24-h Excretion Research Articles

Health effects of the New Nordic Renal Diet in patients with stage 3 and 4 chronic kidney disease, compared with habitual diet: a randomized trial

BackgroundChronic kidney disease (CKD) leads to an accumulation of waste products and causes adverse cardiometabolic effects. ObjectivesWe investigated the health effects of the New Nordic Renal Diet (NNRD), a novel meal pattern reduced in phosphorus, protein, and sodium. MethodsA 26-wk randomized trial compared the NNRD with a habitual diet. The NNRD group received weekly home deliveries of food and recipes. Monthly study visits included fasting blood samples, 24-h urine samples, blood pressure, and anthropometric measurements. Intention-to-treat analysis used linear mixed-effects models. ResultsSixty patients, mean estimated glomerular filtration rate (eGFR) 34 mL/min/1.73 m2 and body mass index of 25–27 kg/m2, were included and 58 completed. Metabolic syndrome was present in 53% (NNRD group) and 57% (control group). The NNRD group (n = 30) reduced their 24-h urine phosphorus excretion by 19% (−153 mg; 95% confidence interval [CI]: −210, −95), control group (n = 30) (no change), between-group difference −171 mg (95% CI: −233, −109; P < 0.001). Proteinuria was reduced by 39% in the NNRD group (−0.33 g/d; 95% CI: −0.47, −0.18), control group (no change), between-group difference −0.34 g/d (95% CI: −0.52, −0.17; P < 0.001). Plasma urea was reduced by −1.5 mmol/L in the NNRD group (95% CI: −2.1, −0.9), control group (no change), between-group difference −1.4 mmol/L (95% CI: −2.0, −0.7; P < 0.001). Systolic blood pressure fell by −5.2 mmHg in the NNRD group (95% CI: −8.4, −2.1), control group (no change), between-group difference −3.9 mmHg (95% CI; −7.6, −0.2; P = 0.04). The NNRD group lost −1.7 kg (95% CI: −2.6, −0.8), control group (no change), between-group difference −2.0 kg (95% CI: −3.0, −1.0; P < 0.001). There were no effects on eGFR during the 26-wk intervention. ConclusionNNRD in moderate CKD reduces phosphorus excretion, proteinuria, systolic blood pressure, and weight, mainly by reducing abdominal fat.This trial was registered at clinicaltrials.gov as NCT04579315.

Is a spot urine sample a good substitution to estimate 24-h urinary sodium excretion in a population ≥ 50years old? A validation study.

A variety of prediction equations have been able to estimate 24-h urinary sodium excretion from spot urine samples; however, Iranians over the age of 50 have not been compared and verified. Using spot urine samples as a substitute for 24-h urine samples to estimate 24-h urine sodium excretion among the population age 50 and older are the purpose of this study. A 24-h urinary sodium excretion was studied by well-known Kawasaki, INTERSALT, Tanaka, and World Health Organization/Pan American Health Organization (WHO/PAHO) formulas. On 360 individuals, the mean bias, agreements between estimated and measured values, correlation, absolute and relative differences, and misclassification rates were evaluated for four equations. As a result, the mean urinary sodium excretion for a 24-h period was 136.3 ± 52.21mmol/24-h, which corresponds to a calculated intake of 9.1 ± 3.8g of salt per day. According to the WHO/PAHO formula, the mean bias between measured values and estimated 24-h urinary sodium excretion is - 21.6mg/day (95% confidence interval (CI) - 144.8, 101.6mg/day), which is the smallest difference compared with the other three formulas. The lowest rate of individual misclassification of salt intake was 40% for WHO/PAHO, especially for those who consumed less than 9g/day, while Kawasaki had the lowest misclassification rate at higher levels of salt intake. As a result of our research, the WHO/PAHO equations accurately predict 24-h urinary sodium excretion among Iranians aged ≥ 50 more than other equations, both at the population level and at the individual level. However, further study is needed in regard to different ages in Iran.

Human biomonitoring of deoxynivalenol (DON) - Assessment of the exposure of young German adults from 1996 - 2021.

