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Anderson CE, Tuokkola J, Qizalbash L, Harmer M, Nelms CL, Stabouli S, Toole B, Polderman N, Desloovere A, Renken-Terhaerdt J, Vega MRW, Snauwaert E, Walle JV, Haffner D, Paglialonga F, Shroff R, Shaw V, Greenbaum LA, Warady BA. Assessment and management of vitamin status in children with CKD stages 2-5, on dialysis and post-transplantation: clinical practice points from the Pediatric Renal Nutrition Taskforce. Pediatr Nephrol 2024; 39:3103-3124. [PMID: 38570350 PMCID: PMC11349803 DOI: 10.1007/s00467-024-06303-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 01/10/2024] [Accepted: 01/10/2024] [Indexed: 04/05/2024]
Abstract
Children with chronic kidney disease (CKD) are at risk for vitamin deficiency or excess. Vitamin status can be affected by diet, supplements, kidney function, medications, and dialysis. Little is known about vitamin requirements in CKD, leading to practice variation.The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric kidney dietitians and pediatric nephrologists, was established to develop evidence-based clinical practice points (CPPs) to address challenges and to serve as a resource for nutritional care. Questions were formulated using PICO (Patient, Intervention, Comparator, Outcomes), and literature searches undertaken to explore clinical practice from assessment to management of vitamin status in children with CKD stages 2-5, on dialysis and post-transplantation (CKD2-5D&T). The CPPs were developed and finalized using a Delphi consensus approach. We present six CPPs for vitamin management for children with CKD2-5D&T. We address assessment, intervention, and monitoring. We recommend avoiding supplementation of vitamin A and suggest water-soluble vitamin supplementation for those on dialysis. In the absence of evidence, a consistent structured approach to vitamin management that considers assessment and monitoring from dietary, physical, and biochemical viewpoints is needed. Careful consideration of the impact of accumulation, losses, comorbidities, and medications needs to be explored for the individual child and vitamin before supplementation can be considered. When supplementing, care needs to be taken not to over-prescribe. Research recommendations are suggested.
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Affiliation(s)
- Caroline E Anderson
- University Hospital Southampton NHS Foundation Trust, Southampton, UK.
- Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, UK.
- University of Winchester, Winchester, UK.
| | - Jetta Tuokkola
- Clinical Nutrition Unit, Internal Medicine and Rehabilitation, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
- Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
| | | | - Matthew Harmer
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | | | - Stella Stabouli
- 1st Department of Pediatrics, Aristotle University, Hippokratio Hospital, Thessaloniki, Greece
| | - Barry Toole
- Great Northern Children's Hospital, Newcastle Upon Tyne, UK
| | | | | | - Jose Renken-Terhaerdt
- Wilhemina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | | | | | - Dieter Haffner
- Hannover Medical School, Children's Hospital, Hannover, Germany
| | - Fabio Paglialonga
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Rukshana Shroff
- University College London Great Ormond Street Hospital Institute of Child Health, London, UK
| | - Vanessa Shaw
- University College London Great Ormond Street Hospital Institute of Child Health, London, UK
| | - Larry A Greenbaum
- Emory University, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
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Determination of Ascorbic Acid in Pharmaceuticals and Food Supplements with the New Potassium Ferrocyanide-Doped Polypyrrole-Modified Platinum Electrode Sensor. CHEMOSENSORS 2022. [DOI: 10.3390/chemosensors10050180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
This paper reports the results obtained from the determination of ascorbic acid with platinum-based voltammetric sensors modified with potassium hexacyanoferrate-doped polypyrrole. The preparation of the modified electrodes was carried out by electrochemical polymerization of pyrrole from aqueous solutions, using chronoamperometry. Polypyrrole films were deposited on the surface of the platinum electrode, by applying a constant potential of 0.8 V for 30 s. The thickness of the polymer film was calculated from the chronoamperometric data, and the value was 0.163 μm. Cyclic voltammetry was the method used for the Pt/PPy-FeCN electrode electrochemical characterization in several types of solution, including KCl, potassium ferrocyanide, and ascorbic acid. The thin doped polymer layer showed excellent sensitivity for ascorbic acid detection. From the voltammetric studies carried out in solutions of different concentrations of ascorbic acid, ranging from 1 to 100 × 10−6 M, a detection limit of 2.5 × 10−7 M was obtained. Validation of the analyses was performed using pharmaceutical products with different concentrations of ascorbic acid, from different manufacturers and presented in various pharmaceutical forms, i.e., intravascular administration ampoules, chewable tablets, and powder for oral suspension.
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Hsu CY, Chen JC, Tsai YC, Chen TW. Low-dose ferrous bisglycinate chelate supplementation in chronic kidney disease and hemodialysis patients. J Chin Med Assoc 2022; 85:566-570. [PMID: 35358119 DOI: 10.1097/jcma.0000000000000725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Provision of parenteral or oral iron supplementation can restore iron stores and maintain stable hemoglobin levels in chronic kidney disease (CKD) and hemodialysis (HD) patients. The route for oral or intravenous (IV) administration of iron depends on the acuity of anemia, costs, and patient tolerance. IV iron can restore iron stores rapidly but also carries higher risks for allergy and infection. Oral iron supplementation is limited by high gastrointestinal adverse effects. METHODS We conducted an open-label trial to study the efficiency of a film-coated iron supplementation tablet, which contains ferrous bisglycinate chelate, vitamin C, and folic acid, in CKD stage 3b to 4 and HD patients. RESULTS Twenty-seven HD patients and 20 CKD patients participated this study. After a 16-week intervention, low-dose ferrous bisglycinate chelate improved serum iron concentration (67.8 vs 87.2 mg/dL, p = 0.04) and transferrin saturation (24.7% vs 31.3%, p = 0.03) in stage 3 to 4 CKD patients, restored iron loss, and maintained stable hemoglobin levels in HD patients. No GI upset events were reported. CONCLUSION Ferrous bisglycinate chelate is a well-tolerated oral iron supplementation for CKD and HD patients.
