ADDIS ABABA UNIVERSITY

SCHOOL OF GRADUATE STUDIES

Prevalence and Risk Factors of Renal Impairment among Rheumatoid

Arthritis Patients Attending Outpatient Department of Tikur Anbessa
Specialized Hospital ,Addis Ababa, Ethiopia.

By: Bethelihem Jima

Advisor: Jigssa Girma (MSc, PHD fellow)

A Thesis submitted to the School of Graduate Studies,Addis Ababa University

in partial fulfillment of the requirements for the Degree of Masters in Clinical
Laboratory Sciences, Clinical chemistry specialty track.

June 2016

ADDIS ABABA UNIVERSITY

SCHOOL OF GRADUATE STUDIES
Prevalence and Risk Factors of Renal Impairment among Rheumatoid Arthritis Patients
Attending Outpatient Department of Tikur Anbessa Specialized Hospital Addis Ababa,
Ethiopia.

By Betelihem Jima
Department of Medical Laboratory Sciences, College of Health Science
Addis Ababa University
Approved by the Examining Board
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Chairman, Dep. Graduate Committee

Signature

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Advisor

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Advisor

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Examiner
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Examiner
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Acknowledgement

Nothing could have been done without the help of Almighty God. He saw and helped me in those
hard times. It is only through him that all things are possible.

I am heartily thankful to my advisor, Mr.Jiggsa Girma, Dr,Addisu Melkie and Dr.Yewendesen

Tesemma for giving me constructive ideas, comments and feedbacks in conducting this research.
What word can express the support and love I have got from my sister Eyerusalem Jima and her
husband Dr.Dellesa Bulcha. Without them I would not have been a person as I am today. Your
courage and commitment for me are kept in my mind to be never erased. I am forever indebted to my
family for their countless support, courage and outstanding commitment for my best. Their love and
unwavering faith in me keep me strong.

My deepest gratitude also goes to Mr. Gebeyehu Dejene for his unlimited support and courage.
Gebe I have no words saying than you are best!!
To all my friends and colleagues, I cannot name each and every one of you personally but Some of
you deserve mention.Mr.Mersha Worku, Amarech Taye and Misikir Mulugeta.

I am also grateful to my cousin, Mr. Damtew Negash for his insightful comments and suggestions on
my thesis.

Finally, I dont want to pass without mentioning the help and support I got from Tikur Anbessa
Hospital Laboratory staffs, and all nurses at Rheumatology Clinic including all study participants.

Table of Contents

Page

Acknowledgement ......................................................................................................................................... i
List of Tables ............................................................................................................................................... iv
List of Abbreviation...................................................................................................................................... v
Abstract........................................................................................................................................................ vi
1. Introduction............................................................................................................................................... 1
1.1 Background ......................................................................................................................................... 1
1.2 Statement of the Problem.................................................................................................................... 3
1.3 Significance of the Study .................................................................................................................... 4
2. Literature Review...................................................................................................................................... 5
3. Objective .................................................................................................................................................10
3.1 General Objective .............................................................................................................................10
3.2 Specific Objective.............................................................................................................................10
4. Method and Materials .............................................................................................................................11
4.1 Study Area ........................................................................................................................................ 11
4.2 Study Design and Study period......................................................................................................... 11
Study Period............................................................................................................................................ 11
4.3. Population ........................................................................................................................................ 11
4.3 1. Source of Population.................................................................................................................11
4.3.2 Study subject..............................................................................................................................11
4.4 Study Variables................................................................................................................................. 12
4.4.1 Independent variable ..................................................................................................................12
4.4.2 Dependent (outcome) variables ................................................................................................. 12
Inclusion criteria ................................................................................................................................. 12
Exclusion criteria ................................................................................................................................12
4.6 Sampling Technique and Procedure ................................................................................................. 12
4.6.1 Sample Size Determination........................................................................................................ 12
4.6.2 Sampling procedures..................................................................................................................13
4.7. Data collection procedures...............................................................................................................13
4.7.1. Demographic data .....................................................................................................................13
ii

4.7.2 Laboratory Data .........................................................................................................................14

4.8. Data management and Quality control.............................................................................................16
4.9 Data Processing and Analysis ........................................................................................................... 16
4.10. Ethical consideration......................................................................................................................17
5. Result of the Study.................................................................................................................................. 18
6. Discussion ...............................................................................................................................................27
7. Strengths and weaknesses of the study ................................................................................................... 31
Strength...................................................................................................................................................31
Limitations .............................................................................................................................................. 31
8. Conclusion and Recommendation .......................................................................................................... 32
8.1. Conclusion ....................................................................................................................................... 32
8.2. Recommendation .............................................................................................................................32
9. References...............................................................................................................................................33
10.Annexes..................................................................................................................................................38
Annex 1: Procedure for tests...................................................................................................................38
Annex 2...................................................................................................................................................41
Annex 3: English version of participant information sheet, consent and Questionnaire ........................42
Annex 4: Questionnaire ..........................................................................................................................45
Declaration..................................................................................................................................................48

iii

List of Tables
Table 1. kidney disease classification and result based on NKF classification, Kenya................. 7

Table 2. Socio demographic characteristics of respondents., Addis Ababa, 2016 ....................... 17

Table 3. Past history and clinical finding of the respondents, Addis Ababa, January 2016 ......... 20

Table 4. Laboratory and clinical finding of the respondents ........................................................ 21

Table 5. Kidney disease classification and result based on NKF classification, at TikurAnbessa
Hospital,Addis Ababa,January201623

Table 6. Drugs used for RA treatment Addis Ababa,January2016.............................................. .23

Table 7. Bivariate and multivariate analysis of factors on RA patients ...24

List of figure
Figure 1 prevalence of Renal Impairment among RA patients....................................22

iv

List of Abbreviation
ACR/EUARA

American Classification of Rheumatoid Arthritis disease and European league against

Rheumatology

AOR

Adjusted Odd Ratio

CVD

Cardio Vascular Disease

CKD

Chronic kidney Disease

DM

Diabetic Mellitus

DMARD

Disease modifying antirheumatic drugs

EDTA

Ethylene Di amine tetra acetic acid

eGFR

Estimated Glomerular Filtration Rate

ESRD

End Stage Renal disease

GFR

Glomerular Filtration Rate

GN

Glomerulo Nephritis

HTN

Hypertension

HU

Hematuria

KD

kidney Disease

NKF

National Kidney Foundation

NSAID

Non Steroid anti Inflammatory Drug

PU

Proteinuria

PI

Principal Investigator

RA

Rheumatoid Arthritis

RF

Rheumatoid Factor

RFT

Renal Function Test

SD

Standard Deviation

SOP

Standard Operating Procedures

SPSS

Statistical Package for Social Science

TASH

Tikur Anbessa Specialized Hospital

WHO

World Health Organization

Abstract
Background: The global burden of chronic degenerative disease is increasing worldwide. Most
developing countries have dual burden with infectious and non-infectious diseases. Kidney
Disease (KD) is a long term health condition and defined as the gradual loss of body and renal
function, death over time. Renal abnormalities were quite prevalent in Rheumatoid Arthritis
(RA) patients and there was significant increase of renal derangement with duration of disease
and severity of disease activity.

Objective: To determine the prevalence of renal impairment and to identify associated risk
factors on Rheumatoid Arthritis Patients at Tikur Anbessa Specialized Hospital(TASH).

