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Early Coaching to Increase Water Intake in CKD.
Ivanova, MD, Gozhenko, AI, Crestanello, T, Ivanov, DD
Annals of nutrition & metabolism. 2020;:69-70
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Abstract
INTRODUCTION In observational studies, increased water intake improves kidney function but not in adults with CKD stage 3 and more. CKD WIT trial has shown a nonsignificant gradual decline in kidney function after 1 year of coaching to increase water intake (CIWI) [1]. We propose that CIWI may benefit in CKD stage 1-2 (G1 and G2) and depends on functional renal functional reserve (RFR) [2, 3]. OBJECTIVE Parallel-group randomized trial was aimed to determinate the effectiveness of CIWI dependence of estimated glomerular filtration rate (eGFR) stage and RFR in adults with CKD 1-2 stages. METHODS CKD WIT trial was taken as the basis for prospective multicenter randomized trial named "Early Coaching to Increase Water Intake in CKD (ECIWIC)." The primary outcome was the change in kidney function by eGFR from baseline to 12 months. Secondary outcomes included 1-year change in urine albumin/Cr ratio, and patient-reported overall quality of health (QH) ranged from 0 (worst possible) to 10 (best possible). CIWI aimed to have the diuresis being 1.7-2 L. There were 4 groups with nondiet sodium restriction which consisted of 31 patients each: 2 groups with CKD G1 and CKD G2, undergoing CIWI and 2 others with CKD G1 and CKD G2 without CIWI (Fig. 1a). Overall checks were made at 0, 6, and 12 months. RFR evaluation was performed using 0.45% sodium chloride oral solution. RESULTS Of our randomized 124 patients (mean age 53.2 years; men 83 [67%], 0 died), mean change in 24-h urine volume was 0.6 L per day in G1 with CIWI group and 0.5 L in G2. No statistically significant data on eGFR depending CIWI were obtained (Fig. 1b). However, the trend suggests that CIWI improves eGFR in CKD G1 (from 95 to 96 mL/min/1.73 m2) and preserves eGFR decline in CKD G2 (78-78). The QH values were also preserved (from 7 to 7 in G1 and G2 groups). Although coaching to maintain the same water intake did not preserve physiological and pathological eGFR decreasing in CKD G1-2 (G1 from 96 to 93, G2 from 76 to 73; t = 0.6, p = 0.29, and p ≤ 0.05 in all groups) and the QH was declined (from 7 to 6 in both groups). An individual analysis of the RFR has shown that patients with RFR more than 50% (G1 19 patients, 61%, and G2 13 patients, 42%) had reliable preservation of eGFR with its increase of 1.5 mL/min on CIWI, while patients with low functional renal reserve had a drop of eGFR at 1.1 mL/min/m2 within 12 months. Patients with low normal serum sodium levels have shown worse results on CIWI. CONCLUSIONS With CKD G1, the CIWI leads to the preservation of the renal function with its increase of GFR per 1 mL/min/m2/per year in comparison with the same water intake. In CKD G2, the CIWI prevents physiological and pathological loss of renal function, and RFR above 50% aids restoration of eGFR both in CKD G1-2. ECIWIC trial demonstrates benefit of CIWI in patients with CKD 1-2 and preserved RFR.
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Free water: A marker of age-related modifications of the cingulum white matter and its association with cognitive decline.
Edde, M, Theaud, G, Rheault, F, Dilharreguy, B, Helmer, C, Dartigues, JF, Amieva, H, Allard, M, Descoteaux, M, Catheline, G
PloS one. 2020;(11):e0242696
Abstract
Diffusion MRI is extensively used to investigate changes in white matter microstructure. However, diffusion measures within white matter tissue can be affected by partial volume effects due to cerebrospinal fluid and white matter hyperintensities, especially in the aging brain. In previous aging studies, the cingulum bundle that plays a central role in the architecture of the brain networks supporting cognitive functions has been associated with cognitive deficits. However, most of these studies did not consider the partial volume effects on diffusion measures. The aim of this study was to evaluate the effect of free water elimination on diffusion measures of the cingulum in a group of 68 healthy elderly individuals. We first determined the effect of free water elimination on conventional DTI measures and then examined the effect of free water elimination on verbal fluency performance over 12 years. The cingulum bundle was reconstructed with a tractography pipeline including a white matter hyperintensities mask to limit the negative impact of hyperintensities on fiber tracking algorithms. We observed that free water elimination increased the ability of conventional DTI measures to detect associations between tissue diffusion measures of the cingulum and changes in verbal fluency in older individuals. Moreover, free water content and mean diffusivity measured along the cingulum were independently associated with changes in verbal fluency. This suggests that both tissue modifications and an increase in interstitial isotropic water would contribute to cognitive decline. These observations reinforce the importance of using free water elimination when studying brain aging and indicate that free water itself could be a relevant marker for age-related cingulum white matter modifications and cognitive decline.
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Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction.