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Affiliation(s)
- Cheng-Yi Hsu
- Division of Nephrology, Department of Medicine, Wei-Gong Memorial Hospital, Miaoli, Taiwan, ROC
| | | | - Yu-Cheng Tsai
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Tzen-Wen Chen
- Division of Nephrology, Department of Medicine, Wei-Gong Memorial Hospital, Miaoli, Taiwan, ROC
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Vollbracht C, Kraft K. Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C. Front Pharmacol 2022; 13:899198. [PMID: 35571085 PMCID: PMC9100929 DOI: 10.3389/fphar.2022.899198] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 04/14/2022] [Indexed: 12/25/2022] Open
Abstract
Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also in Long-COVID. Inflammation and oxidative stress are mutually reinforcing each other, thus contributing to the systemic hyperinflammatory state and coagulopathy which are cardinal pathological mechanisms of severe stages. COVID-19 patients, like other critically ill patients e.g. with pneumonia, very often show severe deficiency of the antioxidant vitamin C. So far, it has not been investigated how long this deficiency lasts or whether patients with long COVID symptoms also suffer from deficiencies. A vitamin C deficit has serious pathological consequences because vitamin C is one of the most effective antioxidants, but also co-factor of many enzymatic processes that affect the immune and nervous system, blood circulation and energy metabolism. Because of its anti-oxidative, anti-inflammatory, endothelial-restoring, and immunomodulatory effects the supportive intravenous (iv) use of supraphysiological doses has been investigated so far in 12 controlled or observational studies with altogether 1578 inpatients with COVID-19. In these studies an improved oxygenation, a decrease in inflammatory markers and a faster recovery were observed. In addition, early treatment with iv high dose vitamin C seems to reduce the risks of severe courses of the disease such as pneumonia and also mortality. Persistent inflammation, thrombosis and a dysregulated immune response (auto-immune phenomena and/or persistent viral load) seem to be major contributors to Long-COVID. Oxidative stress and inflammation are involved in the development and progression of fatigue and neuro-psychiatric symptoms in various diseases by disrupting tissue (e.g. autoantibodies), blood flow (e.g. immune thrombosis) and neurotransmitter metabolism (e.g. excitotoxicity). In oncological diseases, other viral infections and autoimmune diseases, which are often associated with fatigue, cognitive disorders, pain and depression similar to Long-COVID, iv high dose vitamin C was shown to significantly relieve these symptoms. Supportive iv vitamin C in acute COVID-19 might therefore reduce the risk of severe courses and also the development of Long-COVID.
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Affiliation(s)
- Claudia Vollbracht
- Medical Science Department, Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany
| | - Karin Kraft
- Chair of Naturopathy, University Medicine Rostock, Rostock, Germany
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Vitamin C overload may contribute to systemic oxalosis in children receiving dialysis. Pediatr Nephrol 2021; 36:435-441. [PMID: 32772326 DOI: 10.1007/s00467-020-04702-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 06/11/2020] [Accepted: 06/30/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Malnutrition and anorexia are common in children with chronic kidney disease (CKD) and gastrostomy tubes (GT) as well as nasogastric tubes (NGT) have been recommended to maximize nutritional support. The optimal requirement of vitamin C in children with CKD remains to be defined but oxalate is a breakdown product of vitamin C. Elevated vitamin C intake and bone oxalate were identified in two formula-fed dialyzed children with negative genetic testing for primary hyperoxaluria. METHODS We evaluated the impact of nutritional support on serum ascorbic acid and plasma oxalate levels in 13 dialyzed infants and young children. RESULTS All patients were fed by GT or NGT since the first months of life; overall patients were receiving between 145 and 847% of the age-specific DRI for vitamin C. Mean serum ascorbic acid and plasma oxalate levels were elevated (244.7 ± 139.7 μM/L and 44.3 ± 23.1 μM/L, respectively), and values did not differ according to the degree of residual kidney function. Ascorbic acid levels did not correlate with oxalate levels (r = 0.44, p = 0.13). CONCLUSIONS Excessive vitamin C intake may contribute to oxalate accumulation in dialyzed children.
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Raimann JG, Abbas SR, Liu L, Larive B, Beck G, Kotanko P, Levin NW, Handelman G. The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial. BMC Nephrol 2019; 20:179. [PMID: 31101018 PMCID: PMC6525383 DOI: 10.1186/s12882-019-1311-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 03/25/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week. We studied baseline correlations between vitamin C and potentially associated parameters, and the effect of more frequent HD on circulating vitamin C concentrations. METHODS We studied vitamin C levels at baseline and months, 3, 5 and 11. Patients enrolled between 2007 and 2009 into the randomized FHN Daily trial in the East Coast consortium were approached for participation. Predialysis plasma samples were processed with metaphosphoric acid and frozen at - 70 °C for measurement with HPLC. Regression models between baseline log-transformed vitamin C and hemoglobin, CRP, eKt/V, ePCR and PTH, and a linear mixed-effects model to estimate the effect size of more frequent HD on plasma vitamin C, were constructed. RESULTS We studied 44 subjects enrolled in the FHN Daily trial (50 ± 12 years, 36% female, 29% Hispanics and 64% blacks, 60% anuric). Vitamin C correlated significantly with predialysis hemoglobin (r = 0.3; P = 0.03) and PTH (r = - 0.3, P = 0.04), respectively. Vitamin C did not significantly differ at baseline (6×/week, 25.8 ± 25.9 versus 3×/week, 32.6 ± 39.4 μmol/L) and no significant treatment effect on plasma vitamin C concentrations was found [- 26.2 (95%CI -57.5 to 5.1) μmol/L at Month 4 and - 2.5 (95%CI -15.6 to 10.6) μmol/L at Month 12. CONCLUSIONS Based on data from this large randomized-controlled trial no significant effect of the intervention on circulating plasma vitamin C concentrations was found, allaying the concerns that more frequent HD would affect the concentrations of water-soluble vitamins and adversely affect patient's well-being. Correlations between vitamin C and hemoglobin and PTH support the importance of vitamin C for normal bone and mineral metabolism, and anemia management.