The mycotoxin deoxynivalenol (DON) is a frequently found contaminant in cereals and cereal-based products. As a German contribution to the European Joint Programme HBM4EU, we analysed the total DON concentration (tDON) in 24-h urine samples from the German Environmental Specimen Bank (ESB). In total, 360 samples collected in 1996, 2001, 2006, 2011, 2016, and 2021 from young adults in Muenster (Germany), were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) after enzymatic deconjugation of the glucuronide metabolites. tDON was found in concentrations above the lower limit of quantification (0.3μg/L) in 99% of the samples. Medians of the measured concentrations and the daily excretion were 4.3μg/L and 7.9 μg/24h, respectively. For only nine participants, urinary tDON concentrations exceeded the provisional Human biomonitoring guidance value (HBM GV) of 23μg/L. Urinary tDON concentrations were significantly higher for male participants. However, 24-h excretion values normalized to the participant's body weight did not exhibit any significant difference between males and females and the magnitude remained unchanged over the sampling years with exception of the sampling year 2001. Daily intakes were estimated from excretion values. Exceedance of the tolerable daily intake (TDI) of 1μg/kg bw per day was observed for less than 1% of all participants. TDI exceedances were only present in the sampling year 2001 and not in more recent sampling years while exceedance of the HBM guidance value was also observed in 2011 and 2021.

Hypoparathyroidism – management, information needs, and impact on daily living from the patients’ perspective: results from a population-based survey

PurposeHypoparathyriodism (hypoPT) is a rare endocrine disorder. It is not known how hypoPT is managed in Germany or whether patients have unmet information needs or impairments in their daily living.MethodsHypoPT patients at a minimum of 6 months’ post-diagnosis were invited to participate in an online survey through their treating physician or through patient organizations. An extensive questionnaire, which was developed and pilot-tested with hypoPT patients, was administered.ResultsA total of 264 patients with a mean age of 54.5 years (SD: 13.3), 85.2% female and 92% with postsurgical hypoPT, participated in the study. In total, 74% of the patients reported regular monitoring of serum calcium at least every 6 months, with lower control frequencies for phosphate (47%), magnesium (36%), creatinine (54%), and parathyroid hormone (50%), and 24-h urine calcium excretion (36%) on a yearly basis. Information on symptoms of hypo- and hypercalcemia was available in 72 and 45% of the patients. Information needs were related to the disease and its treatment as well as to nutrition, physical activities/sports, and support opportunities. Statistically significant differences for all information needs in association with symptom burden were observed. Hospitalization for hypocalcemia was reported by 32%, nutritional impairments (38%) or impact on work ability (52%) was available among patients with hypoPT.ConclusionHypoPT patients experience impairments in daily living and report unmet information needs. Patient and physician education regarding hypoPT is one of the key concepts for improving the management of patients with hypoPT.

Comparison of random urine protein/creatinine ratio with 24-hour urine protein in suspected pre-eclampsia

IntroductionProteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients. MethodA total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR in random urine samples and protein excretion in the 24-h urine collection was determined by Deming Regression analysis and Pearson correlation on EP evaluator and SPSS respectively. ResultThere was a significant positive correlation between the numerical values obtained by 24-h urine protein and the UPCR (R = 0.88, P < 0.001). Concordance analysis showed 81.1% positive agreement for proteinuria between methods (>300 mg/24hr and >0.3) and 71.4% negative agreement. The clinical sensitivity and specificity of the UPCR was 74% and 69% respectively. ConclusionOverall, UPCR was well correlated with 24-h urine protein and could be an effective and compliant screening tool to indicate proteinuria in preeclamptic patients.

Association between change of albuminuria and left ventricular diastolic function in type 2 diabetes

