The Prevalence of Obesity among Subjects with Chronic Kidney Disease – Cross Sectional Study of Sri Lanka

Background: The burden of chronic kidney disease (CKD) is growing rapidly around the world, particularly in Asia. Over the last two decades Sri Lanka has experienced an epidemic of CKD, especially in the “Mahaweli” river basin in North Central region of the island that was not attributable to conventional risk factors hence widely termed “CKD-unknown”. Similarly, obesity in the region also noted to increase but no formal study explored the obesity burden or its association with increasing CKD in the region.


Background
This was apparently a new form of CKD which was not attributable to conventional risk factors such as diabetes mellitus, hypertension or infection and widely termed as "CKD-unknown" or "CKDu".In the past decade a number of small scale studies were conducted to determine the aetiology, prevalence and complications of CKDu in North Central region [5,[7][8][9][10][11].These hospital-based studies did not provide an accurate estimate of the problem as merely 10% or less of the people with CKD are aware of their diagnosis even in developed countries with better access to medical care [12].A population based cross sectional survey conducted in 2010-2011 reported a point prevalence of CKDu to be 2-3% in this region [5].A later survey in the same endemic region by Jayathilaka and colleagues reported an age standardised prevalence of CKDu of 12.9% for men and 16.9% for women [13].Nonetheless, a well-designed population based cross sectional survey identifying the prevalence of CKD from all causes, not just due to CKDu, has not been conducted to date.Multiple aetiological factors have been postulated for CKDu including chronic exposure to Cadmium, Lead, Arsenic and Ochratoxin-A through food chain [8,9,[13][14][15][16].However, increasing CKDu may be multifactorial and obesity may also be a contributing factor -that has not been systematically studied to date [17].

Significance of the Project
CKD and ESKD are increasingly recognised as major public health problems in the NCP of Sri Lanka.Number of premature deaths in ESKD patients due to lack of access to RRT are also on the rise in this region.Clearly, documenting the magnitude of the problem as well as the availability of its treatment in the region is the essential first step in developing appropriate response to the threat.Our study will provide this vital information enabling the government to plan a coordinated response.The innovative models of delivering preventive care can be organised, especially in rural areas where access to physicians is low.If obesity remains a substantial problem in the region, effective population based approaches to prevention and treatment of obesity may be implemented as part of the wider CKD prevention programmes.Government can be made aware of the number of preventable deaths and must be lobbied to increase access to dialysis for affected individuals where this is affordable in the context of the broader health needs of the population.

Study population
"Mahaweli" river basin development project in 1969-80 was the largest multi-purpose development project conducted in Sri Lanka to date with a view to establish a controlled irrigation system and increase the area of paddy cultivation, manage flood waters, hydro-electricity generation and develop new townships for farmers.
We selected "Mahaweli" development project area C (Girandurukotte) since this population is equally affected by CKD as rest of "Mahaweli' river basin.Moreover, the area C (Girandurukotte) has a small land size, easily accessible dense stable population and reliable demographic data.
CKD is detrimental, may be progressive and can lead to end-stage kidney disease (ESKD) requiring dialysis or a renal transplantation for survival.Individuals with CKD have a reduced life expectancy, and those who progress to ESKD have 20-fold higher mortality rates compared with age-and sex-matched individuals with normal kidney function [18,19].However, if detected early and managed properly, then the otherwise inevitable deterioration in kidney function can be reduced by as much as 50% and may even be reversed, and lead to cost savings [20][21][22].Therefore, it is important to recognise the magnitude of the public health problem, its aetiology, and available resources and plan appropriate response.
1. Describe the prevalence of CKD overall and by stage in "Mahaweli" development project area C (Girandurukotte), in the North Central Province (NCP) of Sri Lanka Aims of the Project 2. Document the prevalence of renal replacement therapy (RRT) overall and by modality in "Mahaweli" development project "Area C (Girandurukotte)", in the NCP of Sri Lanka 3. Describe prevalence of obesity in the same area and assess the association between CKD and obesity