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Affiliation(s)
- Jochen G Raimann
- Renal Research Institute, 315 East 62nd Street, 4th Floor, New York, NY, 10065, USA.
| | - Samer R Abbas
- Renal Research Institute, 315 East 62nd Street, 4th Floor, New York, NY, 10065, USA
| | - Li Liu
- Renal Research Institute, 315 East 62nd Street, 4th Floor, New York, NY, 10065, USA.,Renal Division, Peking University First Hospital, Beijing, People's Republic of China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China
| | | | - Gerald Beck
- Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Peter Kotanko
- Renal Research Institute, 315 East 62nd Street, 4th Floor, New York, NY, 10065, USA.,Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA
| | - Nathan W Levin
- Renal Research Institute, 315 East 62nd Street, 4th Floor, New York, NY, 10065, USA.,Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA
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Khor BH, Narayanan SS, Sahathevan S, Gafor AHA, Daud ZAM, Khosla P, Sabatino A, Fiaccadori E, Chinna K, Karupaiah T. Efficacy of Nutritional Interventions on Inflammatory Markers in Haemodialysis Patients: A Systematic Review and Limited Meta-Analysis. Nutrients 2018; 10:nu10040397. [PMID: 29570616 PMCID: PMC5946182 DOI: 10.3390/nu10040397] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 03/20/2018] [Accepted: 03/21/2018] [Indexed: 12/31/2022] Open
Abstract
Low-grade chronic inflammation is prevalent in patients undergoing haemodialysis (HD) treatment and is linked to the development of premature atherosclerosis and mortality. The non-pharmacological approach to treat inflammation in HD patients through nutritional intervention is well cited. We aimed to assess the efficacy of different nutritional interventions at improving inflammatory outcomes in HD patients, based on markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). We searched PubMed, Cochrane Library, and Embase for randomized controlled trials (RCT) published before June 2017. Inclusion criteria included RCTs on adult patients on maintenance HD treatment with duration of nutritional interventions for a minimum 4 weeks. Risk of bias was assessed using the Jadad score. In total, 46 RCTs experimenting different nutritional interventions were included in the review and categorized into polyphenols rich foods, omega-3 fatty acids, antioxidants, vitamin D, fibres, and probiotics. Meta-analyses indicated significant reduction in CRP levels by omega-3 fatty acids (Random model effect: -0.667 mg/L, p < 0.001) and vitamin E (fixed model effect: -0.257 mg/L, p = 0.005). Evidence for other groups of nutritional interventions was inconclusive. In conclusion, our meta-analysis provided evidence that omega-3 fatty acids and vitamin E could improve inflammatory outcomes in HD patients.
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Affiliation(s)
- Ban-Hock Khor
- Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
| | | | - Sharmela Sahathevan
- Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
| | - Abdul Halim Abdul Gafor
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
| | - Zulfitri Azuan Mat Daud
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
| | - Pramod Khosla
- Department of Nutrition & Food Sciences, College of Liberal Arts & Sciences, Wayne State University, Detroit, MI 48202, USA.
| | - Alice Sabatino
- Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy.
| | - Enrico Fiaccadori
- Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy.
| | - Karuthan Chinna
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
| | - Tilakavati Karupaiah
- Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
- School of BioSciences, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Malaysia.
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Naturally Occurring Compounds: New Potential Weapons against Oxidative Stress in Chronic Kidney Disease. Int J Mol Sci 2017; 18:ijms18071481. [PMID: 28698529 PMCID: PMC5535971 DOI: 10.3390/ijms18071481] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 06/22/2017] [Accepted: 07/08/2017] [Indexed: 12/13/2022] Open
Abstract
Oxidative stress is a well-described imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system of cells and tissues. The overproduction of free radicals damages all components of the cell (proteins, lipids, nucleic acids) and modifies their physiological functions. As widely described, this condition is a biochemical hallmark of chronic kidney disease (CKD) and may dramatically influence the progression of renal impairment and the onset/development of major systemic comorbidities including cardiovascular diseases. This state is exacerbated by exposure of the body to uremic toxins and dialysis, a treatment that, although necessary to ensure patients' survival, exposes cells to non-physiological contact with extracorporeal circuits and membranes with consequent mitochondrial and anti-redox cellular system alterations. Therefore, it is undeniable that counteracting oxidative stress machinery is a major pharmacological target in medicine/nephrology. As a consequence, in recent years several new naturally occurring compounds, administered alone or integrated with classical therapies and an appropriate lifestyle, have been proposed as therapeutic tools for CKD patients. In this paper, we reviewed the recent literature regarding the "pioneering" in vivo testing of these agents and their inclusion in small clinical trials performed in patients affected by CKD.