Abstract Funding Acknowledgements Type of funding sources: None. Background Albuminuria is associated with left ventricular (LV) hypertrophy and diastolic dysfunction in patients with type 2 diabetes (T2DM), however the role of change in albuminuria and cardiac structure and function changes remain unclear. The aim of our study was to investigate the impact of change in albuminuria on changes of echocardiography parameters. Methods Patients with T2DM without cardiovascular disease at baseline were recruited from 2012 to 2016. All patients were performed with detailed echocardiography examination and received urine albumin to creatinine ratio (UACR) or 24-h urine albumin excretion (UAE) test at baseline and follow-up. Multivariable linear regression was applied to estimate the association between albuminuria and changes of echocardiography parameters. Results A total of 199 patients with T2DM were recruited (female, 47.2%; mean age, 61±10 years). Patients were divided into 4 albuminuria change groups according to baseline UACR or UAE level, 8 patients were in macroalbuminuria to none-macroalbuminuria group, 93 in none-macroalbuminuria-stable group, 68 in macroalbuminuria-stable group, and 30 in none-macroalbuminuria to macroalbuminuria group. There was a significant difference in the change of LV diastolic function (estimated by average E/e’) by albuminuria change groups (mean [SD] average E/e’: macroalbuminuria to none-macroalbuminuria, −1.40 [2.83]; none-macroalbuminuria-stable, 0.64 [2.16]; macroalbuminuria-stable, 0.97 [2.59]; non-macroalbuminuria to macroalbuminuria, 1.27 [2.71]; P=0.04). However, the changes in LV mass index (LVMi), ejection fraction (LVEF), E/A, and left atrial volume index (LAVi) between patients in different albuminuria change groups were insignificant. Multivariable regression demonstrated non-macroalbuminuria to macroalbuminuria was associated with increase in average E/e’, compared to patients with macroalbuminuria to none-macroalbuminuria (ß = 1.92, P &amp;lt; 0.05) after adjusting age, sex, hypertension, body mass index, eGFR, and diabetes duration. Conclusion The progression of none-macroalbuminuria to macroalbuminuria was associated with greater deterioration of LV diastolic function.

#2971 LONG-TERM EFFECTS OF THE NEW NORDIC RENAL DIET ON PHOSPHOROUS HOMEOSTASIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 AND 4

Abstract Background and Aims Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. The New Nordic Renal Diet (NNRD) is a whole food approach designed by our group, with low dietary phosphorus content (850 mg/day). In a 1-week study, NNRD had positive effects on phosphorus homeostasis in patients with CKD stage 3-4 [1]. The aim of the present study was to examine the long-term health effects of a dietary intervention with NNRD in patients with CKD stage 3-4 [2]. Method A 26-week randomized, controlled, non-blinded trial comparing the effect of NNRD vs. non-restricted habitual diet. Patients in the NNRD group received weekly home delivery of fresh food items (free of charge) and recipes for five days of the week, and on the remaining two days they were instructed to prepare meals according to the NNRD food principles. The study was designed with seven follow-up visits in the outpatient clinic where fasting blood samples and 24-hour urine collection were delivered. Linear mixed-effects models were used to assess the effects of the intervention, time, and the potential interaction between intervention and time. The primary endpoint was the difference in 24-hour urine phosphorus excretion between the two study groups. Secondary endpoints included fractional phosphorus excretion and plasma fibroblast growth factor 23 (p-FGF23). Results Sixty patients (mean age 54 years, 31 women) with mean eGFR of 34 ml/min/1.73 m2 were included. Two patients were withdrawn due to dialysis initiation. In the NNRD-group (n = 29), mean 24-hour urine phosphorus excretion during the intervention period was 651 mg (SD, 35 mg) vs. 930 mg (SD, 84 mg) in the control group (n = 29), between-group difference 279 (95% CI; -372, -91; P &amp;lt; 0.001) (Figure 1). Mean fractional phosphorus excretion was 11% (SD, 5%) in the NNRD-group and 14% (SD, 7%) in the control group, between-group difference 3% (95% CI; -6.4, -0.8; P = 0.01). Mean p-FGF23 was 162 pg/ml (SD, 130 pg/ml) in the NNRD-group and 215 pg/ml (SD, 230 pg/ml) in the control group, between-group difference 52 pg/ml (95% CI; -100, 73; P = 0.03). P-urea was 3.4 mmol/L lower in the NNRD group (95% CI; -5.3, -0.2, P = 0.03). P-albumin was 1.1 g/L higher in the NNRD group (95% CI; 0.02, 2.4; P = 0.04) and 24-h urine bicarbonate excretion was 4.1 mmol higher in the NNRD group (95% CI; 0.7, 7.5, P = 0.01). There was no difference between study groups in p-phosphorous, p-creatinine, p-potassium, p-calcium, p-lipids, or proteinuria. Conclusion NNRD intervention in the context of fresh food delivery and recipes was feasible and had a major beneficial effect on phosphorous parameters in patients with CKD 3-4.

