Medical and Health Science Journal, Vol. 4, No.2, August 2020 Correspondence: Nor Ain Mior Nizam @2020 Medical and Health Science Journal. 10.33086/mhsj.v4i1.1415 Available at http://journal2.unusa.ac.id/index.php/MHSJ 69 PREVALENCE OF CHRONIC KIDNEY DISEASE AMONG COMMUNITY REMOTE AREAS IN SABAH: POPULATION-BASED STUDY Nor Ain Mior Nizam,* 1 Malehah Mohd Noh 1,2 ,Shamsul Bahari Shamsuddin 1 1 Faculty of Medicine and Health Sciences, University Malaysia Sabah, Kota Kinabalu, 88400, Malaysia 2 Medical Department, Hospital Queen Elizabeth, Kota Kinabalu, 88400, Malaysia * Corresponding author: ain1510@yahoo.com ARTICLE INFO ABSTRACT Article history: Submitted: July, 19 2020 Received in revised form Juli, 21 2020 Accepted: August, 1 2020 In this population-based study, we determined the prevalence of chronic kidney disease (CKD) of community in remote areas of Ranau, Sabah to have accurate information for health-care planning. It also investigated the association of risk factors with the prevalence of CKD. A sample of 270 individuals, compared to the study of the National Health and Morbidity Survey 2011, of the adult population (over 18 years old) undertaken in West Malaysia. We measured the estimated glomerular filtration rate (eGFR) using this CKD-EPI equation. The total prevalence of CKD in this group was 53%. An estimated 3.3% had stage 1 CKD (eGFR >90 ml/min per 1.73m 2 ), 32.6% had stage 2 (eGFR 60–89 ml/min per 1.73m 2 ), 4.1% had stage 3 (eGFR 30–59 ml/min per 1.73m 2 ), 7% had stage 4 (eGFR 15–29 ml/min per 1.73m 2 ), and 6% had stage 5 CKD (eGFR <15 ml/min per 1.73m 2 ). Only 4% of respondents with CKD were aware of their diagnosis. The significant risk factors included family history of kidney disease, alcohol consumption, smoking status, hypertension, diabetes mellitus, and dyslipidemia. Thus, CKD in East Malaysia are common and warrants early detection, and treatment to potentially improve outcomes can be implemented. @2020 Medical and Health Science Journal. 10.33086/mhsj.v4i1.1415 Keywords: Prevalence, Chronic kidney disease, Glomerular filtration rate, Risk Factors INTRODUCTION Chronic Kidney Disease (CKD) is a significant public health issue 1 . It is a worldwide burden attracting major attention due to its rapidly progressing numbers. 2,3 Recent global CKD prevalence is estimated to be between 10 – 15%. 4 A previous study reported 9.1% of West Malaysians to have CKD. 5 CKD can develop gradually, taking months to years, frequently leading to permanent loss of kidney function over time. Harmful effects of CKD are the accumulation of water, waste, and toxic substances in the body that are excreted by the kidneys. The loss of kidney function is known to cause anemia, high blood pressure, bone diseases, and acidosis disorders (excessive acidity of body fluids) associated with cholesterol and fatty acids. As CKD continues to progress, the glomerular filtration rate decrease and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may escalate the mortality and/or morbidity of an individual 1 . As the renal replacement therapy (RRT) in Sabah has been increased up to 2,047 patients and RRT places a large burden on the health-care budget 15 . Therefore, it is important to obtain accurate local data on CKD to facilitate health care planning, especially in remote areas. The objective of this population- based study was to determine the prevalence of CKD among community aged over 18 years in remote areas of Ranau, Sabah. We also studied the association of risk factors with the prevalence of CKD. ORIGINAL ARTICLE mailto:ain1510@yahoo.com Medical and Health Science Journal, Vol. 4, No.2, August 2020 70 MATERIALS AND METHODOLOGY 2.1 Study Area The study was conducted in the district of Ranau, Sabah, North Borneo of Malaysia which comprises a total population of 94,029. More than 85% of the population comprises of the Dusun tribe. 16 2.2 Patient background This study was carried out at the Nephrology Health Care Clinic in Ranau Hospital. Most of the patients aged 18 to 65 years, who gave their consent, were diagnosed as CKD and referred to be assessed by physicians. Simple random sampling was used. Pediatric patients, pregnant women, infections disease patients such as those suffering from HIV, and Hepatitis were excluded. 