Iodine deficiency may cause thyroid dysfunction. The iodine intake in a population is measured by urinary iodine concentration (UIC) in spot samples or 24-h urinary iodine excretion (24UIE). 24UIE is ...considered the gold standard and may be estimated using an equation including UIC, urinary creatinine concentration, sex and age (e24UIE). The aims of this study were to evaluate the preferable timing of UIC when using this equation and assess the variability of UIE. Sixty healthy non-smoking women (n 31) and men (n 29) were included in Gothenburg, Sweden. Twelve urine samples were collected at six fixed times on two separate days. Variability was calculated for UIC, 24UIE, e24UIE, iodine excretion per hour (iHr) and UIC adjusted for creatinine and specific gravity. Median 24UIE was 156 µg/24 h and the median UIC (all spot samples) was 104 µg/l. UIC (P < 0·001), 24UIE (P = 0·001) and e24UIE (P < 0·001) were significantly higher in men. e24UIE was relatively similar to 24UIE. However, when e24UIE was calculated from UIC in the first void, it was about 15 % lower than 24UIE (P < 0·001). iHr was lowest in the morning and highest in the afternoon. Median iHr was higher in men (7·4 v. 5·3 µg/h, P < 0·001). The variability of UIE was higher within individuals than between individuals. This study suggests that most time points for estimation of individual 24UIE are appropriate, but they should preferably not be collected in the first void.
In lactating women, iodine metabolism is regulated and maintained by the kidneys and mammary glands. Limited research exists on how iodine absorbed by lactating women is distributed between the ...kidneys and breasts.
This study aimed to accurately evaluate the total iodine intake (TII), urinary iodine excretion (UIE), and breast milk iodine excretion (BMIE) in lactating women and explore the relationship between TII and total iodine excretion (TIE).
A 7-d iodine metabolism study was conducted on 41 lactating women with a mean age of 30 y in Yuncheng and Gaoqing, China, from December 2021 to August 2023. TII and TIE were calculated by measuring the iodine content in food, water, 24-h urine, feces, and breast milk. The urinary iodine excretion rate (UIER), breast milk iodine excretion rate (BMIER), and partitioning of iodine excretion between urine and breast milk were determined.
Iodine metabolism studies were performed for 285 d. The median TII and TIE values were 255 and 263 μg/d, respectively. With an increase in TII, UIER, and BMIER, the UIE and BMIE to TII ratio exhibited a downward trend. The median UIER, BMIER, and proportion of iodine excreted in urine and breast milk were 51.5%, 38.5%, 52%, and 37%, respectively. When the TII was <120 μg/d, the BMIER decreased with the increase of the TII (β: −0.90; 95% confidence interval: −1.08, −0.72).
When maternal iodine intake is low, the proportion in breast milk increases, ensuring sufficient iodine nutrition for infants. In addition, the UIE of lactating women with adequate iodine concentrations is higher than their BMIE.
This study was registered at clinicaltrials.gov as NCT04492657.
Aims: To test the hypothesis that in non-diabetic patients with early-stage chronic kidney disease (CKD), the renal excretion of urate and glucose transportation are coupled and interconnected.
...Methods: A cross-sectional study of 255 non-diabetic participants with stage 1-2 CKD recruited from our department was conducted. Spearman's correlation and multiple linear regression analyses were used to study the correlation between urinary glucose and renal uric acid excretion. ANOVA was used to compare urinary uric acid excretion among three tertiles of urinary glucose (UG; UG1: UG<0.24 mmol/24 h/1.73 m
2
, UG2: 0.24 mmol/24 h/1.73 m
2
≤ UG≤0.55 mmol/24 h/1.73 m
2
, and UG3: UG>0.55 mmol/24 h/1.73 m
2
), the fractional excretion of glucose (FEG; FEG1: FEG<0.04%, FEG2: 0.04%≤FEG≤0.09%, and FEG3: FEG>0.09%) and the excretion of glucose per volume of glomerular filtration (EgGF; EgGF1: EgGF<1.95 μmol/L, EgGF2: 1.95 μmol/L≤ EgGF≤3.99 μmol/L, and EgGF3: EgGF>3.99 μmol/L).
