Endogenous Erythropoietin and the Association with Inflammation and Mortality in Diabetic Chronic Kidney Disease

Wagner, Martin; Alam, Ahsan; Zimmermann, Josef; Rauh, Katharina; Koljaja-Batzner, Angelika; Raff, Ulrike; Wanner, Christoph; Schramm, Lothar

doi:10.2215/cjn.00380111

Cited by 54 publications

(50 citation statements)

References 44 publications

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“…Their EPO level is stimulated somewhat less than it is in the presence of absolute iron deficiency, which has the strongest effect on EPO production. To note, both our results and those of Wagner et al (35) suggest that inflammation may stimulate EPO independent of Hb level. It is unlikely that the variations of the different pro-and anti-inflammatory cytokines explain the variations in EPO levels.…”

Section: Discussionsupporting

confidence: 81%

“…Wagner et al (35) recently found the same association in diabetes patients with CKD. Experimentally, it is well established that EPO production is downregulated by some EPO, erythropoietin; IQR, interquartile range; mGFR, GFR measured by 51 Cr-EDTA renal clearance; iron index, transferrin saturation (TSAT) $20% indicates normal iron profile, TSAT,20% and ferritin ,40 ng/ml indicate absolute iron deficiency, TSAT ,20% and ferritin $40 ng/ml indicate functional iron deficiency; CRP, C-reactive protein; BMI, body mass index; PCR, urinary protein/creatinine ratio; PTH, parathyroid hormone; ACE inhibitors/ARBs, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.…”

Section: Discussionmentioning

confidence: 62%

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Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Mercadal

Metzger

Casadevall

et al. 2012

Clinical Journal of the American Society of Nephrology

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on behalf of the NephroTest Study Group Summary Background and objectives Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown.Design, setting, participants, & measurements This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage CKD patients not receiving any erythropoiesis-stimulating agent.Results In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] ,13 g/dl in men and 12 g/dl in women), EPO response to Hb level varied by mGFR level. EPO and Hb levels were negatively correlated (r=20.22, P=0.04) when mGFR was .30 ml/min per 1.73 m 2 , whereas they were not correlated when mGFR was ,30 (r=0.09, P=0.3; P for interaction=0.01). In patients with anemia, the ratio of observed EPO to the level predicted by the equation for their Hb level decreased from 0.72 (interquartile range, 0.57-0.95) for mGFR $60 ml/min per 1.73 m 2 to 0.36 (interquartile range, 0.16-0.69) for mGFR ,15. Obesity, diabetes with nephropathy other than diabetic glomerulopathy, absolute iron deficiency, and high C-reactive protein concentrations were associated with increased EPO levels, independent of Hb and mGFR.Conclusions Anemia in CKD is marked by an early relative EPO deficiency, but several factors besides Hb may persistently stimulate EPO synthesis. Although EPO deficiency is likely the main determinant of anemia in patients with advanced CKD, the presence of anemia in those with mGFR .30 ml/min per 1.73 m 2 calls for other explanatory factors.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 62%

Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Mercadal

Metzger

Casadevall

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…Previous studies in nontransplant CKD patients have demonstrated an association between EPO resistance or reduced hematopoietic response to ESAs and poor clinical outcomes, including mortality (11)(12)(13)(14)(15)(16)(17). Resistance to endogenous EPO and mortality has also been reported in patients with chronic heart failure and patients with CKD (21,24,25,33).…”

Section: Discussionmentioning

confidence: 98%

“…In recent observational studies elevated endogenous EPO levels were predictive for mortality both in diabetic patients with CKD (21) and among people aged 85 years and older (22). Moreover, serum EPO was inversely associated with hemoglobin in kidney transplant recipients (23).…”

Section: Introductionmentioning

confidence: 97%

Serum Erythropoietin Level and Mortality in Kidney Transplant Recipients

Molnar

Tabák

Alam

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Posttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients.Design, setting, participants, & measurements We collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 Ϯ 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk.Results During the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 Ϯ 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P ϭ 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR 1SD increase 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR 1SD increase 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups. ConclusionsIn this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.

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“…Residual renal function is thought to be the biggest contributor to Hb levels in CKD patients. It is well known that a positive relationship exists between endogenous erythropoietin concentration and the serum eGFR [21] in CKD patients. The present study was conducted by using a combined database from nine hospitals.…”

Section: Assessment Of the Effects Of Long-acting Esa On Hb Levelmentioning

confidence: 99%

Effect of long-acting erythropoiesis-stimulating agents on hemoglobin levels at the initiation of dialysis

et al. 2016

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Background: The goal of the present study was to explore the differences in effects between erythropoiesisstimulating agent (ESA) types on hemoglobin (Hb) level at the initiation of maintenance dialysis. Methods: This was a cross-sectional study. From January 2006 to October 2012, 2920 patients with end-stage kidney disease commenced hemodialysis (HD) at nine participating hospitals. The criteria for exclusion from the database were (1) presence of cancer or gastrointestinal bleeding and (2) serum C-reactive protein ≥0.3 mg/dL. A total of 1263 patients were entered into the final database. We explored the association of yearly trend of Hb level just before the first HD session with the different types of ESA in the predialysis period. Results: During the 7-year study period, patients' Hb levels at the initiation of dialysis dramatically increased from 8.6 to 9.1 g/dL. Parallel to this increase, the use of long-acting ESA also increased from 0 to 80 %. A higher level of Hb was confirmed in the long-acting ESA group compared with the short-acting group (9.5 vs. 8.7 g/dL, P < 0.01). Multivariate regression analysis showed a strong association of Hb level with the use of long-acting ESA (r = 0.155, P = 0.003), even after adjusting for confounding variables and estimated dose of epoetin.

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Endogenous Erythropoietin and the Association with Inflammation and Mortality in Diabetic Chronic Kidney Disease

Cited by 54 publications

References 44 publications

Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Serum Erythropoietin Level and Mortality in Kidney Transplant Recipients

Effect of long-acting erythropoiesis-stimulating agents on hemoglobin levels at the initiation of dialysis

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