scholarly journals Reduced Plasma Ascorbate and Increased Proportion of Dehydroascorbic Acid Levels in Patients Undergoing Hemodialysis

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1023
Author(s):  
Yuta Doshida ◽  
Mitsuyo Itabashi ◽  
Takashi Takei ◽  
Yuka Takino ◽  
Ayami Sato ◽  
...  

Ascorbate functions as an electron donor and scavenges free radicals. Dehydroascorbic acid (DHA), the oxidized form of ascorbate, is generated as a result of these reactions. While low plasma ascorbate levels have been reported in hemodialysis patients worldwide, no studies have measured DHA because it is not generalized. In this study, we aimed to clarify whether plasma ascorbate levels are low in dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. Moreover, we applied our previously established method to measure the plasma ascorbate and DHA levels in chronic kidney disease (CKD) stage G3–G5 non-hemodialysis-dependent patients, and pre- and post-dialysis plasma ascorbate and DHA levels in CKD stage G5D hemodialysis patients. The sample size was calculated using G-power software. The pre-dialysis plasma total ascorbate levels, including DHA, were significantly (56%) lower in hemodialysis patients than in non-hemodialysis-dependent CKD patients. After dialysis, there was a 40% reduction in the plasma total ascorbate levels. Hemodialysis increased the post-dialysis plasma proportions of DHA from 37% to 55%. The study results demonstrated lower plasma total ascorbate levels in hemodialysis patients compared with in non-hemodialysis-dependent CKD patients; these low levels in hemodialysis patients were further reduced by hemodialysis and increased DHA proportion.

2020 ◽  
Author(s):  
Yuta Doshida ◽  
Mitsuyo Itabashi ◽  
Takashi Takei ◽  
Yuka Takino ◽  
Ayami Sato ◽  
...  

Abstract Background: Low plasma ascorbate levels in hemodialysis patients have been reported worldwide; hence, many end-stage kidney disease patients are forced to restrict their diets, especially potassium-rich fruits and vegetables, to prevent hyperkalemia. In this study, we aimed to clarify whether plasma ascorbate levels are low in Japanese dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. In addition, we aimed to clarify whether there are clinical test items that have a causal relationship with plasma ascorbate levels.Methods: Plasma ascorbate levels in 27 chronic kidney disease (CKD) stage G3–G5 patients (mean age 84 years) and pre- and post-dialysis plasma ascorbate levels in 19 CKD stage G5D hemodialysis patients (mean age 79 years) were determined using high-performance liquid chromatography and electrochemical detection.Results: Pre-dialysis plasma ascorbate levels in hemodialysis patients (12.0 ± 1.4 µM) were significantly lower (by 56%) than those in CKD stage G3–G5 patients (27.1 ± 2.7 µM). After dialysis, there was a 40% reduction in plasma ascorbate levels. Moreover, pre-dialysis ascorbate levels correlated significantly with plasma potassium levels.Conclusions: The study results indicate that Japanese hemodialysis patients have lower plasma ascorbate levels than CKD stage G3–G5 patients and that these low plasma ascorbate levels in hemodialysis patients were further reduced by hemodialysis. To avoid the development of scurvy in hemodialysis patients, it is necessary to take sufficient ascorbate from supplements or medicines.


Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 324
Author(s):  
Yasutoshi Akiyama ◽  
Koichi Kikuchi ◽  
Takafumi Toyohara ◽  
Eikan Mishima ◽  
Chitose Suzuki ◽  
...  

Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations of 122 ionic solutes before and after HD in 11 patients. In addition, we compared the results with those in non-HD patients with chronic kidney disease (CKD) to identify HD patient-specific solutes. We identified 38 solutes whose concentrations were higher in pre-HD than in CKD stage G5. Ten solutes among them did not significantly accumulate in non-HD CKD patients, suggesting that these solutes accumulate specifically in HD patients. We also identified 23 solutes whose concentrations were lower in both pre- and post-HD than in CKD stage G5. The serum levels of 14 solutes among them were not affected by renal function in non-HD patients, suggesting that these solutes tend to be lost specifically in HD patients. Our data demonstrate that HD patients have a markedly different profile of serum uremic solute levels compared to that in non-HD CKD patients. The solutes identified in our study may contribute to the pathophysiology of HD patients.


