24-h Urine Research Articles

Chronic consumption of a bergamot-based beverage does not affect glucose, lipid and inflammatory biomarkers of cardiometabolic risk in healthy subjects: a randomised controlled intervention study.

Background: Pure bergamot juice exerts lipid lowering effects in dyslipidemic subjects. It is unknown whether bergamot-based beverages exert similar effects in healthy subjects. Aim: To assess the effects, if any, of a bergamot-based beverage (BBB, bergamot juice ≤25%) on lipid, metabolic and inflammatory biomarkers. Methods: Forty-five healthy subjects were randomised 1 : 1 to BBB intake (400 mL day-1) (55.5%) or control (44.5%) for 12 weeks. Anthropometric (waist circumference, body mass index (BMI)) and clinical (blood pressure) parameters, blood samples (glucose, glycated haemoglobin, insulinemia, lipid profile, liver and renal function, inflammatory biomarkers) and 24-h urine for the analysis of (poly)phenol metabolites were collected at the baseline and at 12 weeks. Intakes of energy, nutrients and food groups were assessed by a 7-day dietary record. Results: Both groups exhibited a time-related significant decrease in total cholesterol (p = 0.02), fasting plasma glucose (p = 0.016), insulin (p = 0.034), BMI (p < 0.001) and waist circumference (p = 0.04), but with no significant between-arm difference. The urinary profile of metabolites from the BBB-derived (poly)phenols well discriminated the two study groups, documenting good compliance in the intervention arm. Notably, urinary bergamot 3-hydroxy-3-methylglutaryl (HMG) -containing flavanones or derived HMG-containing metabolites were not detectable. BBB was well tolerated and no adverse events were recorded. Conclusion: This first randomized controlled trial of BBB consumption in healthy subjects showed no effects of BBB on the cardiometabolic risk profile. BBB consumption is a safe nutritional adjunct in the context of a well balanced diet.

Adequate Vegetable Intake Improves Metabolic Indices in Healthy Japanese Participants: A Randomized Crossover Study.

We aimed to elucidate the effect of a healthy diet containing adequate amounts of protein and vegetables on metabolic indices. In this randomized crossover study, twenty-two healthy Japanese participants ingested two different test meals: fish diet (F) or fish diet with adequate vegetable content (FV). Each 5-day diet load test was separated by a washout period of at least seven days. Metabolic indices were measured in fasting blood and 24-h urine samples. The delta (Δ) plasma glucose and Δserum low-density lipoprotein (LDL) cholesterol concentrations were significantly larger in the participants in group FV than in group F (p=0.042, p=0.013, respectively). The urinary pH in participants in group F on day 6 was significantly lower than on day 1 (p=0.008), and the Δurinary pH and Δnet gastrointestinal absorption of alkali of participants in group FV tended to be smaller than in group F (p=0.070, p=0.075, respectively). This study showed that a healthy diet containing adequate protein and vegetables reduced the dietary acid load and improved plasma glucose and serum LDL concentrations in healthy Japanese participants.

Effect of a Low Salt Diet on the Progression of Chronic Kidney Disease: A Prospective, Open-Label, Randomized Controlled Trial.

A causal relationship exists between salt intake and hypertension, stroke, and kidney disease. However, whether or not reduced salt intake slows progression of renal diseases has been intensely debated. In this prospective, open-label, randomized controlled trial, we examined the impact of a low salt diet on renal function, blood pressure, and other metabolic parameters. Herein, 194 patients with chronic kidney disease (CKD) stages 1 to 3 were randomized in low salt (intervention) and control groups. The intervention group was provided a low salt diet (1.5 g/day) for 3 months. The control group consumed their usual diet, and daily food intake was recorded in the control group. Renal function tests, 24-h urinary sodium excretion, urinary protein, serum calcium, phosphorus, and electrolyte levels were recorded monthly. After 3 months, the mean reduction in estimated glomerular filtration rate was significantly higher in the control group (mean reduction in eGFR, -3.011 mL/min/1.73 m2; 95% confidence interval (CI) = -5.367, -0.656, P = .013). Blood pressure (BP) decreased significantly in both groups; systolic and diastolic BP reduction at 3 months was significantly greater in the intervention group (systolic BP mean reduction -6.57/-4.29 mmHg; 95% CI = -10.24, -2.89) and diastolic BP mean reduction -6.95, -1.64 mmHg) compared with the control group (systolic BP mean reduction -0.58/-2.63 mmHg; 95%, CI = -4.33, 3.17 and diastolic BP mean reduction -5.34, -0.08 mmHg). The mean reduction in 24-h urine sodium excretion was greater in the intervention group, reaching a significant level at month 2 (-14.45 mmol/day; 95% CI = -27.63, -1.22). Overall, salt restriction can help slow the progression of renal insufficiency and results in statistically significant and clinically important reductions in BP among patients with CKD. NCT05716386 on 28/01/2023.

