Search Results (153)

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, treats type 2 diabetes by blocking renal glucose reabsorption and promoting urinary glucose excretion. This mechanism lowers blood glucose concentrations independently of insulin. The resulting caloric loss also contributes to weight reduction. Although these effects are well documented in patients with diabetes, their magnitude and underlying mechanisms in healthy individuals remain poorly understood. Background/Objectives: We investigated metabolic alterations after a single 10 mg dose of dapagliflozin in healthy adults with normal body-mass indices (BMIs) using untargeted metabolomics. Methods: Thirteen healthy volunteers completed this study. Plasma was collected before and 24 h after dosing. Untargeted metabolic profiling was performed with ultra-high-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry. Results: Twenty-five endogenous metabolites were annotated; ten were putatively identified. Eight metabolites increased significantly, whereas two decreased. Up-regulated metabolites included phosphatidylcholine (PC) species (PC O-36:5, PC 36:3), phosphatidylserine (PS) species (PS 40:2, PS 40:3, PS 36:1, PS 40:4), lysophosphatidylserine 22:1, and uridine. Dehydroepiandrosterone sulfate and bilirubin were down-regulated. According to the Human Metabolome Database, these metabolites participate in glycerophospholipid, branched-chain amino acid, pyrimidine, and steroid-hormone metabolism. Conclusions: Dapagliflozin may affect pathways related to energy metabolism and homeostasis beyond glucose regulation. These data provide a reference for future investigations into energy balance and metabolic flexibility in metabolic disorders. Full article

Gout, a metabolic and autoinflammatory disease, is the most common form of inflammatory arthritis worldwide. Hyperuricemia may result in monosodium urate (MSU) crystals forming and depositing in joints and surrounding tissues, triggering an autoinflammatory response. Effective urate-lowering therapies, as well as anti-inflammatory medications, are used to treat gout. Over the past few decades, new antihyperglycemic drug classes with different modes of action have been added to treat hyperglycemia in type 2 diabetes mellitus (T2DM). Two of these drug classes, sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have reduced cardiovascular and renal events and mortality. Several clinical studies have demonstrated that SGLT2 inhibitors possess urate-lowering properties, which may be beneficial for treating gout patients, particularly those with comorbid T2DM. Regarding SGLT2 inhibitors, some researchers have suggested that their benefits are partly explained by their ability to reduce serum urate (SU) levels, probably through increased urinary uric acid excretion. The effect of GLP-1 RA on SU levels and urinary excretion of uric acid in humans is unclear. This paper reviews the mechanisms of action of SGLT2 inhibitors and GLP-1RA, both approved and in development. Additionally, it examines what is known about their structure–activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects. Full article

Background: Cooking skills represent an important yet often overlooked form of social and cultural capital, influencing dietary quality and health outcomes. As modern societies face growing challenges related to unhealthy eating patterns and a loss of traditional food practices, understanding the societal role of culinary competence becomes critical. This study explored the association between culinary skills, adherence to the Mediterranean diet, and nutritional intake. Methods: Baseline data from 111 adults (60 women; mean age 47.6 ± 10.5 years) participating in the iMC SALT randomized controlled trial (Portugal) were analyzed. Culinary skills were assessed using the Cooking Skills Score, while the dietary intake was evaluated with a Food Frequency Questionnaire and adherence to the Mediterranean diet through the alternative Mediterranean Diet (aMED) Score. Food and beverage processing levels were categorized using the NOVA classification, and the sodium/potassium intake was measured via 24 h urinary excretion. Results: Women demonstrated better culinary skills (5.1 ± 0.9 vs. 4.0 ± 1.1, p < 0.001) and greater adherence to the Mediterranean diet (5.1 ± 1.9 vs. 3.8 ± 1.8, p = 0.001) than men. Better culinary skills were associated with younger age, larger households, and increased adherence to the Mediterranean diet. Culinary skills significantly explained 27.2% of the variance in the Mediterranean diet adherence. Better culinary skills were linked to a greater energy and protein intake; but a lower sodium and potassium intake. Conclusion: These findings highlight culinary skills as a key societal factor shaping dietary behavior and nutritional intake. Promoting culinary education may offer a powerful strategy to address dietary inequalities, support cultural food heritage, and foster healthier, more resilient societies. Full article

