Search Results (157)

Serum creatinine (sCr) and urine output (UO) have long been considered the cornerstones of acute kidney injury (AKI) severity criteria. Many articles were previously published discussing the prognostic relevance of fulfilling either one or both AKI criteria. However, sCr and UO must not be considered independent variables because they are physiologically linked despite having distinct chronologies as AKI markers. An increase in sCr is a late manifestation of decreased renal function and body creatinine accumulation and not an on-time surrogate for a decreasing glomerular filtration rate. On the other hand, oliguria is not a single entity, and its interpretation relies on urine’s biochemical composition as well as its threshold pathological output value, which is somewhat controversial. In the present article, the current practice of evaluating sCr and UO separately is questioned and the idea that they can eventually be considered different expressions of the same variable of interest (the urine creatinine excretion) is highlighted. Full article

Background/Objectives: We evaluated Goreisan, a traditional Chinese medicine, for its effects on nephrotic syndrome in a rat model. Methods: Male Sprague–Dawley rats underwent right nephrectomy at 5 weeks of age, followed by adriamycin administration (5 mg/kg) at 6 and 8 weeks of age to induce nephrotic syndrome. At 10 weeks, rats were divided into three groups: vehicle (control), Goreisan 0.5 g/kg (GL), and Goreisan 1.0 g/kg (GH). Goreisan was administered daily for 4 weeks. At 14 weeks, blood, urine, mRNA expressions, and kidney histopathology were analyzed. Data were analyzed using one-way ANOVA followed by Tukey–Kramer post hoc testing. Results: Goreisan prevented worsening kidney function, with reduced glomerular and tubulointerstitial damage, lower systemic and intrarenal 8-hydroxy-2′-deoxyguanosine levels, and lower plasma aldosterone levels and expression of intrarenal renin–angiotensin–aldosterone system (RAAS)-related factors. Urine volume significantly increased in GL and GH groups compared with the control group. In the GH group, urine volume increased markedly (Δ urine volume: 10.0 ± 2.6 mL/day), whereas it tended to decrease in the Vehicle group (Δ urine volume: −1.3 ± 2.5 mL/day). Urine osmolality was lower in the GH group, with a larger decrease in Δ urine osmolality (−616.3 ± 132.8 mOsm/L). These changes occurred without an increase in urinary sodium excretion, suggesting an aquaretic effect independent of natriuresis. Creatinine clearance (CCr/kg) declined markedly in the Vehicle group but was significantly preserved in the GH group (Δ CCr/kg: −2.2 ± 0.19 vs. −0.7 ± 0.28), indicating renoprotective effects. No differences were found in serum arginine–vasopressin levels. Real-time PCR and immunohistochemical staining showed no significant differences in aquaporin (AQP) mRNA expression (AQP1, AQP2, AQP3, and AQP4), but AQP2 localization to the apical membrane in the collecting ducts was reduced with Goreisan treatment. Conclusions: Goreisan demonstrates kidney-protective and diuretic effects in nephrotic syndrome, potentially through reducing systemic oxidative stress, modulating RAAS activation, and altering AQP2 trafficking. Full article

Background/Objectives: Plant-derived diuretics are attracting increasing interest due to their promising efficacy and improved safety profile compared with synthetic drugs. This study aimed to characterize the phytochemical composition of Astragalus boeticus (A. boeticus) extracts, evaluate their diuretic activity, and assess the oral safety of their main phenolic compound. Methods: Aqueous (AQE) and hydroethanolic (EtOHE) extracts were analyzed using LC–MS/MS, while in silico toxicity prediction of trans-resveratrol was performed using ProTox-II and ADMETlab 2.0. Diuretic activity was evaluated in male Wistar rats (n = 24) divided into four groups: control (distilled water, 10 mL/kg), furosemide (10 mg/kg), AQE (300 mg/kg), and EtOHE (300 mg/kg). Urine and plasma samples were collected after 15 days to determine electrolyte concentrations, creatinine level, creatinine clearance, and hepatic enzyme profile. Results: LC–MS/MS profiling identified fourteen phenolic compounds, with trans-resveratrol (270 µg/g in AQE) being the most abundant, followed by cyanidin-3-O-glucoside and gentisic acid. In silico assessments revealed no hepatotoxic, mutagenic, or neurotoxic effects of trans-resveratrol. Both extracts significantly enhanced urinary output, chloride excretion, and creatinine clearance, while maintaining stable renal and hepatic biochemical parameters, indicating potent diuretic activity without toxicity. Conclusions: A. boeticus extracts demonstrate strong diuretic potential associated with a favorable safety profile, likely linked to their phenolic composition dominated by trans-resveratrol. These findings support the use of A. boeticus as a natural and safe diuretic source. Further investigation is recommended to elucidate its pharmacological mechanisms and therapeutic relevance. Full article