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Oral vitamin C supplementation reduces erythropoietin requirement in hemodialysis patients with functional iron deficiency. Int Urol Nephrol 2016; 48:1519-24. [PMID: 27170339 DOI: 10.1007/s11255-016-1309-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 04/26/2016] [Indexed: 10/21/2022]
Abstract
PURPOSE Functional iron deficiency (FID) is a major cause of persistent anemia in dialysis patients and also contributes to a suboptimal response to erythropoietin (Epo) administration. Vitamin C acts as an enzyme cofactor and enhances mobilization of the ferrous form of iron to transferrin thus increasing its bioavailability. High-dose intravenous vitamin C has been shown to decrease the Epo requirement and improve hemoglobin levels in previous studies. This study assessed the effect of low-dose oral vitamin C on possible reduction in Epo dose requirements in stable hemodialysis patients with FID. METHODS This prospective study included 22 stable hemodialysis patients with FID defined as transferrin saturation (T sat) <30 % and ferritin levels of >100 mcg/L with Epo requirement of ≥4000 U/HD session. Patients received oral vitamin C 250 mg daily for 3 months. Hemoglobin, iron and T sat levels were recorded monthly. No one received iron supplementation during the study period. RESULTS There was a significant reduction in median Epo dose requirement in the 15 patients who completed the study, from 203.1 U/kg/week (95 % CI 188.4-270.6) to 172.8 U/kg/week (95 % CI 160.2-214.8), (P = 0.01). In the seven responders, there was 33 % reduction in Epo dose from their baseline. Despite adjustment of Epo dose, the mean hemoglobin level was significantly increased from 10.1 ± 0.6 to 10.7 ± 0.6 mg/dL (P = 0.03). No adverse effects of oral vitamin C were observed. CONCLUSION Daily low-dose oral vitamin C supplementation reduced Epo dose requirements in hemodialysis patients with FID. Limitations of this study include a small sample size and the lack of measurements of vitamin C and oxalate levels. Despite concerns regarding oral vitamin C absorption in dialysis patients, this study indicates vitamin C was well tolerated by all participants without reported adverse effect.
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Kittisakmontri K, Swangtrakul N, Padungmaneesub W, Charoenkwan P. Gingival Bleeding and Bloody Dialysate: A Case Report of Scurvy in a Child With End-Stage Renal Disease Receiving Peritoneal Dialysis. J Ren Nutr 2016; 26:407-411. [PMID: 27118080 DOI: 10.1053/j.jrn.2016.03.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2015] [Revised: 03/10/2016] [Accepted: 03/14/2016] [Indexed: 01/05/2023] Open
Abstract
Patients with chronic kidney disease (CKD) or end-stage renal disease are at risk for vitamin C deficiency and scurvy due to diet restriction, increased urinary loss of the water-soluble vitamin C with diuretics, and in case of patients who are on dialysis, through dialysates. The condition may be overlooked as the clinical manifestation of scurvy may be subtle, and some presentations may mimic clinical signs in CKD. We reported a case of scurvy presenting with gingival bleeding and blood dialysate in a 6-year-old girl with end-stage renal disease who was on continuous ambulatory peritoneal dialysis. Physical examination showed gingival hyperplasia and bleeding, and the pathognomonic bleeding of perifollicular hemorrhage. The typical radiographic changes were present. The clinical signs and symptoms resolved after ascorbic acid treatment. This case underscores the importance of awareness of the increased risk for vitamin C deficiency in patients with CKD and receiving dialysis.
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Affiliation(s)
- Kulnipa Kittisakmontri
- Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
| | - Napatsayod Swangtrakul
- Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Pimlak Charoenkwan
- Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Zhang L, Coombes J, Pascoe EM, Badve SV, Dalziel K, Cass A, Clarke P, Ferrari P, McDonald SP, Morrish AT, Pedagogos E, Perkovic V, Reidlinger D, Scaria A, Walker R, Vergara LA, Hawley CM, Johnson DW, On Behalf Of The Hero Study Collaborative Group. The effect of pentoxifylline on oxidative stress in chronic kidney disease patients with erythropoiesis-stimulating agent hyporesponsiveness: Sub-study of the HERO trial. Redox Rep 2016; 21:14-23. [PMID: 26083328 DOI: 10.1179/1351000215y.0000000022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
OBJECTIVE Pentoxifylline has previously been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the HERO multi-centre double-blind, randomized controlled trial. The present study evaluated the effects of pentoxifylline on oxidative stress in ESA-hyporesponsive CKD patients. METHODS This sub-study of the HERO trial compared 15 patients in the pentoxifylline arm (400 mg daily) and 17 in the matched placebo arm on oxidative stress markers: plasma total F2-isoprostanes, protein carbonyls, glutathione peroxidase (GPX), and superoxide dismutase (SOD) activities. RESULTS Pentoxifylline did not significantly alter total F2-isoprostanes (adjusted mean difference (MD) 35.01 pg/ml, P = 0.11), SOD activity (MD 0.82 U/ml, P = 0.07), GPX activity (MD -6.06 U/l, P = 0.09), or protein carbonyls (MD -0.04 nmol/mg, P = 0.52). Replicating results from the main study, pentoxifylline significantly increased haemoglobin concentration compared with controls (MD 7.2 g/l, P = 0.04). CONCLUSIONS Pentoxifylline did not alter oxidative stress biomarkers, suggesting that alternative mechanisms may be responsible for the agent's ability to augment haemoglobin levels in CKD patients with ESA-hyporesponsive anaemia.