Fractional excretion of total protein in patients with nephrotic syndrome.

The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

Melittin induces autophagy to alleviate chronic renal failure in 5/6-nephrectomized rats and angiotensin II-induced damage in podocytes.

Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear. A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for in vivo assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an in vitro podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively. In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/LC3I ratio in podocytes. Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.

Activation of TGR5 Increases Urine Concentration by Inducing AQP2 and AQP3 Expression in Renal Medullary Collecting Ducts

Introduction: G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular signaling pathways after interacting with bile acids. TGR5 plays an important role in multiple physiological processes and is considered to be a potential target for the treatment of various metabolic diseases, including type 2 diabetes. Evidence has emerged that genetic deletion of TGR5 results in an increase in basal urine output, suggesting that it may play a critical role in renal water and salt reabsorption. The present study aims to elucidate the effect and mechanism of TGR5 activation on urine concentration. Methods: Mice were treated with TGR5 agonists (LCA and INT-777) for 3 days. The 24-h urine of mice was collected and analyzed for urine biochemical parameters. The mRNA expressions were detected by real-time PCR, and the protein expressions were detected by western blot. Immunohistochemistry and immunofluorescence were performed to examine the cellular location of proteins. The cultured primary medullary collecting duct cells were pretreated with H89 (a PKA inhibitor) for 1 h, followed by 12-h treatment of LCA and INT-777. Luciferase reporter assays were used to detect the effect of CREB on the gene transcription of AQPs. Gel electrophoretic mobility shift assays were used to analyze DNA–protein interactions. Results: Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation. In cultured primary medullary collecting duct cells, LCA and INT-777 dose-dependently upregulated AQP2 and AQP3 expression in a cAMP/PKA-dependent manner. Mechanistically, both AQP2 and AQP3 gene promoter contains a putative CREB-binding site, which can be bound and activated by CREB as assessed by both gene promoter-driven luciferase and gel shift assays. Conclusion: Collectively, our findings demonstrate that activation of TGR5 can promote urine concentration by upregulation of AQP2 and AQP3 expression in renal collecting ducts. TGR5 may represent an attractive target for the treatment of patients with urine concentration defect.

Impact of Plant and Animal Protein-Based Meals on Serum Fibroblast Growth Factor-23 Levels in Healthy Young Men: A Randomized Crossover Trial.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by osteocytes in response to dietary phosphate intake. An increase in FGF23 level is an indicator of excess phosphate intake relative to the residual nephron number. Therefore, avoiding excessive phosphate intake and inhibiting the elevation of serum FGF23 levels are important to preserve the number of functional nephrons. This randomized crossover trial aimed to determine the potential differences in the impacts on serum FGF23 levels between plant protein and animal protein-based meals in individuals with normal renal function. Nine young men were administered plant (no animal protein) or animal protein-based meals (70% of their protein was from animal sources) with the same phosphate content. The test meals consisted of breakfast, lunch, and dinner. Blood samples were collected in the morning, after overnight fasting, and before and after eating the test meals (for two consecutive days at the same hour each day). Furthermore, a 24-h urine sample was obtained on the day the test meal was consumed. No significant interactions were found among serum phosphate, calcium, and 1,25-dihydroxyvitamin D levels. However, after eating plant protein-based meals, serum FGF23 levels decreased and serum intact parathyroid hormone levels increased (interaction, p<0.05). Additionally, urine 24-h phosphate excretion tended to be lower in individuals consuming plant protein-based meals than in those consuming animal protein-based meals (p=0.06). In individuals with normal renal function, plant protein-based meals may prevent an increase in serum FGF23 levels and kidney damage caused by phosphate loading.