#5541 EVALUATION OF PROTEIN MALNUTRITION IN CKD PATIENTS ON LOW-PROTEIN DIET

Abstract Background and Aims Low-protein diet is considered crucial in patients with chronic kidney disease to slow down kidney function deterioration and control metabolic variables such as serum phosphate, urea and bicarbonate. However, low-protein diet may result in malnutrition if patients do not respect nutritional prescription. Thus, the present study examined the risk of protein malnutrition in CKD patients who started a low-protein diet. Method We analysed anthropometric variables, nutrient intake and body composition in 27 patients with CKD stage 4-5 (M/F 15/12; 69±15 years; 72±18 kg; BMI 27.3±7 kg/m2; serum creatinine 4.9±1.9 mg/dl; GFR 11±4 ml/min; 10 diabetic patients) before and after 3-months of low-protein diet (0.6 g/kg). We estimated nutrient intake with a food frequency questionnaire composed of 37 items and administered by a nutritionist who also prescribed the low-protein diet. We also measured body fat mass (FM) and free-fat mass (FFM) and appendicular skeletal muscle mass using bioimpedentiometry analysis (Akern, Florence). Patients having a protein intake lower than 0.6 g/kg at the nutritional survey was defined as malnourished. Results In the whole sample, after a 3-month diet protein intake decreased from 0.87±0.23 to 0.69±0.18 g/kg (p&amp;lt;0.001; Wilcoxon test). Protein intake was positively correlated with 24-h urine excretion of phosphate at baseline (r = 0.69, p = 0.012) and after 3-monts of diet (r = 0.62, p = 0.02). The diet induced a decrease in body weight (72±18 to 70±17 kg; p = 0.001), BMI (27.3±7 to 26.7±6.8 kg/m2; p = 0.001), FM (24±11 to 21±11 kg; p = 0.006), serum phosphate (1.68±0.33 to 1.52±0.32 mmol/l; p = 0.033) and urea (166±53 to 133±42 mg/dl; p&amp;lt;0.001), whereas FFM, expressed as percentage of body weight, significantly increased (69±9 to 73±8%; p = 0.011). Six patients (22%; 3 diabetic patients) had a protein intake lower than 0.6 g/kg after 3-months of diet. Their protein intake was significantly lower than that in the other 21 patients with protein intake above 0.6 g/kg (0.43±0.1 vs 0.77±0.12 g/kg; p&amp;lt;0.001). These patients had lower FM (14±2 vs 26±11 kg; p = 0.03) and protein intake before starting the low-protein diet than the other 21 patients (0.64±0.06 vs 0.94±21 g/kg; p = 0.003). Patients with protein intake lower than 0.6 g/kg slightly decreased FFM after 3 months of diet compared to the value at baseline (52±7 to 50±7 kg; p = 0.07); conversely the other 21 patients did not change FFM (51±10 to 53±11 kg; p = 0.17), but significantly decreased FM (26±11 to 23±12 kg; p&amp;lt;0.001). Conclusion In conclusion, protein malnutrition may occur during a low-protein diet in CKD patients with a low consumption of proteins before starting this diet. Nutritional analysis is necessary to identify CKD patients at risk of protein malnutrition and to adequately follow up CKD patients on low protein diet.