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Affiliation(s)
- Lei Zhang
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,b Department of Nephrology , Guangdong Provincial Hospital of Chinese Medicine , Guangzhou , China
| | - Jeff Coombes
- c School of Human Movement Studies , University of Queensland , Brisbane , Australia
| | - Elaine M Pascoe
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia
| | - Sunil V Badve
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,d Department of Nephrology , Princess Alexandra Hospital , Brisbane , Australia
| | - Kim Dalziel
- e Center for Health Policy, Programs & Economics , University of Melbourne , Australia
| | - Alan Cass
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,f Menzies School of Health Research , Darwin , Australia
| | - Philip Clarke
- e Center for Health Policy, Programs & Economics , University of Melbourne , Australia
| | - Paolo Ferrari
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,g Department of Renal Medicine , Fremantle Hospital , Australia
| | - Stephen P McDonald
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,h Department of Nephrology and Transplantation Services , University of Adelaide at Central Northern Adelaide Renal and Transplantation Services , Australia
| | - Alicia T Morrish
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia
| | - Eugenie Pedagogos
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,i Department of Nephrology , Royal Melbourne Hospital , Australia
| | - Vlado Perkovic
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,j George Institute , Sydney , Australia
| | - Donna Reidlinger
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia
| | - Anish Scaria
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia
| | - Rowan Walker
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,k Department of Renal Medicine , The Alfred Hospital , Melbourne , Australia
| | - Liza A Vergara
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia
| | - Carmel M Hawley
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,d Department of Nephrology , Princess Alexandra Hospital , Brisbane , Australia.,l Translational Research Institute , Brisbane , Australia
| | - David W Johnson
- a Australasian Kidney Trials Network, University of Queensland , Brisbane , Australia.,d Department of Nephrology , Princess Alexandra Hospital , Brisbane , Australia.,l Translational Research Institute , Brisbane , Australia
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Bachar M, Raimann JG, Kotanko P. Impulsive mathematical modeling of ascorbic acid metabolism in healthy subjects. J Theor Biol 2015; 392:35-47. [PMID: 26724712 DOI: 10.1016/j.jtbi.2015.11.030] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Revised: 11/08/2015] [Accepted: 11/26/2015] [Indexed: 12/22/2022]
Abstract
In this work, we develop an impulsive mathematical model of Vitamin C (ascorbic acid) metabolism in healthy subjects for daily intake over a long period of time. The model includes the dynamics of ascorbic acid plasma concentration, the ascorbic acid absorption in the intestines and a novel approach to quantify the glomerular excretion of ascorbic acid. We investigate qualitative and quantitative dynamics. We show the existence and uniqueness of the global asymptotic stability of the periodic solution. We also perform a numerical simulation for the entire time period based on published data reporting parameters reflecting ascorbic acid metabolism at different oral doses of ascorbic acid.
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Affiliation(s)
- Mostafa Bachar
- Department of Mathematics, College of Sciences, King Saud University, Riyadh, Saudi Arabia.
| | - Jochen G Raimann
- Renal Research Institute, 4th Floor, 315 East 62th Street, New York, NY 10065, United States
| | - Peter Kotanko
- Renal Research Institute, 4th Floor, 315 East 62th Street, New York, NY 10065, United States; Icahn School of Medicine at Mount Sinai, 1428 Madison Avenue, New York, NY 10029, United States
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13
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Granata S, Dalla Gassa A, Tomei P, Lupo A, Zaza G. Mitochondria: a new therapeutic target in chronic kidney disease. Nutr Metab (Lond) 2015; 12:49. [PMID: 26612997 PMCID: PMC4660721 DOI: 10.1186/s12986-015-0044-z] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 11/18/2015] [Indexed: 12/24/2022] Open
Abstract
Cellular metabolic changes during chronic kidney disease (CKD) may induce higher production of oxygen radicals that play a significant role in the progression of renal damage and in the onset of important comorbidities. This condition seems to be in part related to dysfunctional mitochondria that cause an increased electron "leakage" from the respiratory chain during oxidative phosphorylation with a consequent generation of reactive oxygen species (ROS). ROS are highly active molecules that may oxidize proteins, lipids and nucleic acids with a consequent damage of cells and tissues. To mitigate this mitochondria-related functional impairment, a variety of agents (including endogenous and food derived antioxidants, natural plants extracts, mitochondria-targeted molecules) combined with conventional therapies could be employed. However, although the anti-oxidant properties of these substances are well known, their use in clinical practice has been only partially investigated. Additionally, for their correct utilization is extremely important to understand their effects, to identify the correct target of intervention and to minimize adverse effects. Therefore, in this manuscript, we reviewed the characteristics of the available mitochondria-targeted anti-oxidant compounds that could be employed routinely in our nephrology, internal medicine and renal transplant centers. Nevertheless, large clinical trials are needed to provide more definitive information about their use and to assess their overall efficacy or toxicity.
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Affiliation(s)
- Simona Granata
- Renal Unit, Department of Medicine, University-Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, VR Italy
| | - Alessandra Dalla Gassa
- Renal Unit, Department of Medicine, University-Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, VR Italy
| | - Paola Tomei
- Renal Unit, Department of Medicine, University-Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, VR Italy
| | - Antonio Lupo
- Renal Unit, Department of Medicine, University-Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, VR Italy
| | - Gianluigi Zaza
- Renal Unit, Department of Medicine, University-Hospital of Verona, Piazzale A. Stefani 1, 37126 Verona, VR Italy
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Ruskovska T, Bennett SJ, Brown CR, Dimitrov S, Kamcev N, Griffiths HR. Ankyrin is the major oxidised protein in erythrocyte membranes from end-stage renal disease patients on chronic haemodialysis and oxidation is decreased by dialysis and vitamin C supplementation. Free Radic Res 2014; 49:175-85. [DOI: 10.3109/10715762.2014.991725] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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15
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Zhang KY, Zuo L. Vitamin C supplementation in patients on maintenance dialysis. World J Clin Urol 2014; 3:344-350. [DOI: 10.5410/wjcu.v3.i3.344] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Revised: 05/28/2014] [Accepted: 09/10/2014] [Indexed: 02/06/2023] Open
Abstract
As one of the most important water-soluble non-enzymatic antioxidants, vitamin C consists of ascorbic acid and its oxidized form, dehydroascorbic acid. Maintenance hemodialysis (MHD) patients have a generally lower plasma vitamin C level compared with general population. Moreover, dialysis patients also exhibit a low plasma vitamin C level, which is largely related with increased inflammation, refractory anemia and oxidative stress. In this review, we described, in great detail, the vitamin C deficiency in MHD patients and its effects on anti-oxidation, anti-inflammation, pro-oxidation and secondary hyperparathyroidism. In addition, we described the possible potential value of vitamin C in anemia, and the side effects of over-doses of vitamin C supplementation in this particular population. In summary, MHD patients may benefit from vitamin C administration. However, further research should be carried out to confirm its potential beneficial effects, optimal dosage and side effects from vitamin C supplementation.
