1

EFFECT OF RECOMBINANT HUMAN ERYTHROPOIETIN (rHuEPO) ON THE QUALITY OF LIFE OF HEMODIALYSIS PATIENTS

A STUDY PRESENTED TO THE DEPARTMENT OF INTERNAL MEDICINE ILOILO DOCTORS HOSPITAL AND MEDICAL CENTER ILOILO CITY

IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE COMPLETION OF RESIDENCY TRAINING IN INTERNAL MEDICINE

BY: MARIE GABRIELLE A. LAGUNA M.D. OCTOBER 2009

2 ABSTRACT This is a prospective, correlational, descriptive study on the effect of Recombinant Human Erythropoietin on the Quality of life (QOL) of hemodialysis patients in Iloilo Doctors Hospital Renal Care Unit, Iloilo City. The study is about the socio-demographic, clinical and laboratory profile and QOL assessment using two measures—Karnofsky Performance Status Scale (KPSS) and Medical Outcomes Short Form Health Survey (SF- 36). Baseline values were initially taken, after which, patients were given their recombinant human erythropoietin dose for four weeks, based on their baseline hemoglobin levels, the duration of their treatment with recombinant human erythropoietin and their weight. There were a total of 36 patients who came in at the Iloilo Doctors Hospital Renal Care Unit who were enrolled in the study. The data were drawn using the Karnofsky Performance Status Scale (KPSS) and the Medical Outcomes Short Form Health Survey (SF 36), a multipurpose, short form health survey with 36 questions which was created by the International Quality of Life Assessment (IQOLA) Project and was documented by nearly 4,000 studies in terms of reliability and validity. The results showed that there is an improvement in hemoglobin, creatinine clearance and serum albumin kevels after 4 weeks of recombinant human erythropoietin treatment. There is also an improvement in physical functioning, bodily pain handling, vitality, social functioning and role emotional; however there is no effect on the physical, general health and mental health after RHuEPO. There is also an improvement in Karnofsky scores after RHuEPO. Hemoglobin is an independent factor in physical functioning. The KPSS and the SF 36 survey has a positive correlation thus the former can be a good choice in patents who are not fully conscious and who cannot answer questions of the SF-36. Bodily pain and physical functioning also affects Karnofsky scoring. Thus this study recommends that further studies should be done regarding the factor which greatly affects physical functioning. Compliance to recombinant human erythropoietin is needed. Every hemodialysis unit should be provided with counselors, psychiatrists or psychologists. Quality of life should be routinely done in every hemodialysis at intervals of 3, 6 or 9 months to see whether the patient improves or deteriorates so that solutions can be done. The Karnofsky Performance Status Scale should take the place of SF-36 in patients who cannot converse or are not fully conscious. Physical Functioning and Bodily pain scores should be elevated in order to maintain a high KPSS score for QOL.

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TABLE OF CONTENTS
Page 1 2 3 INTRODUCTION Background and significance of the Study Review of Related Literature Statement of the Problem Objectives of the Study Scope and Limitation Definition of Terms Conceptual Framework METHODOLOGY Research Design Participants Research Setting Sampling Design Research Instrument Data Gathering Procedure Data Analysis PRESENTATION OF RESULTS, ANALYSIS AND INTERPRETATION DISCUSSION CONCLUSION AND RECOMMENDATION 1 1 3 10 10 11 11 13 14 14 14 15 17 17 19 20

Title Page Abstract Table of Contents List of Tables List of Figures CHAPTER I

CHAPTER II

CHAPTER III

21
CHAPTER IV CHAPTER V 30 38

4

LIST OF TABLES

Page 1.

5

LIST OF FIGURES
Page 1.

6 CHAPTER I INTRODUCTION Background of the Study Chronic kidney disease affects many Filipinos each year and is one of the top ten causes of death among Filipinos wherein 7, 000 die annually due to kidney malfunction. Because of the increasing number of Filipinos with kidney disease, it is now considered among the top seven health problems in the country. Worldwide, there is also an alarming level of kidney disease with more than 500 million persons suffering from some form of kidney damage. In 2006, the Philippine Renal Disease Registry showed that the Province of Iloilo had the most number of patients in Region 6 with end-stage renal disease with 248 patients undergoing hemodialysis in 7 dialysis centers. Anemia is a characteristic feature of chronic kidney disease, which is due to inadequate secretion of erythropoietin. This complication often results to significant cardiovascular morbidity, hospitalization and mortality. Erythropoiesis stimulating agents, since their discovery nearly two decades ago have significantly improved care of patients with renal anemia. However, although several reports have demonstrated the benefits of anemia correction in patients with chronic kidney disease, little reports have been published with regards to the relationship of erythropoiesis stimulating agents to the quality of life among Filipinos. Thus this study aims to asses the quality of life in chronic hemodialysis patients with anemia (hemoglobin level of 13. 5 g/ dL in adult males and <12.0 g/dL in adult females), using the SF-36 questionnaire and the Karnofsky performance scale, and to correlate the results with clinical and laboratory parameters after 4 weeks of recombinant human erythropoietin (RHuEPO) therapy.

7

Review of Related Literature The importance of quality of life as a dimension of health is disclosed in the constitution of the World Health Organization, “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”. 1 Since quality of life is a very important aspect of health, there are a number of survey tools which have been developed to investigate the components of quality of life. Our study utilized the Karnofsky scale and the Medical Outcomes study Short-Form Health Survey (SF-36) The disturbed metabolism caused by the chronic kidney failure has negative effects in the body’s organs and systems. One of the systems being affected is the erythropoietic system, which in turn, gives rise to anemia. Anemia is a state of deficient mass of red blood cells and hemoglobin resulting in insufficient oxygen delivery to the body’s tissues ad organs. The National Kidney Foundation’s clinical practice guidelines define anemia as a hemoglobin level less than 13.5 g/ dl for adult men and less than 12.0 g/ dl for adult women. Chronic kidney disease has been associated with circulating inhibitors of erthropoiesis.
2,3,4

, but great evidence demonstrates the primary role of erythropoietin
5,6,7

deficiency as the major cause of anemia in CKD.

Because anemia results to

symptoms such as fatigue, dyspnea and reduced mental acuity that degrade the individual’s overall experience and quality of life, we must treat this by all means, with the use of recombinant human erythropoietin.