Methods: A hospital based cross sectional study conducted from July 2015 to January 2016 at
Tikur Anbessa Specialized Hospital. The study participants were all patients with a diagnosis of
RA on follow up at Tikur Anbessa Specialized Hospital during the study period and having a
baseline data. The participants interviewed by trained data collectors using pretested and
structured questionnaires. Blood sample was collected for assessment of Urea and Creatinine.
Urine sample was also collected for protein and blood detection. Serum Creatinine was analyzed
by an automated biochemistry machine Mindray 200BS.Urine protein and blood was detected by
chemical test. Finally data was entered and analyzed through SPSS version 20 computer software
packages.
Result: Out of 219 RA patients, 49(22.4%) had renal impairment. Serum Creatinine level in
mg/dl of the patients were with mean and Standard Deviation (SD) of (1.67,0.47SD) with
Adjusted odd ratio(AOR)and(95%CI):14.07(5.09,38.91), Mean (SD) age of the participants
was 43.82 ( 14.03) years and about 75.3% were females. Protienuria 44 (20.1%) with AOR
(95%CI): 1.93(1.68, 5.58) and Body Mass Index (BMI) above 25 with AOR (95%CI): 0.1(0.02,
0.45). showed significant association with the prevalence of renal impairment.

Conclusion: The study revealed that the prevalence of renal impairment in patients with RA is
high. Screening for renal impairment for patients with RA will be very helpful to peak KD at
earlier stage.
vi

1. Introduction
1.1 Background
The global burden of chronic degenerative disease is increasing worldwide. Among those kidney
disease is an increasing global health problem [1]. Due to the fact that it is a silent condition, its
prevalence is considered to be under lo0estimate[2].According to World Health Organizations
(WHO) report,2003, the prevalence of impaired kidney function was estimated to range between
10% to 20% of the adult population in most countries worldwide [3,4].However, a recent study
suggests that the incidence of kidney disease is increasing globally [5]. Chronic kidney disease
(CKD) is reported to be 3-4 times more common in Africa than in developed countries[6].The
incidence of CKD in Ethiopia is rising because of increased risk factors such as RA, high blood
pressure and Diabetes Mellitus (DM) [7,8].

CKD is a long term health condition and defined as the gradual loss of renal function over time.
It has been estimated that more than 500 million individuals globally have CKD, defined by
either kidney damage or glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 [9].The main
epidemiologic significance of disease is due to asymptomatic chronic kidney disease patients in
the early stages of the disease process. However, even in asymptomatic patients, chronic kidney
disease may involve different organs which in turn might result in risk of cardiovascular
diseases, kidney failure, hospitalization and death since there is an increasing prevalence of
kidney disease worldwide [10].

Renal abnormalities were quite prevalent in RA patients and there was significant increase of
renal derangement with duration of disease and severity of disease activity [11]. The reported
kidney disease prevalence in patients with RA ranges from 5%-50% based on studies of different
designs and the true prevalence of kidney disease remains unclear [12].

The prevalence of Renal impairment among RA patients varies across the world from lowest
prevalence in developed nation and highest in Africa [13,14,15,16, 1].

The prevalence of KD is more in blacks than in their white counterparts [17,18]. The higher
prevalence among Africans has been attributed to genetic predisposition, low socio-economic
status and inequities in access to healthcare [19]. As reports of many researches reveal, RA
related kidney disease is one of the leading causes of chronic morbidity in the developed world,
but little is known about the disease burden in Africa [20,21].

Renal disease is a common cause of mortality in patients with rheumatoid arthritis. This may be
as a result of the disease itself, drugs used in treatment and other rheumatoid nephropathy
[7].Since RA patients have not experienced the same improvement in survival as the general
population, the mortality gap between RA patients and individuals without RA has widened [22].
This study is, therefore, meant to identify the magnitude of renal impairment among RA patients
attending at Tikur Anbessa Specialized Hospital.

1.2 Statement of the Problem

Rheumatoid Arthritis is a systemic and chronic inflammatory disease involving mainly the
peripheral joints of hands and feet initially [11].The inflammatory process regularly involves
solid organs, including kidney [11]. RA is characterized by persistent synovitis, systemic
inflammation, and auto antibodies that are associated with progressive disability, systemic
complications, early death and socioeconomic status [23].

What is more, RA is a heterogeneous and progressive autoimmune disease which affects all
ethnic groups throughout the world [24].The WHO considers it as one of the diseases with the
greatest impact on society [25]. And it is the 42nd highest contributor to global disability [26]. It
is also important to note that RA has been recognized as being uncommon in Africa for a long
time [27].Studies revealed that RA is increasing in frequency in East, Central and South Africa
[28,29]. A recent systematic analysis has shown a significant rise in the estimated crude
prevalence of RA in Africa based on the available studies was 0.36% in 1990, which translates
to a burden of 2.3 million affected individuals in 1990. Projections for the African population in
2010 based on the same prevalence rates would suggest a crude prevalence of 0.42% and the
burden increased to 4.3 millions [30].

RA is often seen as a minor health problem and has been neglected in research and resource
allocation throughout Africa despite its potentially fatal systemic manifestations [30].This is also
true in Ethiopia, which implies that awareness creation on the disease burden and disease process
is necessary.
The prevention and management of RA could help reduce other related disease by reducing
shared risk factors and prevalence of systemic manifestations like CKD which is serious health
problems but treatable disease if caught in the early stages [10].
If patients take the treatment without knowing they have kidney disease, it cause series health
condition so, early diagnosis is important. Some of the drugs used for treatment of RA have
severe toxic effects on the kidney even in patients with only mild renal insufficiency and
therefore require dosage adjustment [7].So assessment of kidney function using different
3

laboratory diagnosis system in patients with RA is necessary for appropriate choosing and dosing
of drugs.

1.3 Significance of the Study

Over all the topic has inevitably value for clinical diagnosis and monitoring of RA patients with
early or mild kidney progress to prevent further damage. Therefore this study will use as baseline
survey on the magnitude of renal dysfunction in RA patients as well as associated factors. And
also inform on modes of intervention. Knowledge of the prevalence of renal disease in RA
patient will also useful in order to provide locally applicable data. Knowing the risk factor and
creating awareness may also provide a means of optimizing care. So, this research would help in
identifying key gaps and provide a good means of understanding the disease and the associated
risk factors in the treatment courses.

2. Literature Review
Reported kidney disease prevalence in patients with RA ranges from 5%-50% based on studies
of different designs though the true prevalence of kidney disease remains unclear [12].The
prevalence of KD among RA patients varied across the world from lowest prevalence in
developed nation and highest in Africa ranking from 3%, 9%, 12.75%, 18% and 28%
respectively[13,14,15,16,1]. In the Kenyan study, the risk of CKD among RA patients was 28%
which shows potentially systemic manifestations burden [1].
Retrospective review was done in America in 2014 to identify if RA is associated with a variety
of kidney disorders on 813 patients with RA and 813 non RA individuals [31].According to the
researchers finding the 20 years cumulative incidence of reduced kidney function was higher in
patients with RA compared with non RA participants for eGFR<60mL/min/1.73m2 (25% vs
20%; P= 0.03) [31].The pathogenesis of renal involvement in RA patients is less clearly
understood; however a high prevalence of renal impairment with evidence of reduced GFR and
tubular dysfunction in RA patients is well documented [31].The researchers defined reduced
kidney function as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 [12].
Age is one of important predictors of chronic degenerative diseases. Most prevalence of chronic
disease was higher among elders [1].According to the 2003 World Health Report, the prevalence
of impaired kidney function was estimated to range between 10% and 20% of the adult
population in most countries worldwide[3,4].
Studies revealed that the mean age of RA varies from continent to continent in Kenya,France,
USA and England which was 48.7, 55.2, 56 and 61.6 average years of age respectively
[1,15,14,32]. Age and other co-morbid conditions like diabetes and hypertension also have a
negative impact on their kidney function [1]. Studies done in Helsinki and Russia show that age
of RA patient cohorts in the studies were significantly associated factors with reduced GFR [33].
This shows that the mean age of the disease morbidity is smaller in Africa than white developed
nations which are translated into social and economic disparities, leading to a special
vulnerability of young Africans.

