Mean Urinary Excretion Research Articles

Validity of dietary isothiocyanate intake estimates from a food frequency questionnaire using 24 h urinary isothiocyanate excretion as an objective biomarker: the JPHC-NEXT protocol area.

Isothiocyanate (ITC) is formed via the hydrolysis of glucosinolates by myrosinase, found in cruciferous vegetables. Although myrosinase is inactivated by the cooking process, no studies have incorporated the effect of cooking into the estimation of dietary ITC intake or evaluated the validity. We evaluated the validity of dietary ITC intake estimated from a food frequency questionnaire (FFQ), and urinary ITC levels using 24 h urine samples or a WFR (weighed food record), and evaluated the reproducibility of dietary ITC in two FFQs administered at an interval of 1-year. The JPHC-NEXT Protocol Area included a total of 255 middle-aged participants across Japan. We calculated dietary ITC intake from WFR and two FFQs by assuming that cooked cruciferous vegetables contain zero ITC. Urinary ITC excretion was measured at two points during summer and winter. The validity and reproducibility of dietary ITC intake estimated by FFQ were assessed using Spearman's correlation coefficients. Although we observed a moderate correlation between dietary ITC intake derived from a 12-day WFR and urinary ITC excretion, notwithstanding the cooking process, the correlation between dietary ITC intake estimated by FFQ and mean urinary ITC excretion was low. However, the correlation was improved when we compared urinary ITC excretion and a 3-day WFR or FFQ collected during winter. Our FFQ showed good reproducibility. Although seasonality is a critical factor, dietary ITC intake estimated using an FFQ showed moderate validity and reproducibility and can be used in future epidemiological studies.

Associations Between a Targeted Metabolomics Panel of Urinary Flavonoids and Flavonoid Intakes from Fruits and Vegetables Across Dietary Assessment Periods

Abstract Objectives Aligning dietary intake and food composition data with biomarkers of exposure is critical for advancing assessment methodology. Flavonoids present in fruits and vegetables (FV) are rapidly metabolized and excreted in urine; therefore they may serve as acute intake biomarkers. Yet, the optimal dietary assessment period has not been determined. The objective of this study was to evaluate associations between a targeted metabolomics panel of six urinary flavonoids and dietary intakes of these flavonoids from FV across varying dietary assessment periods. Methods In this cross-sectional study, three-day diet records from 17 individuals were analyzed via Nutrition Data System for Research to determine FV intakes over one-day, two-day, and three-day assessment periods. Dietary flavonoids from FV were estimated via the Phenol-Explorer database; total intakes of targeted flavonoids (quercetin, kaempferol, isorhamnetin, phloretin, naringenin, hesperetin) were calculated by summing aglycone and glycosylated forms. Twenty-four-hour (24-h) urine was collected on the final day of diet records. Urinary flavonoid aglycones were quantified using HPLC; total urinary flavonoids were calculated by summing targeted flavonoids. Spearman correlations between flavonoid intakes and urinary flavonoids were analyzed by dietary assessment period. Results Mean targeted flavonoid intake from FV was 53.6 mg/day. Ten specific FV provided >95% of dietary flavonoids, with greatest contributions from citrus (orange juice, grapefruit, orange) and onion. Mean urinary flavonoid excretion was 9.5 μmol/24-h. Urinary flavonoids were moderately associated with flavonoid intakes from the one-day assessment period on the day prior to urine collection (rs = 0.485, P = 0.048) and summed intakes from the two-day assessment period (rs = 0.598, P = 0.011), but not from intakes over the three-day assessment period. Conclusions Urinary flavonoids are most strongly associated with dietary flavonoids consumed within two days of 24-h urine collection, indicating two-day diet records aligned with 24-h urine collection is optimal for assessing (poly)phenol exposure from FV in future research. Funding Sources OSU CCTS, Rosita Schiller Award, OSU Comprehensive Cancer Center MCC Program, and OSU CAFFRE.

