The Urothelium: Life in a Liquid Environment.

The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high-resistance but adaptable barrier that surveils its mechanochemical environment and communicates changes to underlying tissues including afferent nerve fibers and the smooth muscle. The goal of this review is to summarize new insights into urothelial biology and function that have occurred in the past decade. After familiarizing the reader with key aspects of urothelial histology, we describe new insights into urothelial development and regeneration. This is followed by an extended discussion of urothelial barrier function, including information about the roles of the glycocalyx, ion and water transport, tight junctions, and the cellular and tissue shape changes and other adaptations that accompany expansion and contraction of the lower urinary tract. We also explore evidence that the urothelium can alter the water and solute composition of urine during normal physiology and in response to overdistension. We complete the review by providing an overview of our current knowledge about the urothelial environment, discussing the sensor and transducer functions of the urothelium, exploring the role of circadian rhythms in urothelial gene expression, and describing novel research tools that are likely to further advance our understanding of urothelial biology.

Implementation of pure shift 1 H NMR in metabolic phenotyping for structural information recovery of biofluid metabolites with complex spin systems.

NMR spectroscopy is a mainstay of metabolic profiling approaches to investigation of physiological and pathological processes. The one-dimensional proton pulse sequences typically used in phenotyping large numbers of samples generate spectra that are rich in information but where metabolite identification is often compromised by peak overlap. Recently developed pure shift (PS) NMR spectroscopy, where all J-coupling multiplicities are removed from the spectra, has the potential to simplify the complex proton NMR spectra that arise from biosamples and hence to aid metabolite identification. Here we have evaluated two complementary approaches to spectral simplification: the HOBS (band-selective with real-time acquisition) and the PSYCHE (broadband with pseudo-2D interferogram acquisition) pulse sequences. We compare their relative sensitivities and robustness for deconvolving both urine and serum matrices. Both methods improve resolution of resonances ranging from doublets, triplets and quartets to more complex signals such as doublets of doublets and multiplets in highly overcrowded spectral regions. HOBS is the more sensitive method and takes less time to acquire in comparison with PSYCHE, but can introduce unavoidable artefacts from metabolites with strong couplings, whereas PSYCHE is more adaptable to these types of spin system, although at the expense of sensitivity. Both methods are robust and easy to implement. We also demonstrate that strong coupling artefacts contain latent connectivity information that can be used to enhance metabolite identification. Metabolite identification is a bottleneck in metabolic profiling studies. In the case of NMR, PS experiments can be included in metabolite identification workflows, providing additional capability for biomarker discovery.

Loading-induced antitumor capability of murine and human urine.

While urine has been considered as a useful bio-fluid for health monitoring, its dynamic changes to physical activity are not well understood. We examined urine's possible antitumor capability in response to medium-level, loading-driven physical activity. Urine was collected from mice subjected to 5-minute skeletal loading and human individuals before and after 30-minute step aerobics. Six cancer cell lines (breast, prostate, and pancreas) and a mouse model of the mammary tumor were employed to evaluate the effect of urine. Compared to urine collected prior to loading, urine collected post-activity decreased the cellular viability, proliferation, migration, and invasion of tumor cells, as well as tumor weight in the mammary fat pad. Detection of urinary volatile organic compounds and ELISA assays showed that the loading-conditioned urine reduced cholesterol and elevated dopamine and melatonin. Immunohistochemical fluorescent images presented upregulation of the rate-limiting enzymes for the production of dopamine and melatonin in the brain. Molecular analysis revealed that the antitumor effect was linked to the reduction in molecular vinculin-linked molecular force as well as the downregulation of the Lrp5-CSF1-CD105 regulatory axis. Notably, the survival rate for the high expression levels of Lrp5, CSF1, and CD105 in tumor tissues was significantly lowered in the Cancer Genome Atlas database. Collectively, this study revealed that 5- or 10-minute loading-driven physical activity was sufficient to induce the striking antitumor effect by activating the neuronal signaling and repressing cholesterol synthesis. The result supported the dual role of loading-conditioned urine as a potential tumor suppressor and a source of diagnostic biomarkers.