Rheumatoid arthritis is a disease that predominantly affects females [1]. It is a neglected

tragedy a tragedy in terms burden of the problem [34].According to study in Kenya, the RA
prevalence among Male to Female was 1:8 ratio [1].Study done in Helsinki and Russia revealed
that Female sex was significantly associated with renal impairment [33]. RA is more common in
females; extra-articular manifestations are more common in males and affect about 40% of
patients with a diagnosis of RA [35].
A variety of renal disorders can occur in patients with RA due to the underlying disease to drugs
used to treat the inflammatory process and to concurrent renal disease unrelated to RA which is
more likely [36].Some of the drugs used to manage the problems might have nephrotoxic. There
were also other numerous potential causes of nephropathy in RA, the likes of Nephrotoxicity of
disease-modifying anti rheumatic drugs (DMARDs), non-steroid anti-inflammatory (NSAID)
and analgesic drugs [37].NSAIDs are commonly used in rheumatoid arthritis [38].
Methotrexate is an anti metabolite and a folate analogue.It works via its anti inflammatory
effects and is mainly excreted through the kidney [39]. The pharmacokinetics of low dose
Methotrexate are said to be unpredictable and variable even in patients with normal renal
function [32]. In those with underlying renal dysfunction or those who use Nephrotoxicity drugs
there is decreased renal excretion and serum accumulation of methotrexate with consequent
adverse effects [40].
The dosage of RA related drugs used in patients with renal insufficiency will therefore frequently
require dosage reduction to avoid severe toxicities [15]. Reduced GFR below 60 ml/min/1.73m2
has an essential influence on selection and dosage of medications to avoid adverse events and
further damage to kidneys [12]. Drugs resulted in a raised serum Creatinine concentration in 8 of
14 patients [41].
The incidence of Hematuria at entry did not differ among patients who had been treated with
non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In
some patients with isolated hematuria, the hematuria appeared when the activity of RA was high
and resolved when it was low and 6% presented elevated serum creatinine during a 42 month
observation period [41].Majority of the patients (86.5%) were on at least one DMARD. Use of

NSAIDs and /or prednisone was very frequent (88.5%).Median duration of disease since time of
diagnosis was 4 years [41].
Kidney disease is classified based on cause, estimated glomerular filtration rate (eGFR) category
and albuminuria category. The criteria used are eGFR less than 60 ml/min/1.73m2 (GFR
categories G3aG5) or markers of kidney damage (albuminuria, urine sediment abnormalities,
electrolyte and other abnormalities due to tubular disorders, abnormalities detected by histology,
structural abnormalities detected by imaging and history of kidney transplantation [42]. It is
classified as in table 1 below which was adopted from the Kenyan study [1].

Table 1. Kidney disease classification and result based on NKF classification, Kenya
CKD

Description

Range

Prevalence

G1

Normal or high

Greater than 90

1.8%

G2

Mildy decrease

60-89

3.2%

G3a

Mildy to moderately
decreased

45-59

7.7

G3b

Moderately to
severely decreased

30-44

G4

Severely decreased

15-29

G5

Kidney failure

Less than 15

0.35

Another Prospective cross sectional research was done in British in 2008 on renal insufficiency
(MATRIX) study of 129 patients. Serum Creatinine was normal in 81.4% of the 129 patients
included. According to the National Kidney Foundation (NKF) classification, the distribution by
stage of KD was, using the aMDRD and CG formulae, as follows: stage 1: 11.3% and 11.4%;
stage 2: 20.0% and 20.3%; stage 3: 15.0% and 24.1%; stage 4: 0% and 1.3%; stage 5: 0%.
Proteinuria, hematuria and leucocyturia were observed in 16%, 17% and 20% of the patients,
respectively. Using the MDRD and CG formulae, 36% and 38% of the prescriptions made in
patients with glomerular filtration rate (GFR) <60 ml/min required a dosage adjustment (15).

Hematuria, Proteinuria and Creatinine are sighing of abnormal clinical findings. The clinical
finding shows that Hematuria and Proteinuria were 9(4.1%) and 44(20.1%) and Proteinuria and
hematuria, as detected by urine dipstick analysis, is suggestive of glomerulonephritis (GN) and
massive protein urea is a hallmark of membranous lupus nephritis, amyloid-A amyloidosis or
certain drug toxicities[ 36].

Serum Creatinine is the most commonly used parameter for renal excretory function and is
therefore used to predict the GFR [43]. Amyloidosis is the term for diseases caused by the
extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Secondary
amyloidosis occurs in the setting of chronic inflammatory or infectious diseases [30].

Rheumatoid Arthritis is one of the commonest causes of secondary amyloidosis [20].which is

said to be one of the most severe complications of RA due to its risk of progression to End Stage
Renal Disease (ESRD) [21]. Amyloidosis is more common in patients who have severe, poorly
controlled, Sero-positive and long standing illness [44]. It has been reported to be a cause of
death in 9.5% of RA patients [33].Other studies have attributed amyloidosis to 5-17% of RA
deaths [21]. Unfortunately it may go clinically undetected in up to 50% RA patients [21]. Until
they develop kidney dysfunction in the form of proteinuria, deranged creatinine levels or endstage renal failure [45].

Proteinuria and Hematuria, combined have been associated with an increased mortality rate in
RA patients and they indicate the disease burden and amyloidosis due to the drug effect So,
precise determination of these parameters are important [46]. The incidence of hematuria at
entry did not differ among patients who had been treated with non-steroidal anti-inflammatory
drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated
hematuria, the hematuria appeared when the activity of RA was high and resolved when it was
low and 6% presented elevated serum creatinine during a 42 month observation period
[47].Duration of the disease has significant effect on KD. Health seeking behavior of most the
patient has also the problem to attend modern health care. The lay-health culture presumably has
substantial effects on utilization of health services in regions of the country where poverty and
illiteracy are widespread [48].
8

Cultural norms and beliefs have been shown to delay and sometimes stop from modern health
care. This might give the chance of systemic disease progression to affect organs like kidney.
The longer duration of RA disease exposure has more likely has KD. According to a study in
India, which matched two group of study, it was revealed that group study whose disease
duration was above five years significantly associated with renal impairment than group who has
disease duration of two to five years [49]. According to different studies the average duration of
the disease varies considerably. The Kenyan study shows that the median duration of the disease
since time of diagnosis was 4 years [1]. Renal abnormalities were quite prevalent in RA patients
and there was significant increase of renal derangement with duration of disease and severity of
disease activity [1].

