Search Results (322)

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Background/Objectives: Recent Japanese guidelines recommend using the average sodium-to-potassium (Na/K) ratio from casual urine samples to assess hypertension and cardiovascular risk, suggesting cutoffs of 2 (optimal) and 4 (feasible). We aimed to evaluate the proportion of Korean individuals who would be classified as having elevated Na/K ratios using these cutoffs, based on random urine Na/K measurements obtained from the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset. Methods: We analyzed 50,440 participants from the KNHANES 2016–2023 with available random urine Na and K results. Annual urinary Na/K ratios were calculated, and the prevalence of ratios ≥2 and ≥4 was assessed by age and sex using sampling weights. Results: The weighted median Na/K ratios were consistently lower than the weighted means, indicating skewed distributions. From 2016 to 2023, the weighted median and mean values increased from 2.3 and 2.7 to 2.8 and 3.3, respectively. The prevalence of a Na/K ratio ≥2 increased from 60.5% to 72.0%, and that of a ratio ≥4 increased from 16.9% to 28.3%. A U-shaped trend in Na/K ≥4 prevalence was observed by age, highest among those <20 and ≥70 years. Males had a higher prevalence than females in all age groups except 20–29. Conclusions: A growing proportion of Koreans exceeded Na/K cutoffs of 2 and 4 over time. Age- and sex-specific variation suggests tailored interpretation may be necessary when applying these thresholds in population health monitoring. Full article

This study aimed to evaluate the antibacterial activity of several technical lignins against major environmental bacteria that cause mastitis in dairy cattle. The efficacy of four types of technical lignins against environmental mastitis pathogens was evaluated using MIC and MBC assays. The best candidate, sodium lignosulfonate (NaL-O), was further tested using sawdust bedding substrates. Substrates were prepared in different cleanliness conditions: sawdust only, sawdust plus urine, sawdust plus feces, or sawdust plus a combination of both. The antimicrobial activity of NaL-O against the mixture of environmental mastitis-causing pathogens was determined on days 0, 2, and 6 of incubation. In addition, the components of bedding substrates were analyzed to help understand the dynamics of pathogen loads. In the MIC and MBC assays, NaL-O showed the best antimicrobial performance against all pathogens except Escherichia coli. When testing in the bedding substrates, the addition of NaL-O decreased the concentration of Staphylococcus chromogenes, Streptococcus uberis, and Pseudomonas aeruginosa across all bedding cleanliness levels at d 0, 2, and 6 of incubation. As the incubation time increased, the antimicrobial effect decreased. NaL-O also lowered the counts of E. coli and Klebsiella pneumoniae across all incubation times, but to a lesser extent. The presence of feces significantly reduced the antibacterial effects of NaL-O for these two bacteria. Among the technical lignins tested, NaL-O showed the broadest antibacterial activity against the mastitis pathogens tested. This study suggests that NaL-O has promising potential as a bedding conditioner to control environmental pathogens on dairies due to its low cost, ready availability, and compatibility with sustainable livestock practices. Combined with bedding cleanliness, bedding conditioner application may play a crucial role in reducing the growth of EM pathogens and subsequent mastitis incidence. Full article

Renal function refers to the combined actions of the glomerulus and tubular system to achieve homeostasis in bodily fluids. While the glomerulus is essential in the first step of urine formation through a coordinated filtration mechanism, the tubular system carries out active mechanisms of secretion and reabsorption of solutes and proteins using specific transporters in the epithelial cells. The assessment of renal function usually focuses on glomerular function, so the tubular function is often underestimated as a fundamental part of daily clinical practice. Therefore, it is essential to properly understand the tubular physiological mechanisms and their clinical association with prevalent human pathologies. This review discusses the primary solutes handled by the kidneys, including glucose, amino acids, sodium, potassium, calcium, phosphate, citrate, magnesium and uric acid. Additionally, it emphasizes the significance of physicochemical characteristics of urine, such as pH and osmolarity. The use of a concise methodology for the comprehensive assessment of urine should be strengthened in the basic training of nephrologists when dealing with problems such as water and electrolyte balance disorders, acid-base disorders, and harmful effects of commonly used drugs such as chemotherapy, antibiotics, or diuretics to avoid isolated replacement of the solute without carrying out comprehensive approaches, which can lead to potentially severe complications. Full article