Background: While the mHealth and school-based scale-up intervention for salt reduction (EduSaltS) effectively reduced salt intake and blood pressure among adults living with participating schoolchildren, the sustainability of these effects remains uncertain. This study aimed to evaluate whether these effects persisted one year post intervention. Methods: A one-year follow-up of a cluster randomized controlled trial was conducted, involving 524 children and their 524 adult family members from 20 primary schools. At 24 months, 509 children (97.1%) and 486 adults (92.7%) completed the assessment. Mixed linear models were used to analyze the difference in changes in salt intake between the intervention and control groups at 24 months, compared to baseline and 12 months, as measured by consecutive 24 h urinary sodium excretions. Secondary outcomes included the differences in changes in blood pressure and salt-related knowledge, attitudes, and practices (KAP) scores. Results: The adjusted mean difference in changes in salt intake between groups was −0.34 g/24 h (95% CI: −0.94 to 0.26, p = 0.265) for children and −0.72 g/24 h (95% CI: −1.48 to 0.05, p = 0.065) for adults at 24 months versus baseline. The corresponding differences from 12 to 24 months were −0.09 g/24 h (95% CI: −0.69 to 0.51, p = 0.775) for children and 0.29 g/24 h (95% CI: −0.50 to 1.08, p = 0.468) for adults. The adjusted difference in changes in adult blood pressure showed a slight, nonsignificant rebound at 24 months. The intervention group maintained significantly higher KAP scores than the control group at both 12 and 24 months. Conclusions: The effects of EduSaltS on reducing salt intake and blood pressure in adults diminished slightly one year after the intervention ended. However, sustained improvements in salt-related KAP were observed in both children and adults. Ongoing support is vital to sustain long-term salt-reduction behaviors. Full article

Background: Abnormal sodium-dependent hexose reabsorption in the proximal tubule, accompanied by a functional decrease in sodium and water reabsorption under conditions of increased volemia, may be attributed to a dysfunction of primary transporters related to a genetic defect in the Na,K-ATPase gamma subunit. Methods: We examined two sisters, aged 6 and 8 years, who presented with hypercalciuria, glucosuria, fructosuria, galactosuria, and atypical proteinuria. Primary diabetes, galactosemia, and fructosemia were excluded, suggesting a defect in cellular hexose transport in the proximal tubule. We conducted tests on the family members to assess the impact of gradually increasing volemia, using a water-loading test, on tubular H⁺ transport and urinary excretion of calcium, citrate, endothelin-1 (ET-1), and atypical proteins. Whole-exome sequencing was performed in the affected patients to identify the genetic basis of this phenotype. Results: Extended investigations revealed a complex defect in tubular H⁺ transport, calcium and citrate handling, and atypical proteinuria, resulting from water load-driven overproduction of endothelin-1 (ET-1). Genetic analysis identified a heterozygous pathogenic variant, c.80G>A, p.(Arg27His), in the FXYD2 gene, which encodes the gamma subunit of sodium/potassium-transporting ATPase. Conclusions: Our findings provide evidence that a defect in FXYD2 (splice form a) leads to functional impairment of proximal tubular hexose reabsorption. This is the first report on the metabolic consequences of a pathogenic FXYD2 variant affecting the gamma subunit of sodium/potassium-transporting ATPase in humans. The genotype–phenotype correlation in two siblings with a sodium-dependent defect in fructose, galactose, and glucose renal reabsorption allowed us to characterize a disease with a distinct clinical course and biochemical profile, not previously reported in the medical literature or genetic databases. Analysis of this condition was crucial for the early introduction of reno-protective treatment aimed at slowing the progression of nephropathy and for risk assessment in family members, which was essential for genetic counseling. Full article