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Chen CH, Shu KH, Yang Y. Long-term effects of an oral iron chelator, deferasirox, in hemodialysis patients with iron overload. ACTA ACUST UNITED AC 2014; 20:304-10. [PMID: 25200910 DOI: 10.1179/1607845414y.0000000199] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background/Purpose Retention of excess iron from transfused blood in organs in patients with renal anemia may lead to various systemic complications. Iron chelating agents such as deferasirox (DFX) decrease such iron overload. This study assessed the efficacy, safety, and tolerability of DFX in hemodialysis (HD) patients with iron overload. Methods We retrospectively (February 2008 to June 2012) reviewed data for eight HD patients with end-stage renal disease who were prescribed DFX (15 mg/kg/day) for transfusion-induced iron overload. Baseline and post-treatment levels of hematocrit, ferritin, erythropoietin (EPO), transferrin saturation (TSAT), total and unsaturated iron-binding capacity (TIBC and UIBC, respectively), and blood transfusion volumes were measured. Treatment efficacy was evaluated by observing changes in ferritin and TSAT during the study period; monthly EPO doses and blood transfusions were also recorded. Safety was evaluated in the form of adverse events. Results DFX administration caused statistically significant reductions in TSAT (68.2-49.2%; P = 0.036) and ferritin (3133.1-1215.6 ng/ml; P = 0.017). Significant post-treatment increases in UIBC (63.3-196.6 µg/dl; P = 0.018) and TIBC (210.0-422.4 µg/dl; P = 0.012) were also observed. While there were no significant differences in hematocrit values or EPO requirements after treatment, significant reductions in average monthly transfusion volumes (P = 0.026) were recorded. DFX was generally well tolerated; common adverse effects included nausea, vomiting, diarrhea, and abdominal pain. Conclusion DFX significantly improved iron metabolism in HD patients with iron overload and had an acceptable frequency of adverse effects.
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Locatelli F, Minutolo R. Intestinal adsorption of uraemic toxins: a new strategy for anaemia management? Nephrol Dial Transplant 2014; 29:1620-4. [PMID: 24792372 DOI: 10.1093/ndt/gfu102] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Affiliation(s)
- Francesco Locatelli
- Department of Nephrology, Dialysis and Renal Transplant, Alessandro Manzoni Hospital, Lecco, Italy
| | - Roberto Minutolo
- Division of Nephrology, Department of Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Second University of Naples, Naples, Italy
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van der Weerd NC, Den Hoedt CH, Blankestijn PJ, Bots ML, van den Dorpel MA, Lévesque R, Mazairac AHA, Nubé MJ, Penne EL, ter Wee PM, Grooteman MPC. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST). PLoS One 2014; 9:e94434. [PMID: 24743493 PMCID: PMC3990567 DOI: 10.1371/journal.pone.0094434] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 03/14/2014] [Indexed: 12/17/2022] Open
Abstract
Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [−0.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (−2.52% [−4.72 to −0.31]; P = 0.02 and −49 ng/mL [−103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [−0.4 to 14.5]; P = 0.06). In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance. Trial Registration ClinicalTrials.gov NCT00205556
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Affiliation(s)
- Neelke C. van der Weerd
- Department of Nephrology, Academic Medical Center, Amsterdam, The Netherlands
- Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands
- * E-mail:
| | - Claire H. Den Hoedt
- Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Internal Medicine, Maasstad Hospital, Rotterdam, The Netherlands
| | - Peter J. Blankestijn
- Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Michiel L. Bots
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Renée Lévesque
- Department of Nephrology, Centre Hospitalier de l'Université de Montréal, St-Luc Hospital, Québec, Canada
| | - Albert H. A. Mazairac
- Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Menso J. Nubé
- Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands
- Institute for Cardiovascular Research VU Medical Center (ICaR-VU), VU Medical Center, Amsterdam, The Netherlands
| | - E. Lars Penne
- Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands
- Department of Internal Medicine, Medical Center Alkmaar, Alkmaar, The Netherlands
| | - Pieter M. ter Wee
- Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands
- Institute for Cardiovascular Research VU Medical Center (ICaR-VU), VU Medical Center, Amsterdam, The Netherlands
| | - Muriel P. C. Grooteman
- Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands
- Institute for Cardiovascular Research VU Medical Center (ICaR-VU), VU Medical Center, Amsterdam, The Netherlands
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Steiber AL. Chronic kidney disease: considerations for nutrition interventions. JPEN J Parenter Enteral Nutr 2014; 38:418-26. [PMID: 24637245 DOI: 10.1177/0148607114527315] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Chronic kidney disease (CKD) is highly prevalent and has major health consequences for patients. Caring for patients with CKD requires knowledge of the food supply, renal pathophysiology, and nutrition-related medications used to work synergistically with diet to control the signs and symptoms of the disease. The nutrition care process and International Dietetic and Nutrition Terminology allow for systematic, holistic, quality care of patients with this complex, progressive disease. Nutrition interventions must be designed with the individual patients needs in mind while prioritizing factors with the largest negative impact on health outcomes and mortality risk. New areas of nutrition treatment are emerging that involve a greater focus on micronutrient needs, the microbiome, and vegetarian-style diets. These interventions may improve outcomes by decreasing inflammation, improving energy and protein delivery, and lowering phosphorus, electrolytes, and fluid retention.
