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Saudi J Kidney Dis Transplant 2010;21(6):1066-1072


2010 Saudi Center for Organ Transplantation Saudi Journal
of Kidney Diseases
and Transplantation

Original Article

Epidemiology of Chronic Kidney Disease in the Kingdom of Saudi


Arabia (SEEK-Saudi Investigators) A Pilot Study
Abdulkareem O. Alsuwaida1*, Youssef M.K. Farag2*, Abdulla A. Al Sayyari3, Dujanah Mousa4,
Fayez Alhejaili5, Ali Al-Harbi6, Abdulrahman Housawi7, Bharati V. Mittal2, Ajay K. Singh2
1
Renal Division, King Saud University, Riyadh, Kingdom of Saudi Arabia, 2Renal Division, Brigham
and Womens Hospital and Harvard Medical School, Boston, MA, USA, 3Nephrology Division, King
Saud Bin Abdulaziz University for Health Sciences, 4Department of Nephrology, Riyadh Armed Forces
Hospital, 5Department of Medicine, King Abdulaziz Medical City, 6Department of Internal Medicine,
Security Forces Hospital Program, Riyadh, 7King Faisal Specialist Hospital and Research Center,
Jeddah, Kingdom of Saudi Arabia
*
Both authors (AOA and YMKF) have equally contributed to this manuscript

ABSTRACT. There are no available data about the prevalence of chronic kidney disease (CKD) and
its risk factors in the general population of the kingdom of Saudi Arabia. To estimate the prevalence of
CKD and its associated risk factors in the Saudi population, we conducted a pilot community-based
screening program in commercial centers in Riyadh, Saudi Arabia. Candidates were interviewed and
blood and urine samples were collected. Participants were categorized to their CKD stage according to
their estimated Modification of Diet in Renal Disease (MDRD3)-based, the new Chronic Kidney
Disease Epidemiology Collaboration (CKD-EPI) equation and the presence of albuminuria. The sample
comprised 491 (49.9% were males) adult Saudi nationals. The mean age was 37.4 11.3 years. The over-
all prevalence of CKD was 5.7% and 5.3% using the MDRD-3 and CKD-EPI glomerular filtration
equations, respectively. Gender, age, smoking status, body mass index, hypertension and diabetes mel-
litus were not significant predictors of CKD in our cohort. However, CKD was significantly higher in
the older age groups, higher serum glucose, waist/hip ratio and blood pressure. Only 7.1% of the CKD
patients were aware of their CKD status, while 32.1% were told that they had protein or blood in their
urine and 10.7% had known kidney stones in the past. We conclude that prevalence of CKD in the young
Saudi population is around 5.7%. Our pilot study demonstrated the feasibility of screening for CKD.
Screening of high-risk individuals is likely to be the most cost-effective strategy to detect CKD patients.

Introduction an important problem worldwide.1 However,


data on the burden of CKD in the Arab world
Chronic kidney disease (CKD) is emerging as remains poorly understood. The kingdom of
Correspondence to: Saudi Arabia is the largest country in the Ara-
bian Peninsula in Southwest Asia. It has an
Dr. Ajay K. Singh, estimated population of 28 million, including
Brigham and Womens Hospital, approximately 5.5 million non-nationals.2 Data
Harvard Medical School, 75 Francis Street, available on the exact incidence and prevalence
Boston, MA 02115, USA. of chronic kidney disease is limited to patients
E-mail: asingh@partners.org with end-stage renal disease. In the annual report
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Epidemiology of CKD in the kingdom of Saudi Arabia 1067