Background/Objectives: The urine sodium/potassium (Na/K) ratio can potentially be used to detect dietary habits that contribute to hypertension. In this prospective cohort interventional trial, we aimed to verify whether private insurance sales staff can help clients change their lifestyle habits based on their urinalysis results. Methods: Clients of the life insurance company (20–65 years old) who were considered to have “high risk” lifestyle factors, which was defined as having high values for two or more of the following indicators: body mass index, blood pressure, triglycerides, liver enzymes, and glucose metabolism, were included. The clients were randomly assigned to three groups: a face-to-face (FF) intervention by sales staff (n = 83), non-FF (Non-FF) intervention via a social networking service (n = 87), and no intervention (Control) (n = 58). Urinalysis and surveys about diet and exercise habits were conducted before and after a 3-month interventional period in all groups. Three interventions were performed for the FF and Non-FF groups, including dietary advice based on urinalysis results, education encouraging reduced salt intake and increased locomotor activity, and viewing an educational video. The Control group only received their urinalysis results by mail. Results: The participants’ mean age was 44.0 years old. Significant improvements in estimated potassium intake were observed in the Non-FF group, and significant reductions in urine Na/K ratios were noted in both the FF and Non-FF groups. Multiple logistic regression analysis indicated that watching the video was the most effective factor for decreasing the urine Na/K ratio (odds ratio = 1.869). The total points for dietary behavior, based on the questionnaire, significantly improved among the individuals who watched the video. Conclusions: This study demonstrates the potential for private health insurance companies to contribute to health promotion and introduces a novel strategy for improving lifestyle habits among individuals at high risk of lifestyle-related diseases. Full article

To enhance the signal intensity of kynurenines, which are present at trace concentrations in biological fluids, a novel analytical approach was developed, combining pressure-assisted electrokinetic injection (PAEKI) with a mixed micelle system based on sodium dodecyl sulfate (SDS) and Brij-35. The method was applied to key compounds of the kynurenine pathway, including L-tryptophan, kynurenine, 3-hydroxykynurenine, and kynurenic acid, as well as to the aromatic amino acids (AAs) L-tyrosine and L-phenylalanine. PAEKI was performed by electrokinetic injection for 2 min at −6.5 kV (reversed polarity) and 0.5 psi (3.45 kPa) using a fused silica capillary (50 cm in length, 50 µm inner diameter). The background electrolyte (BGE) consisted of 20 mM Na₂B₄O₇ (pH 9.2), 2 mM Brij-35, 20 mM SDS, and 20% (v/v) methanol (MeOH). The limit of detection (LOD) using a diode array detector (DAD) was 1.2 ng/mL for kynurenine and ranged from 1.5 to 3.0 ng/mL for the other analytes. The application of PAEKI in conjunction with micellar electrokinetic capillary chromatography (MEKC) and solid-phase extraction (SPE) of artificial urine samples resulted in a 146-fold increase in signal intensity for kynurenines compared to that observed using the hydrodynamic injection (HDI) mode. The developed method demonstrates strong potential for determining kynurenine pathway metabolites in complex biological matrices. Full article

