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Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients.
Clin Nephrol. 1999 Oct; 52(4):239-45.CN

Abstract

BACKGROUND

Chronic hemolysis, inadequate production of erythropoietin (EPO) or an impaired response of erythroid stem cells to EPO are the main factors of anemia in end-stage renal disease (ESRD) patients. Oxidative damage of red blood cell (RBC) membrane is a well-established cause of chronic hemolysis in hemodialysis (HD) patients. Administration of high-dose recombinant human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients although all established factors of resistance to rHuEPO therapy have been previously ruled out or corrected.

PATIENTS AND METHODS

We investigated the degree of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months consecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treatment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxidative stress in erythrocyte membrane.

RESULTS

No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and dialysis-related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lactate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of groups B and C. Moreover, a significant inverse relationship was observed between RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together.

CONCLUSION

In conclusion, increased oxidative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established factors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis due to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO.

Authors+Show Affiliations

Nephrology, Tor Vergata University, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10543326

Citation

Gallucci, M T., et al. "Red Blood Cell Membrane Lipid Peroxidation and Resistance to Erythropoietin Therapy in Hemodialysis Patients." Clinical Nephrology, vol. 52, no. 4, 1999, pp. 239-45.
Gallucci MT, Lubrano R, Meloni C, et al. Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients. Clin Nephrol. 1999;52(4):239-45.
Gallucci, M. T., Lubrano, R., Meloni, C., Morosetti, M., Manca di Villahermosa, S., Scoppi, P., Palombo, G., Castello, M. A., & Casciani, C. U. (1999). Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients. Clinical Nephrology, 52(4), 239-45.
Gallucci MT, et al. Red Blood Cell Membrane Lipid Peroxidation and Resistance to Erythropoietin Therapy in Hemodialysis Patients. Clin Nephrol. 1999;52(4):239-45. PubMed PMID: 10543326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients. AU - Gallucci,M T, AU - Lubrano,R, AU - Meloni,C, AU - Morosetti,M, AU - Manca di Villahermosa,S, AU - Scoppi,P, AU - Palombo,G, AU - Castello,M A, AU - Casciani,C U, PY - 1999/10/30/pubmed PY - 1999/10/30/medline PY - 1999/10/30/entrez SP - 239 EP - 45 JF - Clinical nephrology JO - Clin. Nephrol. VL - 52 IS - 4 N2 - BACKGROUND: Chronic hemolysis, inadequate production of erythropoietin (EPO) or an impaired response of erythroid stem cells to EPO are the main factors of anemia in end-stage renal disease (ESRD) patients. Oxidative damage of red blood cell (RBC) membrane is a well-established cause of chronic hemolysis in hemodialysis (HD) patients. Administration of high-dose recombinant human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients although all established factors of resistance to rHuEPO therapy have been previously ruled out or corrected. PATIENTS AND METHODS: We investigated the degree of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months consecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treatment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxidative stress in erythrocyte membrane. RESULTS: No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and dialysis-related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lactate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of groups B and C. Moreover, a significant inverse relationship was observed between RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together. CONCLUSION: In conclusion, increased oxidative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established factors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis due to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO. SN - 0301-0430 UR - https://www.unboundmedicine.com/medline/citation/10543326/Red_blood_cell_membrane_lipid_peroxidation_and_resistance_to_erythropoietin_therapy_in_hemodialysis_patients_ L2 - https://medlineplus.gov/kidneyfailure.html DB - PRIME DP - Unbound Medicine ER -