of the Saudi Center for Organ Transplantation tration was determined by the buffered kinetic
(SCOT),3 the incidence of dialysis in the king- Jaffe reaction without deproteinaization using
dom of Saudi Arabia was 136 new cases per a Cobas 6000 analyzer, and was traceable with
million population (pmp). This compares to 360 isotope dilution mass spectrometry (IDMS). In
pmp in the United States,4 585 pmp in Europe5 addition, the estimated glomerular filtration rate
and to 163 pmp in India.6 (eGFR) was calculated using the Modification
The SEEK-Saudi study (Screening and Early of Diet in Renal Disease (MDRD3) formula
Evaluation of Kidney Disease) is aimed at eva- (eGFR = 175 (serum creatinine in mg/dL)
1.154
luating the burden of CKD and its predictors in age0.203 (0.742 if female) (1.21 if
the kingdom of Saudi Arabia using standar- black) (3). The eGFR was re-calculated using
dized GFR prediction equations. The study also the CKD-EPI9 and the CockcroftGault predi-
aimed to demonstrate the feasibility of perfor- cation equation. Individuals with eGFR values
ming a community-based screening. <60 mL/min per 1.73 m2 or those having albu-
minuria 1+ were defined as having CKD. We
Methods used the National Kidney Foundation (NKF)
criteria for CKD.10 Strata for the presentation
In March 2008 and for 2 months thereafter, of statistics include gender (male or female),
camps in two large commercial centers in age group (18 to 30, 31 to 40, 41 to 50, 51 to
Riyadh, the capital of the kingdom of Saudi 60, or 61 + years), diabetes status (yes or no)
Arabia, were conducted (total of three camps). according to the American Diabetes Associa-
Saudi nationals aged 18 years of age were tion (fasting blood glucose 126 mg/dL, random
invited to participate in the study. All the par- blood glucose 200 mg/dL, on diabetes medi-
ticipants provided informed consent. Screening cation or self-reported diabetes mellitus) and
data were collected on sociodemographic cha- hypertension status (yes or no), either with ele-
racteristics, medical history and medications. vated blood pressure on anti-hypertensive medi-
The presence of CKD and cardiovascular di- cations or self-reported hypertension.
sease, its risk factors and related complica-
tions were also addressed in the questionnaire. Statistical Analysis
Pertinent family history was also documented.
Anthropometric measures (weight, height, mid- The group with CKD and those without were
abdominal and hip circumference), resting blood compared for frequencies of certain demogra-
pressure and heart rate were measured. We phic factors. The Students t-test was used to
used the guidelines of the Seventh Report of evaluate continuous variables and the Chi-
the Joint National Committee on Prevention, square and Fishers exact tests for categorical
Detection, Evaluation and Treatment of High parameters. The significance level was set at P
Blood Pressure (JNC 7).7 Two consecutive <0.05. The mean values were reported as the
standardized blood pressure measurements were mean standard deviation (SD).
recorded with the person seated using a mer-
cury sphygmomanometer. The anthropometric Results
measurements were performed according to
the Anthropometric Standardization Reference A total of 494 subjects participated in the
manual.8 Participants were requested to visit study; three participants were excluded because
the laboratory while fasting so that fresh urine they were either below 18 years of age (n = 2)
and blood samples were collected. Blood and or had a history of kidney transplant (n = 1).
urine specimens were processed for the deter- The mean age of the participants included in
mination of random blood glucose, serum crea- the analysis (n = 491) was 37.41 11.3 years.
tinine, hemoglobin, microalbuminuria, hema- There were 49.9% males (n = 245). The mean
turia and pyuria. We used urine dipstick Bayer body mass index was 29.24 5.7 kg/m2. Other
Multistix 10 SG. Serum creatinine concen- baseline characteristics are shown in Tables 1
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1068 Alsuwaida AO, Farag YM, Al Sayyari AA, et al

Table 1. Demographic characteristic distribution by CKD status.


All By CKD status (eGFR calculated using the
participants MDRD-3 equation)
N = 491 CKD n = 28 Non-CKD n = 463
P
(5.7%) (94.3%)
Age categories (years) 0.046
1830 31.6 28.6 31.7
3140 30.1 21.4 30.7
4150 25.9 25 25.9
5160 10 14.3 9.7
>60 2.4 10.7 1.9
Sex 0.084
Male 49.9 64.3 49
Female 50.1 35.7 51
Education 0.423
<High school 15.9 21.4 15.6
High school 84.1 78.6 84.4
Risk
Ever smoking 16.9 28.6 16.2 0.115
Obesity 43.6 60.7 42.5 0.06
Diabetes 18.3 39.3 17.1 0.003
Elevated blood pressure 17.3 28.6 16.6 0.121
Hypertension 27.7 39.3 27 0.158
History of heart attack 2.4 0 2.6 0.489
History of stroke 0.6 0 0.6 0.838
History of anemia 19.3 14.3 19.7 0.34
History of high cholesterol 21.6 39.3 20.6 0.019
History of peripheral vascular disease 1.6 0 1.7 0.623
History of TB 0.8 0 0.9 0.79
All (%) 100 100 100

