Treatment of Renal Anemia with Recombinant Human Erythropoietin

Schaefer, Roland M.; Hörl, Walter H.; Massry, Shaul G.

doi:10.1159/000167996

Cited by 59 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the introduction of recombinant human erythropoietin (EPO) in 1986, it has been an effective treatment for renal anemia in the majority of patients with end-stage renal disease (ESRD) (Winearls et al, 1986;Schaefer et al, 1989). The most common cause of inadequate response to EPO is generally thought to be absolute or functional iron deficiency (Tarng et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

et al. 2008

View full text Add to dashboard Cite

Genetic polymorphisms may be linked to inter-individual differences in erythropoietin (EPO) resistance. We investigated the -511C/T polymorphism of the IL-1B gene and the I/D polymorphism of the ACE gene for any association with EPO resistance index (ERI) in maintenance hemodialysis patients (n = 167). Because EPO responsiveness is multi-factorial, we also included other possible influences (age, sex, time on dialysis, ACE inhibitor or angiotensin receptor blocker use, ferritin, transferrin saturation, intact PTH, high sensitivity C-reactive protein, albumin, Kt/V, and presence of diabetes mellitus) on ERI in our analyses. Multiple regression analysis showed significant association of the IL-1B-511CC and ACE DD polymorphisms with ERI (P = 0.038 and P = 0.004 in the recessive model, respectively). The combination (C) of alleles of two loci showed that C1 (I-T) was significantly associated with ERI in the co-dominant and recessive models (P = 0.005 and P = 0.0001, respectively). Subjects who did not carry C1 showed significantly decreased ERI (10.10 ± 5.15 IU/kg weight/g hemoglobin) compared to other study subjects (C1/C1 and C1/-; 12.97 ± 4.90 and 15.12 ± 7.43 IU/kg weight/g hemoglobin, respectively). Our study indicates that the IL-1B-511C/T and ACE I/D polymorphisms may be useful genetic markers of EPO requirement in hemodialysis patients. These findings might also provide a new perspective on therapeutic approaches to the treatment of end stage renal disease patients with anemia.

show abstract

Section: Introductionmentioning

confidence: 99%

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Although different factors, among which the increase in hematic viscosity, are recognized as possibly responsible for the pressure rise which often goes along with rHuEPO treatment, up to now a reliable ex planation of the pathogenetic mechanisms of hypertension induced by erythropoietin [1] is still missing. In previous investigations, through the evaluation of the changes brought about by the intravenous administra tion of rHuEPO on the prétibial flux by means of the Xenon 133 clearance, we showed the existence of a direct vasoconstric tive action exerted by erythropoietin on the compliance vasa [2], The presence of endothe lial receptors forthe erythropoietin could give account of such action [3].…”

Section: Influence Of Recombinant Erythropoietin On the Production Ofmentioning

confidence: 99%

Influence of Recombinant Erythropoietin on the Production of Endothelin-1 from Human Umbilical Artery

Buemi

Morabito

Palella

et al. 1993

Nephron

View full text Add to dashboard Cite

Fig-1-Production of immunoreactiveendothelin-l (ir ET-1) in the umbilical artery: electrolytic solution (I);rH uE PO solvent(II);30U of rHuEPO (III).Dear Sir, Induced hypertension due to treatments with recombinant erythropoietin (rHuEPO) is with no doubt the most frequent and impor tant side effect of this hormone therapy, ca pable of conditioning the therapeutic success in subjects affected by anemia from renal failure. Although different factors, among which the increase in hematic viscosity, are recognized as possibly responsible for the pressure rise which often goes along with rHuEPO treatment, up to now a reliable ex planation of the pathogenetic mechanisms of hypertension induced by erythropoietin [1] is still missing. In previous investigations, through the evaluation of the changes brought about by the intravenous administra tion of rHuEPO on the prétibial flux by means of the Xenon 133 clearance, we showed the existence of a direct vasoconstric tive action exerted by erythropoietin on the compliance vasa [2], The presence of endothe lial receptors forthe erythropoietin could give account of such action [3]. Furthermore, in our previous investigations as well as in other investigations [4], it was shown how the in travenous chronic treatment was able to change the plasma levels of endothelin-l, a substance produced by the endothelium, able to induce a high vasoconstriction. Yet, the plasma dosage of endothelin does not seem to correspond to the real activity of the vasal endothelium. Therefore, we wanted to use an experimental model based on the umbilical arteries, where the receptors for endothelin are to be found [5]. The arteries were quickly isolated from umbilical cords from neonates of nonhypertensive mothers with the purpose of evaluating the rHuEPO action on the pro duction of endothelin-1. Our method con sisted in taking, soon after a natural delivery, 10 cm of the median part of the umbilical cord from which we immediately isolated the um bilical artery by means of a stereo microscope which was divided into 3 2-cm long segments. The 1st segment (I) was put in I ml of cold buffered electrolyte solution (4°C), the 2nd (II) was kept in a medium with buffered elec trolyte solution plus 20 pi of rHuEPO solvent (human serum albumin 2,5 m g/m l; sodium 160 mM; chlorides 100 m M: citrate 20 mM), the 3rd (III) was put in I ml cold buffered electrolyte solution and 30 U of rHuEPO with 20 pi of solvent. Then, the 3 umbilical artery segments were kept for 10 min at 37°C, were weighed and the corresponding supernatant frozen at -30°C, the endothelin-1 was dosed with the RIA method (Amersham, UK). The results obtained from 25 umbilical arteries showed the presence of a significant increase in the concentration of endothelin-1 from the medium to which rHuEPO was added ( fig. 1). Results are expressed as means ± S E and Student's test was performed for all compari sons. Therefore, our study seems to confirm the possibility that the vasoconstrictive action played by erythropoietin might be caused by the stimu...

show abstract

“…Nowadays, most dialysis units set their target hemoglobin between 10 and 12 g/dl. Achievement of this target is significantly associated with an improvement in the quality of life, an enhancement of exercise tolerance and an increase in cognitive function [3, 4, 5]. The beneficial effect of increasing hemoglobin on left ventricular hypertrophy also reduces cardiovascular morbidity and mortality in patients on EPO treatment [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Improvement of Nutritional Status in Patients Receiving Maintenance Hemodialysis after Correction of Renal Anemia with Recombinant Human Erythropoietin

Tarng

Huang²,

Doong³

1998

Nephron

View full text Add to dashboard Cite

Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 ± 0.8 g/dl at baseline to 10.7 ± 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 ± 7.5 to 23.6 ± 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.

show abstract

Treatment of Renal Anemia with Recombinant Human Erythropoietin

Cited by 59 publications

References 34 publications

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

Influence of Recombinant Erythropoietin on the Production of Endothelin-1 from Human Umbilical Artery

Improvement of Nutritional Status in Patients Receiving Maintenance Hemodialysis after Correction of Renal Anemia with Recombinant Human Erythropoietin

Contact Info

Product

Resources

About