Increased Synthesis of Liver Erythropoietin with CKD

Seigneux, Sophie de; Lundby, Anne-Kristine; Berchtold, Lena; Berg, Anders H.; Saudan, Patrick; Lundby, Carsten

doi:10.1681/asn.2015050508

Cited by 38 publications

(42 citation statements)

References 18 publications

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“…Therefore, we think that most part of EPO induced by TP0463518 is produced by liver. In HD patients, baseline PMI values were higher than those in peripheral blood and similar to umbilical cord blood in consistent with results of a previous report [12], which suggests that some of EPO in HD patients originates in the liver to compensate for insufficient renal EPO production. After TP0463518 administration in HD patients, PMI values were even higher than umbilical cord values (84.4 ± 3.5 vs. 57.2 ± 5.5%).…”

Section: Discussionsupporting

confidence: 91%

“…4). In CKD study, PMI value in ND patients was similar to that in peripheral blood and lower than umbilical cord blood, which is different from the result in de Seigneux et al [12]. Variation of PMI value may be large between samples and assays, but baseline PMI value greatly increased after TP0463518 administration in ND patients.…”

Section: Discussioncontrasting

confidence: 76%

“…The glycosylation pattern of EPO depends on the producing cell and thus, can indicate its origin [12]. In the HV study, PMI values were elevated after TP0463518 administration from similar levels of peripheral blood, which contains mainly kidney-derived EPO, to similar levels of umbilical cord blood, which contains mainly liver-derived EPO (Fig.…”

Section: Discussionmentioning

confidence: 82%

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Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers

et al. 2018

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Background: TP0463518 is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor developed to aid in the treatment of anemia associated with chronic kidney disease (CKD) and is expected to increase erythropoietin (EPO) derived from liver. Two phase I studies were conducted in healthy volunteers (HV) and CKD patients undergoing hemodialysis (i.e., HD patients) or those not undergoing dialysis (i.e., ND patients). Methods: Pharmacokinetics, pharmacodynamics, and safety profiles of TP0463518 were assessed. Forty HV received single oral doses of TP0463518 at 3, 6, 11, 20, and 36 mg or placebo. Twenty ND patients received single doses of TP0463518 at 1, 6, and 11 mg and 9 HD patients received TP0463518 at 1 and 11 mg doses. To identify the source organ of EPO, glycosylation patterns were determined using percentage migrated isoform (PMI) values. Results: Declining renal function slowed elimination of TP0463518 and increased the mean AUC_0–∞. ∆E_max of serum EPO in 11-mg groups of HV, ND patients, and HD patients were 24.37 ± 11.37, 201.57 ± 130.34, and 1,324.76 ± 1,189.24 mIU/mL respectively. A strong correlation was observed between logarithm conversions of ∆E_max and AUC_0–∞ with correlation coefficients of 0.945. PMI values of blood after TP0463518 administration were elevated to similar or higher levels in comparison with those of umbilical cord blood, which mainly contains liver-derived EPO. Conclusions: TP0463518 induced dose-dependent EPO production, mainly derived from the liver in HV and CKD patients. These results suggest that TP0463518 is a new strategy for treating anemia in CKD, which can be used regardless of renal functions.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 82%

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Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers

et al. 2018

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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: 80%

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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“…Anemia is common in patients with ESRD [27], due to impaired production of renal erythropoietin [28].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Respiratory Complications Associated with End Stage Renal Disease in Northern Saudi Arabia

Alosayfir

Almuzaini

Alateeq

et al. 2016

Romanian Journal of Internal Medicine

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Background. The prevalence of End Stage Renal Disease (ESRD) is increasing in different parts of the Kingdom of Saudi Arabia (KSA), particularly Hail Region. Therefore, the aim of this study was to assess the respiratory complications that associated with ESRD. Methods. In the present study, clinical, imaging and laboratory parameters were identified for 100 ESRD patients with ESRD who were referred to the Pulmonary Medicine Department at King Khalid Hospital. Results. Pulmonary Edema, Pneumonia, and Pleural effusion were identified in 22%, 14%, and 16% of the referred ESRD patients, respectively. Conclusion. Respiratory complications are common among ESRD patients in Hail Region.

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Increased Synthesis of Liver Erythropoietin with CKD

Cited by 38 publications

References 18 publications

Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers

Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers

The HIF System Response to ESA Therapy in CKD‐Anemia

Assessment of Respiratory Complications Associated with End Stage Renal Disease in Northern Saudi Arabia

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