2.3 Sampling method All respondents were randomly interviewed by trained data collectors using a standard validated questionnaire with fully written consent. This was a cross-sectional study where we evaluated 270 respondents. The questionnaires included demographic characteristics, socioeconomic and health status. Physical examination and blood tests were performed. Blood pressure (BP) was measured by Omron Japan Model HEM-907 (Tokyo, Japan), 19 which has been validated and calibrated. BP was measured with the respondent at rest in a sitting position, with the BP set and appropriate-sized cuff at chest level. Two readings were taken 15 min apart, and the average measurement was used for analysis. 2.3.1 Blood Sampling Method Written consent was obtained from the respondents for blood sampling and it was done to determine the serum creatinine (SCr), in which 5ml of blood samples were taken by using a disposable syringe from the vein and collected in a capped plastic sterile tube. The procedures were carried out aseptically and precautions taken during the use of a tourniquet to prevent blood contamination as per protocols. The blood samples were transported by using a cool box and the temperature was maintained at 4ºC and sent immediately to the laboratory within 24 hours. The serum creatinine level was measured by the enzymatic laboratory method of Sabah Gribbles Laboratory, Malaysia. The estimated GFR (measured in millimeters per minute per 1.73m 2 ) was calculated using the CKD-EPI creatinine formula 20 , where e-GFR= 141 x min (Scr / k, 1) a x max (SCr / k, 1) -1,209 x 0.993 age x 1.018 (if female) SCr is serum creatinine (mg / dL), k = 0.7 (female) and 0.9 (male), a = - 0.248 (female) and -0.207 (male), min is the minimum of SCr /k or l and max is the maximum of SCr/k or l. Fasting blood sugar and total cholesterol were estimated by dry method (CardioChek PA, Gribbles Sabah, MY), which has been validated. 18 2.4 Definitions CKD stages 1 and 2 was defined as eGFR > 90 ml/min per 1.73m 2 and 60–89 ml/min per 1.73m 2 , respectively. Stages 3, 4, and 5 were defined as eGFR 30–59, 15–29, and <15 ml/min per 1.73m 2 , respectively, regardless of kidney damage. Diabetes mellitus was defined as a fasting capillary blood glucose level > 6.1 mmol/l on CardioChek, or self-reported diabetes diagnosed by medical personnel, or random capillary blood glucose >11.1 mmol/l. Hypercholesterolemia was defined as random or fasting blood cholesterol > 5.2 mmol/l or self-reported hypercholesterolemia diagnosed by medical personnel. Hypertension was defined as the average of two BP readings with systolic BP >140 and/or diastolic BP > 90mmHg20 and/or self-reported hypertension previously diagnosed by medical personnel. Medical and Health Science Journal, Vol. 4, No. 2, August 2020 71 2.5 Statistical analysis Statistical analyses of data were performed by using SPSS version 26 to identify whether there was any significant prevalence of CKD among the respondents. Data were presented as mean and median for continuous variables and proportion for categorical variables. Prevalence estimates of all outcomes were performed. Factors associated with CKD were assessed using logistic regression. Unadjusted odds ratio between exposure variables and indicators of CKD was determined. Adjusted odds ratios and 95% confidence intervals were estimated. The P-value of <0.05 is considered significant. 2.6 Ethical approval and consent Approval and ethical clearance were given by the National Medical Research Register (NMRR) (Ethics Approval Number: NMRR-18-2615-44151) and the UMS Research committee. The approval also was obtained from the Director of the State Health Department for blood sampling which was conducted by the staff of the health department. All respondents were required to sign a written informed consent form before enrolment. RESULT AND FINDINGS There were 270 respondents consented to participate out of initially 400 targeted, giving a response rate of 68%. Table 1 compares the overall National Health and Morbidity Survey (NHMS) 2011 cohort in West Malaysia aged > 18 years (N=15,147) with the CKD study (N=270). There was no difference observed in the profile of both studies. Table 1 Comparison between National Health and Morbidity Survey (NHMS) cohort samples and CKD samples Socio-demographic Characteristics NHMS cohort (>18 years), N=15,147 CKD Study, N=270 Number Mean Median Number Mean Median IQR Age (years) 15,147 42.2 41.0 270 45.1 46.0 20 Systolic blood Pressure(mmHg) 14,631 129.5 127.0 270 134.7 134.0 20 Diastolic blood pressure (mmHg) 14,630 80.2 80.0 270 84.1 84.0 12 Glucose level (mmol/l) 13,436 6.1 5.4 270 5.3 5.0 1.3 Cholesterol level (mmol/l) 