Beat the heat: Culex quinquefasciatus regulates its body temperature during blood feeding.

Mosquitoes are regarded as one of the most dangerous animals on earth. Because they are responsible for the spread of a wide range of both human and animal pathogens, research of the underlying mechanisms of their feeding behavior and physiology is critical. Among disease vector mosquitoes, Culex quinquefasciatus, a known carrier of West Nile virus and Western Equine Encephalitis, remains relatively understudied. As blood-sucking insects, adaptations (either at the molecular or physiological level) while feeding on warm blood are crucial to their survival, as overheating can result in death due to heat stress. Our research aims to determine how Cx. quinquefasciatus copes with the heat associated with warm blood meal ingestion and possibly uncover the adaptations this species uses to avoid thermal stress. Through the use of thermographic imaging, we analyzed the body temperature of Cx. quinquefasciatus while blood feeding. Infrared thermography has allowed us to identify a cooling strategy, evaporative cooling via the production of fluid droplets, and an overall low body temperature in comparison to the blood temperature during feeding. Understanding Cx. quinquefasciatus' adaptations and the strategies they employ to reduce their body temperature while blood feeding constitutes the first step towards discovering potential targets that could be used for their control.

A Method to Monitor the NAD+ Metabolome-From Mechanistic to Clinical Applications.

Nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH) are coenzymes employed in hundreds of metabolic reactions. NAD+ also serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and ADP-ribosyl cyclases. Given the pivotal role of NAD(H) in health and disease, studying NAD+ metabolism has become essential to monitor genetic- and/or drug-induced perturbations related to metabolic status and diseases (such as ageing, cancer or obesity), and its possible therapies. Here, we present a strategy based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the analysis of the NAD+ metabolome in biological samples. In this method, hydrophilic interaction chromatography (HILIC) was used to separate a total of 18 metabolites belonging to pathways leading to NAD+ biosynthesis, including precursors, intermediates and catabolites. As redox cofactors are known for their instability, a sample preparation procedure was developed to handle a variety of biological matrices: cell models, rodent tissues and biofluids, as well as human biofluids (urine, plasma, serum, whole blood). For clinical applications, quantitative LC-MS/MS for a subset of metabolites was demonstrated for the analysis of the human whole blood of nine volunteers. Using this developed workflow, our methodology allows studying NAD+ biology from mechanistic to clinical applications.

Studying the urine microbiome in superficial bladder cancer: samples obtained by midstream voiding versus cystoscopy.

BACKGROUND: Preliminary data suggest that the urinary microbiome may play a role in bladder cancer. Information regarding the most suitable method of collecting urine specimens is needed for the large population studies needed to address this. To compare microbiome metrics resulting from 16S ribosomal RNA gene sequencing between midstream, voided specimens and those obtained at cystoscopy. METHODS: Adults, with a history of superficial urothelial cell carcinoma (non-muscle invasive bladder cancer) being followed with periodic surveillance cystoscopy had a urine sample collected by a mid-stream, voided technique and then from the bladder at cystoscopy. Urine samples underwent 16S ribosomal RNA gene sequencing on the Illumina MiSeq platform. RESULTS: 22 subjects (8 female, 14 male) were included. There was no significant difference in beta diversity (diversity between samples) in all samples between collection methods. However, analysis by sex revealed a difference between voided and cystoscopy samples from the same individual in males (p = 0.006, Adonis test) but not in females (p = 0.317, Adonis test). No differences were seen by collection method in any alpha diversity (diversity within a sample) measurement or differential abundance of taxa. CONCLUSIONS: Beta diversity of the urine microbiome did differ by collection method for males only. This suggests that the urinary microbiomes of the two collection methods are not equivalent to each other, at least in males, which is the sex that bladder cancer occurs most frequently in. Therefore, the same collection method within a given study should be used.

Comparison of hot water immersion at 37.8°C with or without salt for rapid weight loss in mixed martial arts athletes.

