| Abstract|| |
We attempted in this study to evaluate the attitude of the physicians in The Kingdom of Saudi Arabia (KSA) towards the use of recombinant human erythropoietin (r-HuEPO) in patients on hemodialysis (HD). We sent a questionnaire to 181 physicians in the 147 active dialysis centers in KSA; 110 (74.9 %) of them were under the Ministry of Health (MOH), 14 (9.5%) in Governmental non-MOH hospitals and 23 (15.6 %) were in private hospitals. This covered a population of more than 7300 chronic HD patients. The study was conducted from October to December 2004. Response was obtained from 144 physicians (79.5%), working in 135 dialysis centers (92.5%) that totally treated 7107 (97%) HD patients in the KSA. Of the 144 respondents, 99 (72.8%) responded that they would use r-HuEPO therapy for all new HD patients not guided by hemoglobin (Hb) level. Almost all the respondents would start the patients on a weekly dose of < 200 units/kg, while they would maintain the patients on a weekly dose of < 150 units/kg. Written protocols to guide the administration of rHuEPO were available in only half of the dialysis centers. A total of 83 respondents (58%) would aim at a target Hb of 110-120 g/l while 29 (20.3%) would go higher to 121-130 g/l. There were 51 (37.5%) respondents who considered multi-dose vials of the drug better for expense saving. There were 35 (24.8%) respondents who believed the type of r-HuEPO (alfa, beta) determines the development of the antibodies to r-HuEPO, while 84 (59.6%) had no idea. After regrouping of the respondents according to their affiliation, there was a significantly less percentage of the MOH centers which treated > 70% of the dialysis patients with the drug in comparison with the non-MOH and private sector centers (81% vs 100%, respectively P<0.04). There was a significantly less percentage of MOH than the nonMOH centers to have a written protocol for administration of r-HuEPO (49.1% vs 95% respectively, P<0.0002). In conclusion, a protocol to guide the r-HuEPO therapy in HD patients is lacking in many centers of the KSA and there is a need for increased awareness of the physicians working in those centers in the practical aspects of the use of this drug in the treatment of anemia in this population
Keywords: Erythropoietin, Chronic renal failure, Survey, Therapy.
|How to cite this article:|
Souqiyyeh MZ, Shaheen FA. Attitude of Physicians toward the Use of Erythropoietin in Hemodialysis Patients. Saudi J Kidney Dis Transpl 2005;16:298-305
|How to cite this URL:|
Souqiyyeh MZ, Shaheen FA. Attitude of Physicians toward the Use of Erythropoietin in Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2014 Dec 19];16:298-305. Available from: http://www.sjkdt.org/text.asp?2005/16/3/298/32858
| Introduction|| |
Surveys of the attitudes of physicians about their practices in the dialysis units are one of the tools to evaluate the quality care provided to the patients on regular dialysis. ,,
Recombinant human erythropoietin (r-HuEPO) is well established as the treatment of choice for anemia in patients with chronic renal failure (CRF) with great advantages for decreasing the morbidity and mortality. ,,, Use of rHuEPO eliminates the need for blood transfusion in almost all the cases of anemia in this population. , The expansion of the use of this drug has been restrained by the cost, which significantly contributes to the total cost of dialysis treatment. There are certain factors, which may have an impact on the cost of rHuEPO such as the population, the route of administration, and the pharmaceutical preparation.
| Aim of the Study|| |
We attempt in this study to evaluate the attitude of the physicians in the Kingdom of Saudi Arabia (KSA) towards treatment with r-HuEPO. This includes the number of patients that need to be treated, the dosing, the need for a protocol for treatment with r-HuEPO, the preferred route of administration and the preferred preparation of r-HuEPO. Also, the causes of inadequate response to r- HuEPO and the immunogenic complications of the drug are addressed.
| Materials & Methods|| |
We sent a questionnaire to 181 nephrologists. Of these, 147 were heads of the 147 active dialysis centers in KSA and the other 34 were additional consultants working in their units. The institutions involved 110 (74.9%) centers in the Ministry of Health (MOH), 14 (9.5%) in Governmental, non-MOH hospitals and 23 (15.6%) in private sector hospitals catering to a population of more than 7300 chronic hemodialysis (HD) patients. The questionnaire was mailed to the targeted physicians during October 2004 and responses were received at the Saudi Center for Organ Transplantation (SCOT), Riyadh, KSA during November December 2004.
The questionnaire was intended to evaluate the following components in the practice of physicians who take care of the dialysis patients in the KSA:
- The perception of the physicians about the significance of r-HuEPO therapy and the need for a protocol.