Background: Different types of kidney stones are associated with distinct changes in urine chemistry. Methods: We assessed urinary parameters of 98 patients with calcium oxalate (CaOx) stones one month following endoscopic stone removal. The 24 h urine analysis encompassed the assessment of various parameters, including volume, sodium, chloride, sulfate, nitrate, fluoride, phosphate, calcium, potassium, magnesium, oxalate, uric acid, citrate, creatinine, and pH levels. Results: Hypocitraturia was the most prevalent urinary abnormality (61.2%, n = 63), followed by low urine volume (53%, n = 52) and hypercalciuria (50%, n = 49). We did not find any statistically significant differences between patients with whewellite (COM) (n = 69) and weddellite (COD) stones (n = 29) (p > 0.05). However, oxalate concentration was the only parameter with a statistically significant intergroup difference (p = 0.0297). Additionally, in univariate linear regression analysis, urinary phosphate levels ≥ 48.0 mmol/d showed a trend towards significance (OR 0.17, 95% CI 0.02–1.15, p = 0.0692), indicating that phosphaturia is associated with a significant increase in the odds ratio of COD stones. To further explore metabolic heterogeneity among stone formers, we conducted cluster analysis, which revealed three distinct metabolic subgroups. Cluster 1 was predominantly associated with COM stones (80.5%) and exhibited significantly higher urinary excretion of sodium, calcium, oxalate, phosphate, and uric acid compared to Cluster 2, which had a more balanced distribution of monohydrate and dihydrate stones. Conclusions: These findings suggest that a specific metabolic phenotype may be linked to COM stone formation, providing a framework for risk stratification and personalized prevention strategies in calcium oxalate stone formers. Full article

Background: Addressing high-salt diets in China through interventions can significantly reduce blood pressure (BP) and the associated health risks. Objective: This study aims to evaluate the effectiveness of a comprehensive salt reduction intervention implemented across counties in Zhejiang Province, focusing on system establishment, extensive publicity, and targeted population interventions. Methods: The Salt Reduction and Hypertension Prevention Project was initiated in Zhejiang Province. Cross-sectional surveys were conducted before the intervention and after. The research commenced in 2017 with a baseline survey involving 7512 participants from five counties. Four counties were randomly selected for the intervention, implementing a multifaceted salt reduction strategy, while one county served as a reference without any intervention. The primary outcomes measured were changes in BP and 24 h urinary sodium and potassium excretion. Results: Following the intervention, 24 h urinary potassium excretion experienced a significant increase, rising from 1441.3 (SD 681.9) to 1676.9 (SD 931.4) mg per day, p < 0.001. Utilizing a linear mixed-effects model, the adjusted net difference in urinary sodium changes was calculated to be 394.1 mg per day (95% CI, 133.2 to 655.0) (p = 0.003). There was a notable reduction in systolic blood pressure (SBP) from 131.2 (SD 19.2) to 129.8 mmHg (SD 18.0), and diastolic blood pressure (DBP) also decreased from 80.8 (SD 10.8) to 78.9 mmHg (SD 10.2), p < 0.001. The adjusted net differences for SBP and DBP between the intervention and reference groups were 1.3 (95%CI, 0.5 to 2.1) and 1.4 mmHg (95%CI, 0.9 to 2.0), respectively, p < 0.001. Conclusions: The findings indicate that a multi-sectoral approach, combined with extensive public awareness initiatives and precisely targeted interventions, can significantly increase urinary potassium excretion and reduce sodium and blood pressure. Full article