Background: Pediatric hypertension is an increasingly recognized health concern and is commonly influenced by modifiable factors such as dietary sodium intake and obesity and non-modifiable factors like family history of hypertension. Urinary sodium excretion provides an objective surrogate marker of sodium consumption and may be associated with blood pressure severity. This study aimed to evaluate urinary sodium excretion in children with primary hypertension (PH) and to test the hypothesis that higher sodium excretion is associated with less favorable clinical, biochemical, and blood pressure parameters. Methods: This retrospective, cross-sectional, single-center study analyzed data from 369 hypertensive patients and 59 healthy children. Patients with a confirmed diagnosis of PH and ambulatory blood pressure monitoring results were included in the study group. Clinical, anthropometric, laboratory, echocardiographic, and blood pressure data were examined, and sodium excretion was evaluated using both the spot urine sodium-to-creatinine ratio and 24-h urinary sodium per kilogram of body weight. Results: Children with hypertension exhibited higher urinary sodium excretion compared to the control group. Sodium excretion of the hypertensive group, measured using the sodium/creatinine ratio and 24 h urinary sodium excretion per kilogram, was positively correlated with 25-hydroxyvitamin D, the urinary potassium/creatinine ratio, and the urinary uric acid/creatinine ratio. Moreover, negative correlations were observed for both parameters with age, body weight, serum uric acid, and left ventricular mass. In the multivariate analysis, weighted Z-score (beta = −0.393), age (beta = −0.293), 25-OHD (beta = 0.182), and arterial hypertension in the father (beta = 0.166) predicted 24 h urinary sodium excretion. Children with excessive sodium excretion had a significantly higher systolic blood pressure load over 24 h. Conclusions: Urinary sodium excretion is elevated in children with PH. Children with a lower weight for their age, who are younger, and who have a father with arterial hypertension might be at higher risk of excessive urine excretion. Our findings underscore the clinical importance of dietary sodium reduction as a non-pharmacological therapeutic target, especially in these patient populations. Prospective studies are needed to evaluate its impact on long-term cardiovascular outcomes in this population. Full article

To date, no clinical trial has investigated the potential of CD34⁺ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34⁺ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34⁺ cells weekly for three weeks. At eight weeks, the rats’ renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34⁺ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects. Full article

Cadmium (Cd) is a ubiquitous environmental pollutant with no nutritional value or physiological role in the body. It readily accumulates in various tissues as it is easily absorbed from the diet but only poorly excreted. Due to the widespread contamination of staple foods, exposure to this toxic metal is inevitable for most people. The health risk due to dietary Cd exposure has long been underappreciated. This is primarily due to the use of urinary excretion of β₂-microglobulin (β₂M) as an indicator of an adverse health effect. This study employed advanced benchmark dose (BMD) modeling in a Thai cohort (n = 799) to reassess health risks from dietary Cd exposure. The BMD limit for urinary Cd was identified as 0.17 μg/g creatinine when using a reduction in estimated glomerular filtration rate (eGFR) as the endpoint, whereas no reliable BMD could be established using β₂-microglobulin excretion. Given that eGFR reduction is a more reliable indicator of chronic kidney disease, its use is recommended for deriving health-protective guidelines. The findings demonstrate that the current urinary Cd threshold of 5.24 μg/g creatinine is inadequate, supporting the adoption of a threshold below 0.20 μg/g creatinine in future exposure guidelines. Full article