Most of the time duration of disease on set and duration of treatment started was not the same.
According to study in south Africa, late coming for modern health care after trying traditional
healer, spiritual care, habitual consumption of analgesics and disease progression was common
[50].Late coming of the patient might advance the disease progress and of course this begets the
management more complex and enforces to use more drugs. This is true in all countryside of
Ethiopian and it is also supported by different authors. They cited the habitual consumption of
analgesics or analgesic abuse as contributing to the increasing nephrotoxicity contributes to high
prevalence of CKD [50]. The effects of kidney dysfunction in RA are adverse. A low eGFR
increases cardio-vascular disease (CVD) risk and vice versa [1].

3. Objective
3.1 General Objective
To determine the prevalence of renal impairment and identify associated risk factors in patients
with Rheumatoid Arthritis.

3.2 Specific Objective

The specific objectives of this research are to:
i.

Assess the level of serum Creatinine, Urea, Hematuria and Urine protein among RA
patients.

ii.

Determine different stages of renal problem among RA patients.

iii.

Identify associated risk factors that lead to renal problem among RA patients.

10

4. Method and Materials

4.1 Study Area
This study was conducted at Tikur Anbassa Teaching and Specialized Hospital which is located
at Lideta sub city, Addis Ababa, Ethiopia. It is one of the largest general public hospitals under
the Federal Ministry of Health located in Addis Ababa and also it is the training center for
undergraduate and postgraduate medical students, dentists, nurses, pharmacists, laboratory
technicians and others who shoulder the health problems of the community and the country at
large. It also gives patient diagnostic service for many people in the community.

The hospital is selected as study site for it is the only specialized referral hospital in Addis Ababa
involved in the diagnosis and treatment of RA patients.

4.2 Study Design and Study period

Study Design
A hospital based cross sectional study.

Study Period
This cross sectional study was conducted for a period of 6 months from July 2015 to January
2016.

4.3. Population
4.3 1. Source of Population

All Patients with rheumatology case seen at the rheumatology clinic during the study period
4.3.2 Study subject

All patients with confirmed RA case who have seen at Tikur Anbessa Specialized Hospital
during the study period and having a baseline data.

11

4.4 Study Variables

4.4.1 Independent variable
Independent (determinant) variables include age, sex, weight, smoking, obesity, urine blood and
medication use in the treatment course.
4.4.2 Dependent (outcome) variables
Creatinine,
Urea, and
Estimated GFR
4.5 Inclusion and Exclusion criteria

Inclusion criteria

Patients with RA having greater or equal to 18 years

Adiagnosis of rheumatoid arthritis by a physician using the 2010 ACR/EULAR

classification criteria for RA(annex 2)

Follow up for greater or equal to one year duration.

Base line laboratory data

Provide consent to participate in the study was included.

Exclusion criteria

Patients with known Diabetes Mellitus, Hypertension, Human Immuno Deficiency Virus, and
pregnancy at the time of study were excluded.

4.6 Sampling Technique and Procedure

4.6.1 Sample Size Determination

The sample size is calculated based on single sample size estimation. The value of p is taken
considering 95% confidence interval, 5% margin of error and; the value of p taken was 18%
from the previous study conducted on prevalence of KD on RA patients [51]. The sample size is
calculated using the following standard formula.
12

The sample size n= z (2)2p (1-p)/d2

Where n = Sample size
z (2 )2 =At 95% confidence interval Z value ( = 0.05) = 1.96
p = Proportion of occurrence of the event to be studied
d= Margin of error at (5%) (0.05)
n = (1.96)2 .0.18(1-.18)/(0.05)2
n=227
As computed above, the sample size for this study is 227 .However, we were only able to obtain
219 samples in the given time frame
4.6.2 Sampling procedures
Consecutive sampling technique was employed to include study participants who meet the
inclusion criteria during the study period.

4.7. Data collection procedures

4.7.1. Demographic data
Demographic characteristics and exposure to risk factors
Data collectors or nurses was identified, trained and informed to collect the data as per the prestructured questionnaire. The purpose of the study as well as any related harm and benefit was
explained to the study participants accordingly. Demographic data and potential risk factor of
RA like Cigarette smoking, habit coincident remote site infections and other risk factors were
recorded. (Annex 3).

13

4.7.2 Laboratory Data

i) Blood Sample
During the study, blood sample was collected by using sterile needle, taken carefully, from those
patients that come to rheumatology clinic and screened for RA by physician. Cooler
Boxes with ice packs were used for temporary storage until the sample reach to laboratory.
Samples were delivered to the laboratories at the end of the days collection. Analysis was done
immediately after delivery.
ii) Urine sample
A minimum of 10mls of urine sample was collected by using sterile, capped urine collection.The

urine sample was analyzed for PU and HU at the clinic by dipstick. Results obtained were
recorded immediately during the study performed.
Transportation of specimens: following collection from patients, specimens was transported
carefully to clinical chemistry laboratory within 30 minutes.
Sample processing
Serum Urea, creatinine was determined and finally estimated glomerular filtration was calculated
using CG formulae and urine protein and blood was determined using Urine strip method. Serum
creatinine was analyzed in the renal unit laboratory using the Mindray 01 which is an automatic
biochemistry analyzer and also Urine analysis was performed by the principal investigator(PI) at
the site of collection using the urine chemical test. It was assessed of with the parameters on a
colored visual scale.

Creatinine determination
Method
Modified Jaff method
Reaction Principle
Creatinine + Picric acidCreatinine Picric acid complex
14

At an alkaline solution, creatinine combines with picric acid to form an orange red colored
complex. The absorbency increase is directly proportional to the concentration of creatinine at
505nm wave length.(annex1).

Serum urea determination

Method
Berthelote enzymatic colorimetric method
Principle
Urea

Urease

(NH4+) 2 + CO2

NH4+ + salycilate + NaC1O

nitroprusside Indophenol

The intensity of the color formed is proportional to the urea concentration in the sample at
340nm wave length.
Estimation of GFR: Monitor GFR
Using Cockcroft Gault formula
CG formula: GFR (ml/min) = k (140 age) body weight/SCr (in mol/l). Where, k = 1.04
(female) or 1.23 (male).
KD prevalence was estimated from apparent kidney damage and kidney function and categorized
according to the NKF classification as follows[53].

Stage 1: GFR 90 ml/min: normal Renal Impairment.

Stage 2: GFR 6089 ml/min: mild renal impairment.

Stage 3: GFR 3059 ml/min: moderate renal impairement.

Stage 4: GFR 1529 ml/min: severe renal impairment

Stage 5: GFR <15 ml/min: kidney failure.

15

Urinary protein and blood determination

Test principle for urine protein and blood.
Blood: This test is based on the peroxidase like activity of hemoglobin, which catalyzes the
reaction of diisopropylbenzenedihydroperoxide and 3, 3, 5, 5tetramethylbenzidine. The
resulting color ranges from orange through green and very high levels of blood may cause the
color development to continue to blue (annex 1)

Protein: This test is based on the protein error of indicators principle. At a constant pH, the
development of any green color is due to the presence of protein. Colors range from yellow for
Negative through yellow green and green to green blue for Positive reactions.(annex 1)

4.8. Data management and Quality control

Data quality was ensured through use of standardized data collection materials, pretesting of the
questionnaires, proper training before the start of data collection and intensive supervision during
data collection by the principal investigator. For laboratory analysis Pre analytical, analytical and
post analytical stages of quality assurance that is incorporated in Standard operating procedures
(SOPs) of the Tikur Anbessa clinical chemistry laboratory was strictly followed. In addition,
well trained and experienced laboratory professionals were participate in the laboratory analysis
procedure.