Hot water immersion, known as a hot bath, is used by MMA athletes to produce rapid weight loss (RWL) by means of passive fluid loss. This study investigated the magnitude of body mass losses using a standardized hot bath protocol with or without the addition of salt. In a crossover design, eleven male MMA athletes (28.5 ± 4.6 y; 1.83 ± 0.07 m; 82.5 ± 9.1 kg) performed a 20-min immersion at 37.8°C followed by a 40-min wrap in a warm room. This bath and wrap was performed twice per visit. During one visit, only fresh water was used (FWB), and in the other visit, magnesium sulphate (1.6% wt/vol) was added to the bath (SWB). Prior to each visit, 24 h of carbohydrate, fibre, and fluid restriction was undertaken as part of the RWL protocol. Body mass losses induced by the hot bath protocols were 1.63 ± 0.75 kg and 1.60 ± 0.80 kg for FWB and SWB, respectively, and equivalent to ~2.1% body mass. Under the conditions employed, the magnitude of body mass loss in SWB was similar to FWB. However, further research should explore bathing in a temperature that is consistent with that habitually used by fighters, and/or higher concentrations of salt.

Effects of preventing a temperature decrease during winter on reproduction of male small-egged Kajika, Cottus pollux SE.

To investigate the effects of preventing temperature decrease on the reproductive activity of the male cold-water teleost, Cottus pollux SE, testicular development, serum 11-ketotestosterone (11-KT) levels, and physiological responses associated with nesting behavior (i.e., elevation of serum 11-KT levels and accumulation of urine in the urinary bladder) were observed from November to January. Specifically, males were exposed to three different cooling regimes (control, 16 to 6 °C; H1, 16 to 11 °C; H2, 16 to 14 °C), and the results were compared. In addition, the effects of temperature on male reproductive behavior were also clarified. At higher water temperature regimes, the rate of testicular development and serum 11-KT levels were both higher from November to mid-December than from mid-December to January. However, the results showed that high water temperature regimes in the coldest period of winter did not suppress spermatogenesis completely. Conversely, the physiological responses to nesting were affected by high water temperatures, with serum 11-KT levels increasing and urine accumulation in the urinary bladder being suppressed. Furthermore, frequencies of two behaviors associated with nesting, i.e., body undulation and face displays, were also suppressed under high water temperatures (~ 14 °C) compared with normal temperatures (~ 7 °C) during the breeding season. Based on the physiological and behavioral responses to nesting, findings showed that preventing a water temperature decrease during winter suppresses reproductive activity in Cottus pollux SE.

Effects of Menstrual Cycle Phase on Fluid Regulation during Walking Exercise.

To elucidate the fluid regulation in different menstrual cycle phases during exercise. Sex hormones affect fluid regulation in different ways. Moreover, the renin angiotensin-aldosterone system is activated in the luteal phase in rest. However, there are limited studies on fluid regulation affected by such hormone excretion in the menstrual cycle during exercise, especially during a light walking exercise. A non-invasive method using urine samples to determine menstrual cycle phases was used, and the follicular and luteal phases were successfully confirmed in 10 participants (age, 21 ± 1 years; body mass index, 20.5 ± 2.1 kg/m2). The experimental exercise sessions consisted of 5-min standing and 15-min walking at 2 km/h on 15% slope (approximately 8.3°) on a treadmill. Each participant carried a backpack weighing 5% of her own weight, and performed three sessions of walking exercise. Urine aldosterone excretion was significantly higher in the luteal than in the follicular phase before and after walking (p < 0.05). Urinary excretion of aldosterone was five times higher in the luteal than in the follicular phase before and after walking exercise. Heart rates during walking, after rest, and after recovery were all significantly higher in the luteal than in the follicular phase (p < 0.05). The participants' ratings of perceived exertion during the first and third session of walking in the luteal phase was not higher than that at the follicular phase. The results of our study suggested that increased activity of the renin-angiotensin-aldosterone system in the luteal phase of the menstrual cycle might be further activated during exercise. This may increase the circulatory load, which is reflected as increased heart rate. These results suggested that premenopausal women may better take into account a possibility of an increased circulatory load in the luteal phase even when they perform light exercise.

Enzymes and Pathways of Kavain Bioactivation and Biotransformation.