#2892 CRITICAL ROLE OF SERUM RESPONSE FACTOR IN PODOCYTE EPITHELIAL–MESENCHYMAL TRANSITION OF DIABETIC NEPHROPATHY

Abstract Background and Aims To investigate the expression and function of serum response factor (SRF) in podocyte epithelial–mesenchymal transition (EMT) of diabetic nephropathy (DN). Method Expression of SRF, pSRF, synaptopodin, P-cadherin, ZO-1, α-SMA, FSP-1, fibronectin and collagen-1 were examined in podocytes or renal cortex following high glucose. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 to investigate how SRF influence podocyte EMT in DN. Streptozocin was used to generate DM in rats. Results ① High glucose induced EMT and SRF upregulation in podocytes (Figure 1). High glucose suppressed synaptopodin and ZO-1 expression, and induced SRF, pSRF collagen-1, FSP-1 and α-SMA expression. SRF transferred from cytoplasm to nuclei obviously and the level of SRF was also increased in podocytes after high glucose treatment. ② SRF overexpression mediated EMT, migration and barrier dysfunction of podocytes (Figure 2). Overexpression of exogenous SRF reduced epithelial synaptopodin expression, and increased collagen-1, FSP-1, α-SMA and Snail expression in podocytes. Transwell chamber migration assay showed that overexpression of SRF significantly upregulated the migration of podocytes across the pores of transwell filters. Albumin filtration assay showed that albumin easily diffused across the monolayer of podocytes transfected with SRF cDNA. ③ Inhibition of SRF preserved phenotypes of podocytes in vitro (Figure 3). CCG-1423 selectively suppressed the expression of pSRF and SRF in podocytes after high glucose stimulation. Besides, simultaneous treatment of podocytes with CCG-1423 also significantly abolished the reduction of synaptopodin expression and the induction of collagen-1, FSP-1, α-SMA and Snail expression. CCG-1423 also reduced the transfer of SRF from cytoplasm to nucleus in podocytes treated with high glucose. ④ The effect of CCG-1423 in diabetic rats (Figure 4–-5). CCG-1423 significantly abrogated the reduction of synaptopodin expression and the induction of SRF, collagen-1, α-SMA and FSP-1 expression in renal cortex tissues. Masson and PAS staining demonstrated that renal glomerular fibrosis was present in DM group, and after 8 weeks treatment with CCG-1423, renal glomerular fibrosis was dramatically ameliorated. In addition, CCG-1423 significantly preserved P-cadherin expression and suppressed α-SMA and FN expression in DN rats. More importantly, CCG-1423 dramatically decreased 24-h urine protein excretion by about 50%, and increased serum albumin, compared with DM group. Conclusion Together, increased SRF activity provokes podocytes EMT and dysfunction in DN. Targeting SRF by small molecule inhibitor may be an attractive therapeutic strategy for DN.

RAASi Therapy Attenuates the Association between 24-h Urinary Potassium Excretion and Dietary Potassium Intake in CKD Patients.

The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 ± 13 years and affected by CKD stage 3-4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = -0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients.

Pathophysiological and Diagnostic Aspects of Sarcopenia in Hemodialysis Patients

Chronic kidney disease and renal replacement therapy, particularly hemodialysis, contribute to the development of negative protein balance and muscle dysfunction in dialysis patients, from the development of protein-energy malnutrition to sarcopenia. Due to multifactorial etiology and complex pathophysiological patterns, sarcopenia has proven to be a significant predictor of cardiovascular events and is associated with a higher risk of overall mortality. Screening methods of chronic kidney patients and patients on hemodialysis who are at higher risk of developing sarcopenia, as well as diagnostic methods for this group of patients are not clearly defined, hence methods used for the general population of elderly patients, especially based on the revised European consensus on definition and diagnosis of sarcopenia of the European Working Group on Sarcopenia in Older People (EWGSOP2), are utilized in this subpopulation as well. Therefore, there is a need to define new biomarkers of sarcopenia such as the existing 24h urine excretion of creatinine, a product of estimated glomerular filtration of cystatin C and creatinine or myostatin and their use in routine work with dialysis patients to identify this condition among them and reduce morbidity and mortality.

Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4)

Nedosiran is an N-acetyl-D-galactosamine (GalNAc)–conjugated RNA interference agent targeting hepatic lactate dehydrogenase (encoded by the LDHA gene), the putative enzyme mediating the final step of oxalate production in all three genetic subtypes of primary hyperoxaluria (PH). This phase I study assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous nedosiran in patients with PH subtype 3 (PH3) and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. Single-dose nedosiran 3 mg/kg or placebo was administered in a randomized (2:1), double-blinded manner. Safety/tolerability, 24-h urinary oxalate (Uox) concentrations, and plasma nedosiran concentrations were assessed. The main PD endpoint was the proportion of participants achieving a > 30% decrease from baseline in 24-h Uox at two consecutive visits. Six participants enrolled in and completed the study (nedosiran, n = 4; placebo, n = 2). Nedosiran was well-tolerated and lacked safety concerns. Although the PD response was not met, 24-h Uox excretion declined 24.5% in the nedosiran group and increased 10.5% in the placebo group at Day 85. Three of four nedosiran recipients had a > 30% reduction in 24-h Uox excretion during at least one visit, and one attained near‐normal (i.e., ≥ 0.46 to < 0.60 mmol/24 h; ≥ 1.0 to < 1.3 × upper limit of the normal reference range) 24-h Uox excretion from Day 29 to Day 85. Nedosiran displayed predictable plasma PK. The acceptable safety and trend toward Uox-lowering after single-dose nedosiran treatment enables further clinical development of nedosiran in patients with PH3 who currently have no viable therapeutic options. A plain language summary is available in the supplementary information.