- The average dosing during the induction and maintenance phases of r-HuEPO therapy and the target hemoglobin (Hb) achieved during the treatment.
- The preferences of the physicians of the r-HuEPO preparation that is safe and efficient.
- To compare the international guidelines for the treatment of anemia with r-HuEPO in HD patients with the attitude of the nephrologists in the KSA.
- Furthermore, we compared the responses according to the affiliation of the dialysis centers (MOH, non-MOH and private).
We compared the answers received with the European Best Practice and American (Dialysis outcome quality initiative, DOQI) guidelines, which indicate:
- The need to evaluate anemia in the CRF patients and increase Hb to > 110 g/l. ,,,,
- About 80% of the patients on HD need rHuEPO therapy besides 40% of those on peritoneal dialysis. 
- The average starting dose of r-HuEPO administered subcutaneously is around 50150 units per kg per week (average 40008000 units per week) and the maintenance dose varies from 50-100 units per week (average 6000 units per week). , Administration of the r-HuEPO intravenously increases the required dose by 40-50%. ,,
- A protocol is essential for administration of r-HuEPO in the dialysis patients. 
- The target Hb level for therapy with rHuEPO should be 111-120 g/l and should be achieved in at least 85% of the treated patients. ,,
- The multi-dose vials of r-HuEPO have their advantages though there is a trend towards the use of pre-filled injections. ,
- The subcutaneous route is still the preferred method of administration of r-HuEPO due to the cost savings. ,,
- The resistance or decreased effectiveness to therapy with r-HuEPO is due mostly to iron deficiency, followed by systemic inflammation. Recently, antibodies to some preparations of the r-HuEPO have been described. ,,
- Development of antibodies to r-HuEPO has been responsible for the appearance of a clinical resistance to r-HuEPO due to pure red cell aplasia (PRCA), , which may be due to improper stabilization, storage or handling of some of r-HuEPO preparations. 
| Statistical Methods|| |
Data were entered in a Microsoft Excel file; description of the data and analysis were done by using the statistical program SPSS.
Pearson Chi-Square test was used throughout the analysis to test the significance of differences between groups and sub-groups. Significance is set at P< 0.05.
| Results|| |
A total of 144 out of 181 physicians (79.5%) answered the questionnaire from 135 (92.5%) dialysis centers that treated 7107 (97%) dialysis patients in the KSA. Of them, 109/110 (99.1%) respondents were from the MOH centers, 21/14 (150%) were from non-MOH centers and 14/23 (60.1%) were from the private centers.
[Table - 1] shows the answers related to the usage and dosage of r-HuEPO.
[Table - 2] shows the target hemoglobin and the preferred route for the administration of r-HuEPO. There were 83 (58%) respondents who would aim at a target Hb of 110-120 g/l, while 29 (20.3%) would aim at 121-130 g/l. There were 51 (37.5%) respondents who considered the use of multidose vials more economical, while 57(41.9%) considered them less economical and dangerous.
[Table - 3] shows the physicians' preferences of the r-HuEPO preparations and their awareness of the antibodies to the r-HuEPO. There were 35 (24.8%) respondents who believed the type of r-HuEPO (alfa, beta) affected the development of the antibodies to r-HuEPO, while 22 (15.6%) did not believe so. The vast majority, 84 (59.6%), had no idea. There were 94 (66.2%) respondents who believed that iron deficiency was the most commonly encountered cause of resistance to the treatment with r-HuEPO, while 19 (13.4%) believed the systemic inflammation was the most important factor.
[Table - 4] shows the differences of the responses of the study participants according to their dialysis center affiliation. A significantly higher percentage of the MOH centers administered r-HuEPO only to patients who had low Hb <100-110 g/l than indiscriminately to all new patients when compared with the non-MOH centers (76% vs 52.6%, respectively, P < 0.04). Additionally, there was a significantly lower percentage of MOH centers wherein > 70% of the dialysis patients were given r-HuEPO in comparison to the non-MOH centers (81% vs 100%, respectively P < 0.04).
Finally, we analyzed the respondents according to their answers to the question about the presence or absence of a written protocol for the administration of the r-HuEPO in their respective centers. However, we found no significant differences in the responses about any of the issues in the questionnaire between those who had and those who did not have a written protocol in their centers.
| Discussion|| |
The current study attempted to know the attitudes of the physicians in charge of the HD centers in the KSA towards the use of rHuEPO replacement therapy in the HD patients.
