Evaluation of Anemia Management in Hemodialysis Patients in Gezira Hospital, in Sudan

Anemia of kidney disease is a common but under recognized co-morbid condition that is known to place patients at greater risk of hospitalization, cognitive impairment, cardiovascular diseases and even death. Aims: The aims of this work to investigate current practice of anemia management in hemodialysis patients and to assess the appropriateness of anemia management. Study Design: The study was conducted in Gezira Hospital for Renal Diseases and Surgery. Data on anemia parameters, comorbidities, ESAs dosing and iron supplementation were collected. The data were collected for 6 months retrospectively from December 2005 to July 2006. Patients with ESRD undergoing hemodialysis were included. Patients were excluded if they have cancer or receiving chemotherapy or radiotherapy. Results: Data were collected from 83 patients under hemodialysis. The base line hemoglobin levels in December 2005 revealed that of the 97% of the patients were anemic, because they had hemoglobin levels below the recommended target level (11.0 g/d1). The patients started treatment with erythropoietin (4000IU/wk) for six months, and we found that 6% of patients received regular EPO, 56.6% received it irregularly and 37.3% not EPO, regarding intravenous iron mg/wk 100 mg/2wk), 7.2% of patients regular intravenous iron, 48.2% it irregularly and 44.6% of patients did not received it, Hemoglobin levels were measured in July 2006 to evaluate the effect of treatment in hemoglobin level, we found that 95% of patients were still anemic. This indicates that current treatment strategies were ineffective because the majority of patient failed to reach the recommended hemoglobin level after six months of treatment. This study demonstrate that there is no regular periodical laboratory tests, follow up and treatment for renal anemia.

irregularly and 44.6% of patients did not received it, Hemoglobin levels were measured in July 2006 to evaluate the effect of treatment in hemoglobin level, we found that 95% of patients were still anemic. This indicates that current treatment strategies were ineffective because the majority of patient failed to reach the recommended hemoglobin level after six months of treatment. This study demonstrate that there is no regular periodical laboratory tests, follow up and treatment for renal anemia.

INTRODUCTION
Renal failure is a major cause of morbidity and mortality. It is estimated that per million populations between 100-200 patients die each year in the United States from diseases of the kidney and urinary tract [1]. Optimal management of patient with chronic renal disease is best achieved using a multi-disciplinary approach to address the concurrent medical problems and the complex pharmacotherapeutic regimens.
Alterations in drug disposition that occur with renal impairment and subsequent need for dosage adjustments present additional challenges when determining rational pharmacotherapy [2].

Etiology
End stage renal disease (ESRD) is most often the result of progressive decline in renal function caused by a primary renal disease or as secondary complication of certain systemic diseases, but it may also result from an acute event causing damage to the kidneys. Diabetes Mellitus, hypertension, and chronic glomerulonephritis are the most common causes of ESRD [2].
The World Health Organization defines anemia as hemoglobin concentration lower than 13.0 g/dl in men and postmenopausal women and lower than 12.0 g/dl in other women.
The European Best Practice Guidelines (EBPG) for the management of anemia in patients with chronic kidney disease propose that the lower limit of normal for hemoglobin be 11.5 g/dl in women, 13.5 g/dl in men aged 70 and under, and 12.0 g/dl in men older than age 70.
The National kidney Foundation's Kidney Dialysis Outcomes Quality Initiative (CK/DOQI) recommends work up for anemia in patient with chronic kidney disease if hemoglobin level is less than 11.0 g/dl (Hct<33%) in premenopausal women and prepubertal patients, and when the Hb is less than 12.0g/dl (Hct<37%) in adult men and post menopausal women [3].

Rationale of the Study
Conservative estimates suggest that the number of patients requiring dialysis for CKD is rising at rate of 6-8% per annum, so earlier identification of at risk subjects is needed and greater effort to control the known risk factors for CKD and comorbidities associated with progressive kidney diseases. Therefore this study was designed to evaluate anemia management in hemodialysis patients.

Objectives of the Study
-Determination of hemoglobin level for patients under dialysis in Gezira Hospital for Renal Diseases and Surgery. -Identification of how frequent dialyzed patients take intravenous iron and erythropoietin, and if they don't take it why? -Identification of various regimen of treatment used and titration of these various regimens with increase in hemoglobin -Address the possible causes of suboptimal response to treatment.
The overall objective of this study is to evaluate renal anemia management and therefore the quality of life of renal patients, and this could be achieved only through the appropriate work up to investigate anemia in chronic kidney disease.