8 Previous studies have shown that normalization of hemoglobin improves the quality of life of patients on hemodialysis. In cardiac patients enrolled in the normalization of hematocrit study 7, quality of life was assessed using the Medical Outcomes Study short form Health survey 8 ; as the hematocrit increased, quality of life improved, although few details of the analysis are provided. A prospective randomized double blind crossover study in 14 hemodialysis patients assessed the benefits of full reversal of anemia in stable hemodialysis patients.
9

The total score and psychosocial

dimension score were significantly better when the hemoglobin was normalized. Similar findings were reported by Paintu and colleagues, who found an improvement in exercise capacity when normalization of hematocrit was combined with exercise testing.
10

The

latter, however remained below normal, thus suggesting that the poor exercise capacity in dialysis patients cannot be fully explained by anemia. These results confirm earlier findings by other investigators
11, 12, 13

and implicate a role for anemia per se or local

abnormalities in electrolyte metabolism related to anemia in this clinical abnormality. Several forms of recombinant human erythropoietin are available for the treatment of patients with anemia related to chronic renal failure and ESRD by either the intravenous or subcutaneous route. Epoietin alpha and beta (165 amino acids)
14

are

glycoproteins produced through recombination of the human erythropoietin gene of the chimeric hamster ovary cell. These recombinant human erythropoietin molecules differ modestly in that the beta form contains quantitatively more basic sialic acid residues. The half time (t ½) of epoietin alpha is between 4-12 hours when administered continuously and is prolonged to approximately 28 hours by subcutaneous injection. Evidence based guidelines differ in their ideal initial dosage of recombinant human erythropoietin; for

9 K/DOQI it should be given 80-120/ kg/ week subcutaneously or 120-180 u/kg/ week IV. In European guidelines, it is given 50-150 U/ kg/week SC and IV. In Canadian guidelines, it is given 100-200 U/ kg/ week delivered in doses divided twice or 3 x a week. There are a variety of serious potential complications of therapy, including worsening hypertension, seizures, impaired solute clearance (particularly proteins) and an increased frequency of thrombotic events at but not confined to vascular access in situ. Current medical practice regarding target hemoglobin levels in patients with CKD is derived from the National Kidney Foundation K/DOQI clinical practice guidelines. The target hemoglobin concentration should be more than 11.0 with lower levels associated with adverse outcomes.

Statement of the Problem: What is the Quality of Life of hemodialysis patients on recombinant human erythropoietin therapy at Iloilo Doctors Hospital, Iloilo City?

General Objective: To know the effect of recombinant human erythropoietin on quality of life of hemodialysis patients at Iloilo Doctors Hospital, Iloilo City. Specific Objectives: 1. To assess the Quality of Life of hemodialysis patients at Iloilo Doctors Hospital Renal Care unit, Iloilo City by determining the following parameters after 4 weeks of treatment with recombinant human erythropoietin:

10 a. Karnofsky Performance Status Score b. Physical Functioning c. Role limitations due to physical health problems d. Bodily pain e. General health f. Vitality (energy/ fatigue) g. Social functioning h. Role limitations due to emotional problems i. Mental Health 2. To know the socio demographic profile of these patients 3. To know the clinical and laboratory parameters of their hemodialysis patients before and after treatment with recombinant human erythropoietin for 4 weeks.

Scope and Limitation This study focused on determining the quality of life of hemodialysis patients before and after treatment with recombinant human erythropoietin for 4 weeks. The respondents of this study are limited to those patients who avail of dialysis treatment at Iloilo Doctors Hospital Renal Care unit who were coherent to undergo interview. The tools that were used in the study are the Karnofsky Performance Status Scale and the Short Form Health Survey (SF 36), and the laboratory parameters such as serum creatinine, blood urea nitrogen, hemoglobin and serum albumin.

11 Definition of Terms: 1. Physical Functioning— The person performs all types of physical activities including the most vigorous without limitations due to health. 2. Role limitations due to Physical Health problems—The person has no problems with work or other daily activities. 3. Bodily Pain— The person has no pain or limitations due to pain. 4. General Health— The person evaluates personal health as excellent. 5. Vitality-- The person feels full of pep and energy all of the time 6. Social Functioning-The person performs normal social activities without

interference due to physical or emotional problems 7. Role limitations due to emotional problems—The person has no problems with work or other daily activities 8. Mental Health—The person feels peaceful, happy, and calm all of the time 9. Quality of Life (QOL)-. Patients perception of their Physical wellness, emotional well- being, social status, cognitive ability and self-care/functional or the level of functioning and capacity to care for oneself.

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Conceptual Framework The conceptual framework depicts that the quality of life is modified and affected by sociodemographic factors, hemodialysis treatment, recombinant human erythropoietin treatment, and clinical and laboratory parameters. These factors have reciprocal relationships and are interrelated in predicting the outcome of QOL. There is a one-way arrow between hemodialysis treatment and socio-demographic factors and another arrow between recombinant human erythropoietin treatment and socio demographic factors because their ease of access to treatment depends on socioeconomic status. Thus these four interrelated factors point to and mirror the QOL of the patients. On the other hand, their quality of life will affect treatment compliance as well as their functional recovery for the disease which in turn has a bearing on a patient’s treatment outcomes.

Sociodemographic Factors

Hemodialysis treatment

QOL

Erythropoietin

Clinical and laboratory Parameters

Adherence/ Compliance to treatment and functional recovery

Treatment Outcome

13 CHAPTER II Methodology Research Design This study used a prospective, correlational, descriptive study design. There are two parts in this paper. First quality of Life was assessed using Karnofsky Performance Status Scale and Short Form Health Survey (SF-36). Sociodemographic, clinical and laboratory profiles were also obtained. Then the patients had recombinant human erythropoietin treatment for 4 weeks. In the second part, the Quality of Life , using KPSS and SF-36 were again obtained from these patients and the results compared.

Participants Inclusion Criteria: 1. Male or female, aged 19 years or older. 2. On hemodialysis, either as outpatient or as inpatient, at Iloilo Doctors Hospital Renal Care Unit from June 1, 2009 to August 31, 2009. 3. Anemia (hemoglobin levels of 13. 5 g/ dL in adult males and <12.0 g/dL in adult females) Exclusion Criteria: 1. Daily prednisone dose of at least 10 mg 2. Medical conditions likely to reduce epoietin responsiveness, including concurrent malignancy, therapy with cytotoxic agents, seizure in the preceding year, hypersensitivity to intravenous iron and current pregnancy or breastfeeding.