Background: GLP-1 receptor agonists (GLP-1 RAs) lower glucose and reduce cardiovascular events in type 2 diabetes, with noted renal benefits. Few studies directly compare GLP-1 RAs. This study aims to compare the effects of semaglutide and dulaglutide on renal function decline and proteinuria reduction in diabetic patients. Methods: The present study was conducted at Wanfang Hospital, Taipei Medical University. Diabetic patients using either semaglutide or dulaglutide for more than 1 year in the outpatient department from 1 January 2022 to 30 September 2024 were enrolled retrospectively. The outcome events in the present study included a decline in the estimated glomerular filtration rate (eGFR), an increase in the urine albumin–creatinine ratio (UACR), and patient death. Results: A total of 268 patients on dulaglutide and 747 on semaglutide were included. Baseline eGFR levels were similar in both groups. After 12 months, eGFR levels did not significantly decline in both groups. However, the dulaglutide group showed significantly higher UACR increases than the semaglutide group (p < 0.01). More death events also occurred in the dulaglutide group (p < 0.01). Multivariate logistic regression revealed a higher risk of UACR increase with dulaglutide (p < 0.01). Subgroup analysis found dulaglutide associated with higher UACR in patients younger than 60, males, those with hypertension, without heart failure, those using angiotensin receptor blockers, biguanides, and statins, and those not using sodium-glucose cotransporter-2 inhibitors. Conclusions: Dulaglutide and semaglutide had comparable effects on slowing eGFR decline. However, dulaglutide was less effective in reducing UACR, particularly in the subgroups mentioned above. Full article

The enzyme transglutaminase 2 (TG2) has an open conformation with transamidase activity which crosslinks matrix proteins contributing to fibrosis development. LDN-27219 promotes the closed conformation of TG2, which can enhance vasodilation, but its effects in renal tissue are unknown. We investigated whether LDN-27219 treatment affects albuminuria and markers of renal fibrosis as well as ex vivo vasodilatation. Male C57BL/6 mice (n = 48) underwent unilateral nephrectomy plus insertion of a deoxycorticosterone acetate pellet (DOCA group) or nephrectomy only (sham group). Both groups were randomized to intraperitoneal treatment with either LDN-27219 (8 mg/kg twice daily) or vehicle for 2 weeks. Urine albumin excretion was evaluated by metabolic cages. Kidney tissue fibrosis markers were assessed by qPCR and Western blotting, while the TG2 conformational state was evaluated using native gel electrophoresis. Collagen staining was performed using Picrosirius red and quantified under circularly polarized light. Mesenteric arteries were mounted in wire myographs for evaluation of vasorelaxation. DOCA mouse developed significant albuminuria (p < 0.001 vs. sham), but neither TG2 mRNA nor protein expression was upregulated in the kidney. However, the relative amount of TG2 in the closed conformation was higher in DOCA mice. LDN-27219 did not affect albuminuria, but LDN-27219-treated DOCA mice showed less urine production and less collagen staining than vehicle-treated DOCA mice. LDN-27219 did not affect TG2 mRNA or TG2 protein expression or mRNA of fibrosis markers. LDN-27219-treated mice had enhanced vasorelaxation to the nitric oxide donor sodium nitroprusside. In conclusion, LDN-27219 treatment in the one-kidney DOCA–salt model did not affect renal TG2 mRNA and protein expression or albuminuria but still exerted beneficial effects in terms of reduced kidney fibrosis and urine production in addition to enhanced vasodilatation. Full article

