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1.
Effect of urea cream on sorafenib-associated hand-foot skin reaction in patients with hepatocellular carcinoma: A multicenter, randomised, double-blind controlled study.
Lee, YS, Jung, YK, Kim, JH, Cho, SB, Kim, DY, Kim, MY, Kim, HJ, Seo, YS, Yoon, KT, Hong, YM, et al
European journal of cancer (Oxford, England : 1990). 2020;:19-27
Abstract
BACKGROUND Hand-foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment in patients with hepatocellular carcinoma (HCC). In the present study, we aimed to investigate the role of urea cream in the prevention of HFSR or amelioration of HFSR severity. PATIENTS AND METHODS Patients with HCC were treated with either placebo cream or urea cream for 12 weeks concomitantly with sorafenib treatment. HFSR development, the Hand-Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire score, and adverse events were assessed at 2, 4, 8 and 12 weeks. RESULTS Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analysed. The urea cream group showed a trend towards a lower cumulative incidence of any-grade HFSR (log-rank, P = 0.247) and severe HFSR of grade II or higher (log-rank, P = 0.394) without statistical significance. In the incidence by time point, the incidence of severe HFSR of grade II or higher was significantly lower in the urea cream group than in the placebo control group at 2 weeks (13.8% versus 23.9%, P = 0.042). The urea cream group showed a significantly better HF-QoL questionnaire score than the placebo control group (11.8 versus 19.7, P = 0.014) at 12 weeks. CONCLUSIONS Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream may be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib. TRIAL REGISTRATION ClinicalTrials.gov (NCT03212625).
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2.
Urea reduction ratio may be a simpler approach for measurement of adequacy of intermittent hemodialysis in acute kidney injury.
Liang, KV, Zhang, JH, Palevsky, PM
BMC nephrology. 2019;(1):82
Abstract
BACKGROUND Assessment of adequacy of intermittent hemodialysis (IHD) is conventionally based upon urea kinetic models for calculation of single pool Kt/Vurea (Kt/V), with 1.2 accepted as minimum adequate clearance for thrice weekly IHD. In the Acute Renal Failure Trial Network (ATN) Study, adequacy of IHD in patients with acute kidney injury (AKI) was assessed using Kt/V. However, equations for Kt/V require volume of distribution of urea, which is highly variable in AKI. Therefore, simpler methods are needed to assess adequacy of IHD in AKI. We assessed correlation of urea reduction ratio (URR) with Kt/V and determined URR thresholds corresponding to Kt/V values to determine if URR could be a simpler means to assess the delivered dose of IHD. METHODS Using patients who received IHD for 2.5-6 h and with pre-dialysis BUN ≥20 mg/dL, we plotted URR against Kt/V. We determined URR thresholds (0.60 to 0.75) corresponding to Kt/V ≥ 1.2, 1.3, and 1.4. We generated receiver operating characteristic (ROC) curves for increasing URR values for each level of Kt/V to identify the corresponding thresholds of URR. RESULTS There was strong correlation between URR and Kt/V. ROC curves comparing URR with Kt/V ≥ 1.2, 1.3, and 1.4 had area under the curves (AUC) of 0.99. Sensitivity and specificity of URR ≥0.67 for corresponding values of Kt/V ≥ 1.2 were 0.769 (95% CI: 0.745 to 0.793) and 0.999 (95% CI: 0.997 to 1.000), respectively and the sensitivity and specificity of URR ≥0.67 for corresponding values of Kt/V ≥ 1.4 were 0.998 (95% CI: 0.995 to 1.000) and 0.791 (95% CI: 0.771 to 0.811), respectively. CONCLUSIONS Targeting a URR ≥0.67 provides a simplified means of assessing adequacy of IHD in patients with AKI. Use of URR will enhance ability to assess delivery of small solute clearance and improve adherence with clinical practice guidelines in AKI.
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3.
Efficacy of urine urea nitrogen measurement to assess the compliance with protein restricted diets.