Kavain is an active and major component in Piper methysticum Forst. (kava), which is a widely used dietary supplement for the treatment of anxiety, insomnia, and stress. However, kava-containing products can cause liver toxicity, and its underlying mechanisms are understudied. Cytochrome P450s (CYPs)-mediated bioactivation and biotransformation are highly associated with drug toxicity. In the current study, we profiled the metabolic pathways of kavain in mouse liver, urine, and feces. Overall, 28 kavain metabolites were identified including 17 new ones. The metabolic pathways of kavain include glutathione (GSH) conjugation, oxidation, dehydrogenation, O-demethylation, sulfation, and glucuronidation. The identification of kavain-GSH adducts suggests the formation of reactive metabolites of kavain in the liver. We further illustrated that CYP2C19, a highly polymorphic and inducible enzyme, was the major enzyme contributing to kavain biotransformation and bioactivation. Our data can be used to guide the safe use of kava products by preventing potential herb-drug interactions and hepatotoxicity.

Science and fiction in critical care: established concepts with or without evidence?

In the absence of evidence, therapies are often based on intuition, belief, common sense or gut feeling. Over the years, some treatment strategies may become dogmas that are eventually considered as state-of-the-art and not questioned any longer. This might be a reason why there are many examples of "strange" treatments in medical history that have been applied in the absence of evidence and later abandoned for good reasons.In this article, five dogmas relevant to critical care medicine are discussed and reviewed in the light of the available evidence. Dogma #1 relates to the treatment of oliguria with fluids, diuretics, and vasopressors. In this context, it should be considered that oliguria is a symptom rather than a disease. Thus, once hypovolaemia can be excluded as the underlying reason, there is no justification for giving fluids, which may do more harm than good in euvolaemic or hypervolaemic patients. Similarly, there is no solid evidence for forcing diuresis by administering vasopressors and loop diuretics. Dogma #2 addresses the treatment of crush syndrome patients with aggressive fluid therapy using NaCl 0.9%. In fact, this treatment may aggravate renal injury by iatrogenic metabolic acidosis and subsequent renal hypoperfusion. Dogma #3 concerns the administration of NaCl 0.9% to patients undergoing kidney transplantation. Since these patients are usually characterised by hyperkalaemia, the potassium-free solution NaCl 0.9%, containing exclusively 154 mmol/l of sodium and chloride ions each, is often considered as the fluid of choice. However, large volumes of chloride-rich solutions cause hyperchloraemic acidosis in a dose-dependent manner and induce a potassium shift to the extracellular space, thereby increasing serum potassium levels. Thus, balanced electrolyte solutions are to be preferred in this setting. Dogma #4 relates to the fact that enteral nutrition is often withheld for patients with high residual gastric volume due to the theoretical risk of gastro-oesophageal reflux, potentially resulting in aspiration pneumonitis. Despite controversial discussions, there is no clinical data supporting that residual gastric volume should be generally measured, especially not in patients without a gastro-intestinal surgery and/or motility disorders. Clinical evidence rather suggests that abandoning residual gastric volume monitoring does not increase the incidence of pneumonia, but may benefit patients by facilitating adequate enteral feeding. Finally, dogma #5 is about sedating all mechanically ventilated patients because "fighting" against the respirator may cause insufficient ventilation. This concern needs to be balanced against the unwanted consequences of sedation, such as prolonged mechanical ventilation and intensive care unit length of stay as well as increased risk of delirium. Modern concepts based on adequate analgesia and moderate to no sedation appear to be more suitable.In conclusion, dogmas are still common in clinical practice. Since science rather than fiction should govern our actions in intensive care medicine, it is important to remain critical and challenge long established concepts, especially when the underlying evidence is weak or non-existing.

A retrospective study of the relationship between postoperative urine output and one year transplanted kidney function.