POS-394 SOLITARY FUNCITONING KIDNEY ACQUIRED EARLY IN LIFE IS NOT ASSOCIATED WITH REDUCED RENAL FUNCTIONAL RESERVE COMPARED WITH CONGENITAL SOLITARY FUNCTIONING KIDNEY IN SHEEP

Children born with a solitary functioning kidney (SFK) can develop hypertension and kidney injury. Children who acquire a SFK early in childhood (early acquired; EA-SFK) have a greater incidence of kidney injury compared with those with a congenital SFK (C-SFK). The mechanisms underlying these differences are not well understood. The C-SFK undergoes compensatory nephron hyperplasia. Since no new nephrons form after birth in humans, the degree of nephron deficiency is greater in the EA-SFK compared with C-SFK. In both forms of SFK, the remaining kidney undergoes hypertrophy and increases glomerular filtration rate (GFR) to compensate for the loss of a kidney but this hyperfiltration can promote kidney injury. We hypothesized that owing to greater degree of nephron deficiency, the EA-SFK would undergo a greater a degree of hyperfiltration compared with C-SFK. Additionally, we hypothesized that owing to greater degree of basal hyperfiltration, in response to a challenge, EA-SFK would have a reduced capacity to increase renal functional reserve. Unilateral nephrectomy was performed in sheep fetus at 100 days of gestation (term-150 days; n=9) to induce C-SFK and in the 4-week-old lamb (n=8) to induce EA-SFK. Like the human, no new nephrons form after birth in the sheep. At 8 months of age, mean arterial pressure (MAP), GFR, and urinary protein excretion (UprotV) were measured during an hour baseline and during 120 minutes of a combined infusion of amino acid (0.065ml/kg/h) and dopamine (5µg/kg/min) (AA+DOPA) in conscious lambs. Basal MAP was ~10mmHg lower in the EA-SFK group compared with C-SFK (P=0.003) and basal UprotV was ~50% lower in the EA-SFK compared with C-SFK group (P=0.0003). Basal GFR was ~27% greater in the EA-SFK compared with C-SFK group. In response to AA+DOPA, MAP did not change but UprotV and GFR increased from baseline in both groups. The increase in GFR in EA-SFK group was ~21% greater than the C-SFK group (P=0.08) but the increase in UprotV was similar between the groups. EA-SFK group had higher basal GFR compared with C-SFK demonstrating evidence of hyperfiltration. However, this was not associated with a reduced capacity to increase GFR in response to a combined infusion of amino acid and dopamine. Longer term follow-up maybe needed to determine if the greater basal GFR observed in the EA-SFK group exacerbates kidney injury and causes loss of renal functional reserve overtime.

Urinary sodium excretion and dietary sources of sodium intake in community-dwelling Chinese adults aged 50 years and over.

This study examined Na intake and identified the major food sources of Na in healthy Chinese adults aged ≥50 years in Hong Kong. Participants who completed a baseline assessment of a randomised controlled trial assessing the effectiveness of exercise and nutrition supplementation on improving physical and cognitive functions were included. A single 24-h urine sample and a 3-d diet record were used to measure urinary Na excretion and dietary intake, respectively. The compliances to the WHO (<5 g/d) and China Nutrition Society (<6 g/d) recommendations for salt intake were assessed based on the urinary Na excretion. The relative contribution of sixteen food groups to the dietary Na intake was expressed as percentages. Associations between food groups and urinary Na excretion were analysed using multiple linear regression. Community facilities. Totally, 114 healthy Chinese adults (mean age 60·6 years, 55 % women). The mean urinary Na excretion over 24-h was 2876·6 ± 1249·4 mg/d (7·3 ± 3·2 g salt/d). Overall, 22·8 % of participants met the WHO recommendation and 34·2 % met the Chinese Nutrition Society recommendation for salt intake. The major food sources of dietary Na intake were condiments (42·4 %), cereals and their products (16·8 %) and soups (13·5 %). Higher intakes of seafood and nuts were associated with lower urinary Na excretion. Public health strategies should target healthy Chinese adults in Hong Kong to modify the current patterns of Na intake. Targeting condiments, cereals and their products and soups will be an important strategy to reduce their Na intake.

