| Abstract|| |
The use of recombinant human erythropoietin (rHuEpo) became an essential part of the treatment of anemia in patients with end stage renal failure (ESRF). Our experience at the Hajjah region, Yemen, confirms that the use of rHuEpo significantly increases the level of hemoglobin (HB) and hematocrit (Hct), improves work tolerance and overall quality of life of patients on hemodialysis. The observable improvement occurred in 87.5% of patients. The most prominent factors that caused deterioration in the increment of HB and Hct were infection with malaria and chronic infection. Failure of patients' compliance, largely due to lack of education, was another important factor effecting the results. Many of our patients did not understand the importance of diet and drug regime. It is very important to spend more time on educating such patients.
|How to cite this article:|
AL-Rohani M. Factors Affecting Successful use of Erythropoietin in the Treatment of Anemia in Patients on Hemodialysis: Experience in Hajjah Region, Yemen. Saudi J Kidney Dis Transpl 2001;12:220-3
|How to cite this URL:|
AL-Rohani M. Factors Affecting Successful use of Erythropoietin in the Treatment of Anemia in Patients on Hemodialysis: Experience in Hajjah Region, Yemen. Saudi J Kidney Dis Transpl [serial online] 2001 [cited 2020 May 26];12:220-3. Available from: http://www.sjkdt.org/text.asp?2001/12/2/220/33813
| Introduction|| |
Anemia is one of the major complications of chronic renal failure. It is caused by depletion of erythropoietin (EPO) production. The plasma EPO concentration is usually low due to the severity of the anemia. , Anemia begins to develop when the glomerular filtration rate (GFR) falls bellow 20-30 ml/min/1.73m 2 .  The degree of anemia with end-stage renal failure (ESRF) resulting from autosomal dominant polycystic kidney disease is variable, but is generally of relatively low severity. The most important secondary causes of anemia in dialysis patients are iron deficiency coupled with blood loss, frequent blood sampling for tests, and gastrointestinal bleeding. The iron deficiency causes a hyporesponsiveness of recombinant human erythropoietin (rHuEpo). Modern dialysers and dialysis technology save the blood loss during dialysis (4 to 20 ml/dialysis) and improve the iron stores. Folate and B12 are readily removed by hemodialysis (HD) so patients require oral folate and B12 supplement.  Subcutaneous administration of rHuEpo has subsequently been found to be effective, and may allow lower maintenance doses up to 30%-32%. ,, The major complication of rHuEpo is hypertension ,, as well as hyperkalemia. Platelet aggregation, factor VIII, and fibrinogen improve due to the increase in the red cell mass. These changes may cause access thrombosis and increase the need for heparin during dialysis. ,
| Objectives|| |
The objectives of the study were to assess the effectiveness of rHuEpo in treatment of anemia in patients with ESRF undergoing dialysis, and to study factors that may adversely affect achieving the target of HB> 10 g/dl and Hct > 30%.
| Methods|| |
This study was done between January 1998 and January 2000, in the Saudi Hospital at Hajjah, Yemen. All patients were followed up for at least 12 months. There were 32 patients with ESRF undergoing HD four hourly, twice weekly. Iron was given orally (65 mg of iron sulfate), one to two months before starting rHuEpo and controlled by serum ferritin to reach the acceptable level. Folic acid and vitamin B12 were given orally once daily. rHuEpo was given subcutaneously after each HD session. Its dose was started at 30 U/kg and increased as necessary up to achievement of the target hemoglobin (HB) and Hct. The following data were collected: age, sex, history, physical exam, hematological and biochemical parameters. Serum ferritin was used as the indicator of iron saturation and as a guide for the rHuEpo dosage. The onset of effectiveness of EPO, the need for blood transfusion and the factors contributing to the failure of response were noted.
| Results|| |
The patients' age was between 15 and 72, with a mean of 37.78 years. Male patients were 23 (71.88%). Body weight range was 32.4 kg - 61.1 kg with a mean of 43.37 kg. Blood groups distribution was as follows: O+, 50%; A+, 40.1%; and B+, 9.36%. The doses of rHuEpo ranged from 52.6 u/kg/week up to 416.7 u/kg/week with a mean of 129.02 u/kg/week. The mean serum ferritin level was 265 + 38 µg/l before starting the rHuEpo. Before starting rHuEpo the HB was (4.1-10.3) g/dl with a mean of 6.7 g/dl, and Hct was 14 %-30% with a mean of 20.6% [Table - 1]. Based on increment of HB and Hct levels, our patients were divided into two groups. The first group consisted of 28 patients (87.5%) who showed a consistent increase in HB and Hct. Of these, 22 patients (78.6%) reached the set target of HB and Hct (HB > 10 g/dl and Hct > 30%). Six patients (21.4%), however, had only partial response and did not quite reach the set target of HB and Hct, [Table - 2]. The second group consisted of four patients (12.5%) who had no change in the HB and Hct level [Table - 1]. In the first group, the appetite improved in 92.6% of the patients and exercise capacity improved in 62.9%. Immediately before starting rHuEpo, there were 27 patients (84.4%) with hypertension (13 severe, 8 moderate and 6 mild). During the study phase, the blood pressure was normal in five (15.6%) patients, under good control using medications in 21 patients (65.6%), and uncontrolled in six (18.8%) patients. The major contributing factors to decreases in the rate of increment of HB were malarial attacks (56.25% of patients) and chest infections [Table - 3]. Before using rHuEpo 22 patients (62.5%) needed blood transfusions, but only 9 patients (28.13%) received blood products during the rHuEpo era. The total plasma protein range was 5.87-8.23 with a mean of 6.9 and the albumin range was 3.1-7.48) with a mean of 3.8 g/dl. The serum potassium increased above the normal range in nine patients (28.2%).
