Plasma vitamin C levels in ESRD patients and occurrence of hypochromic erythrocytes

Seibert, Eric; Richter, Anja; Kuhlmann, Martin K.; Wang, Suxin; Levin, Nathan W.; Kotanko, Peter; Handelman, Garry J.

doi:10.1111/hdi.12467

Cited by 7 publications

(6 citation statements)

References 39 publications

(63 reference statements)

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“…Studies in dialysis patients have shown that vitamin C supplementation may lead to decreased serum ferritin levels [22], which is consistent with storage iron mobilization. These reports are supported by previously reported data from several studies [22–28] and confirmed in a recently published meta-analysis by Deved and colleagues [29]. Our data on the correlation between hemoglobin and vitamin C supports this association and the claims made by Deved and others on the importance of considering the prescription of vitamin C in anemia management (Fig.…”

Section: Discussionsupporting

confidence: 92%

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial

et al. 2019

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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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Section: Discussionsupporting

confidence: 92%

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial

et al. 2019

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“…7d ). Many researchers have shown that the bone marrow is the major site of erythropoiesis in humans and mice 41 – 43 . Additionally, a low Hb content per RBC is the result of an insufficient iron content in the bone marrow during erythropoiesis 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Many researchers have shown that the bone marrow is the major site of erythropoiesis in humans and mice 41 – 43 . Additionally, a low Hb content per RBC is the result of an insufficient iron content in the bone marrow during erythropoiesis 43 . This information implied that thiram suppresses bone marrow activity resulting in decreased production of RBCs and that thiram also inhibits angiogenesis by disrupting the blood supply in tibial chondrocytes, which will seriously affect growth and development of the tibial growth plate.…”

Section: Discussionmentioning

confidence: 99%

Tibial dyschondroplasia is highly associated with suppression of tibial angiogenesis through regulating the HIF-1α/VEGF/VEGFR signaling pathway in chickens

Huang

Rehman

Lan

et al. 2017

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Tibial dyschondroplasia (TD) is an intractable poultry problem that is characterized by the appearance of non-vascularized and non-mineralized cartilage masses in tibial growth plates (TGPs). However, the role of angiogenesis inhibition in the occurrence of TD remains unknown. In this study, we found that, compared to low-altitude Arbor Acres chickens (AACs), high-altitude Tibetan chickens showed higher tibial vascular distributions that were accompanied by up-regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and VEGF receptors. These observations provide insights into hypoxia-induced angiogenesis, which may be related to the absence of TD in high-altitude native Tibetan chickens. Importantly, hypoxia experiments also showed that during hypoxia, tibial angiogenesis was enhanced, which was due to pro-angiogenic factor up-regulation (including VEGFA, VEGFR1, VEGFR2, and IL-8), in AACs. Moreover, we observed that thiram-induced TD could strongly inhibit tibial angiogenesis in the hypertrophic zone through coordinated down-regulation of HIF-1α and pro-angiogenic factors, leading to a disruption in the blood supply to the TGP. Taken together, these findings reveal that the occurrence of TD is highly associated with inhibition of tibial angiogenesis through down-regulated expression of HIF-1α, VEGFA and VEGF receptors, which results in suppression of TGP development.

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“…Serum ascorbate levels are inversely correlated with the osmotic fragility of red cells and moreover, in patients with diabetes, lower erythrocyte ascorbate levels are associated with increased RBC rigidity (69). Similarly, in patients with end-stage renal disease, low serum vitamin C levels correlate with hypochromic red cells whereas patients with high vitamin C levels harbor an increased fraction of red cells with normal hemoglobin content (88). These correlative studies are in agreement with ex vivo erythropoiesis assays showing that vitamin C promotes the erythroid differentiation of human hematopoietic progenitors (17).…”

Section: Discussionmentioning

confidence: 99%

Vitamin C deficiency reveals developmental differences between neonatal and adult hematopoiesis

et al. 2022

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Hematopoiesis, a process that results in the differentiation of all blood lineages, is essential throughout life. The production of 1x1012 blood cells per day, including 200x109 erythrocytes, is highly dependent on nutrient consumption. Notably though, the relative requirements for micronutrients during the perinatal period, a critical developmental window for immune cell and erythrocyte differentiation, have not been extensively studied. More specifically, the impact of the vitamin C/ascorbate micronutrient on perinatal as compared to adult hematopoiesis has been difficult to assess in animal models. Even though humans cannot synthesize ascorbate, due to a pseudogenization of the L-gulono-γ-lactone oxidase (GULO) gene, its generation from glucose is an ancestral mammalian trait. Taking advantage of a Gulo-/- mouse model, we show that ascorbic acid deficiency profoundly impacts perinatal hematopoiesis, resulting in a hypocellular bone marrow (BM) with a significant reduction in hematopoietic stem cells, multipotent progenitors, and hematopoietic progenitors. Furthermore, myeloid progenitors exhibited differential sensitivity to vitamin C levels; common myeloid progenitors and megakaryocyte-erythrocyte progenitors were markedly reduced in Gulo-/- pups following vitamin C depletion in the dams, whereas granulocyte-myeloid progenitors were spared, and their frequency was even augmented. Notably, hematopoietic cell subsets were rescued by vitamin C repletion. Consistent with these data, peripheral myeloid cells were maintained in ascorbate-deficient Gulo-/- pups while other lineage-committed hematopoietic cells were decreased. A reduction in B cell numbers was associated with a significantly reduced humoral immune response in ascorbate-depleted Gulo-/- pups but not adult mice. Erythropoiesis was particularly sensitive to vitamin C deprivation during both the perinatal and adult periods, with ascorbate-deficient Gulo-/- pups as well as adult mice exhibiting compensatory splenic differentiation. Furthermore, in the pathological context of hemolytic anemia, vitamin C-deficient adult Gulo-/- mice were not able to sufficiently increase their erythropoietic activity, resulting in a sustained anemia. Thus, vitamin C plays a pivotal role in the maintenance and differentiation of hematopoietic progenitors during the neonatal period and is required throughout life to sustain erythroid differentiation under stress conditions.

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Plasma vitamin C levels in ESRD patients and occurrence of hypochromic erythrocytes

Cited by 7 publications

References 39 publications

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial

Tibial dyschondroplasia is highly associated with suppression of tibial angiogenesis through regulating the HIF-1α/VEGF/VEGFR signaling pathway in chickens

Vitamin C deficiency reveals developmental differences between neonatal and adult hematopoiesis

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