BACKGROUND: Kidney transplantation (KT) is the most obvious method of treating a patient with end-stage renal disease. In the early stages of KT, urine production is considered a marker of successful reperfusion of the kidney after anastomosis. However, there is no clear conclusion about the relationship between initial urine output after KT and 1-year renal function. Thus, we investigated the factors that affect 1-year kidney function after KT, including urine output. METHODS: This retrospective study investigated the relationship between urine output in the 3 days after KT and transplanted kidney prognosis after 1-year. In total, 291 patients (129 living-donor and 162 deceased-donor transplant recipients) were analyzed; 24-h urine volume per body weight (in kilograms) was measured for 3 days postoperatively. The estimated glomerular filtration rate (eGFR), determined by the Modification of Diet in Renal Disease algorithm, was used as an index of renal function. Patients were grouped according to eGFR at 1-year after KT: a good residual function group, eGFR ≥60, and a poor residual function group, eGFR < 60. RESULT: Recipients' factors affecting 1-year eGFR include height (P = 0.03), weight (P = 0.00), and body mass index (P = 0.00). Donor factors affecting 1-year eGFR include age (P = 0.00) and number of human leukocyte antigen (HLA) mismatches (P = 0.00). The urine output for 3 days after KT (postoperative day 1; 2 and 3) was associated with 1-year eGFR in deceased-donor (P = 0.00; P = 0.00 and P = 0.01). And, postoperative urine output was associated with the occurrence of delayed graft function (area under curve (AUC) = 0.913; AUC = 0.984 and AUC = 0.944). CONCLUSION: Although postoperative urine output alone is not enough to predict 1-year GFR, the incidence of delayed graft function can be predicted. Also, the appropriate urine output after KT may differ depending on the type of the transplanted kidney. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health in the Republic of Korea (KCT0003571).

Soluble (pro)renin receptor via ß-catenin enhances urine concentration capability as a target of liver X receptor.

The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the antidiuretic action of sPRR and its potential interaction with liver X receptors (LXRs), which are known regulators of urine-concentrating capability. Water deprivation consistently elevated urinary sPRR excretion in mice and humans. A template-based algorithm for protein-protein interaction predicted the interaction between sPRR and frizzled-8 (FZD8), which subsequently was confirmed by coimmunoprecipitation. A recombinant histidine-tagged sPRR (sPRR-His) in the nanomolar range induced a remarkable increase in the abundance of renal aquaporin 2 (AQP2) protein in primary rat inner medullary collecting duct cells. The AQP2 up-regulation relied on sequential activation of FZD8-dependent ß-catenin signaling and cAMP-PKA pathways. Inhibition of FZD8 or tankyrase in rats induced polyuria, polydipsia, and hyperosmotic urine. Administration of sPRR-His alleviated the symptoms of diabetes insipidus induced in mice by vasopressin 2 receptor antagonism. Administration of the LXR agonist TO901317 to C57/BL6 mice induced polyuria and suppressed renal AQP2 expression associated with reduced renal PRR expression and urinary sPRR excretion. Administration of sPRR-His reversed most of the effects of TO901317. In cultured collecting duct cells, TO901317 suppressed PRR protein expression, sPRR release, and PRR transcriptional activity. Overall we demonstrate, for the first time to our knowledge, that sPRR exerts antidiuretic action via FZD8-dependent stimulation of AQP2 expression and that inhibition of this pathway contributes to the pathogenesis of diabetes insipidus induced by LXR agonism.

Preoperative Urinary pH is Associated with Acute Kidney Injury After Cardiac Surgery in Non-Diabetic Patients.