The results of this study show some good practices compatible with the general practice guidelines in the United States of America (USA) and Europe. The majority of the respondents concurred with the importance of r-HuEPO administration guided by the Hb levels during the induction and maintenance phases of therapy. They believed that the percentage of the patients treated with r-HuEPO should be more than 70% and may, in the opinion of some, reach 90-100%. This latter belief might be responsible for the high percentage of the respondents who considered administering the drug to all new patients. This maybe an exaggerated view because 10-15% of the CRF patients maintain Hb levels above 110 g/l without r-HuEPO.  Furthermore, 62% of the respondents believed that more than 70% of their patients have currently a satisfactory Hb level of at least 110 g/l. This percentage is reasonable, although the universal guidelines recommend that a higher percentage (close to 85%) of the treated patients should attain a Hb >110 g/l with r-HuEPO therapy. ,
On the other hand, some responses might reflect uncertainty about some important aspects of r-HuEPO therapy as addressed by the American and European guidelines. The respondents would use moderately higher average doses per kilogram per patient per week of r-HuEPO than those universally accepted. ,, Almost half of respondents would not use the subcutaneous route for the administration of r-HuEPO and believed this route as less superior than the i.v. route. This is in contrast to all the universal guide lines that recommend the subcutaneous route as "preferred" due to the financial savings of up to 50%. ,, Both the dosing scale and route of administration maybe related to the recent recommendation to use the i.v. route to administer r- HuEPO for some brand names to avoid the immunogenicity that may result in the development of PRCA.  There is a split opinion about the multi-dose vials versus the pre-filled syringes as the preferred methods for the administration of r-HuEPO. Despite the trend of using the pre-filled syringes, the American guidelines still believe there is a role for the multi-dose vials due to the alcoholic preservative in them that acts as a local anesthetic for the subcutaneous stinging in comparison to the less anesthetic acetate buffer that is used in the pre-filled syringes. ,
About 76% of the respondents believed that resistance to therapy with r-HuEPO was due to iron deficiency and systemic inflammation. This is compatible with the universal guidelines. ,, However, there is a considerable minority (18.3%) who could not decide about the most common cause of the resistance to the treatment with the r-HuEPO.
The recent attention directed to the presence of antibodies to r-HuEPO and their role in the development of resistance to the drug was not clear to more than half of the respondents who had no idea about whether there was a difference of the immunogenicity of the different types of r-HuEPO. Furthermore, very few respondents suspected PRCA despite the use of EPREX® by many non-MOH centers in the KSA; EPREX ® is thought to cause PRCA due to the "polysorbate 80" stabilizer that replaced albumin in the manufacturing of this product. The new stabilizer may react with the material in the pre-filled syringes during storage and handling.  The overwhelming majority of the respondents believed the improper storage and handling of the rHuEPO affected the immunogenicity of the drug.
The comparisons in the responses according to the centers' affiliations showed important differences. The great majority of the dialysis centers in the KSA belong to the MOH. The respondents from the MOH centers had less inclination to treat all the HD patients with r-HuEPO and believed more in the multi-dose vials than those in the non-MOH centers.
Finally, the use of protocol to guide the administration of the r-HuEPO by the staff in the HD centers gives rise to a significant positive impact on the practice with considerable savings.  Half of the respondents in our study did not have such a protocol and most of these were from the MOH centers. This may indicate the need for a consensus for national guidelines to be used as a basis for such protocols. In a previous study by SCOT, about the attitudes of the HD centers towards the use iron supplements as adjuvant therapy to the r- HuEPO, we concluded that there is a need for specific protocols for this supplementation.