4.9 Data Processing and Analysis

Data entry and analysis was done using SPSS statistical software version 20.The descriptive
statistics was calculated & logistic regression analysis was done. Variables that show a
significant association were selected for further analysis. In all cases P-value less than 0.05 was
considered as statistically significant. The strength of the association was interpreted using an
odds ratio in a 95% confidence interval. Finally, the results were presented using figures, and
tables.

16

4.10. Ethical consideration

This research project was approved by Departmental Ethics and Research committee of the
Department of Medical Laboratory Sciences, Collage of Health Science and School of Allied
Health Science of Addis Ababa University. Permission was obtained from TikurAnbessa hospital
administrator. Only subjects who gave informed consent were enrolled. Information gathered
from the study participants are kept confidential. Only blood samples intended for study were
drawn and thereafter discarded after analysis. The study results shall be disseminated to health
care providers to aid in patient care.

17

5. Result of the Study

Out of 227 sample size, 219(96%) of respondents who had at least one year follow-up at
rheumatoid clinic at Tikur Anbessa Specialized and Teaching Hospital were identified and
participated in the study. 219 respondents were interviewed.

83(37.9%) of the respondents were in the age range 25-39 years and 78(35%) were in age range
of 40-59, while 36(16.4%) were above 59 and 22 (10%) were in the age range of 15 to 24.
The mean age of the respondents was 43.82 years with Standard Deviation (SD) of 14.03.
Majority of respondents were 123(56.2%) from Amhara ethnic group. Regarding education
status 50(22.8%) were illiterates (unable to read and write), 53(24.2%) have attended primary
education, 60(27.4%) were in secondary education, and 56(25.6) have attended college or
university level education.

Table 2. Socio Demographic Characteristics Of Respondents, Addis Ababa 2016

Variables

Frequency

Percentage(%)

15-24

22

10

25-39

83

37.9

40-59

78

35.7

>60

36

16.4

Un married

55

25.1

Married

120

54.8

Other**

44

20.1

Unable to read and write

50

22.8

Primary

53

24.2

Age

Marital Status

Level of Education

18

Secondary

60

27.4

Collage/University

56

25.6

165

75.3

54

24.7

Yes

53

24.2

No

124

56.2

Sometimes

42

19.2

Amhara

123

56.2

Oromo

53

24.2

Tigray

13

5.9

Others

30

13.7

Sex of the respondent

Female
Male

Alcohol

Ethnicity

NB ** Divorced, widowed, Separated

Majority of the study participants 189(86.3%) had belief that the cause of the disease were
unknown. While others 30 (13.7%) had strong believe that the cause of the disease reported as
cold , curse , some viral disease and others. Vast majority of the respondents 128(58.4%) , 54
(24.7%) and 37(16.9%) live with the disease for the last one to five years, 6-10 and greater than
ten years respectively. The study revealed that 43(19.6%) respondent have been reported RA in
the family history.

19

Table 3. Past history and clinical finding of the respondents, Addis Ababa, January 2016
Variables

Frequency

Percentage

189
30

86.3
13.7

43
176

19.6
80.4

26
193

11.9
88.1

23
159
37

10.5
72.6
16.9

62
15
58
10
6
32
36

28.3
6.8
26.6
4.6
2.7
14.6
16.4

128
54
37

58.4
24.7
16.9

67
63
63

30.6
28.8
28.8

Perception on the cause of the disease

Unknown
Other cause
Having RA family history
Yes
No
Smoking History
Yes
No
Having Regular Exercise
Yes
No
Sometimes
Work History of the respondent
Government
Farmer
Housewife
student
House made
private
No work
Disease Duration
1-5years
6-10 years
>10 years
Respondent Income
Dependent
<1000birr
1001-3000birr

20

>3000birr

26

11.9

Table 4. Laboratory and clinical finding of the respondents, Addis Ababa, January 2016
Variables

Frequency

Percentage(%)

<15

1.4

15-29

3.7

30-59

38

17.3

60-90

80

36.5

>90

90

41.1

Abnormal

72

32.9

Normal

146

67.1

>50

1.8

<10

24

11

10-50

191

87.2

1+

44

20.1

<1

175

79.9

1+

4.1

<1

210

95.9

GFR result in ml/min

Creatinine(mg/dl)

Urea(mg/dl)

Urine Protein

Hematuria

21

As presented in the table 4 above, Majority of the respondent 90(41.1%) and 72(32.9%) have
greater than 90 and 60-90 GFR result. 175(79.9%) and 146(67.1%) have normal urine protein
and creatinine level which is less than one respectively. Majority 101(46.1%) and 17(7.8%) of
the respondent have been developed deformity and swelling, while other have been reported
normal body functions.
Figure 1. Prevalence of Renal Impairment among RA patients,Addis Ababa,January 2016

22%
eGFR Less than 60 ml/min
eGFR greater than 60
ml/min
78%

The prevalence of 22.% with mean and SD[1.78.418SD]

Table 5. kidney disease classification and result based on NKF classification, at

Tikur Anbessa Anbessa Hospital,Addis Ababa,January2016
GFR CATAGORIES(ml/min)

Description

Percentage(%)

Stage 1
Stage2
stage 3
stage4
stage5

Normal renal impairment

Mild renal impairment
Moderate renal impairment
Severe renal impairment
Kidney failure

41.1
36.5
17.3
3.7
1.4

(GFR 90ml/min)
(GFR 60-89ml/min)
(GFR 30-59ml/min)
(GFR 15-29 ml/min)
(GFR <15 ml/min)

22

Table6,Drug Used for RA Treatment, at Tikur Anbessa Specialized Hospital,Addis

Ababa,January2016
Variables

Frequency

Percentage

Types of Medication used in the management

1.Prediensolon,methotriexate,Indomethacin 89
andothers

40.6

27

12.3

30

13.7

54

24.7

2.7

13

5.9

<5

125

57.1

6-10

56

25.6

>10years

38

17.3

2.prediensolon
3.Indomethacin
4.otherNSAID+Prediensolon
5.PrediesolonandMethotriexate
6 Methotriexate

Duration of Medication Taken

NB:-**** other medication mean that medication used to manage other co-morbidity
disease.
Most of the respondent 125(57%) had been on taking medication for less than one years while
17.3% taking different medication above ten years. The frequency of prediensolone,
methotreixate, indomethacine and others 89(40.6%).

23

Table 7.Bivariate and Multivariate analysis of factors associated with Renal Impairment on
RA patients, at TASH ,January 2016,Addis Ababa
Factors

Crude OR

Adjusted OR

eGFR

eGFR

P value

OR

95%CI

Pvalue

OR

95%CI

ml/min

ml/min

<60

>60

>59

21

0.02

7.14

(1.45,35.29)

0.02**

24.15

(2.09.279)

40-59

16

67

0.01

4.23

(1.72,10.41)

0.05**

3.22

( 1.04,10.24)

25-39

16

62

0.12

1.94

(0.85,4.45)

0.02**

3.97

(1.22,12.94)

18-24

16

20

Female

44

121

0.01

3.56

(1.33,9.52)

***

****

***

Male

49

43

89

0.01

6.52

(2.64,12.05)

0.01

8.16

(2.38,28.05)

81

Age

Sex

No.of
medicati
on

Duration
ofmedica
tion

24

>10

10

28

6-10

47

1-5

32

93

0.01

4.20

(2.01,8.57)

***

***

***

4.20

(2.01,8.57)

0.02*

1.93

(1.68,5.53)