Background: Acetazolamide is a carbonic anhydrase inhibitor that inhibits proximal sodium bicarbonate reabsorption, thus increasing urinary bicarbonate excretion. Despite its widespread distribution in the body and beneficial effects on alkaline diuresis, its efficacy and the optimal dosage and duration of acetazolamide in treating metabolic acidosis remain areas of uncertainty. This review aims to assess the effectiveness of acetazolamide in treating chloride depletion alkalosis, mainly induced by diuretics, through a systematic evaluation of clinical research data. Methods: A comprehensive search was conducted on PubMed and Embase. This review included randomized controlled trials, observational studies, and case reports. Data extraction included dose, route, frequency, indication, duration of therapy, patient demographics, and outcomes. Results: A comprehensive search strategy identified 107 studies, of which 7 met the inclusion criteria after full-text review. The reviewed studies encompassed two randomized clinical trials, one case–control study, and three case reports, collectively involving 111 patients with metabolic alkalosis. The studies revealed varied outcomes regarding the efficacy of acetazolamide in treating metabolic alkalosis induced by diuretics. While some trials demonstrated significant improvements in serum bicarbonate levels and acid–base balance, others found no statistically significant reduction in the duration of mechanical ventilation. Case reports highlighted the successful use of acetazolamide in diverse patient populations, including pediatric patients with heart disease and individuals with chronic obstructive pulmonary disease. Conclusions: Acetazolamide holds promise in addressing chloride depletion alkalosis. However, a targeted clinical trial investigating its effectiveness in diuretic-induced metabolic alkalosis must strengthen the existing knowledge base. Full article

Background: PAHO-WHO reports that sodium intake is currently high in the Caribbean. The objective was to estimate sodium (Na) and potassium (K) intakes by 72 h dietary recall and compare them with those obtained from 24 h urinary excretion in Dominican adults. Methods: A total of 69 adults (33 men) completed a 3-day dietary recall with emphasis on added salt and seasonings. The 24 h urine samples were analysed by indirect potentiometry using the membrane ion-selective electrode technique. The WHO-PAHO Questionnaire on Knowledge, Attitudes and Behaviour toward Dietary Salt and Health was completed. Results: Dietary Na intake ranged from 1.0 to 8.3 g. Median dietary and urinary Na concentrations were similar (2.7 and 2.5 mmol/d). Mean dietary Na and K concretertentrations were higher than those excreted in 24 h urine (133.0 ± 59.7 vs. 103.7 ± 44.5 mmol Na/d, p = 0.001; 69.0 ± 21.0 vs. 36 ± 16.3 mmol K/d, p < 0.001). The Na-to-K ratio was lower in dietary than in 24 h urine samples (2.0 ± 1.1 vs. 3.2 ± 1.6 mmol/d, p < 0.001). Urinary Na concentration was associated with sex (r = 0.280, p = 0.020) and obesity (r = 0.244, p = 0.043) and K with sex (r = 0.356, p = 0.003). Urinary Na-to-K was inversely related to age (r= −0.291, p = 0.015). Sex and obesity explained 11% of the variance in urinary Na concentration and sex only of the variance in urinary K concentration. The only significant correlation between dietary and urinary concentrations was that of K (r = 0.342, p = 0.004). This correlation matrix, controlled for overweight and sex, maintained the level of significance and was equal in almost 12% of the data. Conclusions: These data, which are the first data on Na and K intakes in Dominicans assessed by dietary assessment, showed a higher mean sodium intake (mean of dietary recall and urinary excretion data: 2.7 g Na, 6.8 g salt/day) and a lower K intake (2.06 g/day) than the WHO recommendations (<2.0 g Na, ≥3.5 g K). Potassium, but not sodium, intake from 72 h food recall and 24 h urinary excretion showed a correlation when controlling for sex and obesity, but not enough to consider them interchangeable. Full article