Applying stacking ensemble method to predict chronic kidney disease progression in Chinese population based on laboratory information system: a retrospective study.

Chronic kidney disease (CKD) is a major public health issue, and accurate prediction of the progression of kidney failure is critical for clinical decision-making and helps improve patient outcomes. As such, we aimed to develop and externally validate a machine-learned model to predict the progression of CKD using common laboratory variables, demographic characteristics, and an electronic health records database. We developed a predictive model using longitudinal clinical data from a single center for Chinese CKD patients. The cohort included 987 patients who were followed up for more than 24 months. Fifty-three laboratory features were considered for inclusion in the model. The primary outcome in our study was an estimated glomerular filtration rate ≤15 mL/min/1.73 m2 or kidney failure. Machine learning algorithms were applied to the modeling dataset (n = 296), and an external dataset (n = 71) was used for model validation. We assessed model discrimination via area under the curve (AUC) values, accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. Over a median follow-up period of 3.75 years, 148 patients experienced kidney failure. The optimal model was based on stacking different classifier algorithms with six laboratory features, including 24-h urine protein, potassium, glucose, urea, prealbumin and total protein. The model had considerable predictive power, with AUC values of 0.896 and 0.771 in the validation and external datasets, respectively. This model also accurately predicted the progression of renal function in patients over different follow-up periods after their initial assessment. A prediction model that leverages routinely collected laboratory features in the Chinese population can accurately identify patients with CKD at high risk of progressing to kidney failure. An online version of the model can be easily and quickly applied in clinical management and treatment.

Renal Transplantation in Rare Monogenic Urinary Stone Disease – A Single-center Experience

Introduction: Monogenic urinary stone disease (MUSD) tends to be more severe with early onset of symptoms and a higher risk of chronic kidney disease than sporadic USD. The literature on the outcome after renal transplant in patients with certain MUSD is scarce. Materials and Methods: This is a retrospective single-center observational study conducted in a tertiary care renal transplant unit in North India between 2018 and 2021. The renal transplant recipients who developed an end-stage renal disease (ESRD) due to renal calculus disease/nephrocalcinosis were included in the study. All the patients presented to us in an anuric state, and hence, a 24-h urine metabolic profile could not be performed. Ear, nose, and throat and ophthalmological evaluations were done to rule out extrarenal manifestations. These patients were subjected to genetic analysis, i.e., clinical exome sequencing using next-generation sequencing. Results: Out of 283 live renal transplants, 11 patients developed ESRD due to nephrocalcinosis/renal calculus disease. Out of 11, only 4 had genetic mutations and the rest did not have any identifiable genetic mutations. The gene mutations were identified in ADCY10, CLDN16, CaSR, and SLC3A4. The patient with ADCY10 mutation had a strong family history. The clinical phenotype and in silico parameters analysis predicted the variant to be damaging except the one with CaSR mutation which causes Hypocalciuric hypercalcemia syndrome, type 1. Three of four underwent surgical intervention at younger age. All underwent successful live-related renal transplantation, with good graft function on follow-up, without any recurrence of calculus in the allograft. Conclusion: Renal transplantation can be safely proceeded in patients with the above monogenic mutations. Genetic analysis should be a part of pretransplant evaluation in young onset nephrolithiasis and end-stage kidney disease patients to look for a monogenic cause, to assess the risk of recurrence postrenal transplant.

Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Analysis on Chemical Composition of Urinary Calculi and Evaluation on Metabolic Disturbance in 1080 Uyghur, Kazakh and Han Nationality Patients of Xinjiang

Urinary stones pose a significant health concern globally. The incidence rates vary and are influenced by diverse factors. Despite advancements in the treatment modalities, increasing rate of urinary stones necessitates the development of stone prevention strategies and understanding of metabolic risk factors. Objective: To determine the relationship between chemical composition of urinary calculi and evaluation on metabolic disturbance in 1080 Uyghur, Kazakh and Han patients of Xinjiang. Methods: The stone composition of 1080 patients and analysis of 24-h urine and serum biochemistry results of 775 cases was evaluated by infrared spectroscopic analysis and automatic biochemical machine respectively. Results: Among 644 cases of urinary stones, calcium oxalate stones (409 cases) and mixed type stones (436 cases) were predominant. Metabolic disturbances were found in 643 cases (82.97%) out of 775 patients, showing various urinary abnormalities like hyperuricosuria, hyperoxaluria, hyper-phosphaturia, hyper-cystinuria, hypercalciuria, hypomagnesuria, hypocitraturia, and reduced urine volume (&lt;2000ml in 407 cases). Conclusions: Urinary calculi have intimate connection with metabolic evaluation. Metabolic evaluation and composition of urinary calculi have great significance in treatment and prevention of urinary calculi.

Measuring diet by metabolomics: a 14-d controlled feeding study of weighed food intake

BackgroundMetabolomics has the potential to enhance dietary assessment by revealing objective measures of many aspects of human food intake. Although metabolomics studies indicate that hundreds of metabolites are associated with dietary intake, correlations have been modest (e.g., r < 0.50), and few have been evaluated in controlled feeding studies. ObjectivesThe aim of this study was to evaluate associations between metabolites and weighed food and beverage intake in a controlled feeding study of habitual diet. MethodsHealthy postmenopausal females from the Women’s Health Initiative (N = 153) were provided with a customized 2-wk controlled diet designed to emulate their usual diet. Metabolites were measured by liquid chromatography tandem mass spectrometry in end-of-study 24-h urine and fasting serum samples (1293 urine metabolites; 1113 serum metabolites). We calculated partial Pearson correlations between these metabolites and intake of 65 food groups, beverages, and supplements during the feeding study. The threshold for significance was Bonferroni-adjusted to account for multiple testing (5.94 × 10−07 for urine metabolites; 6.91 × 10−07 for serum metabolites). ResultsSignificant diet–metabolite correlations were identified for 23 distinct foods, beverages, and supplements (171 distinct metabolites). Among foods, strong metabolite correlations (r ≥ 0.60) were evident for citrus (highest r = 0.80), dairy (r = 0.65), and broccoli (r = 0.63). Among beverages and supplements, strong correlations were evident for coffee (r = 0.86), alcohol (r = 0.69), multivitamins (r = 0.69), and vitamin E supplements (r = 0.65). Moderate correlations (r = 0.50–0.60) were also observed for avocado, fish, garlic, grains, onion, poultry, and black tea. Correlations were specific; each metabolite correlated with one food, beverage, or supplement, except for metabolites correlated with juice or multivitamins. ConclusionsMetabolite levels had moderate to strong correlations with weighed intake of habitually consumed foods, beverages, and supplements. These findings exceed in magnitude those previously observed in population studies and exemplify the strong potential of metabolomics to contribute to nutrition research.The Women’s Health Initiative is registered at clinicaltrials.gov as NCT00000611.

Population pharmacokinetics and individualized dosing of vancomycin for critically ill patients receiving continuous renal replacement therapy: the role of residual diuresis.

Background: Vancomycin dosing is difficult in critically ill patients receiving continuous renal replacement therapy (CRRT). Previous population pharmacokinetic (PopPK) models seldom consider the effect of residual diuresis, a significant factor of elimination, and thus have poor external utility. This study aimed to build a PopPK model of vancomycin that incorporates daily urine volume to better describe the elimination of vancomycin in these patients. Methods: We performed a multicenter retrospective study that included critically ill patients who received intermittent intravenous vancomycin and CRRT. The PopPK model was developed using the NONMEM program. Goodness-of-fit plots and bootstrap analysis were employed to evaluate the final model. Monte Carlo simulation was performed to explore the optimal dosage regimen with a target area under the curve of ≥400mg/Lh and 400-600mg/L h. Results: Overall, 113 observations available from 71 patients were included in the PopPK model. The pharmacokinetics could be well illustrated by a one-compartment model with first-order elimination, with the 24-h urine volume as a significant covariate of clearance. The final typical clearance was 1.05L/h, and the mean volume of distribution was 69.0L. For patients with anuria or oliguria, a maintenance dosage regimen of 750mg q12h is recommended. Conclusion: Vancomycin pharmacokinetics in critically ill patients receiving CRRT were well described by the developed PopPK model, which incorporates 24-h urine volume as a covariate. This study will help to better understand vancomycin elimination and benefit precision dosing in these patients.