Detailed Research Plan
The area C (Girandurukotte) is a purpose built planned township in the river basin and it's relatively isolated, hence this area has a stable population which is ethnically homogeneous.The houses were built alongside 6 roads, each extending from the town centre to periphery, close to each other leading to relatively higher population density in the area.Area C (Girandurukotte) has a health centre, a public school, a Buddhist temple, a local government agent's office and a playground as public facilities.According to the national census in 2012, 2214 adults (51.2% females) were living in 723 households in area C (Girandurukotte) (http://www.statistics.gov.lk/).Both health centre and local government agent's office have a proper record keeping system and have kept upto-date information about the residents from the inception of this township, making it easier to conduct a reliable study.These records showed that the number of residents diagnosed with CKD was gradually rising over last two decades with the highest increase over last five years; however the actual CKD prevalence in the region remains unknown.

Target population:
We will include all non-institutionalised subjects (18 years or older on 01/01/2017) permanently living in "Mahaweli" development project area C (Giradurukotte).The permanent residency status will be confirmed against the records at the government agent's office and the electoral records.Any person younger than 18 years, visiting or temporary residing in the area at the time of survey will be excluded.

Study design
We will conduct an area wide population based cross sectional survey.Allowing for non-compliance with request to participate, we expect to survey about 2000 participants in 650-700 households from 01 st to 31 st of January 2017.
We will define CKD as reduced estimated glomerular filtration rate (eGFR) and/or presence of proteinuria.CKD will be classified according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines [23].Renal replacement therapy will be defined as receiving any form of maintenance dialysis or with a functioning renal transplant.Obesity will be defined and classified based on body mass index (BMI) according to World Health Organization classification [24].

Outcome definitions
The following definitions will be used where applicable: Proteinuria -albumin/creatinine ratio >2.5mg/mmol (male) and >3.5mg/mmol (females) Haematuria -presence of >10 red blood cells per high power field Anaemia -serum haemoglobin <100 g/l or on Erythropoietin stimulating agents Hypocalcaemia -serum total calcium of < 2.2 mmol/l Hyperphosphatemia -serum phosphate >1.5 mmol/l Body mass index -body weight/height 2 kg/m 2 We will recruit and train 30 data collectors at Hector Kobbekaduwa Agrarian Research and Training Institute, Colombo, Sri Lanka.A data collector will visit each household to record the number of eligible adults, inform residents about the survey and request them to participate (contacting through telephone is not reliable as this facility is not widely available).We will provide with information leaflets and contact details of the data collector if further information is required.If subjects tentatively consent to participate, an appointment will be made in one of the clinic days convenient to them but the formal consent will not be made at this point.We will encourage them to come along with all adults (18 years or older) in the household to the clinic.Repeated visits will be made to contact if not contacted during initial visit (up to a maximum of 3 attempts).On failing to contact after 3 visits alternate methods will be used (ie.through the temple, neighbours or health centre etc.).

Conduct of survey
Data collection and management: We will organise 10 full day clinics over January 2017 at the health centre in area C (Girandurukotte) to review and collect pathology samples from participants.
At the clinic each participant will be consented formally and sign a formal consent form.A trained data collector will conduct the clinical interview using an interviewer administered questioner.Study investigators will take turns to monitor data collection process to ensure uniformity and highest standard.
For each participant following data will be collected: • Demographic and clinical data (age, sex, weight, height, waist circumference, comorbidities, medications etc.) • Socio-economic data (education, income, occupation, race etc.) • Use of RRT and type (haemodialysis, peritoneal dialysis or renal transplant) • Smoking status • Clinic blood pressure (3 measurements 5-10 minutes apart) For each participant following pathology samples will be collected: • A mid-stream urine sample • A trained nurse will draw a peripheral blood sample (about 10ml) Validation procedures: All pathology samples will be analysed at a central laboratory.Samples will be stored under appropriate conditions in the field until transferred to the central laboratory at a leading Private Hospital in Colombo, Sri Lanka.Serum creatinine, haemoglobin, calcium, phosphate, albumin and HbA1c will be reported for each blood sample.Analysing serum parathyroid hormone level is not feasible due to high cost.Serum creatinine will be measured using Integra 800 analyser by Roche Diagnostics, Mannheim, Germany and the GFR will be estimated using CKD-EPI formula [25].The albumin/creatinine ratio and haematuria will be reported for each urine sample.