We conclude that the current practices concerning the r-HuEPO therapy in the dialysis centers in the KSA require refinement. This may come about by agreeing on national guidelines, which will form the basis for protocols within each dialysis center. There is also a need to increase awareness of the physicians in the importance of the usage details of such treatment
| Acknowledgement|| |
We would like to thank the Roche pharmaceuticals- Saudi Arabia for their grant that made this study possible
| References|| |
|1.||Kane MT. The assessment of professional competence. Eval Health Prof 1992;15(2): 163-82. |
|2.||Bender FH, Holley JL. Most nephrologists are primary care providers for chronic dialysis patients: results of a national survey. Am J Kidney Dis 1996;28(1):67-71. |
|3.||Parry RG, Crowe A, Stevens JM, Mason JC, Roderick P. Referral of elderly patients with severe renal failure: questionnaire survey of physicians. BMJ 1996; 313(7055):466. |
|4.||Mocks J, Franke W, Ehmer B, et al. Analysis of safety database for long term epoetin beta treatment. A meta analysis covering 3697 patients. In: Koch KM, Stein G, eds. Pathogenetic and Therapeutic Aspects of Chronic Renal Failure. Marcel Dekker, New York, 1997;163-79. |
|5.||Consensus Development Conference Panel. Morbidity and mortality of renal dialysis: an N1H consensus conference statement. Ann Intern Med 1994;121:62-70. [PUBMED] [FULLTEXT]|
|6.||Grutzmacher P, Scheuermann E, Low I, et al. Correction of renal anaemia by recombinant human erythropoietin: Effects on myocardial function. Contrib Nephrol 1988;66:176-84. |
|7.||Valderrabano F. Quality of life benefits of early anaemia treatment. Nephrol Dial Transplant 2000;15:23-8. |
|8.||Locatelli F, Pisoni RL, Combe C, et al. Anaemia in haemodialysis patients of five European countries: and association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2004; 19:121-32. [PUBMED] [FULLTEXT]|
|9.||Nissenson AR, Swan SK, Lindberg JS, et al. Randomized controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kid Dis 2002;40: 110-8. [PUBMED] [FULLTEXT]|
|10.||Kuriyama S, Tomonari H, Yoshida H et al. Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients. Nephron 1997;77:176-85. |
|11.||Morris KP, Sharp J, Watson S, Coulthard MG. Non-cardiac benefits of human recombinant erythropoietin in end stage renal failure and anaemia. Arch Dis Child 1993;69:580-6. [PUBMED] |
|12.||Sikole A, Polenakovic M, Spirovska V, Polenakovic B, Masin G. Analysis of heart morphology and function following erythropoietin treatment of anemic dialysis patients. Artif Organs 1993;17:977-84. [PUBMED] |
|13.||Bahlmann J, Schoter KH, Scigalla P, et al. Morbidity and mortality in hemodialysis patients with and without erythropoietin treatment: a controlled study. Contrib Nephrol 1991;88:90-106. |
|14.||Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998;339:584-90. [PUBMED] [FULLTEXT]|
|15.||European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 1999;4:Suppl 5:9. |
|16.||European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 1999; 14:suppl 5: 21 |
|17.||National Kidney Foundation K/DOQI clinical practice guidelines 2000 update. Am J Kidney Dis 2001;(37) Suppl 1:207. |
|18.||Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19 Suppl 2:16. |
|19.||Brimble KS, Rabbat CG, McKenna P, Lambert K, Carlisle EJ. Protocolized anemia management with erythropoietin in hemodialysis patients: a randomized controlled trial. J Am Soc Nephrol 2003; 14(10):2654-61. |
|20.||European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 1999;14:Suppl 5:11. |
|21.||National Kidney Foundation K/DOQI clinical practice guidelines 2000 update. Am J Kidney Dis 2001; (37) Suppl 1:191. |
|22.||Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19 Suppl 2:6-9. |
|23.||National Kidney Foundation K/DOQI clinical practice guidelines 2000 update. Am J Kidney Dis 2001;(37) Suppl 1:209. |
|24.||Rossert J, Casadevall N, Eckardt KU. Antierythropoietin antibodies and pure red cell aplasia. J Am Soc Nephrol 2004;15(2):98-406. |
|25.||European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 1999;14:Suppl 5:19. |
|26.||National Kidney Foundation K/DOQI clinical practice guidelines 2000 update. Am J Kidney Dis 2001;(37) Suppl 1:208. |
|27.||Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19 Suppl 2:16. |
|28.||European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 1999;14:Suppl 5:25. |
|29.||National Kidney Foundation K/DOQI clinical practice guidelines 2000 update. Am J Kidney Dis 2001;(37) Suppl 1:212. |
|30.||Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19 Suppl 2:32. |
|31.||European best practice guidelines for the management of anemia in patients with chronic renal failure. Nephrol Dial Transplant 1999;14:Suppl 5:31-2. |
|32.||Locatelli F, Aljama P, Barany P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19 Suppl 2: 4-6. |
|33.||Souqiyyeh MZ, Shaheen FA. Attitude of physicians toward iron supplementation in hemodialysis patients treated with erythropoietin. Saudi J Kidney Dis Transplant 2003;14(2):134-44. |
Muhammad Ziad Souqiyyeh
Saudi Center for Organ Transplantation, P.O. Box 27049, Riyadh, 11417
[Table - 1], [Table - 2], [Table - 3], [Table - 4]