BACKGROUND: Acute kidney injury is a common complication of cardiac surgery that increases morbidity and mortality. The present study aims to analyze the association of preoperative urinary pH with acute kidney injury after isolated coronary artery bypass graft surgery (CABG). METHODS: We retrospectively reviewed the data of 270 adult non-diabetic patients who underwent isolated CABG surgery with normal renal function. The perioperative data of the patients included demographic data, laboratory findings, morbidity, and mortality. The patient population was divided into four groups: Group I, patients with preoperative urinary pH=5; Group II, patients with preoperative urinary pH=5.5; Group III, patients with preoperative urinary pH=6-6.5; and Group IV, patients with preoperative urinary pH ≥ 7.0. Kidney injury was interpreted according to the Kidney Disease: Improving Global Outcomes (KDIGO). RESULTS: There were 108 patients (40%) in Group I, 44 patients (16.3%) in Group II, 78 patients (28.9%) in Group III, and 40 patients (14.8%) in Group IV. Postoperative acute kidney injury (AKI) occurred in 39 patients (36.1%) in Group I, 4 patients (9.1%) in Group II, and 2 patients (2,5%) in Group III. None of the patients developed AKI in Group IV. Renal replacement therapy was required in 8 patients (2.3%) (6 patients from Group I; 2 patients from Group II; P = .016). Thirty-day mortality occurred in 5 patients (1.9%) (5 patients from Group I; none from other groups; P =  .017). All of the patients required renal replacement therapy. Logistic regression analysis revealing the presence of lower pH levels preoperatively was shown to be associated with increased incidence of postoperative AKI (OR: 0.193; 95% CI: 0.103-0.361; P < .001). CONCLUSION: Low preoperative urinary pH (≤5.5) results in severe acute kidney injury and increases the rate of morbidity and mortality after isolated CABG.

Hydration Marker Diagnostic Accuracy to Identify Mild Intracellular and Extracellular Dehydration.

Identifying mild dehydration (≤2% of body mass) is important to prevent the negative effects of more severe dehydration on human health and performance. It is unknown whether a single hydration marker can identify both mild intracellular dehydration (ID) and extracellular dehydration (ED) with adequate diagnostic accuracy (≥0.7 receiver-operating characteristic-area under the curve [ROC-AUC]). Thus, in 15 young healthy men, the authors determined the diagnostic accuracy of 15 hydration markers after three randomized 48-hr trials; euhydration (water 36 ml·kg-1·day-1), ID caused by exercise and 48 hr of fluid restriction (water 2 ml·kg-1·day-1), and ED caused by a 4-hr diuretic-induced diuresis begun at 44 hr (Furosemide 0.65 mg/kg). Body mass was maintained on euhydration, and dehydration was mild on ID and ED (1.9% [0.5%] and 2.0% [0.3%] of body mass, respectively). Urine color, urine specific gravity, plasma osmolality, saliva flow rate, saliva osmolality, heart rate variability, and dry mouth identified ID (ROC-AUC; range 0.70-0.99), and postural heart rate change identified ED (ROC-AUC 0.82). Thirst 0-9 scale (ROC-AUC 0.97 and 0.78 for ID and ED) and urine osmolality (ROC-AUC 0.99 and 0.81 for ID and ED) identified both dehydration types. However, only the thirst 0-9 scale had a common dehydration threshold (≥4; sensitivity and specificity of 100%; 87% and 71%, 87% for ID and ED). In conclusion, using a common dehydration threshold ≥4, the thirst 0-9 scale identified mild intracellular and ED with adequate diagnostic accuracy. In young healthy adults', thirst 0-9 scale is a valid and practical dehydration screening tool.

Time of Onset to Changes in Skin Condition During Exposure to Synthetic Urine: A Prospective Study.