13,742 4.9 4.8 270 5.4 5.1 1.3 Abbreviations: CKD, chronic kidney disease; IQR, interquartile range. Table 2. Prevalence of CKD stages (N=270) CKD Stage Number of respondents Prevalence of CKD (%) Normal 127 0.0 Stage 1 9 3.3 Stage 2 88 32.6 Stage 3 11 4.1 Stage 4 19 7.0 Stage 5 16 6.0 Total 270 53% Abbreviations: CKD, chronic kidney disease Out of 270 respondents, 143 (53%) were diagnosed with CKD based on eGFR measurements (Table 2). Overall, 47% of the respondents had eGFR >90 ml/min per 1.73m 2 which was normal, 3.3% had 4.1% stage 1 CKD, 32.6% had stage 2 CKD, 4.1% had stage 3 CKD, 7.0% had stage 4 CKD and 6.0% had stage 5 CKD (eGFR < 15 ml/min per 1.73m 2 ). Using univariate analysis, the factors associated with significantly increased prevalence of CKD were smoker, alcohol drinker, diabetes, hypertension, dyslipidemia, and family history of kidney disease (Table 3). All the factors associated with CKD was significant (p<0.05). Medical and Health Science Journal, Vol. 4, No.2, August 2020 72 Table 3. Factors associated with CKD Prevalence by Univariate Analysis (N=143) Variable n (%) Adjusted OR (95% CI) P-value Smoking status Smoker 89 (62.2) 2.72 (0.48-3.32) 0.041 Alcohol consumption Drinker 92 (64.3) 3. 28 (2.13- 13.89) 0.005 Diabetes 51 (35.7) 2.89 (1.83-4.06) 0.005 Hypertension 114 (79.7) 3.01 (1.37-8.93) 0.001 Dyslipidemia 69 (48.3) 2.01 (1.12- 1.05) 0.047 Family history of kidney disease 109 (76.2) 5.12 (2.75-9.60) 0.000 OR= odds ratio, CI= confidence interval; P<0.05 with chi-square test DISCUSSIONS CKD is defined by using the Modification of Diet in Renal Disease (MDRD) equation together with CKD-EPI. 6 In South Korea, Taiwan, and Thailand. CKD was defined by using the MDRD equation with eGFR< 60 ml/min per 1.73m 2 . In Beijing, eGFR was measured using calibrated serum creatinine while the Japanese used eGFR and dipstick to define CKD. The demographic characteristic of the CKD study was similar to that of the overall NHMS 2011 cohort (Table 1). There was no difference in the profile of both cohorts except for certain respondents in the CKD sample. This suggests that the CKD study was conducted on a valid representative sample for the population of the remote area i.e. Ranau, Sabah. There was a good response rate of 68%. This study assessed the prevalence of CKD among respondents living in Ranau, Sabah using the GFR. The overall prevalence of CKD in the study was 53%. The prevalence of CKD by stages 1,2,3,4, and 5 were 3.3%, 32.6%, 4.1%, 7.0% and 6.0% respectively. In a previous population-based study reported that the prevalence of CKD stage 5 in Malaysia was 0.36% in people above 18 years of age 5 . Our estimated prevalence of stage 5 CKD was higher than in other studies. This difference in CKD prevalence might be due to the difference in case studies and variables. The prevalence of CKD in West Malaysia of 9.07% is similar to their rate in the region. The prevalence of CKD in Asia varies within South Asia: 10.2% in India, 17.3% in Bangladesh, 16.9% in Pakistan, and 10.6% in Nepal 6, 7 . While, in other Asian regions it was: 17.5% in Thailand, 13% in Japan, 6.8% South Korea, 12% in Taiwan, and 13% in Beijing. The prevalence depends on methodology, CKD definition, and study design incorporated 5 . In this study, a significant association between family history and CKD has been found 8 . Previous studies use lower eGFR and albuminuria to define CKD 9 . The result obtained was positive correlation even after adjusting for age, sex, race, diabetes, hypertension, and socioeconomic background. This study found a significant correlation between smoking and CKD. Tobacco in cigarettes heavily increases the risk for a wide range of chronic conditions including cancer, cardiovascular disease, and respiratory disease. A study found CKD and its relationship with smoking 13 . The study found that smoking increases the risk for both atherosclerotic and non-atherosclerotic vascular disease, hence, directly increasing the vascular and nonvascular morbidity and mortality in patients with CKD. This study also found a significant correlation between alcohol consumption and CKD. Excessive alcohol consumption generally leads to liver damage but few studies have also found that ethanol can cause kidney damage 10 . Along with an unhealthy diet and lifestyle, heavy alcohol consumption can greatly contribute to CKD. However, few studies show that there is no obvious correlation between alcohol and CKD due to confounding factors such as smoking, drug Medical and Health Science Journal, Vol. 4, No. 2, August 2020 73 abuse, used of NSAIDS, high fat diet, and coffee that may interfere in study. 