Pérez, V, Barrera, G, Hirsch, S, Lorca, E, Bunout, DC
Nutricion hospitalaria. 2019;(3):714-717
Abstract
Background: protein restriction is the mainstay of dietary management of chronic kidney disease. Aim: to assess the usefulness of urine urea nitrogen measurement as a marker of protein restriction. Methods: healthy young participants were randomly divided in two groups. During 14 days, one group received a diet containing 30 kcal/kg body weight and 1 g protein/kg body weight and the other group received a diet with the same amount of calories and 0.6 g/kg of proteins. At baseline, seven days and 14 days, 24 h dietary recalls were answered by the participants. They collected 24 hour urine and provided spot urine samples at baseline and at the end of the intervention, to measure creatinine and urea nitrogen. Results: forty-one participants aged 29 ± 5 years completed the follow-up. According to 24h dietary recalls, the group receiving 0.6 g/kg protein reduced significantly the protein intake during the intervention from 0.88 ± 0.06 to 0.59 ± 0.05 g/kg/day. A significant reduction in 24 h urea nitrogen excretion was also observed in this group. In the group receiving 1 g/kg of protein, no significant changes in 24 h urea nitrogen excretion were observed. Among all participants, the odds ratio of observing a reduction in protein intake in the dietary survey was 5.75 (95% confidence intervals 1.29-25.55, p = 0.02), when a reduction in 24 h urea nitrogen excretion corrected by creatinine was observed. No changes were observed in urea nitrogen excretion in spot urine samples. Conclusions: repeated urea nitrogen excretion measured in 24 h urine samples can be a reliable indicator of dietary protein restriction.
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4.
Exploration of muscle loss and metabolic state during prolonged critical illness: Implications for intervention?
Wandrag, L, Brett, SJ, Frost, GS, Bountziouka, V, Hickson, M
PloS one. 2019;(11):e0224565
Abstract
BACKGROUND Muscle wasting in the critically ill is up to 2% per day and delays patient recovery and rehabilitation. It is linked to inflammation, organ failure and severity of illness. The aims of this study were to understand the relationship between muscle depth loss, and nutritional and inflammatory markers during prolonged critical illness. Secondly, to identify when during critical illness catabolism might decrease, such that targeted nutritional strategies may logically be initiated. METHODS This study was conducted in adult intensive care units in two large teaching hospitals. Patients anticipated to be ventilated for >48 hours were included. Serum C-reactive protein (mg/L), urinary urea (mmol/24h), 3-methylhistidine (μmol/24h) and nitrogen balance (g/24h) were measured on days 1, 3, 7 and 14 of the study. Muscle depth (cm) on ultrasound were measured on the same days over the bicep (bicep and brachialis muscle), forearm (flexor compartment of muscle) and thigh (rectus femoris and vastus intermedius). RESULTS Seventy-eight critically ill patients were included with mean age of 59 years (SD: 16) and median Intensive care unit (ICU) length of stay of 10 days (IQR: 6-16). Starting muscle depth, 8.5cm (SD: 3.2) to end muscle depth, 6.8cm (SD: 2.2) were on average significantly different over 14 days, with mean difference -1.67cm (95%CI: -2.3 to -1cm), p<0.0001. Protein breakdown and inflammation continued over 14 days of the study. CONCLUSION Our patients demonstrated a continuous muscle depth loss and negative nitrogen balance over the 14 days of the study. Catabolism remained dominant throughout the study period. No obvious 'nutritional tipping point" to identify anabolism or recovery could be identified in our cohort. Our ICU patient cohort is one with a moderately prolonged stay. This group showed little consistency in data, reflecting the individuality of both disease and response. The data are consistent with a conclusion that a time based assumption of a tipping point does not exist. TRIAL REGISTRATION International Standard Randomised Controlled Trial Number: ISRCTN79066838. Registration 25 July 2012.
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5.
Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease.