PURPOSE: The purpose of this study was to evaluate the impact of incontinence on epithelial-moisture barrier function and the subsequent risk for incontinence-associated dermatitis by exposing healthy volunteers to a premium incontinence pad wet with synthetic urine. DESIGN: Prospective, single-group study. PARTICIPANTS AND SETTING: Thirty women 65 years or older participated in the study. Participants had healthy skin of the buttocks, perineal, and perigenital areas and were not incontinent of urine or stool. The study was conducted at a contracted clinical research facility in Southeastern United States. METHODS: Four hundred milliliters of synthetic urine was distributed across the width of a premium incontinence pad with wicking technology containing a superabsorbent polymer core. Participants laid supine for a total of 4 hours, with the wet pad under the buttocks. Skin assessments were conducted at baseline prior to contact with the wet pad, at 15 minutes, 30 minutes, and 1, 2, and 4 hours after exposure to the synthetic urine. Outcome measures were skin moisture content, cutaneous pH, transepidermal water loss (TEWL), mean coefficient of friction values (static and dynamic), and tolerability evaluations (expert clinical grader-assessed erythema and participant-assessed discomfort). RESULTS: Mean moisture content of the skin increased from 46.19 ± 22.1 to 1845.28 ± 542.7 micro-Siemens (µS) after just 15 minutes of exposure and was significantly increased at all time points compared to baseline (P < .001). Cutaneous pH increased from 5.67 ± 0.5 to 6.25 ± 0.1 after 15 minutes; pH was higher at all time points compared to baseline (P < .001). Passive transfer of water through the stratum corneum (TEWL) showed an increase from 9.02 ± 2.2 g/m/h at baseline to 16.83 ± 5.2 g/m/h at 4 hours (P < .001). There was a significant increase from baseline to 4 hours in mean coefficient of static friction (0.32 ± 0.01 vs 0.47 ± 0.03; P < .00001) as well as mean coefficient of dynamic friction (0.29 ± 0.01 vs 0.42 ± 0.02; P < .00001). There was a significant increase in erythema and an increase in participant-assessed discomfort at all time points (P < .005). CONCLUSIONS: Our findings suggest that impairment of the skin's epithelial-moisture barrier function associated with inflammation and development of incontinence-associated dermatitis begins rapidly after an incontinence event, even with the use of a premium pad with wicking technology. Study findings also suggest that prompt attention to incontinence events is needed to prevent moisture-associated skin damage (incontinence-associated dermatitis) even when absorbent pads are used.

Factors associated with residual urine volume preservation in patients undergoing hemodialysis for end-stage kidney disease in Kinshasa.

BACKGROUND: Decreased residual urine volume (RUV) is associated with higher mortality in hemodialysis (HD). However, few studies have examined RUV in patients on HD in Sub-Saharan Africa. The aim of this study was to identify predictors of RUV among incident hemodialysis patients in Kinshasa. METHODS: This historical cohort study enrolled 250 patients with ESRD undergoing hemodialysis between January 2007 and July 2013 in two hemodialysis centers in Kinshasa. RUV were collected over 24 h at the initiation of HD and 6 and 12 months later during the interdialytic period. We compared the baseline characteristics of the patients according to their initial RUV (≤ 500 ml/day vs >  500 ml/day) using Student's t, Mann-Whitney U and Chi2 tests. Linear mixed-effects models were used to search for predictors of decreased RUV by adding potentially predictive baseline covariates of the evolution of RUV to the effect of time: age, sex, diabetes mellitus, hypertension, diastolic blood pressure, diuretics, angiotensin conversion enzyme inhibitors (ACEI), angiotensin receptor blockers, hypovolemia, chronic tubulointerstitial nephropathy, left ventricular hypertrophy and initial hemodialysis characteristic. A value of p < 0.05 was considered the threshold of statistical significance. RESULTS: The majority of hemodialysis patients were male (68.8%, sex ratio 2.2), with a mean age of 52.5 ± 12.3 years. The population's RUV decreased with time, but with a slight deceleration. The mean RUV values were 680 ± 537 ml/day, 558 ± 442 ml/day and 499 ± 475 ml/day, respectively, at the initiation of HD and at 6 and 12 months later. The use of ACEI at the initiation of HD (beta coefficient 219.5, p < 0.001) and the presence of chronic tubulointerstitial nephropathy (beta coefficient 291.8, p = 0.007) were significantly associated with RUV preservation over time. In contrast, the presence of left ventricular hypertrophy at the initiation of HD was significantly associated with decreased RUV over time (beta coefficient - 133.9, p = 0.029). CONCLUSIONS: Among incident hemodialysis patients, the use of ACEI, the presence of chronic tubulointerstitial nephropathy and reduced left ventricular hypertrophy are associated with greater RUV preservation in the first year of dialysis.

Tear osmolarity is sensitive to exercise-induced fluid loss but is not associated with common hydration measures in a field setting.