Cohort profile update-overview of over 35years of research in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study.

To provide an update on the cohort profile of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study, including objectives, study design, methods and description of the comprehensive data pool, as well as to summarize the most important research findings of recent years. In 1985, the open (dynamic) cohort started to collect information on diet, growth, development, and metabolism of healthy children and adolescents in Dortmund, Germany. Detailed data are collected annually during infancy, childhood, and adolescence of the participants, including a 3-day weighed dietary record, a 24-h urine sample, anthropometric and medical examinations as well as interviews on lifestyle. Even if the basic examination modules have not changed since the start over 35years ago, the DONALD study has been continuously further developed by introducing new modules. As such, participants are also invited for follow-up examinations during adulthood since 2005, including an additional fasting blood withdrawal. Overall, 2375 (♂: 1177; ♀: 1198) participants were recruited in the DONALD study between 1985 and 2022. Data from ~ 30,700 anthropometric measurements, ~ 19,200 dietary records, ~ 10,600 24-h urine and ~ 1300 blood samples are available from an observation period of over 35years. The DONALD study provides a large data pool for longitudinal studies on nutrition, growth, and health in childhood and adolescence, its impact on the development of diseases in early adult life as well as dietary intake trends over more than three decades.

Shear wave elastography of kidneys in children: utility in distinguishing steroid-resistant and steroid-sensitive nephrotic syndrome.

To assess the renal elasticity values using (SWE) and correlate the values with steroid sensitivity to distinguish between steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS) in children. In this IRB-approved cross-sectional study, 83 children (4-14years) diagnosed with nephrotic syndrome were included from July 2021 to December 2022. SWE measurements were done for each kidney's upper pole, interpolar region, and lower pole. Mean as well as median SWE were calculated. Correlation of the renal stiffness values was done with different laboratory findings (blood urea, serum creatinine, 24h urine protein, serum albumin, and serum cholesterol), the grayscale findings (cortical echogenicity, and corticomedullary differentiation), and the final diagnosis of SRNS and SSNS. The statistical tests were done at a significance level of α = 0.05. The median (IQR) overall SWE of kidneys was higher in SRNS group 12.64 (8.4-19.68) kPa than SSNS group 9.87 (8.20-12.56) kPa. The difference was significant (p = 0.004). At a cut-off of ≥ 10.694kPa (AUROC- 0.641), the overall SWE predicted SRNS group with a sensitivity of 70% and a specificity of 63%. A significant correlation (p < 0.05) was found between the SWE and 24-h urine protein, cortical echogenicity, and corticomedullary differentiation in SSNS, while only between SWE and corticomedullary differentiation in SRNS. The mean SWE was higher in children with SRNS. While SWE has potential to differentiate SSNS from SRNS, a different study design where SWE is performed at presentation is needed for confirmation.

The correlation of spot urinary protein-to-creatinine ratio with 24-h urinary protein excretion in various glomerulopathies.