1991 ◽  
Vol 2 (5) ◽  
pp. 1014-1020 ◽  
Author(s):  
M Rodriguez ◽  
A J Felsenfeld ◽  
C Williams ◽  
J A Pederson ◽  
F Llach

Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
IOANNIS GRIVEAS

Abstract Background and Aims Increments of oxidative stress have been addressed as one potential cause for the accelerated atherosclerosis of chronic kidney disease patients. Ascorbate (vitamin-C) represents one of the most prominent antioxidants both in plasma and intracellulary. Unsupplemented dialysis patients have reportedly lower plasma levels of ascorbate in comparison to healthy controls, mostly due to a loss into the dialysate. Purpose of our study was the recording of the experience of the use of Ascorbate-Rich Dialysate in patients under hemodialysis (HD). Method 11 HD patients were recruited for the study. During a period of 8 weeks they were receiving Ascorbate-Rich Dialysate (2g/lt). Ascorbic acid levels were estimated before and at the end of the study period. We also monitored patients’ anemia profile (Hb, Hct, ferritin, TSAT, rhEPO dose), lipid and nutrition status. Results Ascorbic acid values were towards the lower accepted levels in our patients (3.25±1.01 mg/l) at the beginning of the study period. After 8 weeks receiving Ascorbate-Rich Dialysate, acorbic-acid levels were significantly increased (6.87±1.50 mg/l) without transcending the upper accepted limit. During the notice period, our patients were behaved normally without any sort of adverse events. Mean Hct levels remained stable (39.10±3.70% with conventional dialysate vs 39.67±1.59 % with usage of ascorbate-rich dialysate ). The same conclusion was noticed with Hb levels (12.85±1.20 vs 13.15±0.49). Mean rhEPO dose per week (epoetin- alfa) decreased (9000±5200 iu vs 6250±4300 iu, p=NS) and administration of Fe stopped to all of our patients. Ferritin (>700), TSAT (>35) remained stable over the whole study period. Cholesterol, triglycerides and albumin levels did not change significantly with the change of the conventional dialysate to ascorbic-rich one. Conclusion Although our study is limited by small numbers of subjects, short durations of follow-up, our results suggest that compared with standard care, ascorbic acid in dialysate bath is a safe choice to increase ascorbic-acid levels in traditionally vitamic C depleted HD patients within safe limits. This raise seems to favors anemia profile of HD population. Longer term studies are required to confirm these results, determine whether these changes translate into improved patient outcomes and cost-effectiveness.


Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1607
Author(s):  
Anitra C. Carr ◽  
Stephanie Bozonet ◽  
Juliet Pullar ◽  
Emma Spencer ◽  
Patrice Rosengrave ◽  
...  

Vitamin C (ascorbate) plays an important role in neutrophil function and is accumulated by the cells either directly via vitamin C transporters (SVCT) or indirectly following oxidation to dehydroascorbic acid. Septic patients are known to have significantly depleted plasma ascorbate status, but little is known about the ascorbate content of their circulating cells. Therefore, we assessed the ascorbate concentrations of plasma, leukocytes and erythrocytes from septic patients and compared these to healthy controls. Non-fasting blood samples were collected from healthy volunteers (n = 20) and critically ill patients with sepsis (n = 18). The ascorbate content of the plasma and isolated neutrophils and erythrocytes was measured using HPLC and plasma myeloperoxidase concentrations were determined using ELISA. Ex vivo uptake of ascorbate and dehydroascorbic acid by neutrophils from septic patients was also assessed. Neutrophils isolated from septic patients had comparable intracellular ascorbate content to healthy volunteers (0.33 vs. 0.35 nmol/106 cells, p > 0.05), despite significantly lower plasma concentrations than the healthy controls (14 vs. 88 µmol/L, p < 0.001). In contrast, erythrocytes from septic patients had significantly lower intracellular ascorbate content than healthy controls (30 vs. 69 µmol/L, p = 0.002), although this was 2.2-fold higher than the matched plasma concentrations in the patients (p = 0.008). Higher concentrations of myeloperoxidase, a source of reactive oxygen species, were observed in the septic patients relative to healthy controls (194 vs. 14 mg/mL, p < 0.0001). In contrast to neutrophils from healthy volunteers, the neutrophils from septic patients demonstrated elevated uptake of extracellular ascorbate. Overall, neutrophils from septic patients exhibited comparable intracellular ascorbate content to those from healthy controls, despite the patients presenting with hypovitaminosis C. The mechanisms involved are currently uncertain, but could include increased generation of dehydroascorbic acid in septic patients, enhanced basal activation of their neutrophils or upregulation of their vitamin C transporters.