Results: According to the multiple linear regression analysis, FEG and EgGF were positively correlated with the excretion of uric acid per volume of glomerular filtration (EurGF) after adjusting for confounding factors. The EurGF levels in the highest tertiles of UG, FEG and EgGF were higher than those in the lowest tertiles of UG, FEG and EgGF.
Conclusion: Urinary glucose excretion is closely related to renal excretion of uric acid in non-diabetic patients with stage 1-2 CKD.
KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest ...that it could play a role in regulating potassium renal excretion by modulating the activity of the Na
-Cl
cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1
mice had lower plasma levels of K
and Cl
, while exhibiting higher urinary excretion of Na
, Cl
, and K
compared to KS-WNK1
mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K
levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1
mice adapt better to HKD-challenge than KS-WNK1
mice after a potassium-retaining state. The difference in the pNCC/NCC ratio between KS-WNK1
and KS-WNK1
mice after 0KD and HKD indicates a role for KS-WNK1 in both, NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the DCT to respond to extreme changes in potassium intake, such as those occurring in wildlife.
Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA), primarily attributed to the hepatic overproduction and renal underexcretion of UA. Despite the elucidation ...of molecular pathways associated with this underexcretion, the etiology of HUA remains largely unknown. In our study, using by Uox knockout rats, HUA mouse, and cell line models, we discovered that the increased WWC1 levels were associated with decreased renal UA excretion. Additionally, using knockdown and overexpression approaches, we found that WWC1 inhibited UA excretion in renal tubular epithelial cells. Mechanistically, WWC1 activated the Hippo pathway, leading to phosphorylation and subsequent degradation of the downstream transcription factor YAP1, thereby impairing the ABCG2 and OAT3 expression through transcriptional regulation. Consequently, this reduction led to a decrease in UA excretion in renal tubular epithelial cells. In conclusion, our study has elucidated the role of upregulated WWC1 in renal tubular epithelial cells inhibiting the excretion of UA in the kidneys and causing HUA.
The classical concepts of human sodium balance include 1) a total pool of Na
of ≈4,200 mmol (total body sodium, TBS) distributed primarily in the extracellular fluid (ECV) and bone, 2) intake ...variations of 0.03 to ≈6 mmol·kg body mass
·day
, 3) asymptotic transitions between steady states with a halftime (T½) of 21 h, 4) changes in TBS driven by sodium intake measuring ≈1.3 day ΔTBS/Δ(Na
intake/day), 5) adjustment of Na
excretion to match any diet thus providing metabolic steady state, and 6) regulation of TBS via controlled excretion (90-95% renal) mediated by surrogate variables. The present focus areas include 1) uneven, nonosmotic distribution of increments in TBS primarily in "skin," 2) long-term instability of TBS during constant Na
intake, and 3) physiological regulation of renal Na
excretion primarily by neurohumoral mechanisms dependent on ECV rather than arterial pressure. Under physiological conditions 1) the nonosmotic distribution of Na
seems conceptually important, but quantitatively ill defined; 2) long-term variations in TBS represent significant deviations from steady state, but the importance is undetermined; and 3) the neurohumoral mechanisms of sodium homeostasis competing with pressure natriuresis are essential for systematic analysis of short-term and long-term regulation of TBS. Sodium homeostasis and blood pressure regulation are intimately related. Real progress is slow and will accelerate only through recognition of the present level of ignorance. Nonosmotic distribution of sodium, pressure natriuresis, and volume-mediated regulation of renal sodium excretion are essential intertwined concepts in need of clear definitions, conscious models, and future attention.
Fluorescence imaging in the second near‐infrared (NIR‐II) window holds impressive advantages of enhanced penetration depth and improved signal‐to‐noise ratio. Bright NIR‐II fluorophores with renal ...excretion ability and low tissue accumulation are favorable for in vivo molecular imaging applications as they can render the target‐mediated molecular imaging process easily distinguishable. Here, a probe (anti‐PD‐L1‐BGP6) comprising a fluorophore (IR‐BGP6) covalently bonded to the programmed cell death ligand‐1 monoclonal antibody (PD‐L1 mAb) for molecular imaging of immune checkpoint PD‐L1 (a targeting site upregulated in various tumors for cancer imaging) in the NIR‐II window is reported. Through molecular optimization, the bright NIR‐II fluorophore IR‐BGP6 with fast renal excretion (≈91% excretion in general through urine within the first 10 h postinjection) is developed. The conjugate anti‐PD‐L1‐BGP6 succeeds in profiling PD‐L1 expression and realizes efficient noninvasive molecular imaging in vivo, achieving a tumor to normal tissue (T/NT) signal ratio as high as ≈9.5. Compared with the NIR‐II fluorophore with high nonspecific tissue accumulation, IR‐BGP6 derived PD‐L1 imaging significantly enhances the molecular imaging performance, serving as a strong tool for potentially studying underlying mechanism of immunotherapy. The work provides rationales to design renal‐excreted NIR‐II fluorophores and illustrate their advantages for in vivo molecular imaging.