14 3. Patients being prepared for renal transplantation 4. Patients who will not consent

Research Setting The study was conducted at Iloilo Doctors Hospital and Medical Center Renal Care Unit, Iloilo City. Iloilo Doctors Hospital is a tertiary hospital with a 300-bed capacity and ISO certification. The Iloilo Doctors Hospital Renal Care unit caters to patients from Iloilo City, Capiz, Akjlan and Antique. There were 44 patients for a 3month period of June – August 2009. They are in either 2 sets of sessions in a day which starts at 7:30 AM and ends at 5PM; the IDH Renal Care unit is open 24 hours a day for emergency hemodialysis. The unit is well equipped with amenities and facilities needed by the patient in accordance to the ruled and regulations of Department of Health Region 6. They have 6 functional hemodialysis machines and the unit id adjacent to the Medical and Surgical Intensive Care units where patient can have access to critical care equipment and staff. The staff is headed by a nephrologist who is a Fellow of the Philippine College of Physicians and the Philippine Society of Nephrology; 2 active consultant staff nephrologists, visiting nephrologists and 2 resident physicians rotating in Nephrology; a hemodialysis nursing manager, 3 hemodialysis nurses, volunteer nurses and 2 technicians who maintain the machines and facilities. The unit also has access to surgeons who perform hemodialysis access procedures on patients anytime once called.

15 Sampling Design: All patients undergoing hemodialysis at Iloilo Doctors Hospital Renal Care Unit from June to August 2009 were enrolled in the study. The researcher visited the unit everyday to include all the patients within the three-month period. The researcher was able to administer the questions to 36 out of 44 patients at the hemodialysis unit.

Research Instruments: There were 2 measures of QOL used in the study: the Karnofsky Performance Status Scale and the Short Form Health Survey (SF-36). The Karnofsky Performance Status Scale numerically describes in an easily administered, single global score, “the patient’s ability to carry on his normal activity and work, or his need for a certain amount of custodial care, or his dependence on constant medical care.” The description of each 10-point increment is in Table 1. The KPSS was originally developed to evaluate a patient’s response to a chemotherapeutic agent. Nevertheless, the validity and reliability of the KPSS has been well documented. 15, 16, 17

Table I: Karnofsky Performance Status scale 100 Able to carry on normal activity and to work; no special care needed. 90 80 Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed. 70 60 Normal no complaints; no evidence of disease. Able to carry on normal activity; minor signs or symptoms of disease. Normal activity with effort; some signs or symptoms of disease. Cares for self; unable to carry on normal activity or to do active work. Requires occasional assistance, but is able to care for most of his personal needs.

16 Requires considerable assistance and frequent medical care. Disabled; requires special care and assistance. Severely disabled; hospital admission is indicated although death not imminent. Very sick; hospital admission necessary; active supportive treatment necessary. Moribund; fatal processes progressing rapidly. Dead

50 40 30 Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.

20 10 0

The SF 36 questionnaire is a measure which is sensitive to the effect of co morbidity. In it, the data from 36 questions are combined to provide a measure of health related quality of life in eight dimensions. These are: physical functioning, role limitations attributable to physical problems, bodily pain, perception of general health, vitality, social functioning, role limitations attributable to emotional problems and mental health. A score from 0 (lowest health related quality of life) to 100 (highest) is derived for each. The experience to date on SF 36 has been described in nearly 4,000 studies. Its reliability and validity has been well assessed,
18,19

, and narrative data exists for the

general English population. It has also been shown to be valid and acceptable to patients < 65 years old.
20,21

. Although it is increasingly being used as an outcome measure for

patients with end stage renal failure, it has not been formally assessed in this population. A summary of information about SF 36 scales and physical and mental component interpretations is shown in Table II.

17 Table II: Summary of Information about SF-36® Scales and Physical and Mental Component Summary Measures
Correlations Number of

Definition (% observed) Lowest Possible Score (Floor)c Highest Possible Score (Ceiling)c
Performs all types of physical activities including the most vigorous without limitations due to health (38.8%) No problems with work or other daily activities (70.9%)

Scales
Physical Functioning

PCS MCS Items Levels Mean SD Reliability Cla

.85

.12

10

21

84.2

23.3

.93

Very limited in performing all physical 12.3 activities, including bathing or dressing (0.8%) Problems with work or other daily activities as 22.6 a result of physical health (10.3%)

Role-Physical .81 (RP)

.27

4

5

80.9

34.0 .89

Bodily Pain

.76

.28

2

11

75.2

23.7 .90

Very severe and No pain or limitations due to 15.0 extremely limiting pain pain (31.9%) (0.6%) Evaluates personal health as poor and believes it is likely to get worse (0.0%) Evaluates personal health as excellent (7.4%)

General Health (GH)

.69

.37

5

21

71.9

20.3 .81

17.6

Vitality

.47

.65

4

21

60.9

20.9 .86

15.6

Feels tired and worn out Feels full of pep and energy all of the time (0.5%) all of the time (1.5%) Performs normal social activities without interference due to physical or emotional problems (52.3%) No problems with work or other daily activities (71.0%)

Social Functioning

.42

.67

2

9

83.3

22.7 .68

Extreme and frequent interference with normal 25.7 social activities due to physical and emotional problems (0.6%) Problems with work or other daily activities as a result of emotional problems (9.6%)

RoleEmotional (RE)

.16

.78

3

4

81.3

33.0 .82

28.0

Mental Health .17 (MH)

.87

5

26

74.7

18.1 .84

Feelings of nervousness Feels peaceful, happy, and 14.0 and depression all of the calm all of the time (0.2%) time (0.0%) Limitations in self-care, physical, social, and role activities, severe bodily pain, frequent tiredness, health rated "poor" (0.0%) Frequent psychological distress, social and role disability due to emotional problems, health rated "poor" (0.0%) No physical limitations, disabilities, or decrements in well-being, high energy level, health rated "excellent" (0.0%) Frequent positive affect, absence of psychological distress and limitations in usual social/role activities due to emotional problems, health rated "excellent" (0.0%)