Urine
Protein
1+

20

24

0.01

<1

29

146

<18.5

20

31

18.5-24.5

24

108

0.57

0.73

(0.08,0.75)

***

***

***

>25

31

0.01

0.25

(0.26,2.06)

0.03*

0.1

(0.02,0.45)

BMI

NB:* significant < 0.01, ** significant < 0.05, *** Not significant
Multivariate logistic regression analysis carried out by using a model of Hosmer-lemeshow
goodness of fit test and Enter modal to determine the most important statistically significant
variables to look for strength of association.
Result from Bivariate analysis revealed that renal impairment associated with age of the study
participant, Sex, type of medication taking, duration of medication taken, urine protein and BMI
significantly. Out of the total covariate shows significant association in the bivariate age of the
study participant, Sex, type of medication taking, duration of medication taken, creatinine level,
urine protein and BMI significantly associated with renal impairment. But Sex and duration of
medication taken were not show statically significant association in the multivariate analysis.
Age of RA patient was one of strong factors associated with Renal Impairment. The study
shows that older age greater 59 years old AOR (95%CI): 24.15(2.09,279) p value 0.02 , age 4059 AOR (95%CI): 3.22 (1.01,10,234), age 25-39 AOR (95%CI): 3.97 (1.22,12,936) were more
likely developed renal impairment than younger (15-24) respectively.
25

Medication also matter on the problem of renal impairment but patient who have taken more
than two type of medication had 8.16 times more likely to develop renal impairment than who
has taken one type of NSAID's or Methetroxin or predinsolon drugs or other steroidal drugs
AOR (95%CI): 8.16(2.38, 28.05).
The level of Urine protein as determined by dipstick was associated with the degree of renal
impairment. Urine protein level greater than one AOR (95%CI): 1.93 (1.68, 5.53) were more
likely developed KD than protein level less than one.

Body mass index of RA patient was one of strong factors associated with Renal impairment.
The study shows that those who has BMI greater 25 AOR (95%CI):0.01 (0.02, 0.45), p value of
0.03 less likely develop renal impairment.

26

6. Discussion
Prevalence value of 22.4% renal impairment was observed in this study. This is higher than
previously done researches which resulted 18%[16]and12.75% in Europe [15].However, it is a
bit lower than similar study conducted in Kenya resulted 28%[1].This might have happened
because of the sample size considered in the Kenyan study was half lower than this study and the
majority of the study participants age distribution in this study were older than 40 years of age
114(52%)with mean age 43.82 years and SD of 14.03 which is significantly lower than related
studies conducted abroad. The study subjects considered in our study were younger than subjects
participated in related studies in Kenya, France, USA and England with a mean age of 48.7,
55.2, 56 and 61.6 years respectively [52,15,14,and 32] and nearly one fourth 91(41.6%) have
been living with RA for the last 6 to 40 years.

The higher prevalence of KD among Africans has been attributed to genetic predisposition, low
socio-economic status and inequities in access to health care [19]. This is possibly supported by
majority 130(59.4%) of study participants have no income or less than1000 birr per month.

Duration of disease and first visit of modern health care registered with mean of 7.32 and 1.38
respectively. This shows that health seeking behavior of study participant significantly varies
from the Kenyan study [1]. High incidence of KD in our study might be explained by late
coming of patients to modern health care treatment after attending traditional healer, spiritual
care, habitual consumption of analgesics and disease progression.

The finding of this research revealed that age of study participant was one of strong predictors
associated with KD. This is consistent with studies in [1,15,16].And the older the patient the
significant is the risk propensity of KD than younger age. This might possibly be explained by
the fact that old age is a known independent risk factor for KD. As age increases there is a
gradual decrement in the nephrons number and associated decline in GFR. The average RA
patient has approximately 1.6 co-morbidities and the number increases with the patient's age may
be expected more[15]. And a variety of renal disorders can occur in patients with RA due to the

27

underlying disease to drugs used to treat the inflammatory process and to concurrent renal
disease unrelated to RA which is more likely in elderly patients [22].

Drug-induced protein urea was associated with age over 50 years and elevation of C-reactive
protein levels [36]. Even though we did not include HTN and DM, other studies shows that the
prevalence of hypertension and diabetic mellitus among RA patients are higher as compared to
age and sex matched controls a finding in the general population[52].

The study shows that sex of study participant was not significantly associated in multivariate
analysis. This is against study in Helsinki and Russia [33].This might be possible explained by
age of female study participant even if the incidence of RA was common among female sex .The
prevalence of KD in Helsinki significantly associated with the problem than this study. This
might be because of the fact that the mean age of study participants in Helsinki was higher than
this study. The mean age of this study is less than other similar studies done [1,15,14,32,33].

Duration of medication taken so significant in the Bivariate analysis were not as such significant
in the multivariate analysis but patient who have taken more than two type of medication were
more likely to develop renal impairment. This is inconsistent with Kenyan study[1].In our study
RA patients who have been taking combination of three type medication like that of
Predinsolon, Methotrixate ,Indomethaxin and other were significantly associated with renal
impairment. Use of either one or combination of two Predinsolon, Methotrixate, NSAIDs was
not correlated with renal impairment. And lack of association might be explained due to drug
compliance by our study population although this was not assessed by this study [1]. Since this
cross sectional study affected by chicken-egg dilemma or can't establish cause effect
relationships we are not able to establish cause of renal impairment among the drugs.

The association might be confounded by habitual analgesic intake for management of pain which
un prescribed by clinician[50].This is true in all countryside of Ethiopia and it is also supported
by different authors who have cited the habitual consumption of analgesics or analgesic abuse as
contributing to the increasing nephro toxicity contribute to high prevalence of KD [50].

28

Finally other possible general explanation might be the attributed by other drugs use manage for
co-morbidity in RA patients, more number of drugs shows that disease severity in RA was
uncontrolled disease activity. The fact that a given patient uses poly-pharmacy could indicate
that the disease is uncontrolled or the time of the drug combination is delayed and enhanced
disease activity and renal injury.

The blood urea was 28(12.8%) and it was not significantly associated with renal impairment.
Concomitant elevations of blood urea imply renal excretory failure but only at an advanced stage
of kidney damage [36].

Hematuria, Proteinuria and creatinine are sign of abnormal clinical findings. The clinical finding
shows that hematuria and proteinuria was 9(4.1%) and 44(20.1%) respectively and Proteinuria
and hematuria, as detected by urine dipstick analysis, is suggestive of glomerulonephritis (GN)
and massive protein-uria is a hallmark of membranous lupus nephritis, amyloidal-A amyloidosis
or certain drug toxicities[36].

Abnormal Serum Creatinine level of the study was 72[32.9%].Most studies shows that
creatinine is not credible measurement However, the use of serum concentration of creatinine as
an index for the GFR [53].

Urine protein level was one of factors correlated with renal impairment in this study. This is
similarly to study done South Africa and Finland to [7,50]. Macro protein in the urine is one of
sign glomerular injury according to different studies. Production of protein in the urine
(proteinuria) might be explained by systemic RA related vacuities, glomerular injury and micro
vascular injury related to co-morbid chronic medical conditions so ,the longer the duration of
proteinuria is the more the KD progression [44,53,54,55].

High value BMI is one of basic parameter used to measure risk chronic degenerative disease like
HTN, DM and then consequently CKD. But according to this study participant with BMI greater
than 25 were less likely develop renal impairment. It was found to be statistically significantly
associated with renal impairment in this study. This is inconsistent with study in South Africa
29

[50].This is possibly explained by the inverse relationship of BMI and eGFR calculation. Even
if the association of BMI and renal impairment are statistically significant in this study it is not
enough to establish cause effect relationship and biological plausibility.

