in differential diagnosis of TAH. An aSID > 42 mmol/l had a ppv of 79.1% in identifying patients with volume-depleted TAH, whereas a value < 39 mmol/l excluded it with a npv of 76.5%. In patients for whom aSID was inconclusive, a ChU < 15 mmol/l had a ppv of 100% and a npv of 83.3% whereas FUA < 12% had a ppv of 85.7% and a npv of 64.3% in identifying patients with volume-depleted TAH. In patients with TAH, assessment of aSID, potassium and chloride in urine can help identifying patients with volume-depleted TAH requiring fluid substitution from patients with SIAD-like TAH requiring fluid restriction.

Changes of serum uric acid level during acute gout flare and related factors.

By studying the changes of serum uric acid (SUA) in acute stage and remission stage of gouty arthritis, we aimed to explore the relationship between the changes of SUA level and free glucocorticoids and inflammatory factors. A prospective, longitudinal study was conducted on 50 acute gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. Blood and 24-hour urine samples were collected during the acute phase and two weeks after the initial visit. Patients with acute gouty arthritis were treated primarily with colchicine and nonsteroidal anti-inflammatory drugs. A total of 32 patients completed the two-week follow-up trial. SUA levels were significantly downregulated during the acute flare than after the flare (464.14 ± 90.97 vs. 527.36 ± 86.90 μmol/L, p < 0.001). The 24-hour fractional excretion of uric acid (24 h FEur) (5.54 ± 2.82% vs. 4.68 ± 2.83%, p < 0.001) and 24-hour urinary uric acid excretion (24 h Uur) (663.08 ± 249.48 μmol/L vs. 540.87 ± 263.18 μmol/L, p = 0.001) increased significantly in patients during the acute phase. The percent change in SUA was associated with those in 24 h FEur and C-reactive protein. Meanwhile, the percent change in 24 h Uur was associated with those in 24-hour urinary free cortisol, percent change in interleukin 1β and interleukin 6. Decreased SUA level during the acute gout flare was associated with increased excretion of urinary uric acid. Inflammatory factors and bioactive free glucocorticoids may play significant roles in this process.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.