Proteinuria is an important and well-known biomarker of many forms of kidney injury. Its quantitation is of particular importance in the diagnosis and management of glomerular diseases. Its quantification can be done by several methods. Among these, the measurement of 24-h urinary protein excretion is the gold standard method. However, it is cumbersome, time-consuming, and inconvenient for patients and is not completely foolproof. Many alternative methods have been tested over time albeit with conflicting results. Among the latter, the measurement of urine protein-to-creatinine ratio (uPCR) in single-voided urinary samples is widely used. The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation, whereas others did not. To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single large-volume nephrological center in Pakistan. This cross-sectional, observational study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from September 2017 to March 2018. All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled. All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations. A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample. The data of patients were collected in a proforma. SPSS version 20.0 was used for statistical analysis. A total of 157 patients were included. Their mean age was 30.45 ± 12.11 years. There were 94 (59.8%) males and 63 (40.2%) females. The mean 24-h urinary protein excretion was 3192.78 ± 1959.79 mg and the mean spot uPCR was 3.16 ± 1.52 in all patients. A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion (r = 0.342, P = 0.01) among all patients. On subgroup analysis, a slightly better correlation was found in patients older than 47 years (r = 0.78), and those with body mass index > 25 kg/m2 (r = 0.45). The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods. Overall, the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies. The agreement between the two methods was also poor. Hence, there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.

Spironolactone improves left atrial function and atrioventricular coupling in patients with resistant hypertension.

To determine the blood pressure independent effects of spironolactone on left atrial (LA) size and function in patients with resistant hypertension (RHTN). Patients with RHTN (n = 36, mean age 55 ± 7) were prospectively recruited. Spironolactone was initiated at 25mg/day and increased to 50mg/day after 4 weeks. Other antihypertensives were withdrawn to maintain constant blood pressure. Cardiac magnetic resonance imaging was performed at baseline and after 6 months of spironolactone treatment and changes in LA functional metrics were assessed. LA size and function parameters were improved (p < 0.05) from baseline to month-6: LA volumes indexed to body surface area (LAVI) were reduced (LAVImaximum 41.4±12 vs. 33.2±9.7 mL/m2; LAVIpre-A 32.6±9.8 vs. 25.6±8.1 mL/m2; median LAVIminimum 18.5 [13.9-24.8] vs. 14.1 [10.9-19.2] mL/m2); left atrioventricular coupling index was reduced (28.2±11.5 vs. 22.7±9.2%); LA emptying fractions (LAEF) were increased (median total LAEF 52.4 [48.7-60.3] vs. 55.9 [50.3-61.1] %; active LAEF 40.2±8.6 vs. 43.1±7.8%). LA global longitudinal strain in the active phase was increased (16.3±4.1 vs. 17.8±4.2%). The effect of spironolactone was similar in patients with high (N = 18) and normal (N = 18) aldosterone status (defined by plasma renin activity and 24-h urine aldosterone). Treatment of RHTN with spironolactone is associated with improvements in LA size and function, and atrioventricular coupling, regardless of whether aldosterone levels were normal or high at baseline. This study suggests the need for larger prospective studies examining effects of mineralocorticoid receptor antagonists on atrial function and atrioventricular coupling.

Metabolomic Insights on Potassium Excretion, Blood Pressure, and Glucose Homeostasis: The African-PREDICT Study

BackgroundLow-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods. ObjectivesUsing metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension. MethodsA total of 440 White and 350 Black adults from the African-PREDICT study (aged 20–30 y) were included. Twenty-four-hour blood pressure (BP) was measured. Potassium, sodium, and fasting glucose concentrations were analyzed in 24-h urine and plasma samples. Liquid chromatography-tandem mass spectrometry-based metabolomics included the analyses of amino acids and acylcarnitines in spot urine samples. ResultsBlack participants had lower urinary potassium concentrations than Whites (36.6 compared with 51.1 mmol/d; P < 0.001). In White but not Black adults, urinary potassium correlated positively with 2-aminoadipic acid (2-AAA) (r = 0.176), C3-[propionyl]carnitine (r = 0.137), C4-[butyryl]carnitine (r = 0.169) and C5-[isovaleryl]carnitine (r = 0.167) in unadjusted and 2-AAA (r = 0.158) and C4-carnitine (r = 0.160) in adjusted analyses (all P < 0.05 and q < 0.05). Elevated C0-, C3-, and C5-carnitine in turn were positively associated with systolic BP (Black and White groups), diastolic BP (Black group), and glucose (White group) (all P < 0.05). ConclusionsRacial differences are an important consideration when investigating nutrient–metabolite relationships and the role thereof in cardiovascular disease. Only in White adults did urinary potassium associate with 2-AAA and short-chain acylcarnitines. These metabolites were positively related to BP and fasting plasma glucose concentrations. In White adults, the metabolomic profiles related to potassium excretion may contribute to BP regulation and glucose homeostasis.This trial was registered at clinicaltrials.gov as NCT03292094.