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Kosmadakis G, Da Costa Correia E, Carceles O, Somda F, Aguilera D. Vitamins in dialysis: who, when and how much? Ren Fail 2014; 36:638-50. [DOI: 10.3109/0886022x.2014.882714] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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McCullough PA, Akrawinthawong K. Ascorbic Acid for the Prevention of Contrast-Induced Acute Kidney Injury. J Am Coll Cardiol 2013; 62:2176-7. [DOI: 10.1016/j.jacc.2013.07.066] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 07/29/2013] [Indexed: 01/21/2023]
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22
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Clase CM, Ki V, Holden RM. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: a review. Semin Dial 2013; 26:546-67. [PMID: 23859229 PMCID: PMC4285924 DOI: 10.1111/sdi.12099] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
People with low glomerular filtration rate and people on dialysis are spontaneously at risk for vitamin deficiency because of the potential for problems with decreased appetite and decreased sense of smell and taste, leading to decreased intake, and because decreased energy or decreased cognitive ability results in difficulties in shopping and cooking. Imposed dietary restrictions because of their renal dysfunction and because of comorbidities such as hypertension and diabetes exacerbate this problem. Finally, particularly for water-soluble vitamins, loss may occur into the dialysate. We did not identify any randomized trials of administering daily doses close to the recommended daily allowances of these vitamins. In people who are eating at all, deficiencies of B5 and B7 seem unlikely. It is unclear whether supplements of B2 and B3 are necessary. Because of dialyzability and documented evidence of insufficiency in dialysis patients, B1 supplementation is likely to be helpful. B6, B9, and B12 are implicated in the hyperhomocysteinemia observed in patients on dialysis. These vitamins have been studied in combinations, in high doses, with the hope of reducing cardiovascular outcomes. No reductions in patient-important outcomes were seen in adequately powered randomized trials. Because of their involvement in the homocysteine pathway, however, supplementation with lower doses, close to the recommended daily allowances, may be helpful. Vitamin C deficiency is common in patients on dialysis who are not taking supplements: low-dose supplements are warranted. Vitamins for dialysis patients contain most or all of the B vitamins and low-dose vitamin C. We are not aware of any medical reasons to choose one over another.
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Affiliation(s)
- Catherine M Clase
- Department of Medicine, McMaster UniversityHamilton, ON, Canada
- Department of Clinical Epidemiology, McMaster UniversityHamilton, ON, Canada
| | - Vincent Ki
- Department of Medicine, McMaster UniversityHamilton, ON, Canada
| | - Rachel M Holden
- Department of Medicine, Queen's UniversityKingston, ON, Canada
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23
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Shah HH, Fishbane SN. How can erythropoeitin-stimulating agent use be reduced in chronic dialysis patients?: Adjuvant therapies to reduce erythropoiesis-stimulating agent dose requirements. Semin Dial 2013; 26:543-5. [PMID: 23763709 DOI: 10.1111/sdi.12108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Hitesh H Shah
- Division of Kidney Diseases and Hypertension, Department of Medicine, North Shore University Hospital and Long Island Jewish Medical Center, Hofstra North Shore-LlJ School of Medicine, Great Neck, New York
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Raimann JG, Levin NW, Craig RG, Sirover W, Kotanko P, Handelman G. Is vitamin C intake too low in dialysis patients? Semin Dial 2012; 26:1-5. [PMID: 23106569 DOI: 10.1111/sdi.12030] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Vitamin C has several well-established roles in physiology including synthesis of collagen, carnitine and epinephrine, absorption of dietary iron, and mobilization of storage iron for erythropoeisis. Loss of several of these functions explains the pathology of scurvy, where defective collagen synthesis and anemia are major symptoms. Vitamin C deficiency is very common in dialysis patients and may arise from dialytic vitamin C clearance, restricted intake of vitamin C-rich foods, and increased vitamin C catabolism in vivo from inflammation. In the dialysis population, greater vitamin C intake may be needed for optimal health. Relationships between intake, body distribution, inflammation, and dialytic losses are complex and need further study. Concern about vitamin C metabolism leading to accumulation of tissue oxalate has led to the recommendation that vitamin C intake equals, but not exceeds, the intake recommended for the general population. Vitamin C deficiency in dialysis patients may have clinical consequences; a study in Renal Research Institute clinics found an association with periodontal disease. Data also support a role for vitamin C in prevention of dialysis-related anemia. New research questions are proposed in this editorial, with a discussion of strategies to determine the optimal provision of vitamin C for CKD patients.
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25
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Cai K, Jiang S, Ren C, He Y. Significant damage-rescuing effects of wood vinegar extract in living Caenorhabditis elegans under oxidative stress. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2012; 92:29-36. [PMID: 21953290 DOI: 10.1002/jsfa.4624] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2011] [Revised: 07/21/2011] [Accepted: 07/27/2011] [Indexed: 05/16/2023]
Abstract
BACKGROUND Wood vinegar (WV), a byproduct from the charcoal production process, has been reported to have excellent antioxidant capability by chemical examination. However, the biological effect of WV in living animals is still unknown. In this study, a simple model organism, the nematode Caenorhabditis elegans, was used as an in vivo system to assess the biological effects of wood vinegar through the development, lifespan, brood size, germline cell apoptosis and superoxide dismutase (SOD) level. RESULTS Wood vinegar extract (WVE) promoted the development, prolonged the lifespan and increased the brood size in reactive oxidative species (ROS)-sensitive mutant worms. WVE treatment rescued the effects of damage in germline cell apoptosis and SOD upregulation induced by paraquat, an ROS generator, to the control level. Additionally, WVE showed comparative ability in rescuing damage as compared with L-ascorbic acid and α-tocopherol. CONCLUSION WVE treatment exhibits a remedial/beneficial effect on ROS-sensitive mutant under normal cultural conditions and on wild-type worms under oxidative stress. ROS scavenging is involved in the damage-rescuing mechanism. This study will provide a basal biological and nutritional exploration for the use of WV as a functional food, and for the substitution of chemical antioxidants with side effects in food.