Estimated 24-Hour urinary sodium and potassium excretion in adults in the Northwest Region of Morocco, 2017

BackgroundExcessive sodium (Na) and insufficient potassium (K) intake contribute to a high risk of cardiovascular events. Morocco lacks data on actual Na and K intake in adults. We estimated mean Na and K intake in a Moroccan population of adults residing in the Northwest region using 24-h urinary excretion and examined their association with blood pressure (BP).MethodsA total of 371 adults from this region, who were recruited for the STEPs Survey Morocco 2017, completed demographic, anthropometric as well as BP data and provided a valid 24-h urine collection according to the standard World Health Organization (WHO) protocol. Multiple Linear Regression analysis was used to examine the association between 24-h urinary sodium (24-hUNa) and 24-h potassium excretion (24-hUK) with BP.ResultsMean Na excretion was 2794 mg/day and mean K excretion was 1898 mg/day. Overall, only 114 (30.7%) adults met the WHO recommendation for Na intake (< 2000 mg/d) and 31 (8.4%) met the adequate level for K intake (⩾3510 mg/d). There was no association between 24-hUNa and 24-hUK with BP (P > 0.05 for all).ConclusionNa intake was higher and K intake was lower than WHO recommendations in the study population. There was no association between estimated Na and K intake levels with BP in this population.

Comparison of Magnesium Status Using 24-h Urine Magnesium Content and Magnesium Fraction Excretion in PCOS with Non-PCOS Control Women: a Cross-sectional Study.

Magnesium (Mg) is the second most frequent intracellular cation, having an important role in normal enzyme function and insulin secretion. Polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age and often associated with insulin resistance. Two systematic reviews and meta-analyses have been conducted to compare mean serum Mg levels between PCOS and control groups. Both studies detected unexplained heterogeneity among input studies and the two conclusions contradict each other, while approximately 1% of total body Mg is present in extracellular fluid (ECF) and serum Mg level does not represent Mg status well. For the first time, we investigated magnesium renal fraction excretion (FEMg) and compared mean values between PCOS and non-PCOS control women. This study is a cross-sectional analysis conducted at an academic medical center. Forty-four women were included in the PCOS group based on the Rotterdam criteria and 50 non-PCOS women were included in the control group. Statistical analysis of the relationship between 24-h urinary Mg content and FEMg, and also physical and metabolic variables, was performed. Main outcome measurements are 24-h urinary Mg content and FEMg. Mean values of 24-h urinary Mg content and FEMg did not significantly differ between PCOS and control groups (P = 0.22 and P = 0.24, respectively). Also, serum Mg levels and Ca/Mg ratio were similar between the groups (P = 0.17 and P = 0.26, respectively). Our data suggested Mg status in the PCOS group was similar to the non-PCOS control group and both were not magnesium deficient. For further investigation, we recommend using FEMg for evaluating Mg status rather than serum Mg levels. Considering collection of background diet is helpful and desired for future studies.

The association between sodium intake and coronary and carotid atherosclerosis in the general Swedish population.

