Anemia of chronic kidney disease: Treat it, but not too aggressively

Nakhoul, Georges; Simon, James F.

doi:10.3949/ccjm.83a.15065

Cited by 46 publications

(36 citation statements)

References 116 publications

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“…EPO is a glycoprotein hormone with a molecular mass of 30.4 kDa composed of a single 165 amino acid residues chain to which four glycans are attached (3). EPO is primarily produced by peritubular interstitial cells in the deep cortex and outer medulla of kidneys of the adult and in hepatocytes in the fetus (21). These cells are sensitive to hypoxia and once they are sensed, it leads to an increased EPO production (22).…”

Section: Discussionmentioning

confidence: 99%

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Interpretation of Erythropoietin and Haemoglobin Levels in Patients with Various Stages of Chronic Kidney Disease

Panjeta¹,

Tahirovic²,

Sofić³

et al. 2017

Journal of Medical Biochemistry

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SummaryBackgroundThe production of erythrocytes is regulated by the hormone erythropoietin (EPO), which maintains the blood haemoglobin (Hb) levels constant under normal conditions. Human EPO is a glycoprotein hormone and its synthesis is controlled by the hypoxia-inducible transcription factor. The aim of this study was to establish EPO and Hb levels in patients with chronic kidney disease (CKD), as well as in control subjects, and to investigate the relationship between these parameters.MethodsThis cross-sectional, observational study included 356 subjects with CKD divided into 4 subgroups according to their glomerular filtration rate (GFR). The control group consisted of 206 age and sex matched healthy subjects with GFR rate ≥90 mL/min/1.73 m2. EPO, Hb and serum creatinine levels were determined by using immunochemical and spectrophotometric methods. GFR was determined using the MDRD formula.ResultsThe CKD patients had significantly lower levels of haemoglobin (p<0.0005) and hematocrit (p<0.0005) compared to control group. Our results showed that Hb levels decreased, whereas serum creatinine increased with the increasing renal failure. The CKD patients in all four groups had significantly lower (p<0.0005) Hb levels, and significantly higher (p<0.0005) creatinine levels compared to the control group. The median EPO in group I and II were significantly higher (p=0.002; p=0.018), while median EPO in group III and IV were significantly lower (p=0.03; p=0.011) compared to the control group.ConclusionsIn patients with CKD, GFR positively correlated with Hb and EPO, while the correlation between GFR and serum creatinine was negative.

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Section: Discussionmentioning

confidence: 99%

“…If these components are lacking for a prolonged time, erythropoiesis and biosynthesis of haemoglobin slows and anaemia may result (2, 24). Anaemia is a common finding in patients with CKD and is primarily due to reduced production of erythropoietin in the kidney and shortened red cell survival (21).…”

Section: Discussionmentioning

confidence: 99%

Interpretation of Erythropoietin and Haemoglobin Levels in Patients with Various Stages of Chronic Kidney Disease

Panjeta¹,

Tahirovic²,

Sofić³

et al. 2017

Journal of Medical Biochemistry

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“…Standard anemia treatment in CKD patients involves the administration of recombinant human erythropoietin, including epoetin α and epoetin β, due to the fact that a decrease in erythropoietin production in the kidneys is the key reason which underlines anemia [91]. Continuous erythropoiesis receptor activators which are a pegylated form of recombinant human erythropoietin with extended serum half-life allowing for longer dosing intervals (every 2 weeks) is currently gaining popularity in the community of dialysis patients [92]. Generally, the initial doses of epoetin-alfa or epoetin-beta dosing are from 20 to 50 IU/kg body weight three times a week.…”

Section: Anemia Treatment With Esamentioning

confidence: 99%

“…No differences were found in the abovementioned parameters between high and low hemoglobin groups [93]. However, three large randomized controlled trials (The Normal Hematocrit Study (NHCT) [90], The Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial [94], and The Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) [18] demonstrated that establishing and reaching higher hemoglobin targets may be harmful to patients [92]. The re-analysis of results obtained in two large trials (CHOIR and the Cardiovascular Risk Reduction by Early Anemia Treatment (CREATE)) trials revealed that patients who despite receiving higher doses did not achieve their target hemoglobin had worse outcomes [95,96].…”