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Affiliation(s)
- Kezhou Cai
- School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, China
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27
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Jiang H, Harrison FE, Jain K, Benjamin S, May JM, Graves JP, Zeldin DC, Falck JR, Hammock BD, McGiff JC. Vitamin C activation of the biosynthesis of epoxyeicosatrienoic acids. ACTA ACUST UNITED AC 2012; 3:204-218. [PMID: 24660109 DOI: 10.4236/abb.2012.33029] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The cardiovascular effects of vitamin C (VitC) could be mediated by epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC-dependent microsomal formation of cis- and trans-EETs and the regulation of EET levels in rat isolated perfused kidneys and in vivo. VitC biphasically stimulated rat kidney microsomal cis- and trans-EET formation in a ratio of 1:2, involving the participation of lipid hydroperoxides (LOOHs), Fe2+, and cytochrome P450 (CYP). Levels of LOOHs correlated with microsomal EET production. LOOH stimulation of CYP isoforms resulted in preferred trans-over cis-EET formation from arachidonic acid and was associated with the cleavage of LOOHs, which indicated a CYP peroxygenase activity. EETs contributed to VitC-induced vasodilator responses in rat isolated perfused kidneys. VitC (1 mg/ml) given in the drinking water for 9 days doubled rat urinary EET excretion, increased plasma levels of EETs, mostly trans-EETs, by 40%, and reduced plasma levels of 20-hydroxyeicosatetraenoic acid. Depletion of VitC in brain cortex and kidney tissues by more than 20- and 50-fold, respectively, in gulonolactone oxidase-knockout mice was associated with mild increases in tissue EETs. These data suggest that LOOHs are a determinant factor for EET formation in vivo in which VitC exerts a key regulatory effect. VitC-activated CYP peroxygenase activity may represent a CYP interaction with lipoxygenases and cyclooxygenases to mediate the cardiovascular effects of VitC via formation of EETs.
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Affiliation(s)
- Houli Jiang
- Department of Pharmacology, New York Medical College, Valhalla, New York, USA
| | - Fiona E Harrison
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
| | - Kavita Jain
- Department of Pharmacology, New York Medical College, Valhalla, New York, USA
| | - Samantha Benjamin
- Department of Pharmacology, New York Medical College, Valhalla, New York, USA
| | - James M May
- Department of Pharmacology, New York Medical College, Valhalla, New York, USA
| | - Joan P Graves
- NIH/NIEHS, Research Triangle Park, North Carolina, USA
| | | | - John R Falck
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Bruce D Hammock
- Entomology and Cancer Center, University of California, Davis, California, USA
| | - John C McGiff
- Department of Pharmacology, New York Medical College, Valhalla, New York, USA
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Peter S, Mestel S, Thaler M, Reichart E, Mennel S. [Corneal opacity in a contact lens wearer on hemodialysis for renal failure]. Ophthalmologe 2011; 109:68-70. [PMID: 21956749 DOI: 10.1007/s00347-011-2429-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
A 53-year-old contact lens wearer on renal dialysis developed visual impairment due to corneal opacity. The opacity was of a crystalline type and diffusely scattered in the anterior cornea. As oxalosis was suspected ascorbic acid was immediately omitted from the dialysis treatment schedule. Within a few weeks the visual acuity recovered and the corneas became nearly clear. The cornea is an uncommon manifestation site for oxalosis. Nevertheless, one should be aware of this possible sign for oxalosis, which can be a life-threatening complication of treatment with high dose ascorbic acid.
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Affiliation(s)
- S Peter
- Abteilung für Augenheilkunde, Landeskrankenhaus Feldkirch, Carinagasse 47, 6800, Feldkirch, Österreich.
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Rho M. Do pentoxifylline and ascorbic acid improve erythropoiesis stimulating agent resistance? Semin Dial 2011; 24:378-9. [PMID: 21801213 DOI: 10.1111/j.1525-139x.2011.00894.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Mira Rho
- Section of Nephrology, Department of Medicine, Saint Mary's Hospital, Waterbury Yale University School of Medicine, New Haven, Connecticut 06706, USA.
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Bello AK, Wiebe N, Garg AX, Tonelli M. Basics of systematic reviews and meta-analyses for the nephrologist. Nephron Clin Pract 2011; 119:c50-60; discussion c61. [PMID: 21677439 DOI: 10.1159/000324432] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Renal practitioners are expected to apply the best available evidence from rigorous scientific research to clinical decision-making and also for policy-making for those involved. Advances in information technology and unprecedented access to data have simplified the process for the search of best available evidence to guide practice. However, it is challenging to cope with the increasing volume of publications in nephrology and other areas of medicine. Accordingly, systematic reviews and meta-analysis have greatly facilitated best practice and effective clinical decision-making. Conducting a systematic review/meta-analysis involves a number of steps that start with protocol development and research question formulation, design and study selection criteria, followed by retrieval of potentially relevant studies, selection of those studies to be included and evaluation of a study's risk of bias. Systematic reviews and meta-analyses have both strengths and weaknesses. Many of the perceived limitations of meta-analysis are not inherent in the methodology, but actually represent deficits in the conduct or reporting of individual primary studies. With the continuous proliferation of published renal clinical studies, such publications will continue to be an important resource for clinicians and researchers in nephrology. It is therefore important for nephrologists to keep abreast of developments in this field, which requires some knowledge about how these studies are conducted, reported and how to appraise them for application to clinical practice or policy-making.
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Affiliation(s)
- Aminu K Bello
- Division of Nephrology, University of Alberta, Edmonton, AB, Canada
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Ciceri P, Volpi E, Brenna I, Arnaboldi L, Neri L, Brancaccio D, Cozzolino M. Combined effects of ascorbic acid and phosphate on rat VSMC osteoblastic differentiation. Nephrol Dial Transplant 2011; 27:122-7. [DOI: 10.1093/ndt/gfr284] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Del Vecchio L, Locatelli F, Carini M. What We Know About Oxidative Stress in Patients with Chronic Kidney Disease on Dialysis-Clinical Effects, Potential Treatment, and Prevention. Semin Dial 2011; 24:56-64. [PMID: 21299632 DOI: 10.1111/j.1525-139x.2010.00819.x] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Lucia Del Vecchio
- Department of Nephrology, Dialysis, and Renal Transplant, A Manzoni Hospital, Lecco, Italy
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