and 2. nificant difference between males and females


regarding the presence of macroalbuminuria
Estimation of Kidney Function by urine dipstick. However, the youngest age
We calculated eGFR using the MDRD-3, the group (18 to 30 years) in our cohort had the
CKD-EPI and the CockcroftGault equations highest prevalence of macroalbuminuria, of
(Table 3). The mean eGFR was 107.77 23.97 30.8% (P = 0.042).
mL/min/1.73 m2. The overall prevalence of
mildly decreased kidney function (GFR 6089 Prevalence of CKD
mL/min per 1.73 m2) was 20.8%. Low GFR We observed that the overall CKD preva-
was more common in males (61.8%) than in lence of all stages was 5.7%. The prevalence
females (38.2%) (P = 0.008). Mildly decreased of CKD stages 1, 2 and 3 was 3.5%, 1.6% and
GFR was highest among the age groups 31 to 0.6%, respectively. Comparison between the
40 years and 41 to 50 years, 29.4% and 38.2% two groups (participants with CKD versus par-
respectively (P = 0.000). The prevalence of ticipants without CKD) is presented in Tables
decreased GFR (GFR 15 to 59 mL/min per 1 and 2. There was no significant difference
1.73 m2) was 0.4% and exclusively in females. between the two groups by age, gender, level
None of the participants had stage 5 CKD. of education, smoking status, hypertension and
obesity. There was moderate negative correla-
Prevalence of Albuminuria tion (Spearmans rho = -0.209) between the
The overall prevalence of macroalbuminuria eGFR and the number of smoking years, but
(by urine dipstick) was 5.3%. There was no sig- was not strong enough to reach statistical sig-
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Epidemiology of CKD in the kingdom of Saudi Arabia 1069

Table 2. Mean values of selected clinical and laboratory screening data collected in SEEK-Saudi and by
chronic kidney disease (CKD) status.
By CKD Status (eGFR calculated using MDRD-3
All participants Equation)
CKD Non-CKD
P
Mean SD Mean SD Mean SD
Age 37.41 11.3 41.39 13.312 37.17 11.136 0.055
Height 163.68 9 165.25 9.4178 163.582 8.98 0.342
Weight 78.18 15.51 83.31 16.924 77.87 15.39 0.071
BMI 29.24 5.7 30.65 6.3456 29.15 5.66 0.177
Waist circumference 92.57 15.3 100.57 16.785 92.09 15.085 0.004
Hip circumference 107.53 12.98 109.48 12.342 107.41 13.024 0.414
Waist/hip ratio 0.86 0.13 0.916 0.0987 0.86 0.126 0.022
Average SBP 117.69 16.53 126.93 19.568 117.13 16.182 0.002
Average DBP 77.11 11.34 84.125 10.0707 76.68 11.28 0.001
Hemoglobin 13.87 1.72 14.604 1.7409 13.828 1.71 0.02
Serum glucose 107.47 38.1 143.327 84.205 105.3 32.29 0.000
Serum creatinine 0.75 0.18 0.873 0.255 0.74 0.169 0.000
eGFR (MDRD) 107.77 23.97 95.75 28.35 108.5 23.52 0.006
Urine protein/creatinine ratio 0.12 0.11 0.2689 0.2645 0.1068 0.088 0.000

nificance (P = 0.06). There was a higher CKD 10.7% had known kidney stones in the past
prevalence in the older age group (P = 0.046). (Table 4).
The CKD group had a higher serum fasting
glucose level (P < 0.000) and a lower hemo- Discussion
globin level (P = 0.02).
We performed a sensitivity analysis (Table 3) In our study, the overall prevalence of CKD
using the CockcroftGault equation and the was 5.7% (based on the eGFR MDRD-3 equa-
new CKD-EPI equation for estimation of GFR. tion). The prevalence did not change substan-
When using the CG equation, prevalence of tially when we used the CockcroftGault equa-
CKD was found to be 8.6%. The overall CKD tion and the new CKD-EPI equation for esti-
prevalence of all stages was 5.3%. The per- mation of GFR. The overall prevalence of
centage of CKD patients decreased, especially mildly decreased kidney function (GFR 60 to
in the higher age groups (41 to 50 years and 51 89 mL/min per 1.73 m2) was 20.8%. Older age
to 60 years). and higher fasting serum glucose were sug-
gested to be risk factors for CKD.
Awareness of CKD status and CKD symptoms This study is a part of the Global SEEK
Only 7.1% of the CKD patients knew that Project; Screening and Early Evaluation of
they had CKD, while 32.1% were told that Kidney disease, and used the methodology that
they have protein or blood in their urine and was employed in India and Thailand. CKD in
Table 3. Stages of chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR)
measured by different equations or estimates.
CKD-EPI MDRD-3 Cockcroft-Gault Serum Creatinine
> 1.5 mg/dL
CKD patients n=26 CKD patients CKD patients n=42 CKD patients n=1
(5.3%) n=28 (5.7%) (8.6%) (0.2%)
n % n % n %
Stage 1 20 76.9 17 60.7 24 57.1
Stage 2 5 19.2 8 28.6 17 40.5
Stage 3 1 3.8 3 10.7 1 2.4
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1070 Alsuwaida AO, Farag YM, Al Sayyari AA, et al