This investigation (i) examined changes in tear osmolarity in response to fluid loss that occurs with exercise in a field setting, and (ii) compared tear osmolarity with common field and laboratory hydration measures.  Sixty-three participants [age 27.8 ± 8.4 years, body mass 72.15 ± 10.61 kg] completed a self-paced 10 km run outside on a predetermined course. Body mass, tear fluid, venous blood and urine samples were collected immediately before and after exercise.  Significant (p < 0.001) reductions in body mass (1.71 ± 0.44%) and increases in tear osmolarity (8 ± 15 mOsm.L-1), plasma osmolality (7 ± 8 mOsm.kg-1), and urine specific gravity (0.0014 ± 0.0042 g.mL-1; p = 0.008) were observed following exercise. Pre- to post-exercise change in tear osmolarity was not significantly correlated (all p > 0.05) with plasma osmolality (rs = 0.24), urine osmolality (rs = 0.14), urine specific gravity (rs = 0.13) or relative body mass loss (r = 0.20).  Tear osmolarity is responsive to exercise-induced fluid loss but does not correlate with the changes observed using other common measures of hydration status in the field setting. Practitioners shouldn't directly compare or replace other common hydration measures with tear osmolarity in the field. ABBREVIATIONS: BML: Body Mass Loss; CV: Coefficient of Variation; Posm: Plasma osmolality; SD: Standard Deviation; Tosm: Tear Osmolarity; Uosm: Urine Osmolality; USG: Urine Specific Gravity; WBGT: Wet bulb globe thermometer.

Urine exosomes from healthy and hypertensive pregnancies display elevated level of α-subunit and cleaved α- and γ-subunits of the epithelial sodium channel-ENaC.

Preeclampsia is characterized by hypertension, proteinuria, suppression of plasma renin-angiotensin-aldosterone, and impaired urine sodium excretion. Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and promote Na+ reabsorption and urine K+ loss. Plasma and urine was sampled from patients with preeclampsia, healthy pregnant controls and non-pregnant women, and from patients with nephrostomy catheters. Aldosterone concentration, urine plasminogen, and protein were determined. Exosomes were isolated by ultracentrifugation. Immunoblotting was used to detect exosome markers; γ-ENaC (two different epitopes within the inhibitory peptide tract), α-ENaC, and renal outer medullary K-channel (ROMK) and compared with human kidney cortex homogenate. Urine total plasmin(ogen) was significantly increased in preeclampsia, plasma and urine aldosterone was higher in pregnancy compared to non-pregnancy, and the urine Na/K ratio was lower in preeclampsia compared to healthy pregnancy. Exosome markers ALIX and AQP-2 were stably associated with exosomes across groups. Exosomal α-ENaC-subunit migrated at 75 kDa and dominantly at 50 kDa and was significantly elevated in pregnancy. In human kidney cortex tissue and two of four pelvis catheter urine, ~90-100 kDa full-length γ-ENaC was detected while no full-length γ-ENaC but 75, 60, and 37 kDa variants dominated in voided urine exosomes. There was no difference in γ-ENaC protein abundances between healthy pregnancy and preeclampsia. ROMK was detected inconsistently in urine exosomes. Pregnancy and preeclampsia were associated with increased abundance of furin-cleaved α-ENaC subunit while γ-subunit appeared predominantly in cleaved form independently of conditions and with a significant contribution from post-renal cleavage.

Relationship between Sodium Intake and Water Intake: The False and the True.

BACKGROUND: Generally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial. The purpose of this review is to provide examples of how the kidney handles water in relation to salt intake/output. It is based on re-analysis of previously published studies in which salt intake was adjusted to several different levels in the same subjects, and in databases of epidemiologic studies in populations on an ad libitum diet. Summary and Key Messages: These re-analyses allow us to draw the following conclusions: (1) In a steady state situation, the urine volume (and thus the fluid intake) remains unchanged over a large range of sodium intakes. The adaptation to a higher sodium excretion rests only on changes in urinary sodium concentration. However, above a certain limit, this concentration cannot increase further and the urine volume may then increase. (2) In population studies, it is not legitimate to assume that sodium is responsible for changes in urine volume, since people who eat more sodium also eat more of other nutrients leading to an increase in the excretion of potassium, urea and other solutes, besides sodium. (3) After an abrupt increase in sodium intake, fluid intake is increased in the first few days, but urine volume does not change. The extra fluid drunk is responsible for an increase in body weight.