Background: Cardiovascular diseases are the leading cause of death globally, with hypertension and high sodium intake being major contributors. Accurate estimation of sodium intake is essential, but 24 h urine collection, the gold standard, is cumbersome and impractical for routine clinical use. Existing spot urine-based prediction formulae lack accuracy at the individual and population level. Objective: To develop and validate population-specific formulas for estimating 24 h urinary sodium excretion from spot urine samples using data from a representative Swiss adult population. Methods: Models with and without urea and potassium were developed incorporating age, sex, and anthropometry-based, population-specific, estimated urinary creatinine excretion values. Data quality was rigorously controlled, and model performance was compared to the INTERSALT, Kawasaki, and Tanaka formulae and to a nocturnal timed urine collection used to calculate hourly creatinine excretion. Results: Models based on first morning urine demonstrated improved accuracy (AUCs: Swiss anthropometric model 0.85 (95% CI: 0.80–0.90), Swiss anthropometric model with urea 0.86 (95% CI: 0.81–0.91)) and lower bias (−5.5 mmol/24 h for the Swiss anthropometric model and −2.86 mmol/24 h for the Swiss anthropometric model with urea) compared to existing equations. Performance was consistent across clinically relevant sodium intake thresholds and the models were therefore suitable for use in clinical settings. A timed nocturnal urine collection further improves accuracy. Conclusions: These new simple and reliable formulae provide a promising and practical tool for estimating sodium intake from first morning urine spot in adult European populations, and are potentially applicable in clinical settings. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Background/Objectives: Menopause leads to estrogen deficiency, which negatively affects bone density, skin integrity, and hair health in women. This study aimed to evaluate the effects of fish-derived collagen peptides, calcium, and vitamin D3 supplementation on body composition, bone turnover markers, skin condition, and hair loss in menopausal women. Methods: Participants were randomized into four groups: placebo (G01), 1000 mg calcium + 400 IU vitamin D3 (G02), 5 g collagen (G03), and 1000 mg calcium + 400 IU vitamin D3 + 5 g collagen (G04). Participants received daily supplementation for six months. Body composition, biochemical bone markers (P1NP, BAP, osteocalcin), skin hydration, elasticity, transepidermal water loss (TEWL), and hair loss were assessed at baseline and follow-ups. Results: No significant changes were observed in body composition or bone biomarkers including P1NP, BAP, and osteocalcin across groups. Serum creatinine, ALT, and AST levels remained within normal ranges. Serum calcium levels remained stable, and urinary calcium excretion slightly increased in calcium-supplemented groups, indicating no adverse effects on kidney or liver function. G02 and G04 exhibited slightly decreased serum calcium levels compared to G01 and G03. However, G04 showed significantly improved skin hydration by 23% and skin elasticity by 8.52% compared to baseline after six months, whereas the placebo group showed negligible changes. G03 also showed notable improvement in elasticity by 12.23%, indicating collagen’s dominant role. The G02, G03, and G04 also significantly retarded hair shedding compared to the placebo (G01) group. TEWL did not significantly change in any group. Conclusions: These findings suggest that six-month supplementation with collagen peptides, particularly when combined with calcium and vitamin D, improves skin hydration and elasticity in menopausal women. Full article

Background/Objectives: Although essential for oxygen transport and DNA synthesis, excess iron is toxic and can damage organs such as the kidneys. Research has shown that iron overload induces kidney injury, and aging contributes to kidney dysfunction through functional and structural changes. The interaction between iron overload and aging remains poorly understood. Therefore, this study investigated their combined effects on renal microstructure and function using an iron-dextran-injected mouse model. Methods: Young and old mice were divided into control and iron overload groups, renal function was evaluated by serum creatinine and albuminuria, and urinary iron excretion was also measured to assess iron handling. The structural changes were assessed using histological analysis and electron microscopy. Results: Although the iron overload groups had similar blood iron levels, the old iron overload group exhibited significantly higher levels of albuminuria, urinary iron excretion, and serum creatinine compared with the young group. In the iron overload model, histological and ultrastructural analyses demonstrated iron accumulation in mesangial and endothelial cells, glomerular basement membrane thickening, and foot process widening, which were more pronounced in aged mice, suggesting that aging exacerbates iron-induced kidney injury. Conclusions: These findings demonstrate that aging increases susceptibility to iron-induced kidney injury, as shown by the accelerated glomerular injury observed in iron-overloaded aged mice. Therefore, elucidating the effects of aging on iron metabolism may contribute to identifying approaches for reducing age-associated renal injury. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