Physical Component Summary

35

567b

50.0

10.0 .92

5.7

Mental Component Summary

35

493b

50.0

10.0 .88

6.3

Note. From Ware, Kosinski, and Keller (1994). a CI=95% confidence interval b Numberof levels observed at baseline; scores rounded to the first decimal place (n=2,474). d Scores for eight scales are the percentage of the total possible score achieved for each of these scales. Scores for PCS and MCS are Data Gathering

18 The researcher visited the IDH Renal Care Unit everyday within the months of June- August 2009. The researcher first obtained sociodemographic data from the patients. She introduced herself to them and asked permission to each of them to become a part of the study. After being given consent, the researcher administered the 2 QOL instruments to the participants during the dialysis sessions. Clinical and laboratory data were obtained from the patients’ records at the IDH renal care unit. The patients were then given their weekly 2-3x dosages of recombinant human erythropoietin injections for 4 weeks. The dosage was based on their initial and maintenance doses as prescribed by their attending nephrologists and based on their weight and hemoglobin levels. After 4 weeks, laboratory parameters such as serum creatinine, BUN, hemoglobin and albumin were again obtained. Creatinine Clearance was solved using the Cockroft-Gault equation. The 2 QOL measures were again administered and adverse effects to the treatment were noted, as well as the mean systolic blood pressure at the end of the 4 week treatment. Afterwards, the data collected in the questions such as the demographic, clinical and laboratory profiles were tallied. The 2 QOL measures were translated in the Hiligaynon dialect which most of them could speak and understand as well. The results of the SF-36 survey were then encoded in COES software. The data obtained were transcribed by the researcher the soonest possible time to minimize errors. Data Gathering Descriptive statistics were used to analyze the data. The mean scores were obtained for each domain among all the participants.

19 CHAPTER III Presentation of Results, Analysis and Interpretation I. Demographic and Laboratory profile

Table III. Basic Socio-Demographic Data of patients at Iloilo Doctors Hospital Renal Care Unit. Category F Mean SD Percentage (%) A. Sex Male 21 58% Female 15 42% Total 36 100% B. Age 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100 Total C.Marital Status Single Married Separated Widowed Total D.Occupation Unemployed Semiskilled Senior Employee Total 0 0 4 1 9 12 4 6 0 0 36 0 0 27.75 0 47.43 56.50 64 73.43 0 0 0 0 2.872 0 2.878 2.844 3.742 2.637 0 0 0 0 11 3 25 33 11 17 0 0 100

5 27 1 3 36 1 33 2 36

14 75 3 8 100 3 92 5 100

20 E.Level of Education Nil Primary Secondary Higher Education Total

0 0 3 33 36

0 0 8 92 100

The respondents of this study were 36 patients who underwent hemodialysis at Iloilo Doctors Hospital Renal Care Unit during the months of June to August 2009 (3month period). When classified as to sex, 21 (or 58%) were males and 15 (42%) were females. When classified as to age, patients within the age range of 51-60 years old were recorded to compose the majority who underwent hemodialysis during the months of June to August 2009 (33%) with a standard deviation of 2.844. Meanwhile, patients belonging to ages 0-12, 10-20, 81-90 and 91-100 years old brackets were recorded as the lowest rates to undergo hemodialysis with a result of 0. When classified as to marital status, 5 or 14 % were single while 27 or 75% are married. 3 or 8% are widowed. When classified as to occupation, 1 or 3% were unemployed. 33 or 92% are semis-0killed and 2 or 5% are senior employees. When classified as to education, 33 or 92% attained higher education (college degree) Note: All entries that got 1 were constant.

21 Table IV. Duration of hemodialysis of patients (in months) at Iloilo Dcotors Hospital Renal Care Unit at the time of data collection (June to August 2009) Category F Percentage (%) Months 0-15 29 80 16-30 3 8 31-45 0 0 46-60 0 0 61-75 0 0 76-90 1 3 91-105 0 0 106-120 1 3 121-135 1 3 136-150 1 3 Total 36 100% Table IV shows the patient’s duration of hemodialysis at the time of data collection, with a mean of 15.65 months and a standard deviation of 32. 88. Majority of the patients (29 or 80%) have been undergoing hemodialysis for 0-15 months, while 3 or 8% have been undergoing hemodialysis for 16-30 months.

Laboratory Parameters observed in patients Table V: Mean Baseline Laboratory Parameters observed in patients Parameters HD Patients (N=36) Serum creatinine (umol/L) 817.16 +/- 370.19 Blood urea nitrogen (mmol/L) 22.64 +/- 21.57 Creatinine clearance (ml/min) 8.66 +/- 4.49 Hemoglobin concentration (g/dl) 96 +/- 8.77 Serum albumin (g/L) 36.17 +/- 11.2 Table V shows the baseline serum creatinine levels of patients (in umol/l) at Iloilo Doctors Hospital Renal care Unit at the time of data collection, with a mean of 817.16 umol/L and a standard deviation of 370.19. The mean blood urea nitrogen observed in these patients is 22.64mmol/L, with a standard deviation of 21.57. The baseline creatinine

22 clearance is 8.66 ml/min, with a standard deviation of 4.49. The baseline hemoglobin level is 96 g/dl, with standard deviation of 8.77. The Baseline serum albumin level is 36.17 g/L, with a standard deviation of 11.2. Table VI. Laboratory Parameters observed in patients after 4 weeks of recombinant human erythropoietin therapy and the percent change from the baseline. Parameters Baseline Hemodialysis patients Post RHuEPO % change from baseline 1.50 % 7.59% 0 0.13% 2.84%

Serum Creatinine (mmol/L) Blood Urea Nitrogen (mmol/L) Creatinine Clearance (ml/min) Hemoglobin concentration (g/dl)\ Serum albumin (g/L)

817. 16 +/- 370. 19 22.64 +/- 21.57 8.66 +/- 4.49 96+/- 8.77 36.17 +/- 11.2

804.16 +/- 393.21 24.36 +/- 8.52 8.66 +/- 4.49 96.13 +/- 8.77 37.2 +/- 11.2

Table VI shows the laboratory parameters observed in patients after 4 weeks of recombinant human erythropoietin therapy and the percent change from the baseline. There is a slight drop in serum creatinine levels (1.5%) after 4 weeks of treatment with RHuEPO. However, there is a noted increase in BUN levels. There is no change in creatinine clearance observed. There was slight improvement in hemoglobin concentration observed in treatment with RHuEPO for 4 weeks, as well as an improvement in serum albumin levels.