Table 4. Awareness of chronic kidney disease (CKD) status or CKD symptoms.


Study cohort CKD patients
n = 419 n = 28
Even been told to have protein or blood in the urine 68 (13.8%) 9 (32.1%)
Have burning sensation during urination 197 (40.1%) 14 (50%)
Known kidney disease 24 (4.9%) 2 (7.1%)
Known kidney stones 39 (7.9%) 3 (10.7%)

this cohort was largely explained by the presence 95% CI 5.9211.98).13 In the study from Beijing,
of albuminuria rather than reduced GFR. This the prevalence rose from 10% in the age group
indicates that people may experience kidney 1839 years to 30.5% in those >70 years of
damage before their eGFR decreases below 60 age.11
mL/min per 1.73 m2. The majority of subjects When we used the CKD-EPI equation, the
were classified into CKD stages 1 and 2. This prevalence of CKD in our study was 5.3%. In
is lower than other reported prevalence from addition, when we remodeled our data using
different parts of the world. For example, the the CKD-EPI equation, the evaluation of cor-
overall prevalence in Beijing, China, was relations with specific risk factors was similar
13.0%.11 In USA, the prevalence rate over to the data generated from the MDRD-3 equa-
19992004 was 13.1% in all four stages of tion (Table 1, 2 and 3). Sensitivity analysis for
CKD (1.8%, 3.2%, 7.7% and 0.35% for stages the prevalence of CKD was also performed
1, 2, 3 and 4, respectively).12 A population of using the CockcroftGault (CG) equation to
American Indians and Alaska Natives was generate an estimate of creatinine clearance.
screened for CKD as part of the Kidney Early Prevalence of CKD was higher (8.6%) using
Evaluation Program (KEEP). In this popula- the CG equation. Nevertheless, regardless of
tion, the prevalence of any CKD was found to the equations used to classify CKD, the burden
be 29% and of low GFR (defined as <60 mL/ of CKD was predominant in stage 1 (76.9%,
min/1.73 m2) was 17%. (Jolly). The low preva- 60.7% and 57.1% using the CKD-EPI, MDRD-
lence of CKD in our study compared with other 3 and CG equations, respectively). The factors
studies might be explained by the fact that the associated with the presence of CKD in our
mean age in our study population was lower. group included older age group (P = 0.046)
The strongest predictor of low GFR in the and higher serum fasting glucose (P < 0.000).
KEEP study was older age (61+ years OR 8.42, CKD was also found in patients with a higher

30
25
PercentageswithloweGFR

25

20
1830years
15 3140years
4150years
10 8.2
5160years
5.2 5.5
4.1 Above60years
5

0
AgeofSubjectswithCKD

Figure 1. Participants detected with chronic kidney disease (CKD) among the different age groups.
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Epidemiology of CKD in the kingdom of Saudi Arabia 1071