30

7. Strengths and weaknesses of the study

Strength

The study is conducted using adequate sample size, good sampling technique and
procedures like selection bias was minimized

Pretested data collection tool was utilized

Adequate training was given to data collectors

The study was conducted with strict and Strong supervision.

Limitations

Since the study was cross-sectional, due to its inherent behavior, it can't establish exact
cause and effect relationship.

The association of

Sero positivity with renal impairment was not assessed and

prevalence of chronic medical conditions were also incorporated into the study.

Because it was a cross sectional, we cannot ascertain whether the patients have stable
creatinine.

The GFR calculating formulae are known to perform differently among different ethnic
groups and are not validated among Ethiopians.

We have used previous physician clinical assessment and diagnosis to enroll patient as
having RA. Some non-RA patients with other rheumatologic problems might be included
as RA.

31

8. Conclusion and Recommendation

8.1. Conclusion
The study indicates that the prevalence of renal impairment among study participants was high.
Though Proteinuria can be from different causes, Proteinuria is a marker of progression in renal
impairment.

Old age is a known independent risk factor for renal impairment irrespective of the underlying
disease. As age increases there is a gradual decrement in the nephrons number and associated
decline in GFR. What is more, above three listed drug taking, protienuria and BMI were found to
be significantly associated with renal impairment. This still implies that patients with rheumatoid
arthritis require screening for kidney disease, regular monitoring of progression and initiation of
appropriate management especially with long-term follow up.

8.2. Recommendation
Based on the finding of this study due attention should be given for RA patients.
Use of drugs that increase the risk of KD like NSAIDS needs to be reduced among
patients with RA.
Early screening to detect KD so that treatment to mitigate progression can be initiated.
Awareness creation programs should be initiated to medical practitioners and the
population at large about RA disease burden and disease process.
Patient medical record system should be improved.
More studies should be done because data on renal impairment in rheumatoid arthritis is
small in developing countries.

32

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49.Aggarval HK, Singh H, Jain D, et al. Histofunctional status of kidney in patients with
Rheumatoid Arthritis. Dicle Med J 2011;38: 375-381.
50. Afolabi EA -Kuteyi A ,Arogundade FA , Prevalence of chronic kidney disease in a Nigerian
family practice population, South African Family Practice, 2009. 51:2, 132-137
51. Hill AJ, Thomson RJ, Hunter JA, Traynor JP: The prevalence of chronic kidney disease in
rheumatology outpatients. Scott Med J 2009, 54:9-12.
52. .Kirui F, Oyoo GO, Ogola EN, Amayo EO. Cardiovascular risk factors in patients with
rheumatoid arthritis at Kenyatta National Hospital.African J Rheumatol. 2013;1(1):1522.

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53. National Kidney Foundation. K/DOQI Clinical Practice Guidelines For Chronic Kidney
Disease: Evaluation, Classification And Stratification. Am J Kid Dis 2002;39(2 suppl):S1
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54 .Karstila.K , Incidence and Prognosis of Renal Disease and Measurement of Renal Function
in Patient with Rheumatoid ArthritisTampered 2009, Finland.
55. Johnson CA, Levey AS, Coresh J, Levin A, Lau J, Eknoyan G. Clinical practice guidelines
for chronic kidney disease in adults. Part I: Definition, disease stages, evaluation, treatment
and risk factors. Am Fam Physician2004;70:86976.
56. Abioye-Kuteyi EA, Akinsola A, Ezeoma IT. Renal disease: the need for community-based
screening in rural Nigeria. Afr J Med Pract 1999;6(5):198201

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10.Annexes

Annex 1: Procedure for tests

I Procedure for Creatinine determination
Method
Modified Jaff method
Reaction Principle
Creatinine + Picric acid

Creatinine Picric acid complex

At an alkaline solution, creatinine combines with picric acid to form an orange-red colored
complex. The absorbency increase is directly proportional to the concentration of creatinine.
Procedure
Method

End Point

Wavelength

505nm

Temperature

370c

Sample volume

5l

Reagent volume

500l

Standard

2mg/dl

1. Quality control
All control sera with known cholesterol values determined by this method.
Normal values
For Men up to 1.1
For women up to 0.9
Storage and stability
Up to expiration date indicated on the label, when stored unopened at 2-8

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II Procedure for Urea/BUN (Blood Urea Nitrogen) Test

Urea
Test method Berthelot enzymatic colorimetric method
Method
Urease Glutamate Dehydrogenase, UVmethod.
Principle
Urea

urease

(NH4+)2 + CO2

NH4+ + salycilate + NaC1O nitroprusside Indophenol

The intensity of the color formed is proportional to the urea concentration in the sample at wave
length of 340nm.
Sample
Serum or Plasma
Quality control
All control sera with known cholesterol values determined by this method
Normal values
For Men 10 up to 50
For women 10 up to 50
Estimated GFR
Using Cockcroft Gault formula
CG formula: GFR (ml/min) = k (140 age) body weight/SCr (in mol/l). Where, k = 1.04
(female) or 1.23 (male).
KD prevalence was estimated from apparent kidney damage and kidney function and categorized
according to the NKF classification as follows:

Stage 1: GFR 90 ml/min: normal kidney functions with markers of kidney damage.

Stage 2: GFR 6089 ml/min: mild reduction of GFR with markers of kidney damage.

Stage 3: GFR 3059 ml/min: moderate reduction of GFR.

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Stage 4: GFR 1529 ml/min: severe reduction of GFR.

Stage 5: GFR <15 ml/min: kidney failure.

Procedure for Urine test of protein and blood

Reaction principle
Urine test principle for blood and protein
Blood: This test is based on the peroxidase like activity of hemoglobin, which catalyzes the
reaction of diisopropylbenzenedihydroperoxide and 3, 3, 5, 5tetramethylbenzidine. The
resulting color ranges from orange through green very high levels of blood may cause the color
development to continue to blue.
Protein: This test is based on the protein error of indicators principle. At a constant pH, the
development of any green color is due to the presence of protein. Colors range from yellow for
Negative through yellow green and green to green blue for Positive reactions.
Procedure For urine protein and blood
1. Collect fresh urine specimen in a clean, dry container. Mix well immediately before testing.
2. Remove one strip from bottle and replace cap completely immerse reagent areas of the strip in
fresh urine and remove immediately to avoid dissolving out reagents.
3.While removing, run the edge of the entire length of the strip against the rim of the urine
container remove excess urine. Hold the strip in a horizontal position to prevent possible mixing
of chemicals from adjacent reagent areas and/or contaminating the hands with urine.
4. Compare reagent areas to corresponding Color Chart on the bottle label at the time specified.
Hold strip close to color blocks and match carefully. Avoid laying the strip directly on the Color
Chart, as this will result in the urine soiling the chart. Protein areas may also be read immediately
or at any time up to 2 minutes after dipping.
Reference Ranges:
Blood:
Erythrocyte excretion up to 5 RBC/uL may be expected in normal urine.
Normal urine should produce no color reaction and is reported as negative.
Protein

Normal urine should produce no color reaction and is reported as negative.