Background/Objectives: In diabetic ketoacidosis (DKA), absolute insulin deficiency and elevation of counter-regulatory hormones may cause osmotic diuresis and water and electrolyte loss, which may lead to dehydration and renal failure. Fluids with high Na content are preferred in the DKA fluid therapy algorithm due to the association of Na with β-Hydroxybutyrate (β-HB) and the renal excretion of Na-β-HB. However, these fluids may cause hyperchloremic metabolic acidosis due to their high chloride concentration. In the literature, base-excess chloride (BE_Cl) has been suggested as a better approach for assessing the effect of chloride on acid–base status. Our aim in this study was to investigate the effect of fluids with BE_Cl values less than zero versus those with values equal to or greater than zero on the metabolic acid–base status in the first 6 h of DKA. Methods: This retrospective study included DKA cases managed in the tertiary intensive care units of five hospitals in the last 10 years. Patients were divided into two groups according to the Na-Cl difference of the administered fluids during the first 6 h of treatment: Group I [GI, fluids with Na-Cl difference = 0, chloride-rich group] and Group II [GII, fluids with Na-Cl difference > 32 mmol, chloride non-rich group]. Demographic data, blood gas analysis results, types and amounts of administered fluids, urea–creatinine values, and urine ketone levels were recorded. Results: Thirty-five patients with DKA in the ICU were included in the study (GI; 22 patients, GII; 13 patients). There was no difference between the patients in the two groups in terms of age, gender, and LOS-ICU. According to the distribution of the administered fluids, the main fluid administered in GI was 0.9% NaCl, whereas in the GII, it was bicarbonate, Isolyte-S, and 0.9% NaCl. In GI, the chloride load administered was higher; the BE_Cl level of the fluids was lower than in GII. At the end of the first 6 h, although sodium and strong ion gap values were similar, patients in GI were more acidotic due to iatrogenic hyperchloremia and, as a result, were more hypocapnic than GII. Conclusions: In conclusion, administering chloride-rich fluids in DKA may help reduce unmeasured anion acidosis. Still, risks cause iatrogenic hyperchloremic acidosis, which can hinder the expected resolution of acidosis and increase respiratory workload. Therefore, it is suggested that DKA guidelines be revised to recommend an individualized approach that avoids chloride-rich fluids and includes monitoring of metabolic parameters like Cl and BE_Cl. Full article

Aldosterone, a mineralocorticoid hormone synthesised in the adrenal cortex, is essential for maintaining electrolyte balance and fluid homeostasis. Its role in feline physiology remains underexplored, despite its importance in regulating sodium reabsorption and potassium excretion via mineralocorticoid receptors in renal tubules. This study is warranted given aldosterone’s importance in cats, particularly in light of their unique physiological traits, including highly concentrated urine and sensitivity to hydration status. Primary hyperaldosteronism, the most common feline adrenocortical disorder, contributes to arterial hypertension and chronic kidney disease, yet often remains underdiagnosed due to overlapping symptoms like hypokalaemia and hypertension. This research aimed to validate a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to measure serum aldosterone and to establish a reference interval in a population of healthy cats across a broad age range. The method demonstrated high precision and accuracy, with inter-assay coefficients of variation under 15%. Analysis of 49 healthy cats (40 young, 9 old) revealed a reference interval of 5.0–78.4 pg/mL (13.8–217.2 pmol/L). These findings provide a robust framework for diagnosing aldosterone-related disorders in cats and underscore the need for species-specific diagnostic tools. Improved understanding of aldosterone’s role could refine treatment strategies and enhance outcomes for affected feline patients. Full article

Background/Aim: Appropriate dietary assessment plays a crucial role in individualized nutritional therapy for individuals with type 2 diabetes mellitus (T2DM). Daily dietary variations must be considered in the estimation of usual dietary intake, and such data are limited in individuals with T2DM. This study aimed to evaluate within- and between-individual variations in protein, sodium, potassium, and phosphorus intakes estimated from 24 h urine collection (24 h UC) and semi-weighted dietary records (DRs) in Japanese individuals with T2DM. Methods: This study included 39 Japanese individuals (26 males, 13 females; mean age 64.6 years) with T2DM who attended two hospitals. Protein, sodium, potassium, and phosphorus intakes were estimated using 2-day 24 h UC and 3-day DRs and within- and between-individual variations were calculated using a one-way analysis of variance. Results: The mean protein, potassium, and phosphorus intakes did not significantly differ between 24 h UC and DRs. However, sodium intake was lower when estimated by DRs than by 24 h UC. The coefficients of within-individual variation (CV_w) differed between 24 h UC and DRs. For protein and phosphorus, the CV_w values were smaller by 12.5% and 8.0% in males and 2.3% and 3.0% in females, respectively, for 24 h UC than DRs. For sodium and potassium, the CV_w values were smaller by 7.0% and 4.8% in males, but larger by 5.0% and 3.3% in females, respectively, for 24 h UC than DRs. Conclusions: Our findings demonstrated that 24 h UC showed smaller within-individual variations than DRs for protein and phosphorus in both sexes, with sex-specific differences for sodium and potassium. Full article