Background: The differential effects of post-exercise rehydration beverages on inflammatory processes and organ protection remain incompletely characterized. This study investigated how beverages with distinct compositions influence urinary biomarkers following endurance exercise. Methods: In a randomized crossover design, eight trained male runners performed 6000 m pace running followed by consumption of 500 mL of either: water (Drink 1), hypotonic sports drink (Drink 2, 200 mOsm/L), oral rehydration solution (Drink 3, 270 mOsm/L), or modified hypotonic formulation (Drink 4, 200 mOsm/L). After 60 min, participants completed a 1000 m time trial. Urine samples were collected at baseline, post-6000 m, and post-1000 m for analysis of biochemical parameters and inflammatory cytokines. Results: No significant differences in 1000 m performance were observed between trials. Drink 3 significantly reduced creatinine and uric acid excretion compared to other beverages (p < 0.05), suggesting decreased waste product elimination. Creatinine-corrected intestinal fatty acid-binding protein values were lower with Drinks 2 and 3, indicating potential intestinal protection. Notably, Drink 4 showed modest but significant enhancement of IL-4 excretion (p < 0.05, ηp² = 0.347), demonstrating beverage-specific modulation of anti-inflammatory cytokines with moderate effect sizes. Conclusions: Different beverage formulations exert distinct effects on waste product elimination, intestinal organ damage markers, and inflammatory cytokine profiles. These findings suggest that beverage selection should be tailored to specific recovery priorities and training contexts. Full article

A key factor in calculating dairy cows’ nitrogen (N) excretion is knowing the amount of daily excreted urine. The present study aimed to investigate two methods to calculate the daily urine volume (UV) excreted using spot urine samples. Data were obtained from nine balance experiments involving 47 lactating and seven non-lactating German Holstein cows, with an average body weight (BW) of 620 ± 95 kg and an average age of 5.6 ± 1.4 years. Daily urinary creatinine (Cr) and UVs were known for all animals. The first method was developed by linearly regressing the daily excreted amount of Cr in urine against BW (p < 0.001; R² = 0.51; RSE: 2.8). The slope of the regression was used to calculate UV. The second method includes a non-linear regression of UV on Cr concentration in urine, allowing direct estimation of UV without knowledge of BW (p < 0.001; RSE: 8.13). Both estimation methods were compared to the standard method to determine UV from balance trials using Lin’s concordance correlation coefficient (CCC) and Bland–Altman plots. The first method had a CCC of 0.81, and the second method had a CCC of 0.85. Both methods can confidently be applied to calculate UV. Therefore, the second method is usable if BW is unavailable. Full article

Objectives: This study investigated the effects and mechanisms of electrolyzed alkaline water (EAW), a type of drinking water, on hyperuricemia (HUA) in mice. Methods: A hyperuricemia model was established by intraperitoneal injection of potassium oxonate and free access to a high-purine diet. EAW was provided ad libitum for 21 days. Results: The results showed that EAW had little impact on the levels of blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, albumin, or xanthine oxidase in mice (p > 0.05). Interestingly, EAW ingestion induced significant reductions in uric acid and creatinine levels (p < 0.05), along with increased urinary uric acid excretion (p < 0.05) and less renal pathological changes in mice. Additionally, EAW upregulated GLUT9 gene expression (p > 0.05) and downregulated URAT1 protein expression. Conclusions: In conclusion, this study demonstrates that EAW promotes uric acid excretion by downregulating URAT1 and GLUT9 protein expression, resulting in a significant reduction in uric acid levels. 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