Section: Anemia Treatment With Esamentioning

confidence: 99%

The Influence of Inflammation on Anemia in CKD Patients

Gluba-Brzózka

Franczyk

Olszewski

et al. 2020

IJMS

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Anemia is frequently observed in the course of chronic kidney disease (CKD) and it is associated with diminishing the quality of a patient’s life. It also enhances morbidity and mortality and hastens the CKD progression rate. Patients with CKD frequently suffer from a chronic inflammatory state which is related to a vast range of underlying factors. The results of studies have demonstrated that persistent inflammation may contribute to the variability in Hb levels and hyporesponsiveness to erythropoietin stimulating agents (ESA), which are frequently observed in CKD patients. The understanding of the impact of inflammatory cytokines on erythropoietin production and hepcidin synthesis will enable one to unravel the net of interactions of multiple factors involved in the pathogenesis of the anemia of chronic disease. It seems that anti-cytokine and anti-oxidative treatment strategies may be the future of pharmacological interventions aiming at the treatment of inflammation-associated hyporesponsiveness to ESA. The discovery of new therapeutic approaches towards the treatment of anemia in CKD patients has become highly awaited. The treatment of anemia with erythropoietin (EPO) was associated with great benefits for some patients but not all.

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“…1 A common complication of CKD is anemia associated with reduced erythropoietin (EPO) activity, iron deficiency, and inflammation. 2,3 Anemia is present in >90% of dialysis patients 4 and contributes to excess morbidity and mortality. 5 Erythropoiesis-stimulating agents (ESAs), composed mainly of recombinant forms of EPO, are the only drugs approved internationally to treat severe anemia in patients with CKD.…”

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confidence: 99%

Oral Hypoxia‐Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG‐4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo‐Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients

Provenzano

Tumlin

Zabaneh³

et al. 2020

The Journal of Clinical Pharma

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Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end-stage renal disease with anemia on hemodialysis. Seventeen patients, on epoetin-alfa maintenance therapy with stable hemoglobin levels ≥10 g/dL, had epoetin-alfa discontinued on day 3 and were enrolled in this double-blind placebo-controlled study. Two cohorts were randomized 3:1 (roxadustat: placebo). Patients received single doses of roxadustat (1 or 2 mg/kg) or placebo 1 hour after hemodialysis on day 1 and 2 hours before dialysis on day 8. Maximum plasma concentration and area under the plasma concentration-time curve for patients receiving roxadustat were slightly more than dose proportional and elimination half-life ranged from 14.7 to 19.4 hours. Roxadustat was highly protein bound (99%) in plasma, and dialysis contributed a small fraction of the total clearance: only 4.56% and 3.04% of roxadustat recovered from the 1 and 2 mg/kg dose groups, respectively. Roxadustat induced transient elevations of endogenous erythropoietin that peaked between 7 and 14 hours after dosing and returned to baseline by 48 hours after dosing. Peak median endogenous erythropoietin levels were 96 mIU/mL and 268 mIU/mL for the 1-and 2-mg/kg doses, respectively, within physiologic range of endogenous erythropoietin responses to hypoxia at high altitude or after blood loss. No serious adverse events were reported, and there were no treatment-or dose-related trends in adverse event incidence.

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Anemia of chronic kidney disease: Treat it, but not too aggressively

Cited by 46 publications

References 116 publications

Interpretation of Erythropoietin and Haemoglobin Levels in Patients with Various Stages of Chronic Kidney Disease

Interpretation of Erythropoietin and Haemoglobin Levels in Patients with Various Stages of Chronic Kidney Disease

The Influence of Inflammation on Anemia in CKD Patients

Oral Hypoxia‐Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG‐4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo‐Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients

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