Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans

Lundby, Anne-Kristine; Keiser, Stefanie; Siebenmann, Christoph; Schäffer, Leonhard; Lundby, Carsten

doi:10.1007/s00421-014-2844-7

Cited by 28 publications

(38 citation statements)

References 28 publications

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“…Patients with CKD had PMI values higher than those of healthy controls and rhEpo-containing samples. Patients with CKD exhibited glycosylation patterns very similar to the umbilical cord samples, which are considered to be mainly of hepatic origin 5,9 (Figure 2). Using absolute PMI values, patients with CKD presented a PMI of 36.16 11.7% that was markedly higher than that in healthy controls (9.263.8%; P,0.01) and furthermore, also higher compared with rhEpo-containing control samples (1.46 1.4%; P,0.01), whereas the CKD PMI values did not differ from the PMI values from venous umbilical cord plasma samples (53.96 10.6%; P.0.05).…”

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confidence: 83%

“…An Epo purification kit from MAIIA Diagnostics (Uppsala, Sweden) was used to purify Epo from patient and control plasma samples and four umbilical cord plasma samples obtained from the University Hospital of Zürich. 9 The purifications were performed according to the directions by the company, which are briefly described here: 1.5-2 ml plasma was diluted in sample dilution buffer to a final volume of 20 ml and loaded to disposable anti-Epo columns with immobilized monoclonal anti-Epo antibody 3F6, which very specifically captures both endogenous and rhEpo. The Epo was eluted with 50 ml desorption buffer into Eppendorf tubes containing 5 ml adjustment buffer containing Tween 20 and BSA.…”

Section: Measurementsmentioning

confidence: 99%

“…9 Healthy volunteers were used as controls for kidney Epo, whereas umbilical cord Epo and rhEpo provided in the MAIIA Diagnostics Kit were used as controls for liverderived Epo and synthetic Epo, respectively. PMI as a percentage is calculated as the ratio of Epo migration in a low versus high N-acetylglucosamine-containing solution for a given sample.…”

Section: Measurementsmentioning

confidence: 99%

“…For this purpose, blood samples obtained from patients with stages 2-5 CKD were compared with those collected from healthy controls with respect to their Epo glycolysation pattern, which is specific to its synthesizing cell. 8,9 We also analyzed Epo glycosylation in nine patients on dialysis not treated with recombinant human erythropoietin (rhEpo).…”

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confidence: 99%

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Increased Synthesis of Liver Erythropoietin with CKD

Seigneux

Lundby

Berchtold

et al. 2016

JASN

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Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0-20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6-9.0 IU/L; P,0.01), these patients were moderately anemic (mean6SD; hemoglobin =1186 17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1611.7%) differed from that in healthy controls (PMI=9.263.8%; P,0.01) but not from that in umbilical cord plasma (PMI=53.9610.6%; P.0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.

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confidence: 83%

Section: Measurementsmentioning

confidence: 99%

Section: Measurementsmentioning

confidence: 99%

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confidence: 99%

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Increased Synthesis of Liver Erythropoietin with CKD

Seigneux

Lundby

Berchtold

et al. 2016

JASN

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“…It was also reported that patients with anemia can switch EPO production from the kidney to the liver [30,31], as can be shown by glycoform analysis of EPO. Indeed, the posttranslational EPO glycosylation is specific of the synthesizing cells, giving rise to different EPO glycoforms that can be used to localize EPO synthesis [30,32].…”

Section: Introductionmentioning

confidence: 99%

The HIF System Response to ESA Therapy in CKD‐Anemia

Ribeiro¹,

Belo²,

Reis³

et al. 2017

Hypoxia and Human Diseases

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Anemia is a common complication of chronic kidney disease (CKD) associated with disease progression and increased mortality. This anemia is mainly due to inadequate production of erythropoietin (EPO) by the failing kidneys, resulting from the reduction in renal EPO-producing cells (REPC) or from dysregulation of the hypoxia-inducible factor (HIF) system that regulates several genes related to hypoxia, angiogenesis, fibrosis and glucose metabolism, among others. In this chapter, we present a review on the HIF system in CKD-anemia, the HIF response to erythropoiesis-stimulating agents (ESA) therapy and its potential involvement in the development of ESA resistance by enhancing kidney fibrosis and inflammation. Due to concerns related to ESA use, new drugs to correct anemia are under study, being the prolyl hydroxylase inhibitors the most promising candidates.

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