Di Iorio, BR, Marzocco, S, Bellasi, A, De Simone, E, Dal Piaz, F, Rocchetti, MT, Cosola, C, Di Micco, L, Gesualdo, L
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018;(5):804-813
Abstract
BACKGROUND Protein carbamylation is one of the non-enzymatic reactions involved in protein molecular ageing. We sought to investigate the relationship between urea levels and protein carbamylation, and whether a Mediterranean diet (MD) and a very low protein diet (VLPD) reduce protein carbamylation through reduction in urea levels in patients with chronic kidney disease (CKD). METHODS This is a prospective, randomized, crossover controlled trial that investigated 60 patients with CKD grades 3B-4 (46 males, mean age of 67 years). The enrolled CKD patients were randomly assigned (1:1) to two different nutritional treatment arms: (i) 3 months of free diet (FD), 6 months of VLPD, 3 months of FD and 6 months of MD; and (ii) 3 months of FD, 6 months of MD, 3 months of FD and 6 months of VLPD. Blood levels of lysine (Lys) and homocitrulline (Hcit) and their ratio were used as markers of cyanate levels. Due to a lack of pre-existing data on the potential effects of different dietary regimens and in light of the exploratory nature of the study, no formal sample size estimation was carried out. RESULTS At study completion, lower diastolic blood pressure and decreased serum levels of urea, sodium, phosphorus and parathyroid hormone, but higher serum levels of bicarbonate and haemoglobin, were noted with MD and VLPD. When compared with FD, both MD and VLPD were also associated with a decrease in serum Hcit levels and Hcit/Lys ratios (P < 0.001). Notably, reductions in urea levels correlated with substantial reductions in Hcit levels (R2 = 0.16 and 0.17 for VLPD and MD, respectively). CONCLUSION In conclusion, nutritional treatments that significantly decrease serum levels of urea are associated with reduced protein carbamylation.
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6.
The Influence of Prebiotic Arabinoxylan Oligosaccharides on Microbiota Derived Uremic Retention Solutes in Patients with Chronic Kidney Disease: A Randomized Controlled Trial.
Poesen, R, Evenepoel, P, de Loor, H, Delcour, JA, Courtin, CM, Kuypers, D, Augustijns, P, Verbeke, K, Meijers, B
PloS one. 2016;(4):e0153893
Abstract
UNLABELLED The colonic microbial metabolism is a key contributor to uremic retention solutes accumulating in patients with CKD, relating to adverse outcomes and insulin resistance. Whether prebiotics can reduce intestinal generation of these microbial metabolites and improve insulin resistance in CKD patients not yet on dialysis remains unknown. We performed a randomized, placebo-controlled, double-blind, cross-over study in 40 patients with eGFR between 15 and 45 ml/min/1.73 m2. Patients were randomized to sequential treatment with prebiotic arabinoxylan oligosaccharides (AXOS) (10 g twice daily) and maltodextrin for 4 weeks, or vice versa, with a 4-week wash-out period between both intervention periods. Serum levels and 24h urinary excretion of p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate, trimethylamine N-oxide and phenylacetylglutamine were determined at each time point using liquid chromatography-tandem mass spectrometry. In addition, insulin resistance was estimated by the homeostatic model assessment (HOMA-IR). A total of 39 patients completed the study. We observed no significant effect of AXOS on serum p-cresyl sulfate (P 0.42), p-cresyl glucuronide (P 0.59), indoxyl sulfate (P 0.70) and phenylacetylglutamine (P 0.41) and a small, albeit significant decreasing effect on serum trimethylamine N-oxide (P 0.04). There were neither effect of AXOS on 24h urinary excretion of p-cresyl sulfate (P 0.31), p-cresyl glucuronide (P 0.23), indoxyl sulfate (P 0.87) and phenylacetylglutamine (P 0.43), nor on 24h urinary excretion of trimethylamine N-oxide (P 0.97). In addition, we observed no significant change in HOMA-IR (P 0.93). In conclusion, we could not demonstrate an influence of prebiotic AXOS on microbiota derived uremic retention solutes and insulin resistance in patients with CKD not yet on dialysis. Further study is necessary to elucidate whether prebiotic therapy with other characteristics, higher cumulative exposure or in different patient populations may be of benefit. TRIAL REGISTRATION Clinicaltrials.gov NCT02141815.