23 The mean systolic BP taken before the start of erythropoietin therapy was 140 +/22. The mean systolic blood pressure after 4 weeks of treatment with erythropoietin was 140 +/- 32. There were no adverse reactions noted by patients after the 4 week period.

II.

Quality of Life Assessment

Table VII. QOL parameters, baseline values, scores after 4 weeks of recombinant erythropoietin therapy and their percent change. Parameters Physical functioning Role physical Bodily Pain General Health Vitality Social Functioning Role emotional Mental Health Karnofsky score Baseline values 58.19 +/- 47.20 31.25 +/- 62.26 46.33 +/- 16.14 71.08 +/- 15.25 62.5 +/- 12. 67 63.33 +/- 19.67 92.61% +/- 0 64.55 +/- 10.18 64.16 +/- 20 After 4 weeks of RhuEPO 68.88 +/- 47 22.22 +/- 62 50.77 +/- 16 64.41 +/- 15.25 63.05 +/- 12 70.58 +/- 19.5 100 +/- 0 60.44 +/- 10 66.11 +/- 20 % change 18.37% 28.89% 9.58% 9.38% 0.88% 11.44% 7.97% 6.36% 3.03%

Table VII shows the various QOL parameters of SF-36, the Karnofsky Performance Status score, their baseline values, their values after 4 weeks of erythropoietin therapy and their percent change. Note that there is an improvement in

24 physical functioning, bodily pain handling, vitality, social functioning, role emotional and Karnofsky score. However there is decrease in role physical, general health and mental health areas.

Figure I. Correlation between SF-36 and Karnofsky Scores prior to erythropoietin therapy.
10 0

8 0

6 0

S - 6Ite F3 m S oe cr s
4 0

2 0

0 5 0 6 0 7 0 8 0 9 0

K r o k S oe an fs y c r s
R leE o n l o mtio a kro k an fs y P y ic l F n tio in hs a uc n g kro k an fs y S c l F n tio in o ia u c n g kro k an fs y F lin fo R leE o n l it e r o mtio a kr o k an fs y F lin fo P y ic l it e r h s a F n tio in uc n g kr o k an fs y F lin fo S c l F n tio in it e r o ia u c n g kr o k an fs y

RS L e r =0 0 q in a .0 5 RS L e r =0 0 q in a .0 9 RS L e r =0 4 q in a .0 6

r = -0.07, p = 0.70 : r = 0.09, p = 0.59 : r = 0.22, p = 0.21

Figure II. Correlation between SF-36 and Karnofsky Scores after erythropoietin therapy.

25

140

120

100

SF-36 Item Score

80

60

40

20

0 50 60 70 80 90

Karnofsky Scores

Role Em otional karnofsky Physical Functioning karnofsky Social Functioning karnofsky

Fit line for Role Em otional karnofsky Fit line for Physical Functioning karnofsky Fit line for Social Functioning karnofsky

R Sq Linear = 0.161 R Sq Linear = 0.286 R Sq Linear = 0.142

r = 0.401*, p = 0.015 : r = 0.535**, p = 0.001 : r = -0.377*, p = 0.023

Figures I and II shows the correlation of Karnofsky score with 3 SF 36 items. The results showed positive correlation regardless of the erythropoietin treatment. Figure III. Correlation between hemoglobin and physical functioning score in patients after 4 weeks of ESA Therapy
115

110

105

Hemoglobin

100

95

90

85 0 20 40 60 80 100 R Sq Linear = 0.025

Physical Functioning

r = -0.159, p = 0.543

26 Figure III is aboot the correlation of hemoglobin levels with ohysical function. The graph shows a negative correlation betweem hemoglobin levels and physical functioning.

Figure IV: Correlation of Karnofsky scores with the different SF 36 items

r = 0.28, p = 0.09 : r = 0.38*, p = 0.02 : r = -0.22, p = 0.19 ; r = 0.53** , p = 0.001 ; r = -0.37*, p = 0.03

Table 1. Multiple Regression Analysis - Forward
a Coefficients

Model 1 2

(Constant) Physical Functioning (Constant) Physical Functioning Bodily Pain

Unstandardized Coefficients B Std. Error 59.480 5.039 .235 .064 71.624 6.758 .319 .069 -.365 .146

Standardized Coefficients Beta .531 .722 -.388

t 11.804 3.651 10.599 4.642 -2.496

Sig. .000 .001 .000 .000 .018

a. Dependent Variable: karnofsky

27 Two variables were found to be affecting Karnofsky scores namely Physical Functioning and Bodily Pain. The equation is Ykarnofsky score = 71.624+0.319 xPhysical Functioning – 0.365 xBodily Pain + ε

CHAPTER IV DISCUSSION

The effect of recombinant human erythropoietin treatment may be attributed by some studies to be due to its reversing effect on the diminution of erythrocyte survival in CKD. In this study, we have found out that there is some improvement in hemoglobin levels, although minimal, after recombinant human erythropoietin treatment for 4 weeks. This may be the reason for such. Schwartz et al
23

have shown that erythrocytes in CKD

have a significantly reduced survival with a half life of as low as 22 days. Polenakovich and Sikole studied 40 chronic hemodialysis patients. Prior to initiation of RHuEPO treatment, the mean erythrocyte half life was 23.3 +/- 2.6 days. After 12 days of treatment, the mean erythrocyte half life increased slightly to 27.2 +/- 4.1 days and after discontinuing RHuEPO for 12 months, the erythrocyte half life decreased again to 22.1 +/- 3.6 days. Increased erythrocyte antioxidant level after RHuEPO treatment may contribute to improved red cell survival. There is also a significant improvement I creatinine clearance. This agrees with the findings of various investigators regarding the relationship of hemoglobin with creatinine clearance. A study by Radtke HW et al showed that serum erythropoietin levels in patients with kidney disease were generally higher than in normal subjects. With