Background: Salt intake in China was high and a series of salt reduction measures were accordingly carried out recently. Our study aimed to assess the long-term effect of a scale-up community randomized controlled trial (RCT); Methods: Individuals between the ages of 18 and 75, from six provinces in China, were recruited and randomized into control (n = 1347) and intervention (n = 1346) groups. A one-year salt reduction intervention was first implemented in the intervention group, followed by a two-year scale-up intervention in both groups. The 24 h urine sample, anthropometric measurement, and knowledge, attitude, and practice (KAP) of salt reduction, as well as lifestyle information, were collected at baseline, after one-year RCT (mid-term evaluation, n = 2456), and two-year scale-up intervention (terminal evaluation, n = 2267); Results: Both control (351.82 mg/24 h, p < 0.001) and intervention (192.84 mg/24 h, p = 0.006) groups showed a decrease in 24 h urinary sodium excretion from baseline to terminal evaluation. Except for an increase in 24 h urinary potassium excretion (85.03 mg/24 h, p = 0.004) and a decrease in systolic blood pressure (SBP) (2.95 mm Hg, p < 0.001) in the intervention group at the mid-term assessment, no statistically significant differences in other indicators were found between two groups. The KAP of salt reduction in two groups was gradually improved; Conclusions: After one-year RCT and two-year scale-up, all participants showed a decreasing trend in 24 h urinary sodium excretion and an increase in salt reduction KAP. The community salt reduction intervention package has the potential for broader application across other regions in China. Full article

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium–glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease. Full article

Various inflammatory and renal biomarkers have already been assessed for monitoring the response to anti-leishmanial therapy in canine leishmaniosis. This study assessed the parasite load, various inflammatory and renal biomarkers pre- and post-treatment, and any association between the studied variables and the degree of disease severity at diagnosis. This is a prospective cohort study of 30 client-owned dogs with leishmaniosis, classified according to LeishVet’s guidelines as stage I (n = 2), stage IIa (n = 7), stage IIb (n = 6), stage III (n = 8), and stage IV (n = 7). In addition to Leishmania real-time PCR in the bone marrow, blood and urine, previously studied biomarkers, and several inflammatory and renal markers never investigated in canine leishmaniosis, such as fibrinogen, antithrombin, urinary fractional excretion of sodium, and urinary amylase-to-creatinine ratio were measured pre- and post-treatment (meglumine antimoniate or miltefosine + allopurinol). A positive Leishmania real-time PCR in the blood at diagnosis predicted a positive Leishmania real-time PCR in the bone marrow post-treatment (p = 0.003). Following treatment, antithrombin and urinary amylase-to-creatinine ratio were significantly changed (p < 0.001, respectively). Urinary amylase-to-creatinine ratio, total iron-binding capacity, and antithrombin were the variables most strongly associated with disease severity (p < 0.005, respectively). Urinary amylase-to-creatinine ratio can be a useful marker to monitor treatment response and to classify the degree of disease severity. Full article

Background: Albuminuria and albumin excretion rate (AER) are important risk factors for chronic kidney disease (CKD) development. Despite the extensive evidence of the influence of sodium and potassium on cardiovascular health, the existing evidence regarding their impact on albuminuria and kidney disease is limited and inconsistent. Our study aimed to assess the correlation between urinary sodium and potassium excretion, and the sodium-to-potassium ratio (Na/K ratio) with impaired kidney function, particularly the AER and albuminuria. Materials and Methods: Data were collected from the Lithuanian NATRIJOD study. A total of 826 single 24-h urine samples from individuals aged 18 to 69 were collected and analyzed for their sodium and potassium levels, Na/K ratio, and AER. Albuminuria was defined as an AER exceeding 30 mg/24 h. Results: The participant mean age was 47.2 ± 12.1 years; 48.5% of the participants were male. The prevalence of albuminuria was 3%. Correlation analysis revealed a positive correlation between AER and urinary sodium excretion (r_s = 0.21; p < 0.001) and urinary potassium excretion (r_s = 0.28; p < 0.001). In univariate linear regression analysis, sodium and potassium excretion and the Na/K ratio were significant AER predictors with β coefficients of 0.028 (95% CI: 0.015; 0.041; p < 0.001), 0.040 (95% CI: 0.003; 0.077; p = 0.035), and 1.234 (95% CI: 0.210; 2.259; p = 0.018), respectively. In the multivariable model, only urinary sodium excretion remained significant, with a β coefficient of 0.028 (95% CI: 0.016; 0.041). Potential albuminuria predictive factors identified via univariate logistic regression included urinary sodium excretion (OR 1.00; 95% CI: 1:00; 1.01) and the Na/K ratio (OR 1.53; 95% CI: 1.11; 2.05). However, these factors became statistically insignificant in the multivariate model. Conclusions: Urinary sodium and potassium excretion and the Na/K ratio are significantly associated with kidney damage, considering the assessed 24-h albumin excretion rate and presence of albuminuria content. Full article