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7.
Network Analysis of Metabolite GWAS Hits: Implication of CPS1 and the Urea Cycle in Weight Maintenance.
Matone, A, Scott-Boyer, MP, Carayol, J, Fazelzadeh, P, Lefebvre, G, Valsesia, A, Charon, C, Vervoort, J, Astrup, A, Saris, WH, et al
PloS one. 2016;(3):e0150495
Abstract
BACKGROUND AND SCOPE Weight loss success is dependent on the ability to refrain from regaining the lost weight in time. This feature was shown to be largely variable among individuals, and these differences, with their underlying molecular processes, are diverse and not completely elucidated. Altered plasma metabolites concentration could partly explain weight loss maintenance mechanisms. In the present work, a systems biology approach has been applied to investigate the potential mechanisms involved in weight loss maintenance within the Diogenes weight-loss intervention study. METHODS AND RESULTS A genome wide association study identified SNPs associated with plasma glycine levels within the CPS1 (Carbamoyl-Phosphate Synthase 1) gene (rs10206976, p-value = 4.709e-11 and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tissue showed that CPS1 expression levels were associated with successful weight maintenance and with several SNPs within CPS1 (cis-eQTL). In order to contextualize these results, a gene-metabolite interaction network of CPS1 and glycine has been built and analyzed, showing functional enrichment in genes involved in lipid metabolism and one carbon pool by folate pathways. CONCLUSIONS CPS1 is the rate-limiting enzyme for the urea cycle, catalyzing carbamoyl phosphate from ammonia and bicarbonate in the mitochondria. Glycine and CPS1 are connected through the one-carbon pool by the folate pathway and the urea cycle. Furthermore, glycine could be linked to metabolic health and insulin sensitivity through the betaine osmolyte. These considerations, and the results from the present study, highlight a possible role of CPS1 and related pathways in weight loss maintenance, suggesting that it might be partly genetically determined in humans.
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8.
Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma.
Ren, Z, Zhu, K, Kang, H, Lu, M, Qu, Z, Lu, L, Song, T, Zhou, W, Wang, H, Yang, W, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;(8):894-900
Abstract
PURPOSE To assess whether urea-based cream (UBC) has prophylactic benefits on sorafenib-induced hand-foot skin reaction (HFSR) in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS In this randomized, open-label trial, 871 patients with advanced HCC throughout China were treated with 10% UBC three times per day plus best supportive care (BSC; n = 439) or BSC alone excluding all creams (n = 432), starting on day 1 of sorafenib treatment, for up to 12 weeks. HFSR was assessed every 2 weeks and at 14 weeks for patients completing the study. Once HFSR occurred, patients were allowed any cream, including a UBC. RESULTS The 12-week incidence of any grade HFSR was significantly lower in the UBC group versus the BSC-alone group (56.0% v 73.6%, respectively; odds ratio [OR], 0.457; 95% CI, 0.344 to 0.608; P < .001), as was the incidence of grade ≥ 2 HFSR (20.7% v 29.2%, respectively; OR, 0.635; 95% CI, 0.466 to 0.866; P = .004). Median time to first occurrence of HFSR was significantly longer in the UBC group than the BSC-alone group (84 v 34 days, respectively; hazard ratio, 0.658; 95% CI, 0.541 to 0.799; P < .001). Elevated AST was associated with increased risk of HFSR but did not alter the treatment effect of UBC. UBC plus BSC, compared with BSC alone, did not affect the sorafenib dose reduction or interruption rate (9.1% v 11.8%, respectively; P = .1937), response rate (11.1% v 10.1%, respectively; P = .6674), or disease control rate (98.8% v 98.2%, respectively; P = .5350) at week 12. CONCLUSION UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared with BSC. Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HFSR are warranted.
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9.