Study of iodine nutrition level in pregnant south Indian subjects in third trimester

Objective: Aim of the present study is to analyse the nutritional status of iodine among pregnant women by measuring urinary excretion and do the correlation with thyroid hormone and auto antibodies. Materials and Methods: one hundred pregnant women with third trimester gestation and one hundred age-matched non-pregnant were included in study. Results: Urinary Iodine excretion and serum TSH, fT4, fT3, AMA and ATG were estimated were estimated for case and control groups. The mean urinary iodine excretion concentration (UIC) in pregnant women was 290.17±91.71 µg/L. Excess urinary iodine excretion was found in 69%. There were elevated serum AMA levels in 36 pregnant women and that positive correlated with excess iodine. Conclusion: The pregnant women had no iodine deficiency, rather had high urinary iodine concentrations indicating more than adequate iodine intake. The excess urinary iodine level may tiger the thyroid auto antibody. Keywords: Urinary iodine excretion (UIE), thyroid stimulating hormone (TSH), free thyroxine (fT4), free tri-iodothyronine (fT3), anti-microsomal antibody (AMA), anti-thyroglobulin antibody (ATA), pregnancy, iodine excess.

Study of iodine nutrition level in pregnant south Indian subjects in third trimester

Objective: Aim of the present study is to analyse the nutritional status of iodine among pregnant women by measuring urinary excretion and do the correlation with thyroid hormone and auto antibodies Materials and Methods:one hundred pregnant women with third trimester gestation and one hundred age-matched non-pregnant were included in study. Results:Urinary Iodine excretion and serum TSH, fT4, fT3, AMA and ATG were estimated were estimated for case and control groups. The mean urinary iodine excretion concentration (UIC) in pregnant women was 290.17±91.71 µg/L. Excess urinary iodine excretion was found in 69%. There were elevated serum AMA levels in 36 pregnant women and that positive correlated with excess iodine. Conclusion:The pregnant women had no iodine deficiency, rather had high urinary iodine concentrations indicating more than adequate iodine intake. The excess urinary iodine level may tiger the thyroid auto antibody. Keywords: Urinary iodine excretion (UIE), Thyroid stimulating hormone (TSH), Free thyroxine (fT4), Free tri-iodothyronine (fT3), Anti-microsomal antibody (AMA), Anti-thyroglobulin antibody (ATA), pregnancy, Iodine excess

Adequately iodized salt is an important strategy to prevent iodine insufficiency in pregnant women living in Central Java, Indonesia.

Iodine is an essential micronutrient for cognitive development and growth. Optimal intakes are critical during pregnancy. We report the iodine status and thyroid function of pregnant women living in areas previously affected by severe iodine deficiency and in longstanding iodine sufficient areas in Java, Indonesia. This cross-sectional study was conducted in Magelang, Java, from July to November 2015, in four sub-districts; two previously affected by severe iodine deficiency (area 1) and two that were iodine-sufficient (area 2). Iodine intake was estimated using median urinary iodine concentration in spot samples and mean urinary iodine excretion in 3 x 24-hour samples, thyroid hormones (thyroid-stimulating hormone and free thyroxine) were measured in venous blood samples, and iodine content of household salt samples was estimated by titration. We recruited a total of 244 pregnant women, 123 in area 1 and 121 in area 2. Urinary iodine results suggested adequate habitual iodine intakes in both areas (median urinary iodine concentration in area 1: 222 μg/l (interquartile range 189, 276 μg/l), area 2: 264 μg/l (interquartile range 172, 284 μg/l), however, the risk of inadequate intakes increased with advancing trimester (Odds Ratio = 2.59 (95% CI 1.19–5.67) and 3.85 (95% CI 1.64–9.02) at second and third trimesters, respectively). Estimated prevalence of thyroid function disorders was generally low. Salt was iodized to approximately 40 ppm and foods rich in native iodine did not contribute significantly to dietary intakes. Adequately iodized salt continues to prevent iodine insufficiency in pregnant women living in areas previously affected by severe iodine deficiency in Java, Indonesia. Monitoring and surveillance, particularly in vulnerable groups, should be emphasized to ensure iodine sufficiency prevails.