Gitelman syndrome (GS) is a rare autosomal recessive renal tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria due to mutations in the SLC12A3 gene. This case report presents a 54-year-old African American female with near syncope and palpitations. The patient had a history of intermittent palpitations and generalized anxiety disorder and was previously diagnosed with GS. On presentation, the patient exhibited symptoms of severe hypokalemia and hypomagnesemia, attributed to medication non-adherence. Laboratory tests confirmed critically low potassium and magnesium levels, with elevated urine sodium and chloride. Treatment was initiated with oral and intravenous potassium and magnesium, leading to the normalization of electrolyte levels. This case highlights the challenges of managing GS, particularly in patients facing socioeconomic barriers that impede medication adherence and healthcare access. Personalized patient education, combined with comprehensive healthcare resources, is essential to mitigate complications and improve long-term outcomes in such cases. Full article

Diuretics are a class of pharmacological agents that promote the renal excretion of water and electrolytes, increasing urine output and reducing fluid retention. They play a critical role in the management of edematous syndromes, irrespective of their etiology (cardiac, renal, or hepatic), as well as in the treatment of hypertension (HTA). The mechanism of action of diuretics can be classified as either renal, as seen with saluretic diuretics that inhibit sodium and water reabsorption at various segments of the nephron, or extrarenal, involving alterations in the glomerular filtration pressure or osmotic mechanisms. Based on their site of action and mechanism, diuretics are categorized into multiple classes, including loop diuretics, thiazide and thiazide-like diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. These agents are frequently used in combination with other antihypertensive or heart failure medications to optimize therapeutic efficacy. By reducing the blood volume and peripheral vascular resistance, diuretics improve cardiac function, lower blood pressure, and enhance exercise tolerance. Additionally, they are employed in managing chronic kidney disease (CKD), electrolyte imbalances, and specific metabolic disorders. Given the potential for adverse effects such as electrolyte disturbances and renal dysfunction, diuretic therapy should be individualized, with the careful monitoring of the dosage, patient response, and comorbid conditions. Patient education on adherence, lifestyle modifications, and the recognition of side effects is essential for optimizing the therapeutic outcomes and minimizing the risks associated with diuretic therapy. Full article

Maintaining optimal hydration is critical for physiological function, particularly during intense physical activities, in which dehydration or overhydration can impair performance and recovery. Traditional methods for monitoring hydration status, such as body weight changes, bioelectrical impedance, and urine specific gravity, are limited by inconvenience and lack of real-time capability. This study introduces a novel graphene-based dual-sensing electrochemical sensor for the rapid and non-invasive quantification of sodium and potassium concentrations in human sweat, key biomarkers of hydration status. Leveraging graphene’s exceptional conductivity and functionalization potential, the sensor employs open-circuit potentiometry (OCP) to achieve high sensitivity and selectivity in detecting sodium and potassium. The sensor performance was validated against that of a commercial analyzer and ICP-OES, demonstrating a near-Nernstian response (61.93 mV/decade for sodium and 61.21 mV/decade for potassium detection) and a linear detection range spanning from 0.1 mM to 100 mM for both sodium and potassium monitoring in sweat. Sweat samples from an athlete during endurance exercise confirmed the sensor’s reliability, with results closely matching those of ICP-OES and outperforming the commercial analyzer in regards to accuracy and sample efficiency. This work represents a cross-validated study of a sweat-based sensor with a second analytical technique, highlighting its potential as a real-time hydration monitoring tool for use in sports and beyond. Full article