28 decreasing levels of creatinine clearance in the range of 20-90 ml/min, mean serum erythropoietin concentration increases as mean hematocrit decreases. With severe renal insufficiency (creatinine clearance < 209 ml./ min), serum erythropoietin levels were markedly decreased for the degree of anemia present. 22 Serum albumin was also said to improve after RHuEPO treatment. In reference to this is a study done by Thomas and associates which dealt with the contribution of proteinuria to anemia in diabetes among Australian patients with Type II diabetes. The prevalence of anemia was found to increase greatly in patients with macroalbuminuria as compared to microalbuminuria or no albuminuria regarding this matter. Our findings also revealed an improvement in physical functioning, bodily pain, vitality, social functioning and role emotional. Physical functioning means that the patient is able to perform all types of physical activities without limitations due to health. Increased performance may be due to the correction of anemia, which results to an increased delivery of oxygen to body tissues. Bodily pain means that the patient has no pain or no limitations due to pain. Vitality means that the patient is full of pep and energy all the time. Social functioning means the person performs social activities without interference. However, our study also found out that recombinant human erythropoietin does not lead to any improvement to role physical, mental health and general health. A low score in role physical means that there are problems in work and in daily activities as a result of physical health. A low score in general health means that the person evaluates
25

. Thus further studies are needed

29 his or her own health as poor and believes it is likely to get worse. A low score in mental health means that there is feeling of nervousness and depression all the time. There was also an improvement in Karnofsky scores after RHuEPO therapy, and this means that the patient’s ability to carry out his normal work and activity improves after therapy. The mean score of 60 means that the patient requires occasional assistance, but can perform his or her activities well. This study has also shown a positive correlation between KPSS and SF-36 through physical functioning, social functioning and mental health. Thus it agrees to the findings of other investigators that although KPSS is physician dependent with little or no input from the patient in contrast to SF 36, it may replace SF-36 in patients who are not conscious enough or are ill and not able to converse well to respond to questions and may serve its purpose well. There is a negative correlation between hemoglobin concentration and physical activity scores. This agrees with the study of Mingardi et al
26

which said that there is not

association between HRQOL and hemoglobin. Perhaps there is a factor, not anemia or a low hemoglobin, which greatly affects physical functioning in patients with end stage renal disease, and this call for further studies to prove this fact. Another interesting finding in our study is the fact that among the 8 domains of the SF-36 survey, the two factors which greatly affect Karnofsky Scores are Physical Functioning and bodily pain. Thus we should address these two factors well, so that a person’s performance can be maximized to his full potential. Addressing these two problem factors are maybe the keys in raising our Karnofsky scores.

30 CHAPTER V SUMMARY, CONCLUSIONS AND RECOMMENDATIONS

In summary, the study examined the quality of life of hemodialysis patients in Iloilo Doctors Hospital renal Care Unit before and after 4 weeks of treatment with recombinant Human erythropoietin (RHuEPO), under a prospective, correlational, prospective design. The results showed that there is an improvement in hemoglobin, creatinine clearance and serum albumin kevels after 4 weeks of recombinant human erythropoietin treatment. There is also an improvement in physical functioning, bodily pain handling, vitality, social functioning and role emotional; however there is not effect on the physical, general health and mental health after RHuEPO. There is also an improvement in Karnofsky scores after RHuEPO. Hemoglobin is an independent factor in physical functioning. The KPSS and the SF 36 survey have a positive correlation thus the former can be a good choice in patents who are both fully conscious and who cannot answer questions of the SF-36. Bodily pain and physical functioning also affects Karnofsky scoring. Thus study therefore recommends the following: 1. Further studies should be done regarding the factor which greatly affects physical functioning, since hemoglobin is ruled out as a factor, as shown in our study.

31 2. Compliance to recombinant human erythropoietin is needed so that the patient can function well everyday with minimal assistance, can tolerate body pain well, can increase vitality and can make one function well. 3. Every hemodialysis unit should be provided with counselors, psychiatrists or psychologists so that quality of life can be maintained in our patients. 4. Quality of life should be routinely done in every hemodialysis at intervals of 3, 6 or 0=9 months to see whether the patient improves or deteriorates so that solutions can be done. 5. The Karnofsky Performance Straus Scale should take the place of SF-36 in patients who cannot converse or are not fully conscious. 6. Physical Functioning and Bodily pain scores should be elevated in order to maintain a high KPSS score for QOL.

32 REFERENCES

1.

El-Achkan TM, Ohmit SE, Mc Cullogh PA et al. Higher prevalence of anemia of diabetes mellitus in moderate kidney insufficiency. The Kidney Early Evaluation Program Kidney Int 67: 1483-1488, 2005

2. RadtkeHW, Rege AB, Lamaeche B et al. Identification of spermine as an inhibitor of erthropoiesis in chronic renal failure. 3. Massry SG: Is Parathyroid hormone a uremic toxin? Nephron 19:125-139, 1977 4. Fisher JW, Hatch FE, Roh BL et al. Erythropoietin inhibitor in kidney extracts for anemic uremic subjects. Blood 31 (4) 440-452, 1968 5. Erslev AJ: Berbard A: The rate and control of baseline red cell production in hematologically wise stable patients with uremia. J Lab Clin Med 126: 283-286, 1997 6. Eschbach, JW. The anemia of chronic renal failure: Pathophysiology and the effects of recombinant human erythropoietin. Kidney Int 18(6): 732-745, 1989. 7. Bernard A, Bolton WK, Bromme JK et al: The effects of normal as compared with low hematocrit values in patients with cardiac disease whoa re receiving hemodialysis and epoietin. N Eng J Med 339: 584-590, 1998. 8. McHarvey CA. Ware JE, Raczec AE. The MOS 36-1 short form Health survey (SF-36) II: Psychometric and clinical tests of validity in managing physical and mental health. Med Lane 31:247, 263, 1993.