Effects of within-person variability in spot urinary sodium measurements on the associations with blood pressure and risk of cardiovascular disease in 0.5 Million adults in UK Biobank

Abstract Background Randomised control trials have demonstrated direct positive and causal associations of 24-hr measurements of urinary sodium excretion on blood pressure. However, prospective studies, which often used spot (not 24-hr) measurements of urinary sodium, have reported J-shaped associations with higher risks of cardiovascular disease (CVD) at sodium intake &amp;lt;4 g/day. The reasons for the discrepant results are not fully understood, but have prompted some to question the World Health Organisation's recommendations to restrict sodium intake to &amp;lt;2.3g/day. Purpose We examined the effects of within-person variability in spot urinary sodium (UNa) measurements on immediate and delayed associations of UNa with blood pressure at baseline and at resurvey, and with incident cardiovascular disease in the UK Biobank (UKB). Methods Baseline spot urine samples were measured in 502,619 adults at baseline and in 20,346 participants who were resurveyed at 4 years after baseline. Linear regression was used to assess associations of baseline UNa measurements with systolic blood pressure (SBP; mmHg) at baseline and at resurvey. Cox regression was used estimate the associations between baseline measures of UNa with incident CVD events (recorded from linkage with hospital records). All analyses were adjusted for confounders and corrected for regression dilution bias. Results After excluding participants with prevalent diseases, the primary analyses involved 386,060 adults who were followed-up for a median of 7.8 years, during which ∼13,000 CVD events occurred. Estimated mean (SD) urinary sodium excretion was 77.4 mmol/L (SD 44.4, IQR = 42.8–103.7 mmol/L), and mean SBP/DBP were 137.5/82.3 (SD 18.5/10.1) mmHg, respectively. Within-person variability in UNa was high, with a self-correlation of 0.35 at 4 years between measurements. After adjustment for confounders and correction for regression dilution bias, a 100 mmol/L higher UNa was associated with an immediate 3.2 mmHg higher SBP (95% confidence interval [CI]: 2.8–3.6) in cross-sectional analyses (Figure 1). However, the corresponding associations of baseline UNa with SBP at resurvey was completely attenuated (p=0.20). The predicted risk of CVD was 1.06 (95% CI 1.06–1.07, p&amp;lt;0.001) for a 3.2 mmHg higher SBP, but the observed risk for a 100 mmol/L higher UNa was 0.95 (95% CI 0.82–1.10, p=0.47) (Figure 1). Conclusions While spot measurements of UNa were strongly associated with immediate effects on SBP, the magnitude of within-person variability in UNa precluded detection of associations with SBP several years after baseline or with risk of CVD. The extreme within-person variability in spot UNa may explain the discrepant results of the trials and observational studies of sodium and blood pressure. Figure 1. Spot UNa with SBP and CVD in UK Biobank Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Core funding from the Medical Research Council-Population Health Research Unit, British Heart Foundation

Comparative Study of Slow Infusion versus Bolus Doses of Albumin and Furosemide Infusion to Mobilize Refractory Ascites in Decompensated Chronic Liver Disease.

Combined use of furosemide with albumin is an approved therapy to overcome diuretic resistance in treatment of ascites in decompensated chronic liver disease. Bolus dosing of diuretics has its own limitations due to pre-existing hypotension, post diuretic sodium retention and braking phenomenon. Slow albumin and furosemide Infusion has been shown to mobilize large ascites with improved diuresis and hemodynamic stability in decompensated chronic liver disease. This study was undertaken to compare efficacy and safety of infusion therapy vs bolus therapy in term the management of refractory ascites. Decompensated chronic liver disease patients with refractory ascites were randomly assigned into two groups of 15 each - Bolus therapy (intravenous albumin and furosemide as boluses) and Infusion therapy (furosemide infusion at 2mg/hour and albumin at 2g/hour for three days). Diuresis, natriuresis, change in abdominal girth and body weight, and hemodynamic stability (change in SBP) were compared between the two groups. Infusion therapy, as compared to bolus therapy, showed a significantly better diuresis (mean urinary output increment 483ml vs 243ml, p <0.001), natriuresis (mean urinary sodium excretion increment 35.2 mEq/L vs 16.6 mEq/L, p = 0.004),decrease in abdominal circumference (6.1cm vs 3.0cm, p<0.001) and decrease in body weight (5.53 Kg vs 2.86 Kg, p < 0.001). The complications of renal impairment were also lower in the Infusion group. Infusion of furosemide and albumin is a potential safer and effective therapeutic option in the management of refractory ascites with better natriuresis, higher urine output, and higher decrement in abdominal circumference and body weight, and lesser side effects.

Similar pharmacokinetics of three dosing regimens comprising two oral delayed-release mesalamine formulations in healthy adult volunteers: Randomised, open-label, parallel-group study.