2018 ◽  
Vol 9 (01) ◽  
Author(s):  
Praful Prabhuappa Kapse ◽  
Manisha Kiran

Caring for the persons with first episode psychosis is challenging and demanding. It may lead to the increased burden, expressed emotions among the caregivers. The numerous studies have shown that high burden and negative expressed emotions among caregivers can lead to early relapse in the patients with first episode psychosis. To evaluate the effects of the brief psychoeducation on the caregivers burden and expressed emotions. A quasi experimental - before and after with control group research design was adopted for the study. A total of 60 caregivers have participated in the study, of which 30 caregivers in experimental group and 30 caregivers in the control group. Family Burden Interview Schedule (Pai and Kapoor, 1981) and Attitude Questionnaire (Sethi et al., 1981) was used to assess caregiver's burden and expressed emotions. At end of the psychoeducation intervention, burden among caregivers and negative expressed emotions of the caregivers have significantly reduced. The positive expressed emotions have been increased. Study results demonstrates the importance of psychoeducation intervention in reducing the burden and negative expressed emotions.


Author(s):  
Firas Ajam ◽  
Arda Akoluk ◽  
Anas Alrefaee ◽  
Natasha Campbell ◽  
Avais Masud ◽  
...  

ABSTRACT Background: The electrocardiogram (ECG) can aid in identification of chronic kidney disease (CKD) patients at high risk for cardiovascular diseases. Cohort studies describe ECG abnormalities in patients on hemodialysis (HD), but we did not find data comparing ECG abnormalities among patients with normal kidney function or peritoneal dialysis (PD) to those on hemodialysis. We hypothesized that ECG conduction abnormalities would be more common, and cardiac conduction interval times longer, among patients on hemodialysis vs. those on peritoneal dialysis and CKD 1 or 2. Methods: Retrospective review of adult inpatients’ charts, comparing those with billing codes for “Hemodialysis” vs. inpatients without those charges, and an outpatient peritoneal dialysis cohort. Patients with CKD 3 or 4 were excluded. Results: One hundred and sixty-seven charts were reviewed. ECG conduction intervals were consistently and statistically longer among hemodialysis patients (n=88) vs. peritoneal dialysis (n=22) and CKD stage 1 and 2 (n=57): PR (175±35 vs 160±44 vs 157±22 msec) (p=0.009), QRS (115±32 vs. 111±31 vs 91±18 msec) (p=0.001), QT (411±71 vs. 403±46 vs 374±55 msec) (p=0.006), QTc (487±49 vs. 464±38 vs 452±52 msec) (p=0.0001). The only significantly different conduction abnormality was prevalence of left bundle branch block: 13.6% among HD patients, 5% in PD, and 2% in CKD 1 and 2 (p=0.03). Conclusion: To our knowledge, this is the first study to report that ECG conduction intervals are significantly longer as one progresses from CKD Stage 1 and 2, to PD, to HD. These and other data support the need for future research to utilize ECG conduction times to identify dialysis patients who could potentially benefit from proactive cardiac evaluations and risk reduction.


2020 ◽  
Vol 24 (4) ◽  
pp. 61-66
Author(s):  
V. A. Kovalevskiy ◽  
A. N. Shishkin

INTRODUCTION. In patients with CKD stage 5 receiving hemodialysis as the main method of renal replacement therapy (RRT), the endocrine system organs, including the thyroid gland, are affected over time. The study of changes in the thyroid status is an urgent task. AIM OF STUDY. Study of functional and gender characteristics of the thyroid status, depending on the duration of patients stay on hemodialysis. PATIENTS AND METHODS. The thyroid status was measured in 108 patients (44 women and 64 men, average age 51.7±15.4 years) undergoing hemodialysis. Patients were divided into quartiles according to the duration of stay on the RRT: group 1 4 – 25 months (28 people), group 2 41 – 59 months (26 people), group 3 68 – 97 months (26 people) and the fourth more than 100 months (28 people). We performed correlation analysis and comparison between groups on the level of free T 4, TSH, the ratio of fT4 to TSH. RESULTS. The average value of fT4 was 11.95±2.07 pmol / ml and TSH 1.5± 0.94 mcME/ml. Significant differences in thyroid status were obtained between the first and second groups in terms of TSH level and ratio fT 4 to TSH (P<0.01) – the level of TSH in the second group is higher (0.74 to 2.1 mсME/ml) and the ratio of fT4 to TSH is lower (13.09 to 4.91). In total, thyroid dysfunction was detected in 20.3% of the examined patients. CONCLUSION. Thus, deviations in the thyroid status occur after 2 years of being on RRT by hemodialysis. In patients who have been on RRT for more than 5 years, the thyroid status stabilizes. The reasons for this phenomenon are completely incomprehensible.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jinmei Yin ◽  
Jun Yin ◽  
Rongli Lian ◽  
Peiqiu Li ◽  
Jing Zheng