By optimizing the molecular structure, a bright second near‐infrared (NIR‐II) fluorophore IR‐BGP6 exhibiting fast renal excretion kinetics is developed. Benefiting from the low tissue accumulation, high brightness, and advantages of imaging in the NIR‐II window, the anti‐PD‐L1‐BGP6 conjugate demonstrates efficient molecular imaging of immune checkpoint PD‐L1 in vivo, providing a potential probe for in‐depth study of underlying mechanism of immunotherapy.
The circadian rhythm of urinary sodium excretion is related to the diurnal blood pressure regulation (BP) and the nocturnal dipping pattern. The renal sodium excretion expressed as daytime/nighttime ...ratio impacts BP, but a limited number of studies have investigated this topic to date. In this cross-sectional study, we aimed to investigate the impact of different daily patterns of sodium excretion (comparing low with high ratios) on BP and nocturnal dipping and to explore the relationship with age. Twenty-four-hour ambulatory BP monitoring and daytime and nighttime urinary sodium collections were used to assess 1062 subjects in Switzerland. Analyses were performed according to the day/night urinary sodium excretion ratio quartiles (Q1-Q4) and by age group (≤50 and ≥50 years). Subjects in Q1 can be considered low excretors of sodium during the daytime since the rate of sodium excretion during the daytime was 40% lower than that of subjects in Q4. Quartiles of the day/night urinary sodium excretion ratio showed that subjects in Q1 were 7 years older and had respectively 6 and 5 mmHg higher nighttime systolic and diastolic BP and a higher nocturnal dipping compared with subjects in Q4 (
-value ≤0.001). Associations found were significant only for subjects older than 50 years (all
< 0.05). The present results suggest that a decreased capacity to excrete sodium during daytime is more prevalent as age increases and that it impacts nighttime blood pressure and nocturnal dipping in older subjects.
Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen ...excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for dry matter content and nitrogen concentration. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01): 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l (creatinine), and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL) and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than in HO cows (P < 0.01). Urea and creatinine concentrations in urine and saliva did not differ among breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). Despite greater urea, creatinine, and SDMA concentrations in blood as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal.
Marine flatfishes have a low metabolic rate and routinely encounter large fluctuations in salinity, and are therefore of interest in the study of diffusive water flux (a proxy for transcellular water ...permeability), oxygen consumption (ṀO
2
), ammonia excretion and urea-N excretion as a function of salinity and seawater Ca
2+
. These parameters were measured in two coastal marine flatfishes, Pacific sanddab and Rock sole acclimated to 31 ppt and exposed acutely (for up to 3 h), to environmentally relevant salinities of 45, 15.5, or 7.5 ppt. In both species, diffusive water flux and ammonia excretion rates increased as salinity decreased. ṀO
2
and urea-N excretion rates remained relatively unchanged. Nitrogen quotient analysis indicated increased oxidation of protein at lower salinity. A second experimental series was performed on Rock sole to separate the effects of salinity from those of ambient Ca
2+
. In direct contrast to the significant increase seen at 7.5 ppt, reducing salinity from 31 ppt to 7.5 ppt while maintaining Ca
2+
at 10 mM or increasing it to 20 mM resulted in no change in diffusive water flux rate, demonstrating that reduced Ca
2+
, rather than reduced salinity itself, is the primary cause for the increases in diffusive water flux. However, ammonia excretion rate increased when salinity was decreased and Ca
2+
was increased compared to 31 ppt with added Ca
2+
. Our results demonstrate that both diffusive water flux and ammonia excretion rates are a function of salinity, that neither are coupled to ṀO
2
, and that ambient Ca
2+
also plays a role in these rates.