AimsMesalamine is the first‐line therapy for treating mild‐to‐moderate ulcerative colitis. Multiple mesalamine formulations are available, with similar safety and efficacy profiles. Mesalamine is commonly administered as divided dosing, although once‐daily dosing may provide benefits for patients. We evaluated the pharmacokinetics of three dosing regimens of two oral delayed‐release mesalamine formulations in healthy adult volunteers.MethodsA randomised, open‐label, parallel‐group study of mesalamine pharmacokinetics following Lialda 2 × 1.2 g once daily (QD) (dose A), Asacol 6 × 400 mg QD (dose B), or Asacol 2 × 400 mg three times daily (TID) (dose C) over 7 days. Assessments included 5‐aminosalicylic acid (5‐ASA) and N‐acetyl 5‐aminosalicylic acid (N‐Ac‐5‐ASA, primary metabolite) pharmacokinetics (A e(%), AUC0‐24 and C max), safety and tolerability.ResultsAll enrolled volunteers (n = 37) completed the study. Steady state was achieved for all treatments by day 4. Ratios (95% CI) of means for steady‐state AUC0‐24 (dose A vs B 90.3% [39.8, 204.8], dose A vs C 123.5% [55.3, 275.7], dose B vs C 136.8% [61.3, 305.5]) and C max (dose A vs B 106.0% [46.4, 242.2], dose A vs C 133.0% [59.1, 299.0], dose B vs C 125.5% [55.8, 282.1]) were similar for all 5‐ASA treatments. Mean urinary excretion of 5‐ASA plus N‐Ac‐5‐ASA was comparable between treatments (dose A 21.3%, dose B 20.2%, dose C 17.9%). All treatment regimens were well tolerated; no safety issues were observed.ConclusionsPlasma and urine pharmacokinetics for Asacol TID, Asacol QD, and Lialda QD are similar, suggesting similar daily systemic exposures can be obtained with either TID or QD dosing. NCT00751699.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

BackgroundHigher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease.MethodsIn a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed.ResultsA total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], −1.9 to 1.9; P=0.99). The mean decrease in the iohexol-based GFR was −3.0 ml per minute per 1.73 m2 per year with allopurinol and −2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, −0.6 ml per minute per 1.73 m2 per year; 95% CI, −1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups.ConclusionsWe found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.)

Assessment of Iodine Status in Iranian Students Aged 8-10 Years: Monitoring the National Program for the Prevention and Control of Iodine Deficiency Disorders in 2016

Iodine is a key element in the synthesis of thyroid hormones. The deficiency of the secretion of them will Reduce IQ, disturbance in the psychomotor growth and shortened height. Urinary iodine is a good indicator of iodine intake status. Urinary iodine status in at-risk groups is one of the most important indicators of community status. All 56 universities/medical faculties in Iran should determine and report median urinary iodine and its relative distribution in school children aged 8 to 10 yr, to determine the status of urine output. The sample size in each university/college is 240 students and the cluster sampling method (48 clusters in each area in 2016) and based on probability Measurement. The amount of urinary iodine was measured quantitatively by acid digestion. The mean urinary iodine excretion was estimated at 18.61 μg/dl. The median urinary iodine concentration in 52 universities was sufficient, and the national mean of urinary iodine excretion rate was 19.3 μg/dl. The iodine status was estimated in the optimal range in 65.6% of the students and in only 4.7% in the range of moderate and severe deficits, based on the urinary iodine index. Iodine is sufficient in most parts of the country. The implementation of the country's national program for the prevention and control of iodine deficiency disorders has made more important the quality control of the collaborative laboratories of this program than before. Moreover, it is absolutely essential to avoid excessive iodine in order to prevent possible side effects.

Disentangling the Relationships Between the Renin-Angiotensin-Aldosterone System, Calcium Physiology, and Risk for Kidney Stones.