LIMITATIONS OF THE PROCEDURE:
Substances that cause abnormal urine color, such as drugs containing axo dyes (e.g., Pyridium
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Annex 2
The 2010 ACR/EULAR criteria for classification of rheumatoid arthritis
Classification criteria for RA (score-based algorithm: add score of categories AD;
A score of 6/10 is needed for classification of a patient as having definite RA
A. Joint involvement
1 large joint =0
2-10 large joints =1
1-3 small joints (with or without involvement of large joints) =2
4-10 small joints (with or without involvement of large joints) =3
>10 joints (at least 1 small joint) =5
B. Serology (at least 1 test result is needed for classification)
Negative RF and negative ACPA =0
Low-positive RF or low-positive ACPA =2
High-positive RF or high-positive ACPA =3
C. Acute-phase reactants (at least 1 test result is needed for classification)
Normal CRP and normal ESR = 0
Abnormal CRP or abnormal ESR =1
D. Duration of symptoms
<6 weeks = 0
6 weeks =1

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Annex 3: English version of participant information sheet, consent and

Questionnaire
I. Participant information sheet
Department of Medical Laboratory Science, Collage of Allied Health Sciences, Addis Ababa
University, Addis Ababa, Ethiopia
Title of the Research Project: Assessment of renal function test and risk factor associated with
rheumatoid arthritis patients, at Black Lion Hospital, Addis Ababa, Ethiopia First of all we
would like to thank you in advance for your cooperation and consent in participation in this
study. Please read or listen when it is read for you about the general information of the study. If
you have any question regarding the study please ask freely.
Background information
Background: Rheumatoid arthritis (RA) is a common autoimmune disease that is associated with
progressive disability, systemic complications, early death and socioeconomic costs. Therefore
the knowledge of the causative agents of RA will be helpful in the control of RA and correcting
the life style of patients.
Aim of the study
The purpose of this study is to determine renal function and to identify associated risk
factor for rheumatoid arthritis disease at Black Lion Hospital, Addis Ababa, Ethiopia.
Benefits for participants
Study participants will not have any financial incentives or other inducements from participating
on this study. However, based on the diagnosis result you will be treated accordingly. Most
importantly, the result of the study will be beneficial to design effective prevention and control
measure to RA disease hence, you are indirectly benefiting other patients and the society in this
respect.

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Risks and complication

There are no anticipated risks to your participation. Venus blood sample will be collected once.
During collection of sample you may feel some discomfort but this does not produce serious
pain.
Confidentiality
There is no sensitive issue that you will be asked related with your social desirability but any
information that is obtained in connection with this study and that can be identified with you will
remain confidential. Participants will not be prohibited to stop or withdraw at any time from the
study. Only interested participants can retrieve their own lab result using their code number. The
information collected about you will be coded using numbers. No personal information will be
disclosed to third party or will not appear in any report from this study.
Assurance of Principal Investigator
I put my signature below to confirm you that I take over the responsibility for the scientific
ethical and technical conduct of the research project and for provision of progress reports for all
stakeholders of the research project.
Betelihem Jima (PI)
Signature: __________________ Date: __________________
Note: If you have any questions about this study you should feel free to ask now or anytime
throughout the study by contacting:
PI Address: Betelihem Jima : Department of Medical Laboratory Sciences, Collage of Allied
Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
E-mail:meetbety2013@gmail.com

Tell: 0921370100

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II. Informed consent

I have been informed about the objective of the study entitled Assessment of kidney function
and Associated Risk factor on Rheumatoid Arthritis patient at Tikur Anbessa Hospital Addis
Ababa. Iam also informed that all information contained within the questionnaire are to be kept
confidential. Moreover, I have been well-informed of my right to refuse information, decline to
cooperate and drop out of the study if I want and none of my actions will have any bearing at all
on my overall health care.
Therefore, with full understanding of the situations I agree to give the entire necessary
information for laboratory analysis. I have had the opportunity to ask questions about the project
and received clarification to my satisfaction in a language I understand. I was also told that
results for the renal function test will be given to the health facility and that I may ask the
information if I want.
I ___________________________________ hereby give my consent for giving of the requested
Information and specimen for this study.
Participant code:__________________ Signature: _________________
Date: _________________________

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Annex 4: Questionnaire
Addis Ababa University Collage of Health Sciences, School of Allied Health Science
Department of Medical Laboratory Science. Questionnaire on prevalence of kidney disease and
associated risk factor on Rheumatoid Arthritis patients at black lion hospital.
Patient Identification
Facility name ________________ Year __________ Participant code ________Participants
address
(Sub city) ________ Telephone ____________ signature__________
Name of the ward ___________________________Block___________
Data collector name_________________________date____________signature__________

I. Socio Demographic Characteristics of the Study participants.

1. Age ________
2. Sex

1) Male 2) Female

3. Marital status 1) Married 2) Unmarried 3) Divorced 4) Widowed

4. Your level of education (1) Illiterate (2) Primary (3) Secondary (4) Tertiary
5.

Occupation. (1) Government employee (2) House wife (3) Student (4) Merchant
(5) House servant (6) Others (specify)______________

6. Your monthly income (in Ethiopian birr) ________

7. Ethnicity. (1) Amhara (2) Oromo (3) Tigray (4) Gurage (5) Somalia 6) Others (specify)
_______

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I Behavioral Measurement

Do you smoke cigarette? 1) Yes 2) No 3)Ex smoker

Do you consume alcoholic drink? Alcoholic drinks include beer, wine, and any of the
local alcohols like Tej, Tela etc.1) Never 2) Rarely less than or equal to once a month 3)
Regularly small dose (for greater than or equal to one occasion per week and less than 2
glass/bottle on each occasions) 4) Regularly high dose (For greater than or equal to one
occasion per week and more than 3 glass/bottle on each occasions

10 How do you characterize your regular physical activity?1)Sedentary 2)Moderate

3)Vigorous
III Rheumatoid arthritis associated questions
11 Date of visit (in the hospital)(dd/mm/yy) ______
12 Specific sign of the disease ______
13 What is the cause of the disease? 1) car accident wound 2) Bullet injury 3) post operation
surgical site infection 4) skin infection 5) burn wound 6) other (specify ) ______
14 Is there any person from family that has such disease previously?
15 Do you have any chronic Underlying diseases? 1) Yes 2)No
16 If you say yes please specify ________________________
17 Are you taking medication for it? 1) yes 2) No
18 If you say yes please specify ________________________
19 The duration of the disease_______________________
20. weight and height of the respondent-------------------------------

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IV. Laboratory Data

19. Date of specimen collection__________________
20.Urea test result ________________________
21.Creatinine test result ________________________
22. Clearance test result________________________
23. Urine protein test result________________________
24. Urine blood test result________________________
V. Comments____________________________________________________
Name of principal investigator ___________________________________________
Signature ________________ Date ______________

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Declaration
I, the undersigned, declare that this is my original work, has not been presented for a degree in
Addis Ababa University or any other universities. I also declare that all sources of materials used
for the proposal have been duly acknowledged.
Name of the candidate: Betelihem Jima (BSc)
Signature______________________
Place: Addis Ababa University School of Medical Laboratory Sciences, Ethiopia
Date of submission_____/_______/__________
This work has been submitted with my approval as university advisor.
Name of advisor: Jigssa Girma (MSC, PHD FELLOW )
Signature ____________________
Place: Addis Ababa University School of Medical Laboratory Sciences, Ethiopia
Date of submission______/______/________
Name of advisor: Addisu Melkie(MD)
Signature ____________________
Place: TikurAnbessa Teaching and Specialized Hospital
Date of submission______/______/________

48