Diagnostic value of random urine protein/creatinine ratio for preeclampsia

ObjectiveThe 24-h urine protein remains the gold standard to diagnose proteinuria in suspected preeclamptic patients. However, this test is time consuming and sometimes inaccurate. In this study, we aimed to analyse the correlation between the random urine protein/creatinine ratio (UPCR) and 24-h urine protein and to explore the clinical value of UPCR in the diagnosis of preeclampsia. MethodWe retrospectively evaluated 109 pregnant women from our hospital who had hypertensive diseases. They were grouped according to time of urine collection and disease severity to compare differences in random urine protein, urine creatinine, and UPCR. The correlation between the UPCR and 24-h urine protein was determined by Pearson's linear correlation. ResultsWe found no statistically significant differences in random urine protein, urine creatinine, or UPCR among the four time of sampling groups. Further, random urine protein, UPCR, and 24-h urine protein between the gestational hypertension and preeclampsia groups differed significantly (P < 0.001). Correlation analysis showed significant positive correlation between random urine protein, and 24-h urine protein, and UPCR and 24-h urine protein, with r values of 0.789 and 0.810, respectively. According to the receiver operating characteristic (ROC) curve, the optimal threshold, sensitivity, specificity, and area under the curve of UPCR for the diagnosis of preeclampsia were 0.456 g/mmol, 67.8 %, 78.3 %, and 0.747, respectively (95 % confidence interval [CI], 0.65–0.844). ConclusionThis study indicated that UPCR is significantly correlated with 24-h urine protein and is expected to replace the 24-h urine protein test as a diagnostic indicator of preeclampsia.

Ameliorative effects of Modified Huangqi Chifeng decoction on podocyte injury via autophagy mediated by PI3K/AKT/mTOR and AMPK/mTOR pathways

Ethnopharmacological relevanceProteinuria is recognized as a risk factor for the exacerbation of chronic kidney disease. Modified Huangqi Chifeng decoction (MHCD) has distinct advantages in reducing proteinuria. Our previous experimental results have shown that MHCD can inhibit excessive autophagy. However, the specific mechanism by which MHCD regulates autophagy needs to be further explored. Aim of the studyIn this study, in vivo and in vitro experiments were conducted to further clarify the protective mechanism of MHCD on the kidney and podocytes by regulating autophagy based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathways. Materials and methodsBy a single injection via the tail vein, Sprague–Dawley rats received Adriamycin (5 mg/kg) to establish a model of proteinuria nephropathy. They were divided into control, model, MHCD, 3-methyladenine (3 MA), 3 MA + MHCD, and telmisartan groups and were administered continuously for 6 weeks. The MHCD-containing serum was prepared, and a model of podocyte injury induced by Adriamycin (0.2 μg/mL) was established. ResultsMHCD reduced the 24-h urine protein levels and relieved pathological kidney damage. During autophagy in the kidneys of rats with Adriamycin-induced nephropathy, the PI3K/AKT/mTOR signaling pathway is inhibited, while the AMPK/mTOR signaling pathway is activated. MHCD antagonized these effects, thereby inhibiting excessive autophagy. MHCD alleviated Adriamycin-induced podocyte autophagy, as demonstrated using Pik3r1 siRNA and an overexpression plasmid for Prkaa1/Prkaa2. Furthermore, MHCD could activate the PI3K/AKT/mTOR signaling pathway while suppressing the AMPK/mTOR signaling pathway. ConclusionsThis study demonstrated that MHCD can activate the interaction between the PI3K/AKT/mTOR and the AMPK/mTOR signaling pathways to maintain autophagy balance, inhibit excessive autophagy, and play a role in protecting the kidneys and podocytes.