Complex relationships between aldosterone and calcium homeostasis have been proposed. To disentangle the influence of aldosterone and intravascular volume on calcium physiology. Patient-oriented and epidemiology studies. Clinical research center and nationwide cohorts. Patient-oriented study (n = 18): Participants were evaluated after completing a sodium-restricted (RES) diet to contract intravascular volume and after a liberalized-sodium (LIB) diet to expand intravascular volume. Cross-sectional studies (n = 3755): the association between 24h urinary sodium and calcium excretion and risk for kidney stones was assessed. Patient-oriented study: compared to a RES-diet, a LIB-diet suppressed renin activity (LIB: 0.3 [0.1, 0.4] vs. RES: 3.1 [1.7, 5.3] ng/mL/h; P < 0.001) and plasma aldosterone (LIB: 2.0 [2.0, 2.7] vs. RES: 20.0 [16.1, 31.0] vs. ng/dL; P < 0.001), but increased calciuria (LIB: 238.4 ± 112.3 vs. RES: 112.9 ± 60.8 mg/24hr; P < 0.0001) and decreased serum calcium (LIB: 8.9 ± 0.3 vs. RES: 9.8 ± 0.4 mg/dL; P < 0.0001). Epidemiology study: mean urinary calcium excretion was higher with greater urinary sodium excretion. Compared to a urinary sodium excretion of < 120 mEq/day, a urinary sodium excretion of ≥220 mEq/day was associated with a higher risk for having kidney stones in women (risk ratio = 1.79 [95% confidence interval 1.05, 3.04]) and men (risk ratio = 2.06 [95% confidence interval 1.27, 3.32]). High dietary sodium intake suppresses aldosterone, decreases serum calcium, and increases calciuria and the risk for developing kidney stones. Our findings help disentangle the influences of volume from aldosterone on calcium homeostasis and provide support for the recommendation to restrict dietary sodium for kidney stone prevention.

Effects of Cataract Surgery on Melatonin Secretion in Adults 60 Years and Older

Cataract surgery, which increases perception of light, may increase melatonin secretion. Melatonin secretion has been associated with depression, diabetes, cognitive impairment, and breast cancer. To date, no evidence from a randomized clinical trial exists to support this cataract surgery hypothesis. To determine whether cataract surgery modifies the melatonin secretion at 3 months after cataract surgery in 169 adult patients. A parallel-group randomized clinical trial was conducted at a single referral center from July 1, 2014, to June 30, 2017. Data were analyzed from January 1, 2018, to March 31, 2019. Patients were aged 60 years or older, had no history of cataract surgery, and had cataracts with grade 2 or higher nuclear opacifications based on the Lens Opacities Classification System III. Analyses were based on intention to treat. Patients were randomized 1:1:1:1 to receive cataract surgery using artificial clear intraocular lens (IOL) or yellow IOL. Group 1 received prompt surgery with clear IOL, group 2, prompt surgery with yellow IOL, group 3, delayed surgery with clear IOL, and group 4, delayed surgery with yellow IOL. The intervention group consisted of groups 1 and 2, and the control group consisted of groups 3 and 4. Urinary melatonin excretion in the intervention group was measured at 3 months after surgery, and urinary melatonin excretion in the control group was measured before delayed surgery. Of the 169 randomized patients, 97 were men (57.4%). The mean (SD) age was 75.7 (6.7) years. Mean urinary melatonin excretion was calculated as standardized urinary concentration, the ratio of urinary concentration to urinary creatinine concentration (nanograms per milligram of creatinine), in the intervention group after cataract surgery. Mean urinary melatonin excretion was significantly higher than in the control group (adjusted mean difference of creatinine concentration, 0.159 log ng/mg, 95% CI, 0.045-0.273; P = .007) independent of baseline urinary melatonin excretion and potential confounders. Subgroup analysis comparing group 1 with group 3 revealed that concentration of urinary melatonin excretion in patients who received clear IOLs was higher than the control group by creatinine concentration 0.212 log ng/mg (95% CI of the difference, 0.058-0.365; P = .008). However, the difference between patients in group 2 and group 4 was not significant (adjusted mean difference for creatinine excretion, 0.083 log ng/mg, 95% CI, -0.087 to 0.253; P = .33). The difference of concentration of mean urinary melatonin excretion between patients in group 1 and those in group 2 was not significant (95% CI of the difference for creatinine concentration, -0.19 to 0.40 log ng/mg; P = .48). The findings in this study support the hypothesis that cataract surgery increases melatonin secretion. The effect of clear IOLs vs yellow IOLs on these outcomes was not shown to be different. UMIN-CTR Identifier: UMIN000014559.