PATIENTS AND METHODOLOGY
The study was conducted in Gezira Hospital for Renal diseases and Surgery. All patients with ESRD undergoing hemodialysis were included. Patients were excluded if they have cancer or are receiving chemotherapy or radiotherapy. Data on anemia parameters, erythropoietin (EPO) dosing, iron supplementation, in addition to demographic data were collected. The data were collected over a 6 months period retrospectively from December 2005 and July 2006.
Patients were divided into 5 groups according to the treatment they received:
Most incidences of the disease were in the last six years which represent 81% of the sample. Approximately 54% of patients in the survey had been on hemodialysis for 1-3 years The etiology of the disease is unknown for the majority of patients (69%), on the other hand the most frequent cause of end stage renal disease is hypertensive nephrosclerosis (12%).
In order to test whether the average level of hemoglobin for patients in 12/2005 differ from the standard level, one sample t test was used, and the result revealed that there was very significant differences (P=0.000) compared with the standard level of EBPG (11 g/dl). When this test was repeated in 7/2006, the same result was obtained.

Erythropoietin (EPO)
Of the entire sample 6% of patients received regular EPO(dose interval 4000IU/week) and the result is that one patient reached Hb level between 11-13 g/dl, three patients in level of 8-10 g/dl, and one patient in the level of 5-7 g/dl. Those who received EPO irregularly (56.6%), 35 of them attain Hb level between 5-7 g/dl, 12 patients in level between 8-10 g/dl and the rest of patients (37.3%) not receive EPO Table 3.

DISCUSSION
Normal concentrations of hemoglobin are generally considered to be within the range of 13-15 g/dl for women and 14-16 for men. However, when treating anemia, the US NKF-DOQI Clinical practice guidelines recommended a target Hb concentration of 11-12 g/dl and Hct of 33-36% (NKF-DOQI).
In this study when Hb levels in December 2005 were compared to the target level of 11 g/dl according to the EBPG, we found that all patients were anemic (only 3% of patients in the level of 11-13 g/dl), and this is true as anemia often occurs early in the course of chronic renal insufficiency [4] and if patients  started treatment with extremely low Hb concentrations, they should reach this target within 4 months of starting treatment regardless of age, gender or ethnicity (EBPG). In this study after six months of treatment the resulting Hb in July 2006 is still so far from the target level (only five patients were in the level of 11-13 g/dl, and the majority of patients failed to be near or reach the target level and this due to lack of proper evaluation of individual patient's needs, coupled to concerns regarding funding, in addition to poor follow up and lack of both periodical laboratory tests and clear regimen to follow.
The primary cause of anemia in patients with CKD is insufficient production of erythropoietin by the diseased kidneys [5]. Erythropoiesis stimulating agents should be given to all patients with CKD with Hb levels consistently below 11 g/dl where all causes of anemia have been excluded [6]. In the present study we found that 31 patients not received EPO and even those who received it only 5 of them took it regularly and its positive effect is that one patient reached level of 11-13 g/dl, so this interpret that Hb levels consistency after six months of treatment was due either to irregular use of EPO or absence of EPO treatment.
Although there is synergistic relationship between EPO and I.V iron, regular I.V iron was taken by only six patients and its positive effect in Hb levels in July 2006 was clear although it is mild. All patients should take I.V iron, because iron deficiency may develop secondary to sustained stimulation of RBCs production with administration of exogenous EPO and chronic blood loss, which increase the demand for iron. Identification and management of iron deficiency through regular follow up testing and iron supplementation is essential for adequate RBCs production [2], however in this study no test done to check iron status in our patients and this may be the main cause of failure of treatment.
Regarding treatment, we observed that there were five different groups of treatment practices and all failed to correct anemia, except mild improvement on those who received combination of EPO plus I.V iron and Ferrous sulphate plus folic acid capsule.
Many causes contribute to the failure of treatment or suboptimal response to treatment. One of these causes is that some patients stop treatment according to their own evaluation (e.g. More than 80% of patients had not received treatment due to financial problems and as a result they received EPO and I.V iron irregularly and sometimes took one of them and this lead to inadequate response to treatment, so patient's financial state is considered the backbone upon which all attempts to optimize treatment and improve patient's outcomes depend. From our adherence to patients, the majority of them are very poor and idle (53%) and if we had a look on those who are still working (about 35%) they had a problem in balancing their need for regular treatment and their responsibilities toward their families and they prefer to support their families and received treatment when their financial state improved. In addition those who came from outside Wad Medani for dialysis session had additional burden, they must had enough money both to meet their life needs and treatment.
Lastly, lack of closer collaboration between patients and physicians lead to failure of treatment. In this study the majority of patients lack understanding of benefit of correcting anemia and some of them declare that they made changes in their treatment depending on their own evaluation(sometimes increase or decrease doses and sometimes disappointed an stop treatment) without consideration of physician instructions, so educational programme which involve discussion on renal function, blood pressure control, bone disease and dietary advice is very important because it will result in greater willingness to comply with treatment and achieved successful therapy.

CONCLUSION
In conclusion, early intervention improve anemia management in hemodialysis patients particularly through evaluation of causes of inadequate response. Further studies should be done because the area need more extensive work to put a clear policy in treatment of renal anemia.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.