| Discussion|| |
Patients with renal failure demonstrate depressed exercise capacity. The improvement of these parameters is associated with increased Hct to the 30-36% range.  In our group the improvement of appetite, and exercise capacity was significant, 92.6% and 62.9% respectively, the greatest improvement was reported when HB was > 11.5 g/dl, according to data from "Optimizing Anemia Therapy in CRF".  In our group the increase of HB and Hct was achieved in 28 patients (87.5%).
One of our patients entered the study with HB 10.3 g/dl and Hct 30% because he had polycystic kidney disease. Iron stores are best assessed by measurements of serum ferritin concentration, , with concentrations less than 80 to 100 ug/l suggesting iron deficiencies. In our patients, with oral iron supplementation, the serum ferritin reached up to 882.5 ug/l with a mean of 256 ug/l, which is more than 200 ug/l, the accepted level for substitution. , Data from Saudi Arabia suggest that intravenous iron saccharate (100 mg/month) is effective and safe in patients on hemodialysis receiving rHuEpo, 12 but the intravenous iron was not our alternative choice. The mean rHuEpo dose was 129 u/kg/week, given subcutaneously (sc). There are controversies in the studies about the administration of rHuEpo and the dose requirement in intravenous (iv) and sc administration. Winearle and coworker showed that sc administration reduced the required dose of rHuEpo,  whereas, Schoen marker did not find any difference in mode of administration.  Hyperkalemia, found in 28.2% of our patients, was treated by Calcium resunium. It cannot be attributed solely to rHuEpo since many of our patients did not follow the dietary regimes prescribed to them. Resistant hypertension was found in 18.8% of our patients. This is not as high as reports that claimed up to 35% of their patients had increase of blood pressure or worsening of control with rHuEpo therapy.  In treatment of hypertension we used up to four combinations of antihypertensive drugs.
Compliance in taking medications and following fluid restriction and dietary advises will affect the degree of blood pressure control. Patient education in these aspects cannot be overemphasized. Blood transfusion poses a number of risks to dialysis patients, including risks of blood borne viruses and other infections, iron overload, transfusion reactions, anaphylaxis, erythroid marrow suppression and HLA sensitization.  Reduction in the need for regular blood transfusion is one of the best markers of rHuEpo benefits in addition to the marked improvement in anemia-related symptoms. , In our group there was a significant reduction in required transfusion from 62.5% to 28.13%. Patients with hematocrit levels less than 30% are reported to have significantly higher risk of all-cause and cause-specific death.  Malaria is endemic in Hajjah region, and it is well known that it causes anemia on its own right. About 56% of our patients had at least one attack of malaria during the period of the study causing reduction in HB level, which was reversed after treatment of the malaria infection. In this study we were not able to evaluate the effect of rHuEpo in the left ventricle as well as on the thrombosis.
| References|| |
|1.||Winearls CG. Recombinant human 10 erythro-poietin: 10 years of clinical experience. Nephrol Dial Transplant 1998;13(Suppl 2):3-8. |
|2.||Valderrabano F. Recombinant 11 erythropoietin: 10 years of clinical experience. Nephrol Dial Transplant 1997;12(Suppl):2-9. |
|3.||Himmelfarb J, Hillman RS. Anemia in chronic renal failure. The NKF primer on kidney diseases, 2nd edition: Chapter 72. Himmelfarb J. Hematologic manifestations of renal failure. |
|4.||Macdougall IC. Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin. Nephrol Dial Transplant 1998;13(Suppl 2):23-7. [PUBMED] [FULLTEXT]|
|5.||Schaefer RM, Schaefer L. Iron monitoring and supplementation: how do we achieve the best results? Optimizing anemia therapy in CRF, Symposium, Crete, 1998;17-19. |
|6.||Horl WH. Measurement of hypochromic red blood cells is not the first line procedure to identify the patients with iron deficiency. Nephrol Dial Transplant 1998; 13:850-1. |
|7.||House AA. Transfusion and recombinant human erythropoietin requirements differ between dialysis modalities. Nephrol Dial Transplant 1998;13:1763-9. |
|8.||De Schoenmarkere GE. Co-worker, the hematopoietic effect of recombinant human erythropoietin in hemodialysis is inde-pendent of the mode of administration (i.v, sc). Nephrol Dial Transplant 1998;13: 1770-75. |
|9.||Nissenson AR, Besareb A, Bolton WK, Goodkin DA, Schwab SJ. Target hema-tocrit during erythropoietin therapy. Nephrol Dial Transplant 1997;12:1813-16. |
|10.||Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999;10(3):610-9. |
|11.||Abu Romeh S, Huraib S, Murray N, et al. Maintenance intravenous iron therapy in hemodialysis patients receiving recombinant human erythropoietin. Saudi J Kidney Dis Transplant 1999;10(1):21-5. |
Department of Nephrology, Saudi Hospital at Hajjah, P.O. Box 4365, Hudaidah
[Table - 1], [Table - 2], [Table - 3]