Abstract Background Hyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients’ adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients. Objective To develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program. Design A non-randomized, single-arm, single-center trial lasting for 6 months. Setting This program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China. Participants Patients on maintenance hemodialysis with hyperphosphatemia. Methods An intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled percentage of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed. Results The proportion of controlled serum phosphorus was significantly increased from 43.5 to 54.9% (P<0.001). The scores on the knowledge of phosphate control were improved significantly from 59.0 ± 18.9 to 80.6 ± 12.4 (P < 0.001). The proportion of high adherence to phosphate binders was increased dramatically from 21.9 to 44.5% (P < 0.001). Conclusion The intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients. Trial registration Chinese Clinical Trial Registry, ChiCTR2100042017. Retrospectively registered January 12th, 2021.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 839.2-840
Author(s):  
C. Vesel ◽  
A. Morton ◽  
M. Francis-Sedlak ◽  
B. Lamoreaux

Background:NHANES data indicate that approximately 9.2 million Americans have gout,1 with a small subset having uncontrolled disease.2 Pegloticase is a PEGylated recombinant uricase enzyme indicated for treating uncontrolled gout that markedly reduces serum uric acid levels (sUA)3 and resolves tophi in treatment responders.4 Despite pegloticase availability in the US for many years, real world demographics of pegloticase users in the treatment of uncontrolled gout have not been previously reported in a population-based cohort.Objectives:This study utilized a large US claims database to examine demographics and co-morbidities of uncontrolled gout patients treated with pegloticase. Kidney function before and after pegloticase treatment and concomitant therapy with immunomodulators were also examined.Methods:The TriNetX Diamond database includes de-identified data from 4.3 million US patients with gout (as of September 2019), including demographics, medical diagnoses, laboratory values, procedures (e.g. infusions, surgeries), and pharmacy data. Patients who had received ≥1 pegloticase infusion were included in these analyses. The number of infusions was evaluated for a subgroup of patients who were in the database ≥3 months before and ≥2 years after the first pegloticase infusion (i.e. first infusion prior to September 2017) to ensure only complete courses of therapy were captured. In this subpopulation, kidney function before and after pegloticase therapy was examined, along with the presence of immunomodulation prescriptions (methotrexate, mycophenolate mofetil, azathioprine, leflunomide) within 60 days prior to and 14 days after the first pegloticase infusion.Results:1494 patients treated with pegloticase were identified. Patients were 63.1 ± 14.0 years of age (range: 23–91), mostly male (82%), and white (76%). Mean sUA prior to pegloticase was 8.7 ± 2.4 mg/dL (n=50), indicating uncontrolled gout in the identified population. The most commonly reported comorbidities were chronic kidney disease (CKD, 48%), essential hypertension (71%), type 2 diabetes (39%), and cardiovascular disease (38%), similar to pegloticase pivotal Phase 3 trial populations. In patients with pre-therapy kidney function measures (n=134), pre-treatment eGFR averaged 61.2 ± 25.7 ml/min/1.73 m2, with 44% having Stage 3-5 CKD. In patients with complete therapy course capture and pre- and post-therapy eGFR measures (n=48), kidney function remained stable (change in eGFR: -2.9 ± 18.2 ml/min/1.73 m2) and CKD stage remained the same or improved in 81% of patients. In 791 patients with complete treatment course capture, patients had received 8.7 ± 13.8 infusions (median: 3, IQR: 2-10). Of these, 189 (24%) patients received only 1 pegloticase infusion and 173 (22%) received ≥12 infusions. As the data cut-off for this analysis pre-dated emerging data on the use of immunomodulation as co-therapy, only 19 of 791 (2%) patients received immunomodulation co-therapy with pegloticase.Conclusion:This relatively large group of patients with uncontrolled gout treated with pegloticase had similar patient characteristics of those studied in the phase 3 randomized clinical trials. Patients with uncontrolled gout are significantly burdened with systemic co-morbid diseases. The majority of patients had stable or improved kidney function following pegloticase treatment. As these results reflect patients initiating treatment prior to 2018, before co-treatment with immunomodulation was introduced, this cohort only included a small percentage of patients who were co-treated with an immunomodulator. Future studies using more current datasets are needed to evaluate real world outcomes in patients treated with pegloticase/immunomodulator co-therapy and to evaluate the impact of systemic co-morbid diseases.References:[1]Chen-Xu M, et al. Arthritis Rheumatol 2019 71:991-999.[2]Fels E, Sundy JS. Curr Opin Rheumatol 2008;20:198-202.[3]Sundy J, et al. JAMA 2011;306:711-720.[4]Mandell BF, et al. Arthritis Res Ther 2018;20:286.Disclosure of Interests:Claudia Vesel Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Allan Morton Speakers bureau: Sanofi, Amgen, and Horizon, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc.


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