33 9. McMahon LP, Mason k, Skinnes SL et al. Effects of hemoglobin normalization on quality of life and cardiovascular parameters in end sate renal failure. Nephrol Dial Yanoplat 15: 1475-1430, 2000. 10. Pointer P, Moore g, Carlson L et al. Effect of exercise testing plus normalization of hematocrit on exercise capacity and health related quality of life. Am J Kidney Dis 39: 257-265, 2002. 11. Mc Horney CA, Ware JE, Raczec AE: The MOS 36-item short form health survey (SF-36) II. Psychometric and clinical tests of validity in meaning physical and mental health constructs. Med Lane 31: 247-263, 1993. 12. Suzuki, M, Tsutsui M, Yokohama A, Hirasan Y. Normalization of hematocrit with recombinant human erythropoietin in chronic hemodialysis patients dies not improve their exercise tolerance abilities. Artif Organ 19: 1258-1261, 1995 13. Mc Mahon LP, MKenn MJ, et al: Physical Performance and associated electrolyte changes for hemoglobin normalization: a comparative study is hemodialysis patients. Nephrol Dial Transplant 14: 1182-1187, 1999. 14. Egrie J: The cloning and production of recombinant human erythropoietin. Pharmacotherapy 101 Suppl 2: 3-8, 1990. 15. Yates JW, Chaler B, McKegney FP. Evaluation of patients with advanced cancer using the Karnofsky Performance Status. Cancer 1980; 45: 2220-4. 16. Mot V, Caliberte L. The Karnofsky Performance Status scale, an examination of its reliability and validity in a research setting. Connect 1984; 53: 2002-7 17. Schag, CC Heinricvh RL et al. Karnofsky Performance Status Scale: reliability, validity, guidelines. J. Clinical Oncol 1984: 2: 1987-93.

34 18. Outcomes Briefing Issue 4. UK Clearinghouse for health Outcome, Notfield Institute of Health, 1994. 19. Brazier, JE, Harper R et al. Validating the SF 36 health survey questionnaire— new outcome measure for primary care. BMJ 1993: 305, 160-4. 20. Lynns RA, Pery HM. Evidence for the validity of the short form 36 questionnaire (SF 36) in an elderly population. Age, Aging 1994: 23:182-4 21. Singleton N, Tuner A. SF 36 is suitable for elderly patients. BMJ 1993: 307: 1267 22. Radtke, HW. Serum erythrocyte concentration in chronic renal failure> Relationship to excretory renal function. Blood 54(4): 877-884, 1979. 23. Schwarts, AB, Kelch B et al. One year of RHuEPO therapy prolongs RBC survival and may stabilize RBC membranes despite natural progression of chronic renal failure to anemia and trend for dialysis. ASA 10 Trans 36 (3) M691-M696, 1990 24. Palenakp, VM, Sikole A: Is erythropoietin treatment a crucial factor for red blood cells. J A J. Nephro 7 (8): 1178-1188, 1996 25. Thomas MC, Mac Isaac RJ et al, Anemia in patients with type I diabetes. J Clinical Endocrine Metabolism 89 (9) 4359-4363, 2004.

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APPENDIX A Quality of life Questionnaire
PAGPAHANUGOT KA PASYENTE (CONSENT FORM) Pangalan : ____________________________________ Edad : ___________

Ginahatag ko ang pahanugot kay Dr. ______________________ nga amo ang duktor nga nagatuon nahanungod sa epekto sang erythropoietin sa kalidad sang kabuhi sa mga pasyente nga nagadialysis diri sa Iloilo Doctors Hospital Renal Care Unit. Ginapamatud-an ko subong nga: 1. Lubos ko nga naintiendihan ang ginahimo nga pagtulon-an nahanungod sini. 2. Ginpaintiende sa akon ang kaayuhan sang sini nga pag-tulun-an kag ang mayo nga igadulot sini sa pareho ko nga nagadialysis. 3. Ginhatagan ako sang tiyempo para makapamangkot nahanungod sa ini nga pagtuon. 4. Nakaintiende ako na wede ko bawion ang akon pagpahanugot sa maski ano oras kung gusto ko kag kung nabatyagan ko nga malain ini para sa akon.

________________________ Ngalan kag Pirma ka Pasyente/Tagapag-alaga

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Survey nahanungod sa Ikaayong-lawas sang mga pasyente nga naga Dialysis (SF36)
Today’s Date:_________ Name: Last:_______________________ First: _______________ Date of Birth: __________ Ang ini nga survey nagapangayu sang imu opinion bahin sa imo panglawason. Palihug sabat sang ini nga mga pamangkot. 1- Anu ang masiling mo parte sa imu panglawason?: 1. Excellente gid 2. Tama gid ka mayo 3. Maayu 4. medyo mayo man 5. Pigado gid 2- Ikumpara sang nagligad nga tuig, kumusta ang panglawasun mo? 1. Mas mayo kesa nagligad nga tuig 2. Maayu-ayo na lang kesa nagligad nga tuig 3. Daw pareho man lang 4. Mas malala kesa nagligad nga tuig. 5. Grabe gid kalala kesa nagligad nga tuig

3- Ang ini nga mga pamangkot parte sa mga ginaobra mo sa pang-adlaw-adlaw. May limitasyon bala ng imo pag obra sa mga pang adlaw-adlaw nga buluhaton? Mga bulohaton 1. Huo, 2. Huo, 3. Indi gid Limitado Medyo limitado, katama limitado masulhay gid a) Makapoy na mga bulohaton, pareho sang pagdalagan, 1. 2. Huo, 3. Indi pagpanghakwat sing mabug-at, isports? Huo, medyo gid limitado, limitado limitado masulhay gid katama b) Medyo makapoy na buluhaton, pareho sang pagtulod sang 1. 2. Huo, 3. Indi lamesa, panilihig o paghampang sang golf? Huo, medyo gid limitado, limitado limitado masulhay gid katama c) Pagpanghakwat o bitbit mga grocery? 1. 2. Huo, 3. Indi Huo, medyo gid limitado, limitado limitado masulhay gid katama d) Kung magsaka ikaw sa madamu nga hagdanan? 1. 2. Huo, 3. Indi Huo, medyo gid limitado, limitado limitado masulhay gid katama e) Kung magsaka ikaw sa isa lang ka hagdanan? 1. 2. Huo, 3. Indi Huo, medyo gid limitado, limitado limitado masulhay gid katama

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f) Pagduko, pagluhod? 1. Huo, limitado katama 1. Huo, limitado katama 1. Huo, limitado katama 1. Huo, limitado katama 1. Huo, limitado katama 2. Huo, medyo limitado 2. Huo, medyo limitado 2. Huo, medyo limitado 2. Huo, medyo limitado 2. Huo, medyo limitado 3. Indi gid limitado, masulhay gid 3. Indi gid limitado, masulhay gid 3. Indi gid limitado, masulhay gid 3. Indi gid limitado, masulhay gid 3. Indi gid limitado, masulhay gid

g) Paglakat sang sobra isa ka milya?

h) Maglakat sa mga balay sang imo kaingod?

i) Maglakat sa isa lang ka balay nga imo kaingod?

j) Ang pagpaligo mo o pag-ilis?