A high intake of salt raises blood pressure and the risk of cardiovascular disease. Previous studies have reported on the association between salt intake and carotid stenosis, but the association with coronary atherosclerosis has not been reported. Therefore, this project aimed at studying the association between salt intake and both carotid and coronary atherosclerosis in a contemporary community-based cohort. Estimated 24-h sodium excretion (est24hNa) was calculated by the Kawasaki formula for participants of two sites (Uppsala and Malmö) of the Swedish Cardiopulmonary bioImage Study, who underwent a coronary computed tomography (n = 9623) and measurement of coronary artery calcium score (CACS, n = 10 289). Carotid ultrasound was used to detect carotid plaques (n = 10 700). Ordered logistic regression was used to calculate odds ratios (OR) per 1000 mg increase in est24hNa. We also investigated potential J-formed associations using quintiles of est24hNa. Increased est24hNa was associated with increased occurrence of carotid plaques [OR: 1.09, P < 0.001, confidence interval (CI): 1.06-1.12], higher CACS (OR: 1.16, P < 0.001, CI: 1.12-1.19), and coronary artery stenosis (OR: 1.17, P < 0.001, CI: 1.13-1.20) in minimal adjusted models. Associations were abolished when adjusting for blood pressure. When adjusting for established cardiovascular risk factors (not including blood pressure), associations remained for carotid plaques but not for coronary atherosclerosis. There was no evidence of J-formed associations. Higher est24hNa was associated with both coronary and carotid atherosclerosis in minimal adjusted models. The association seemed mainly mediated by blood pressure but to some degree also influenced by other established cardiovascular risk factors.

Reference intervals for LC-MS /MS measurements of plasma renin activity, aldosterone, angiotensin II, and 24-hour urinary aldosterone in Northern Chinese Han population

BackgroundExamination of aldosterone to Renin Ratio (ARR) and plasma aldosterone concentration (PAC) or 24-h urinary aldosterone excretion (24-h UALD) was the necessary tests in confirmatory tests for primary aldosteronism (PA). We developed a combined liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for plasma renin activity (PRA), PAC, and angiotensin II (Ang II) and investigated their reference intervals (RIs) in northern Chinese Han population. The RIs of 24-h UALD excretion were also studied using LC-MS/MS. MethodsA total of 309 healthy volunteers were recruited in 3 cities in China. PRA, PAC, Ang II, and 24-h UALD were measured using the laboratory-developed LC-MS/MS. Multiple linear regression and the variance component model were applied to determine if the RI needed to be split. The RIs of PRA, PAC, and Ang II were determined using the nonparametric percentile method. ResultsThe laboratory-developed LC-MS/MS method was verified and showed good performance. Standard deviation ratio (SDR) sex for PAC and SDR region for Ang II are 0.466 and 0.407, respectively, indicating that the RIs of PAC and Ang II must be divided by sex and region, respectively. In addition, the SDR 24hUK for 24-h UALD is 0.579, indicating that the RI of 24-h UALD must be partitioned by urine potassium. ConclusionRIs were established for tests related to the renin-angiotensin-aldosterone system in the apparently healthy northern Chinese Han population by the LC-MS/MS method.

The application of new complex indicators in the detection of urine

BackgroundAccurate diagnosis and assessment of hematuria is crucial for the early detection of chronic kidney disease(CKD). As instability of urinary RBC count (URBC) often results with clinical uncertainty, therefore new urinary indexes are demanded to improve the accuracy of diagnosis of hematuria. In this study, we aimed to investigate the benefit of applying new complex indicators based on random urine red blood cell counts confirmed in hematuric kidney diseases.MethodsAll patients enrolled underwent renal biopsy, and their clinical information was collected. Urinary and blood biomedical indexes were implemented with red blood cell counts to derive complex indicators. Patients were divided into two groups (hematuria-dominant renal histologic lesions and non-hematuria-dominant renal histologic lesions) based on their renal pathological manifestations. The target index was determined by comparing the predictive capabilities of the candidate parameters for hematuric kidney diseases. Hematuria stratification was divided into four categories based on the scale of complex indicators and distributional features. The practicality of the new complex indicators was demonstrated by fitting candidate parameters to models comprising demographic information.ResultsA total of 1,066 cases (678 hematuria-dominant renal histologic lesions) were included in this study, with a mean age of 44.9 ± 15 years. In differentiating hematuria-dominant renal histologic lesion from the non-hematuria-dominant renal histologic lesion, the AUC value of “The ratio of the random URBC to 24-h albumin excretion” was 0.76, higher than the standard approach of Lg (URBC) [AUC = 0.744] (95% Confidence interval (CI) 0.712 ~ 0.776). The odds ratio of hematuria-dominant renal histologic lesion (Type I) increased from Q2 (3.81, 95% CI 2.66 ~ 5.50) to Q4 (14.17, 95% CI 9.09 ~ 22.72). The predictive model, composed of stratification of new composite indexes, basic demographic characteristics, and biochemical parameters, performed best with AUC value of 0.869 (95% CI 0.856–0.905).ConclusionThe new urinary complex indicators improved the diagnostic accuracy of hematuria and may serve as a useful parameter for screening hematuric kidney diseases.

