UNASSIGNED: Tolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU).
UNASSIGNED: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up.
UNASSIGNED: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m2 during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34).
UNASSIGNED: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.

暂无摘要。

The risk of dehydration in older adults with neurocognitive disorder (NCD) is controversial. The purpose of this study was to assess hydration status, its determinants, and water intake sources in older adults with NCD. A sample of 30 participants (≥60 years) was included. Sociodemographic, clinical data and one 24-h urine sample were collected. Urinary osmolality, sodium, potassium, volume, and creatinine were quantified. Inadequate hydration status corresponded to urine osmolality > 500 mOsm/Kg, or a negative Free Water Reserve (FWR). Two 24-h food recalls were used to assess dietary intake and water sources. The adequacy of total water intake (TWI) was estimated according to EFSA. The contribution of food and beverages to TWI was calculated, and their associations with the urinary osmolality median were tested. Of the total number of participants, 30% were classified as having inadequate hydration status, with no differences between sexes. Regarding TWI, 68.4% of women and 77.8% of men did not reach the reference values. Water (23%), followed by soup (17%), contributed the most to TWI, while vegetables (2%) and alcoholic/other beverages (3%) contributed the least. According to the median urinary osmolality, there was no significant difference in sociodemographic/clinical characteristics. It is critical not to overlook hydration in this vulnerable population.

UNASSIGNED: Tolvaptan (TV) is the first vasopressin-receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). No publications report TV experience in real clinical practice during the first year of treatment.
UNASSIGNED: A prospective study of an initial cohort of 220 rapidly progressing patients treated with TV for 12 months. The tolerability of TV, the evolution of the estimated glomerular filtration rate (eGFR), analytical parameters, and blood pressure were analyzed.
UNASSIGNED: A total of 163 patients (78.2%) received TV for 1 year. The main causes of treatment withdrawal were the aquaretic effects (11%), eGFR deterioration (5%), and hepatic toxicity (2.3%). eGFR decreased significantly after 1 month of treatment without further changes. The decrease in eGFR in the first month was higher in patients with an initially higher eGFR. The eGFR drop during the first year of treatment with TV was lower than that reported by patients in the 2 years prior to TV treatment (-1.7 ± 7.6 vs. -4.4 ± 4.8 mL/min, p = 0.003). Serum sodium and uric acid concentrations increased, and morning urinary osmolality decreased in the first month, with no further changes. Blood pressure decreased significantly without changes in antihypertensive medication.
UNASSIGNED: TV treatment is well tolerated by most patients. Liver toxicity is very rare and self-limited. TV reduces eGFR in the first month without showing further changes during the first year of treatment. Patients with a higher starting eGFR will suffer a greater initial drop, with a longer recovery. We suggest using the eGFR observed after a month of treatment as the reference for future comparisons and calculating the rate of eGFR decline in patients undergoing TV treatment.

Split renal function measured in a diuretic renogram is the most popular tool in initial assessment and follow-up of patients with ureteropelvic junction obstruction (UPJO). This study aims to evaluate the use of maximum urinary osmolality after desmopressin administration (DDAVP) to detect renal dysfunction.
56 children (33 males, 23 females) diagnosed with UPJO underwent quantification of the maximum urinary osmolality (UOsm) at diagnosis. 41 of these children (28 males, 13 females) underwent surgery for UPJO and quantification of the UOsm before and after the surgical intervention (six to 18 months postoperatively) and were included in this longitudinal study.
At diagnosis, UOsm measured after desmopressin administration was abnormal in 64% of patients. After surgical intervention, this rate decreased to 53%. At initial assessment, high creatinine levels were found in 32% of infants younger than one year of age. Albumin/Cr and NAG/Cr ratios were elevated in 12% and 7% of cases, respectively. After surgical intervention, an improvement in the NAG/creatinine ratio and creatinine levels was observed. Preoperative split renal function of the affected kidney was less than 45% in 39% of cases, normal in 44%, and greater than 55% in 17%; in these three subgroups, no differences in renal function markers were found.
The most sensitive parameter to detect alterations in renal function in children with UPJO is the UOsm and, therefore, the most useful in the follow-up after surgery. No correlation was found between other functional and morphological parameters obtained on renal ultrasound and renogram.

To investigate school policies and practices related to drinking fluids and toileting and test their association with children\'s hydration status and toilet behaviors.
Cross-sectional study in 2014.
Seventeen Belgian primary schools.
A total of 416 children (aged 7-13 years).
Hydration was measured by urinary osmolality in a pooled school-day sample and by impedance-based body water percentage. Children reported how much they liked school toilets. School policy and practices were reported by schools on 59 items over 10 policy components.
Multilevel logistic regression analyses adjusted for age, sex, region and socioeconomic status.
School\'s weaknesses were the lack of policy participation by parents and children; official agreements (only in 11%); organizing education on drinking and toilet visits; and toilet infrastructure. Children\'s hydration was higher in schools that (1) made water available, (2) organized toilet and drinking related education, (3) had formal agreements on drinking and toilet visits, and (4) had good toilet maintenance. Children liked school toilets more in schools that (1) organized toilet and drinking related education, (2) had an official policy on drinking, (3) had good toilet infrastructure, and (4) allowed policy participation by parents and children.
Specific action points for school management and government to improve children\'s hydration at school were detected by focusing on both drinking and toilet practices/infrastructure.

Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin.
We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline.
Not applicable.
The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk.
ClinicalTrials.gov NCT02967653 . Registered in February 2017.

High fluid intake has been universally recommended for kidney stone prophylaxis. We evaluated 24-h urine osmolality regarded as the best biomarker of optimal hydration and upper metastable limit osmolality after water evaporation from urine sample to the onset of spontaneous crystallization and its usefulness as a new risk index that would describe an individual lithogenic potential. We collected 24-h urine from 257 pediatric patients with kidney stones and 270 controls. After volume and osmolality assessment, the urine samples were subjected to volume reduction in vacuum rotavapor continued to the onset of an induced urinary crystallization. The upper metastable limit osmolality of urine sample was calculated based on its initial osmolality value and the amount of water reduction. Pediatric stone formers presented with higher urine volume and lower urine osmolality than healthy controls. Despite that, their urine samples required much lower volume reduction to induce the spontaneous crystallization than those of controls. The ROC analysis revealed an AUC for the upper metastable limit osmolality of 0.9300 (95% CI 0.9104-0.9496) for distinguishing between stone formers and healthy subjects. At the cutoff of 2696 mOsm/kg, the test provided sensitivity and specificity of 0.8638 and 0.8189, respectively. 24-h urine osmolality provided the information about current hydration status, whereas evaporation test estimated the urinary potential to crystalize dependent on urine composition. Upper metastable limit osmolality may estimate the individual lithogenic capability and identify people at risk to stone formation when exposed to dehydration.

OBJECTIVE: Dehydration has been related to several health aspects, and children are especially vulnerable. Since children spend a large time at school, we aim to examine children\'s hydration status at school-start and its change during the school-day by objective measures. To identify subpopulations at risk, determinants of hydration were tested.
METHODS: In 371 Belgian 7-13-year-old children, hydration was measured by (1) urinary osmolality at school-start and by a pooled school-day sample; (2) body water% by impedance; (3) parental reported beverage consumption; (4) urination frequency. Linear regression analyses were used to test putative predictors of hydration status: age, sex, parental education, region (Dutch-speaking versus French-speaking part of Belgium), diet quality and adiposity.
RESULTS: A mean osmolality of 888 mosmol/kg was found in the school-start sample and 767 mosmol/kg in the school-day sample. This resulted in, respectively, 76 and 54 % of the children being dehydrated (>800 mosmol/kg). In 45 % of the children, the hydration level decreased over the school-day. Also the body water% as derived from bio-impedance (57 % ±4), the reported average daily beverage intake (911 ml) and the lower urination frequency during weekdays versus weekend days confirmed the low hydration status in our school population. Boys, Walloon children and those with higher adiposity were at increased risk of low hydration level. Diet quality was not the predictor of hydration status.
CONCLUSIONS: Hydration status at school appeared problematic in this population. This emphasizes the need for more resources and attention by school management and governmental organizations. Herein, especially Walloon schools and boys should be reached.

BACKGROUND: Researchers have increasingly sought noninvasive methods to determine health and nutritional status in humans. Easy and painless to collect, human urine is a source of noninvasive biomarkers.
OBJECTIVE: We aimed to explore the relation between systemic oxidative stress biomarkers excreted in urine and urinary osmolality (Uosm).
METHODS: The current trial was a descriptive, cross-sectional study. We collected seventy-eight samples of 24-h urine in preschoolers who were attending daycare centers in the Western Highlands province of Quetzaltenango, Guatemala. After we measured the total urine volume (Uvol), the aliquot was stored for the later determination of Uosm as a hydration biomarker and to measure 15-isoprostane F2t (F2-Iso) and 8-hydroxydeoxyguanosine (8-OHdG) as biomarkers of cellular oxidation with the use of ELISA assay kits in Spain. Descriptive statistics and linear [Spearman rank-order (rs)] and nonlinear (goodness-of-fit) correlations were performed.
RESULTS: Twenty-four hour Uvols ranged from 65 to 1670 mL, whereas the Uosm varied between 115 and 1102 mOsm/kg. With respect to oxidative biomarkers, the 24-h urinary output of F2-Iso and 8-OHdG had median values of 748 and 2793 ng/d, respectively. The Uvol correlated inversely and significantly with the concentrations of both oxidative biomarkers (F2-Iso rs = -0.603, P < 0.001; 8-OHdG rs = -0.433, P < 0.001), whereas the Uosm was correlated in a direct manner (F2-Iso rs = 0.541, P < 0.001; 8-OHdG rs = 0.782, P < 0.001) when analyzed as a concentration. Associations were weaker when they were analyzed as the total 24-h production.
CONCLUSIONS: Preschool children from the Western Highlands of Guatemala show strong correlations between hydration status measured through the use of Uosm and biomarkers of oxidative stress in urine. Thus, a relatively superior hydration status is associated with a quantitative reduction in urinary excretion of systemic oxidation products. This trial was registered at clinicaltrials.gov as NCT02203890.