Background: Research into the pivotal role of potassium in chronic diseases and their comorbidities remains scarce. Our aim is to elucidate the relationship between potassium and chronic diseases, including comorbid conditions, and to provide evidence-based recommendations for potassium intake in patients. Methods: This study is anchored in a representative, population-based survey conducted in Zhejiang Province, China, in 2017, encompassing participants aged 18 to 69 years. Data collection included questionnaire responses, physical measurements, and biological samples, obtained through a multistage cluster random sampling method. A subset of 1496 participants provided complete 24 h urine samples. Results: The median age of the participants was 48.0 years (interquartile range [IQR] 24.0), with 51.1% being female, and hypertension was identified in more than one third (35.6%) of the participants. The prevalence of diabetes was approximately 9.0%, dyslipidemia was found in 34.2%, and microalbuminuria in 8.8%. The 24 h urinary excretion levels were 3613.3 mg/24 h (IQR 2161.7) for sodium and 1366.0 mg/24 h (IQR 824.9) for potassium, respectively. Potassium excretion exhibited an inverse relationship with blood pressure. Furthermore, a positive correlation was observed between potassium excretion and high-density lipoprotein cholesterol (HDL-C) levels, with an elevation of 0.03 mmol/L (95% confidence interval [CI] 0.00 to 0.05). In binary logistic regression analysis, individuals in the fourth quartile of potassium excretion (Q4) exhibited an odds ratio (OR) of 0.56 (95% CI 0.36–0.87) for hypertension compared to those in the first quartile (Q1). Urinary potassium excretion was inversely associated with low HDL-C levels, with Q4 individuals having 0.62 times the odds of having low HDL-C levels (OR, 0.62; 95% CI 0.39–1.00) compared to Q1. Conclusions: Potassium excretion demonstrated a direct negative correlation with certain comorbidities. This study underscores the pivotal role of potassium in the management of chronic diseases and associated comorbidities, thereby highlighting the significance of potassium in both public health initiatives and clinical practice. Full article

Background/Objectives: Blood pressure (BP) is characterized by a circadian rhythm (Circr) with lower nighttime values, called dipping. Non-dipping is associated with higher CVD risk. The Circr of urinary sodium excretion (NaCle), peaking during the day, is linked to BP patterns. Physical activity (PA) is known to improve BP control and enhance the dipping phenomenon, but its possible effect on NaCle remains unclarified. This study aimed to investigate the correlation between PA and the Circr of NaCle and to determine if the relationship is independent of age, sex, BP values, dipping pattern, and salt intake. Methods: A pilot cross-sectional analysis was conducted using data from the Ticino Epidemiological Stiffness Study, involving 953 participants in Switzerland. Data collection included standardized questionnaires, blood samples, 24 h urine collections, and ambulatory BP monitoring. Participants were categorized into sedentary, partially active, and active. The effect of PA, NaCl intake, and dipping on the day/night NaCle ratio was assessed with multivariable linear regressions. Results: Participants’ median age was 49 years, with 78% having normal BP values and 47% exhibiting a dipping pattern; 51% were classified as sedentary and 22% as partially active. The median NaCl intake was 7.9 g/day. The youngest subjects had a higher hourly NaCle ratio compared to older subjects. Higher NaCl intake correlated with increased BP, a phenomenon more pronounced in men and younger subjects. The hourly day/night NaCle ratio positively correlates with dipping; however, PA did not show a significant correlation with the NaCle ratio. Conclusions: This study indicates that while the day/night NaCle ratio correlates with the dipping pattern, PA is unrelated to the circadian rhythm of renal sodium handling. The beneficial effects of PA on BP and cardiovascular health thus appear to be mediated through mechanisms other than NaCle. These are explorative findings only but relativize the need for further investigations on the topic. Full article