17 Diabetes is associated with hypertension was closely associated with the development of CKD. 11 This is due to an increase in deterioration in glomerular filtration in renal damage caused by diabetes together with hypertension amplifying vascular damage which later leads to renal insufficiency. Elevation of blood pressure both caused by and resulting in increased progression of kidney disease leads to an intermingled cause and effect relationship between hypertension and CKD. CKD was independently associated with type 2 DM and longer duration of DM. This corresponds with the finding of several studies that reported that the likelihood of developing CKD was greater among patients with a longer duration of diabetes. CKD is estimated to affect 50% of patients with type 2 DM. Improvement in cardiovascular survival in a patient with type 2 DM has contributed to patients surviving longer, allowing sufficient time to develop renal disease 14 . The study also found a significant association between CKD and dyslipidemia. Dyslipidemia is a common complication associated with the decline in GFR. Patients with CKD usually have dyslipidemia or more specifically hypertriglyceridemia due to increased concentration of lipoprotein that is rich with triglyceride. Hypertriglyceridemia occurs because of two reasons; delayed catabolism and the increase in hepatic production of triglyceride-rich lipoproteins. Delayed catabolism is mainly responsible for increasing the concentration of triglyceride- rich lipoprotein in CKD patients 12 . In this study, the following limitations should be considered. First, we were not able to take the underlying risk factors into accounts such as ethnicity, geographical, nationality, and type of herbal medication used. Second, the cross-sectional design of the study makes it impossible to infer the causal relationship between indicators of CKD and associated factors. Third, as Ranau is just one of the districts in the state of Sabah, the prevalence of CKD reported could not be generalized to the whole Sabah population. Fourth, people who were aware that they had CKD were more likely to agree to participate in the study which may lead to overestimation in the prevalence of CKD. Fifth, there is also a possibility of overestimation of CKD due to potential selection bias from missing data. Lastly, the study subjects were recruited from a single hospital which may limit the generalizations of the findings of this study. Therefore, these findings cannot represent symptoms of CKD of the whole population. Thus, the prevalence of CKD is higher than what is reported in other studies on kidney disease (probably due to sample sizes and different geographical areas). It is also dependent upon smoking, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, and family history. These factors should be considered 'high risk' in Malaysia, and early detection of CKD in these groups should be implemented. CONCLUSION Prevalence of CKD among community remote areas Sabah was 53%. The significant risk factors associated with CKD in this study were family history of kidney disease, alcohol consumption, smoking status, hypertension, dyslipidemia, and diabetes mellitus. Thus, CKD in East Malaysia is common, early detection and treatment among these communities to potentially improve outcomes can be implemented. Further research should look into the impact of other variables such as type of occupation, and source of water intake as these are potential risk factors for impairment of renal function. CONFLICT OF INTEREST The authors declare that they have no conflicts of interest. ACKNOWLEDGEMENT Upmost acknowledgment should be prioritized to the University Malaysia Sabah for the funding by the Top-down Grant with Medical and Health Science Journal, Vol. 4, No.2, August 2020 74 ethics approval number: NMRR-18-2615- 44151. Sincere gratitude expressed to the director of Ranau Hospital, Malaysia, for blood sampling which was conducted by staff of the health department and assess to patients’ medical records. The authors are grateful to the staff in the Department of Medical and Nephrology clinic is offering active cooperation. Last but not least, thankfulness delivered to one and all for their willingness to contribute to this paper. 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