4- Sa sulod sang nagligad nga apat ka semana, may ara ka bala mga problema sa imo nga ikaayong-lawas? Yes No a) Limitado na bala ang tyempo sang pag-obra mo? 1. huo 2. Indi b) Limitado na bala ang mga buluhaton nga maobra mo? 1. huo 2. Indi c)Limitado ka man bala sa iban mo nga gina pang-obra? 1. huo 2. Indi d) Nabudlayan ka gid bala sa pag-obra? 1. huo 2. Indi 5. Sa nagligad nga apat ka semana, may mga problema ka bala nga nagadulot sa imo sang pagugtas o pagkasubo o pagka emosyonal? Yes No a) Gamay na lang bala ang tiempo sang pag-obra mo tungod 1. huo 2. Indi sang imo pagkaemosyonal? b) Gamay na lang bala ang buluhaton nga maobra mo tungod sa 1. huo 2. Indi imu pagka-emosyonal? c) Indi na bala mayo ang imo pang-obra tungod sa imo 1. huo 2. Indi pagkaemosyonal? 6. Sa sulod sang nagligad nga apat ka semana, grabe gid bala ang epekto sang imo ginabatyag sa imo relasyon sa imo mga abyan, kapamilya kag mga kakailala? 1. Daw wala man epekto 2. Gamay man lang 3. Tama-tama lang 4. Medyo may epekto 5. Grabe gid ang epekto 7. Ano gid kadaku ang sakit sa imo kalawasan sa sulod sang nagligad nga 4 ka semana? 1. Wala 2. Tuman ka diyutay 3. Gamay lang 4. Medyo lang 5. Masyado kasakit 6. Grabe gid nga kasakit

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8. Sa sulod sang nagligad nga 4 ka semana, naestorbo bala ang imo pang-adlaw adlaw nga buluhaton? 1. Wala gid 2. Gamay lang 3. Medyo lang 4. Daw naestorbo 5. Grabe gid 9. Ang ini nga mga pamangkot parte sa imo na ginabatyag sa nagligad nga apat ka semana. Sa nagligad nga apat ka semana, pirme ka lang bala… 1. Sa 2.Kalaba 3. Pirme 4. Kung 5. Daw tanan na nan nga lang kis-a lang wala man tiyempo tiyempo a) Puno sang kalipay kag 1. Sa 2. 3. 4. 5. Daw kaanyag? tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo b) May pagkanerbyos? 1. Sa 2. 3. 4. 5. Daw tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo c) Nagabatyag sang grabe nga 1. Sa 2. 3. 4. 5. Daw kasubo? tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo d) Nagabatyag sang 1. Sa 2. 3. 4. 5. Daw pagkasulhay kag katawhay? tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo e) Puno sang enerhiya? 1. Sa 2. 3. 4. 5. Daw tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo f) Nagabatyag sang depression? 1. Sa 2. 3. 4. 5. Daw tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo g) Grabe na pagpalamuypoy? 1. Sa 2. 3. 4. 5. Daw tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo h) Malipayon bala ikaw na 1. Sa 2. 3. 4. 5. Daw klase sang tawu? tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo i) Pirme bala ikaw ginakapoy? 1. Sa 2. 3. 4. 5. Daw tanan Kalaban Pirme lang Kung wala man nga an nga kis-a lang tiyempo tiyempo

6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid 6. Wala gid

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10. Sa sulod sang nagligad nga 4 ka bulan, ano kadaku ang tiyempo nga naistorbo ang imo pangabuhi sang mga problema mo sa ikayong-lawas kag mga problema emosyonal? 1. Sa tanan nga tiyempo 2. Kalabanan nga tiyempo 3. Kung kis-a 4. Gamay lang na tiyempo 5. Wala man 11. Ano kamatuod ang ini nga mga butang para sa imo? 1. Huo, 2. Malapit matuod sa gid ini kamatuoran a) May madasig ako magmasakit 1. 2. kesa sa iban nga tawu? Huo, Malapit sa matuod kamatuoran gid ini b) Maayo ang akon ikayong-lawas 1. 2. pareho sang iban? Huo, Malapit sa matuod kamatuoran gid ini c) Naga expectar ako na maglala 1. 2. ang akon ginabatyag? Huo, Malapit sa matuod kamatuoran gid ini d) Maayo ang akon ikaayong lawas? 1. 2. Huo, Malapit sa matuod kamatuoran gid ini Madamu gid nga salamat!  3. Wala ako kabalu 3. Wala ako kabalu 3. Wala ako kabalu 3. Wala ako kabalu 3. Wala ako kabalu 4. Daw indi man 4. Daw indi man 4. Daw indi man 4. Daw indi man 4. Daw indi man 5. Indi gid 5. Indi gid 5. Indi gid 5. Indi gid 5. Indi gid

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Patient Data Form A. Demographic profile: Name:______________________________________ Age:_____________ Sex:________ Hosiptal:___________________________________Date:____________________ Marital Status: Single:_____ Married:_______ Divorced:________ Widowed______ Occupation: Unemployed:_________ Semiskilled:_________ Senior Employee:_______ Level of Education: Nil: _____ Primary:_____ Secondary:______ Higher education:____ Duration of hemodialysis in years:______________ B. Laboratory profile: First Testing: Date:_________________ Serum creatinine (umol/L):____________________ Blood urea nitrogen (mmol/L):_______________________ Hemoglobin concentration:__________________________ C. HRQOL: Karnofsky performance score:_______________ SF-36:__________

Second Testing: (after 4 weeks from the first testing) Date:_________________ Compliance with erythropoietin: Good:____ Fair:_________ Poor:______ Serum creatinine (umol/L):____________________ Blood urea nitrogen (mmol/L):_______________________ Hemoglobin concentration:__________________________ C. HRQOL: Karnofsky performance score:__________________ SF-36:_______________

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