Maternal Glucocorticoid Metabolism Across Pregnancy: A Potential Mechanism Underlying Fetal Glucocorticoid Exposure

Across pregnancy, maternal serum cortisol levels increase up to 3-fold. It is not known whether maternal peripheral cortisol metabolism and clearance change across pregnancy or influence fetal cortisol exposure and development. The primary study objective was to compare maternal urinary glucocorticoid metabolites, as markers of cortisol metabolism and clearance, between the second and third trimester of pregnancy. Secondary objectives were to test associations of total maternal urinary glucocorticoid excretion, with maternal serum cortisol levels and offspring birth weight z score. A total of 151 women with singleton pregnancies, recruited from prenatal clinic at the Pittsburgh site of the Measurement of Maternal Stress (MOMS) study, had 24-hour urine collections during both the second and third trimesters. Between the second and third trimester, total urinary glucocorticoid excretion increased (ratio of geometric means [RGM] 1.37, 95% CI 1.22-1.52, P < .001), and there was an increase in calculated 5β-reductase compared to 5α-reductase activity (RGM 3.41, 95% CI 3.04-3.83, P < .001). During the third trimester total urinary glucocorticoid excretion and serum cortisol were negatively correlated (r = -0.179, P = .029). Mean total urinary glucocorticoid excretion across both trimesters and offspring birth weight z score were positively associated (β = 0.314, P = .001). The estimated activity of maternal enzymes responsible for cortisol metabolism change between the second and third trimester of pregnancy. Additionally, maternal peripheral metabolism and clearance of cortisol may serve as a novel mechanism affecting fetal cortisol exposure and growth.

Association between urinary potassium excretion and blood pressure: A systematic review and meta-analysis of observational studies.

Background:The evidence base regarding the association between urinary potassium and blood pressure (BP), or risk of hypertension, is inconsistent. Therefore, we sought to conduct a qualitative and quantitative literature review on the association between potassium excretion and BP.Materials and Methods:Medline, Scopus, Web of Science, Science Direct, and Google Scholar were searched up to June 2020. All observational studies that reported BP and measured potassium excretion in overnight or 24-h urine samples were included. Correlation coefficients, mean urinary potassium excretion, and odds ratio (ORs) of hypertension were extracted from the included studies. There were no language or publication date restrictions.Results:Overall, twelve observational studies, including 16,174 subjects, were identified for inclusion in the present meta-analysis, and 21 effect sizes were extracted. Pooled mean potassium excretion was 3.46 mmol/24 h higher in normotensive individuals compared with hypertensive subjects (95% confidence interval [CI]: 0.61, 6.31). High urinary potassium excretion was not associated with the risk of hypertension (OR: 0.95; 95% CI: 0.79, 1.13). The pooled correlation coefficient between BP and urinary potassium was not significant (ES: 0.01; 95% CI: −0.03, 0.05). However, a subgroup analysis by age indicated a significant positive correlation between urinary potassium and systolic BP in children (ES: 0.12; 95% CI: 0.04, 0.19).Conclusion:24 h urinary potassium excretion was not correlated to BP and risk of hypertension. In contrast, mean urinary potassium excretion was higher in normotensive individuals compared with hypertensive counterparts. Future studies should focus on the association between different sources of dietary potassium and BP.

Efficacy and safety of calcium carbonate in normophosphataemic patients with chronic kidney disease Stages 3 and 4.

BackgroundDisordered bone and mineral metabolism are a common complication of chronic kidney disease (CKD). Phosphate binders are often prescribed in advanced CKD, when hyperphosphataemia develops. Little is known about the role of these drugs in earlier stages, when serum phosphorus levels are kept in the normal range by increased urinary excretion.MethodsA retrospective, controlled observational study was conducted on a cohort of 78 pre-dialysis patients. Subjects had CKD Stage 3 or 4, normal serum phosphorus levels and increased urinary fractional excretion of phosphate. Thirty-eight patients receiving calcium carbonate for 24 months were compared with 40 patients under no phosphate binders, regarding mineral metabolism parameters and vascular calcification scores.ResultsCalcium carbonate decreased mean urinary fractional excretion of phosphate and median 24-h urine phosphorus, whereas no significant change was seen in the control group. Mean serum phosphorus and median serum intact parathyroid hormone (iPTH) remained stable in treated patients but increased in the control group. Vascular calcification, assessed by Kauppila and Adragão scores, worsened under calcium carbonate with no significant change in the control group.ConclusionsCalcium carbonate reduced urinary phosphate excretion and prevented the rise in phosphorus and iPTH serum levels in a cohort of normophosphataemic pre-dialysis patients. However, treatment was associated with increased vascular calcification, suggesting that calcium-based phosphate binders are not a safe option for CKD patients.