Vorasayan, P, Bevers, MB, Beslow, LA, Sze, G, Molyneaux, BJ, Hinson, HE, Simard, JM, von Kummer, R, Sheth, KN, Kimberly, WT
Stroke. 2019;(11):3021-3027
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Background and Purpose- Prior studies have shown a linear relationship between computed tomography (CT)-derived radiodensity and water uptake, or brain edema, within stroke lesions. To test the hypothesis that intravenous glibenclamide (glyburide; BIIB093) reduces ischemic brain water uptake, we quantified the lesional net water uptake (NWU) on serial CT scans from patients enrolled in the phase 2 GAMES-RP Trial (Glyburide Advantage in Malignant Edema and Stroke). Methods- This was a post hoc exploratory analysis of the GAMES-RP study. Noncontrast CT scans performed between admission and day 7 (n=264) were analyzed in the GAMES-RP modified intention-to-treat sample. Quantitative change in CT radiodensity (ie, NWU) and midline shift (MLS) was measured. The gray and white matter NWU were also examined separately. Repeated-measures mixed-effects models were used to assess the effect of intravenous glibenclamide on MLS or NWU. Results- A median of 3 CT scans (interquartile range, 2-4) were performed per patient during the first 7 days after stroke. In a repeated-measures regression model, greater NWU was associated with increased MLS (β=0.23; 95% CI, 0.20-0.26; P<0.001). Treatment with intravenous glibenclamide was associated with reduced NWU (β=-2.80; 95% CI, -5.07 to -0.53; P=0.016) and reduced MLS (β=-1.50; 95% CI, -2.71 to -0.28; P=0.016). Treatment with intravenous glibenclamide reduced both gray and white matter water uptake. In mediation analysis, gray matter NWU (β=0.15; 95% CI, 0.11-0.20; P<0.001) contributed to a greater proportion of MLS mass effect, as compared with white matter NWU (β=0.08; 95% CI, 0.03-0.13; P=0.001). Conclusions- In this phase 2 post hoc analysis, intravenous glibenclamide reduced both water accumulation and mass effect after large hemispheric infarction. This study demonstrates NWU is a quantitative and modifiable biomarker of ischemic brain edema accumulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.
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Effect of Coaching to Increase Water Intake on Kidney Function Decline in Adults With Chronic Kidney Disease: The CKD WIT Randomized Clinical Trial.
Clark, WF, Sontrop, JM, Huang, SH, Gallo, K, Moist, L, House, AA, Cuerden, MS, Weir, MA, Bagga, A, Brimble, S, et al
JAMA. 2018;(18):1870-1879
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IMPORTANCE In observational studies, increased water intake is associated with better kidney function. OBJECTIVE To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L. INTERVENTIONS Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake. MAIN OUTCOMES AND MEASURES The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]). RESULTS Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0.3 to 0.3; P = .22). CONCLUSIONS AND RELEVANCE Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01766687.
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Computed tomography-based quantification of lesion water uptake identifies patients within 4.5 hours of stroke onset: A multicenter observational study.
Minnerup, J, Broocks, G, Kalkoffen, J, Langner, S, Knauth, M, Psychogios, MN, Wersching, H, Teuber, A, Heindel, W, Eckert, B, et al
Annals of neurology. 2016;(6):924-934
Abstract
OBJECTIVE Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours, the time window of thrombolysis. METHODS Perfusion CT was used to identify ischemic brain tissue, and its density was measured in native CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. The optimal cutoff value of water uptake distinguishing stroke onset within and beyond 4.5 hours was calculated in patients with proximal middle cerebral artery occlusion (derivation cohort) with known time of symptom onset. The so-derived cutoff value was validated in a prospective cohort from other stroke centers. RESULTS Of 178 patients of the derivation cohort, 147 (82.6%) had CT within 4.5 hours. Percentage water uptake was significantly lower in patients with stroke onset within compared to beyond 4.5 hours. The area under the receiver operating characteristic curve for distinguishing these patient groups according to percentage water uptake was 0.999 (95% confidence interval = 0.996-1.000, p < 0.001) with an optimal cutoff value of 11.5%. Applying this cutoff to the validation cohort of 240 patients, sensitivity was 98.6%, specificity 90.5%, positive predictive value 99.1%, and negative predictive value 86.4%. INTERPRETATION Quantification of brain water uptake identifies stroke patients with symptom onset within 4.5 hours with high accuracy and may guide the decision to use thrombolysis in patients with unknown time of stroke onset. Ann Neurol 2016;80:924-934.
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The doubly labeled water method produces highly reproducible longitudinal results in nutrition studies.
Wong, WW, Roberts, SB, Racette, SB, Das, SK, Redman, LM, Rochon, J, Bhapkar, MV, Clarke, LL, Kraus, WE
The Journal of nutrition. 2014;(5):777-83
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The doubly labeled water (DLW) method is considered the reference method for the measurement of energy expenditure under free-living conditions. However, the reproducibility of the DLW method in longitudinal studies is not well documented. This study was designed to evaluate the longitudinal reproducibility of the DLW method using 2 protocols developed and implemented in a multicenter clinical trial-the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). To document the longitudinal reproducibility of the DLW method, 2 protocols, 1 based on repeated analysis of dose dilutions over the course of the clinical trial (dose-dilution protocol) and 1 based on repeated but blinded analysis of randomly selected DLW studies (test-retest protocol), were carried out. The dose-dilution protocol showed that the theoretical fractional turnover rates for (2)H and (18)O and the difference between the 2 fractional turnover rates were reproducible to within 1% and 5%, respectively, over 4.5 y. The Bland-Altman pair-wise comparisons of the results generated from 50 test-retest DLW studies showed that the fractional turnover rates and isotope dilution spaces for (2)H and (18)O, and total energy expenditure, were highly reproducible over 2.4 y. Our results show that the DLW method is reproducible in longitudinal studies and confirm the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5-4.4 y. The 2 protocols can be adopted by other laboratories to document the longitudinal reproducibility of their measurements to ensure the long-term outcomes of interest are meaningful biologically. This trial was registered at clinicaltrials.gov as NCT00427193.
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Treatment with propranolol of 6 patients with idiopathic aquagenic pruritus.
Nosbaum, A, Pecquet, C, Bayrou, O, Amsler, E, Nicolas, JF, Bérard, F, Francès, C
The Journal of allergy and clinical immunology. 2011;(5):1113