High Casein-Lactalbumin Diet Accelerates Blood Coagulation in Rats

This study investigates the influence of a high protein intake on normal hemostasis, fluid balance and organ growth. Adult rats were fed semipurified diets that contained either 18 or 56 g/100 g casein-lactalbumin for 2 wk, and the following functions were measured: food and water intake, weight gain, blood pressure, bleeding and clotting time, ADP-stimulated platelet aggregation, thrombin time, prothrombin time and partial thromboplastin time. Although food intake was depressed by the high protein diet, weight gain was not affected by the regimen. Water consumption, 24-h urine excretion and kidney weight were significantly greater in rats fed the high protein diet than in controls. High protein intake resulted in shorter barbiturate-induced sleeping time. Bleeding time and clotting time were significantly lower in rats fed the high protein diet for 7 d. However, heart rate, mean arterial pressure, plasma protein and osmolarity, platelet aggregation, prothrombin time, partial thromboplastin time and thrombin time did not differ significantly. Because a high protein intake caused rapid coagulation of blood in rats without affecting the activity of clotting factors, we suggest that this diet sensitized rats to factors that initiate clotting in vivo.

Validation of spot urine in estimating 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets in healthy adults

Purpose To evaluate the validity of spot urine assay methods in estimating the 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets. Materials and methods Twelve healthy volunteers were asked to adhere to 3 dietary sodium targets (3.3–5.0g/day,<3.3 g/day and >5.0 g/day) for three consecutive weeks and to measure salt excretion daily in spot urine samples using a self-monitoring device. On day 7 of each week, 24-h urine was collected to compare measured with estimated 24-h salt excretion (by the Kawasaki, Tanaka and INTERSALT equations). Results Correlation coefficients relating measured and estimated 24-h sodium excretion were low and not significant for Kawasaki and INTERSALT and moderate for the Tanaka equation (τ 0.56–0.64,p<.05). Bland–Altman plots showed considerable differences between estimated and measured sodium excretion across all salt diets. Over 40% of the participants showed an absolute difference between measured and estimated 24-h sodium of more than 1000 mg/day. The correlation coefficients between 24-h and spot Na/K ratio were 0.67, 0.94 and 0.85(p<.05), and mean differences were 0.59, 0.06 and 0.48 for the intermediate, low and high sodium diets, respectively. Conclusion These findings do not support estimation of individual 24-h salt excretion from spot urine by the Kawasaki, Tanaka, or INTERSALT formula.

Changes in zinc and manganese concentrations in cisplatin-induced acute kidney injury

Cisplatin (CDDP) is a widely used anticancer drug, but acute kidney injury (AKI) is one of the most important dose-limiting factors. Trace metal elements are present in various concentrations in the body and play an important role in maintaining normal vital functions. However, the relationship between CDDP-induced AKI and trace metal elements is unknown. In this study, we cultured human renal proximal tubular epithelial cells in the presence of CDDP (0, 12.5, 25, 50 μM) and analyzed the concentration of trace elements in medium after 24 h. We found that CDDP significantly increased the concentrations of zinc (Zn) and manganese (Mn) in medium and significantly decreased them in lysate. Therefore, we examined the effects of CDDP (3 mg/kg, i.p.) administration on serum and urinary Zn and Mn concentrations in rats. The results showed that urinary excretion of Zn and Mn increased in CDDP-treated rats 5 days after administration. Also, 5 days after administration, pyknosis, nuclear loss, loss of the brush border membrane, and DNA fragmentation were observed, and serum creatinine and blood urea nitrogen levels were found to be significantly increased. These data suggested that 24-h excretion of Zn and Mn might reflect on CDDP induced nephropathy. Monitoring urinary Zn and Mn excretion may be beneficial in detecting AKI, but further studies are needed for clinical application.