waist/hip ratio (P = 0.022) and higher systolic the urban population and healthier participants.
and diastolic blood pressure (P = 0.002 and P = A large study is currently planned. This could
0.001, respectively). Although smoking status be an explanation for why our CKD estimates
was not significantly different (P = 0.115) bet- are lower than those presented in earlier stu-
ween the CKD and non-CKD groups, there dies. The US National Health and Nutrition
was a moderately negative correlation (Spear- Examination Survey (NHANES) used a repre-
mans rho = -0.209) between the eGFR and the sentative cross-sectional, multistage, clustered
number of smoking years, but this was not probability samples of the US civilian non-
strong enough to reach statistical significance institutionalized population and reported a CKD
(P = 0.06). The association between cigarette prevalence of 18.3%.19 On the other hand, the
smoking and CKD has been observed in seve- Kidney Early Evaluation Program (KEEP)
ral previous reports.14,15 This is particularly offered a free health camp-based screening
noteworthy in the Saudi Arabian population program for individuals at increased risk of de-
since there is a higher prevalence of current veloping kidney disease and reported an even
cigarette smoking16 compared with previous higher prevalence of 26.2%. Because the ma-
studies among males in Saudi Arabia 5 years jority of the population in Saudi Arabia lives
ago (4.7%).17 in urban areas and large cities, we believe that
We also observed a strong association bet- our numbers are likely to be representative of
ween the serum fasting glucose level and CKD. the urban Saudi population. In our pilot study,
Although the prevalence of diabetes mellitus we measured albuminuria on only one occasion.
in Saudi Arabia is among the highest in the Since there is a significant variation in the
world,18 we believe that our study was not albumin excretion rates, our estimate of the
sufficiently powered to confirm the association rate of albuminuria may be imprecise. Further-
between CKD and diabetes mellitus. More- more, other possible limiting factors include a
over, we enrolled relatively healthy and young small sample size and restriction of our study
subjects. to only Saudi nationals.
Obesity is associated with CKD, and we did We conclude that our pilot study does de-
observe this in our cohort, since our CKD sub- monstrate the feasibility of the screening and
jects manifested significantly larger waist cir- early detection of CKD in a Saudi population.
cumference than the non-CKD group (P = However, our data should generalize the Saudi
0.004). However, since BMI 30 is the criteria population with caution, and we plan to con-
for obesity, it is possible that our study was not duct further studies with a larger sample size
powered enough to detect the effect of obesity. and more sophisticated sampling techniques to
This is supported by the fact that 60.7% and evaluate the prevalence and risk factors for
42.5% of the CKD and non-CKD subjects were CKD.
obese, respectively.
We observed a significantly higher preva- Acknowledgement
lence of CKD (25%) in participants above 60
years of age in comparison with the younger Dr. Ajay K. Singh is the Chair of the SEEK-
age groups, in addition to diabetes mellitus Global Steering Committee. The SEEK-Saudi
(58.33%,) and hypertension (58.33%) (Figure investigators would like to thank Magdy A.
1). Finally, we detected a low awareness of the Abd El-Hameed, Product Manager Eprex,
CKD status and CKD symptoms in our cohort. Janssen-Cilag branch in the Gulf Cooperation
This implies false awareness. Council (GCC) countries for his generous sup-
Our study has several limitations. The most port throughout the project period. We also
important is that bias may have been intro- would like to thank Dania Daye, MD-PhD
duced because of the sampling technique used student and HHMI-NIBIB* Interfaces Scholar
in our study. We used a camp-based module in at the University of Pennsylvania School of
this pilot study that could have biased toward Medicine, for her instrumental contribution in
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1072 Alsuwaida AO, Farag YM, Al Sayyari AA, et al

the CKD-EPI eGFR equation results. Committee on Prevention, Detection, Evaluation,


*HHMI: Howard Hughes Medical Institute, and Treatment of High Blood Pressure (JNC 7).
NIBIB: National Institute of Biomedical Imaging http://www.nhlbi.nih.gov/guidelines/hypertensi
and Bioengineering on/ accessed September 20, 2008.
8. Anthropometric Standardization Reference
Manual by Timothy G. Lohman. ISBN
Disclosure 0873223314.
9. Levey AS, Stevens LA, Schmid CH, et al. A
The study was funded by a research grant new equation to estimate glomerular filtration
from the Janssen-Cilag branch in the Gulf rate. Ann Intern Med 2009;150(9):604-12.
Cooperation Council (GCC) and institutional 10. National Kidney Foundation. K/DOQI clinical
funds from the College of Medicine Research practice guidelines for chronic kidney disease:
Center at King Saud University. Dr. Ajay K. Evaluation, classification, and stratification.
Singh reports having received research support Am J Kidney Dis 2002;39(2 Suppl 1):S1-266.
and consulting fees from Amgen Inc, Johnson 11. Zhang L, Zhang P, Wang F, et al. Prevalence
and factors associated with CKD: A population
and Johnson, Roche, AMAG Pharmaceuticals
study from Beijing. Am J Kidney Dis 2008;
Inc. and Watson Pharmaceuticals. He is on the 51:373-84.
Speakers Bureau for Watson Pharmaceuticals 12. Coresh J, Selvin E, Stevens LA, et al. Preva-
and Johnson and Johnson. lence of chronic kidney disease in the United
States. JAMA 2007;298(17):2038-47.
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