Plaque pH in caries-free and caries-active young individuals before and after frequent rinses with sucrose and urea solution.
Hassan, H, Lingström, P, Carlén, A
Caries research. 2015;(1):18-25
Abstract
OBJECTIVE To examine pH in the approximal dental biofilm after acid and alkali formation from sucrose and urea, after an adaptation period to these substances, in caries-free (CF) and caries-active (CA) individuals. Saliva flow and buffer capacity, and aciduric bacteria in saliva and plaque were also examined. MATERIAL AND METHODS Twenty adolescents and young adults (15-21 years) with no caries (n = 10, D(m + i)MFS = 0) or ≥1 new manifest lesions/year (n = 10, DmMFS = 3.4 ± 1.8) participated. After plaque sampling, interproximal plaque pH was measured using the strip method before (baseline) and up to 30 min (final pH) after random distribution of a 1-min rinse with 10 ml of 10% sucrose or 0.25% urea. This procedure was repeated after a 1-week adaptation period of rinsing 5 times/day with 10 ml of the selected solution. After a 2-week washout period the second solution was similarly tested. Mutans streptococci, lactobacilli and pH 5.2-tolerant bacteria were analyzed by culturing. RESULTS In the CF group, acid adaptation resulted in lowering of baseline and final plaque pH values after a sugar challenge, and in increased numbers of bacteria growing at pH 5.2, which was increased also after alkali adaptation. In the CA group, the final pH was decreased after acid adaptation. No clear effects of alkali adaptation were seen in this group. CONCLUSION One-week daily rinses with sucrose and urea had the most pronounced effect on the CF group, resulting in increased plaque acidogenicity from the sugar rinses and increased number of acid-tolerant plaque bacteria from both rinses.
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10.
Effect of urine urea nitrogen and protein intake adjusted by using the estimated urine creatinine excretion rate on the antiproteinuric effect of angiotensin II type I receptor blockers.
Chin, HJ, Kim, DK, Park, JH, Shin, SJ, Lee, SH, Choi, BS, Kim, S, Lim, CS
Nutrition (Burbank, Los Angeles County, Calif.). 2015;(11-12):1333-8
Abstract
OBJECTIVES The aim of this study was to determine the role of protein intake on proteinuria in chronic kidney disease (CKD), as it is presently not conclusive. METHODS This is a subanalysis of data from an open-label, case-controlled, randomized clinical trial on education about low-salt diets (NCT01552954). We estimated the urine excretion rate of parameters in a day, adjusted by using the equation for estimating urine creatinine excretion, and analyzed the effect of urine urea nitrogen (UUN), as well as estimating protein intake on the level of albuminuria in hypertensive patients with chronic kidney disease. RESULTS Among 174 participants from whom complete 24-h urine specimens were collected, the estimates from the Tanaka equation resulted in the highest accuracy for the urinary excretion rate of creatinine, sodium, albumin, and UUN. Among 227 participants, the baseline value of estimated urine albumin excretion (eUalb) was positively correlated with the estimated UUN (eUUN) or protein intake according to eUUN (P = 0.012 and P = 0.038, respectively). We were able to calculate the ratios of eUalb and eUUN in 221 participants and grouped them according to the ratio of eUUN during 16-wk trial period. The proportion of patients that achieved a decrement of eUalb ≥25% during 16 wk with an angiotensin II type I receptor blocker (ARB) medication was 80% (24 of 30) in group 1, with eUUN ratio ≤-25%; 82.2% (111 of 135) in group 2, with eUUN ratio between -25% and 25%; and 66.1% (37 and 56) in group 3, with eUUN ratio ≥25% (P = 0.048). The probability of a decrease in albuminuria with ARB treatment was lower in patients with an increase of eUUN or protein intake during the 16 wk of ARB treatment, as observed in multiple logistic regression analysis as well. CONCLUSIONS The estimated urine urea excretion rate showed a positive association with the level of albuminuria in hypertensive patients with chronic kidney disease. The increase of eUUN excretion ameliorated the antiproteinuric effect of ARB.