Tryptophan Intake and Tryptophan Losses in Hemodialysis Patients: A Balance Study.

Tryptophan depletion is common in hemodialysis patients. The cause of this depletion remains largely unknown, but reduced nutritional tryptophan intake, losses during dialysis or an increased catabolism due to an inflammatory state are likely contributors. Currently, little is known about tryptophan homeostasis in hemodialysis patients. We assessed dietary tryptophan intake, measured plasma tryptophan during dialysis, and measured the combined urinary and dialysate excretion of tryptophan in 40 hemodialysis patients (66 ± 15 years and 68% male). Patients had low tryptophan concentrations (27 ± 9 µmol/L) before dialysis. Mean dietary tryptophan intake was 4454 ± 1149 µmol/24 h. Mean urinary tryptophan excretion was 15.0 ± 12.3 μmol/24 h, dialysate excretion was 209 ± 67 μmol/24 h and combined excretion was 219 ± 66 µmol/24 h, indicating only 5% of dietary tryptophan intake was excreted. No associations were found between plasma tryptophan concentration and tryptophan intake, plasma kynurenine/tryptophan ratio or inflammatory markers. During dialysis, mean plasma tryptophan concentration increased 16% to 31 ± 8 µmol/L. Intradialytic increase in plasma tryptophan was associated with a lower risk of mortality, independent of age, sex and dialysis vintage (HR: 0.87 [0.76–0.99]; P = 0.04). Tryptophan intake was well above the dietary recommendations and, although tryptophan was removed during dialysis, mean plasma tryptophan increased during dialysis. The cause of this phenomenon is unknown, but it appears to be protective.

A sensitive LC-MS/MS method to determine ginkgolide B in human plasma and urine: application in a pharmacokinetics and excretion study of healthy Chinese subjects

1. Ginkgolide B (GB), the most active of the ginkgolides, has been developed as a new drug for the treatment of vascular insufficiency; however, the pharmacokinetics of GB remain unclear. Here, we investigated the pharmacokinetics and urine excretion properties of GB in healthy Chinese subjects administered single- and multiple-dose injectable GB based on a new LC-MS/MS method.2. GB pharmacokinetics were found to be dose-dependent from 20 to 60 mg. GB reached a steady state by day 6 with once-daily dosing at 40 mg. Systemic exposure to GB, as characterised by AUC0–∞, indicated accumulation following repeated once-daily dosing for seven consecutive days. The mean urinary cumulative excretion rate of GB in response to 20, 40, and 60 mg GB was 41.9 ± 18.5%, 32.9 ± 12.2%, and 43.9 ± 8.5%, respectively.3. Dose-proportional pharmacokinetics of GB were observed after intravenous administration in healthy subjects. A gradual reduction in the volume of distribution and slight change in mean resistance time led us to conjecture the limited accumulation of GB based on distribution equilibrium in vivo.4. This comprehensive study of the clinical pharmacokinetics of GB will provide useful information for its application and further development.

A pilot study to relationship between urinary protein excretion and muscle strengthening in patients with acute onset renal disease.

The purpose of this study was to investigate urine protein excretion and the effect of muscle strengthening in patients with renal disease. Twenty-eight patients (18 to 87 years old) with acute onset renal disease were treated with steroids at the Hospital of Shiga University of Medical Science. Maximum quadriceps force was measured, and 20-minutes sessions in resistance training were started. After 5 weeks, maximum quadriceps force was measured again. Quadriceps force showed no significant difference between before and after intervention. There was negative correlation between mean urinary protein excretion and amount of change in quadriceps force over the 5 weeks (r=-0.40, p=0.038). We observed the patients with reduced urine protein excretion are tends to easier to obtain muscle strengthening. On the other hand, there is a possibility that the patients with increased urine protein excretion are hard to obtain muscle strengthening, during the intervention.