An observational study in Chronic Kidney Diseases, Non-Communicable Chronic Diseases and Non-communicable Disease, sponsored by Liverpool School of Tropical Medicine. Recruiting at 1 site in Malawi. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-15.
Sponsored by Liverpool School of Tropical Medicine · Observational
Worldwide, the number of people living with long-term health conditions, including chronic kidney disease (CKD), is increasing. CKD is usually asymptomatic in early stages but can progress to advanced disease, including kidney failure, causing significant morbidity and mortality.
In low-income countries of sub-Saharan Africa, including Malawi, treatments for kidney failure are not yet widely available and are prohibitively expensive . It is therefore vital to:
(a) Prevent development of CKD in the first place (b) Detect CKD earlier so that more cost-effective treatments can be given to slow progression.
There is little evidence on factors that drive CKD progression in Malawi, or on interventions that may be cost-effective for improving detection and slowing disease progression in this setting. This PhD will address these knowledge gaps, through the following aims:
Background:
CKD prevalence is rising most rapidly in sub-Saharan Africa (current estimates 13-15%), where health systems are least equipped to tackle it (1-7). Malawi has only one nephrologist for a population of over 19 million and kidney replacement therapy (KRT), which consumes disproportionate healthcare spending, remains extremely limited (8,9).
Historically there has been insufficient data on CKD in LMICs owing to difficulties accessing diagnostics and uncertainty regarding the most appropriate context-specific methods for estimating kidney function (10).
Recent research by the African Research on Kidney Disease (ARK) group using measured GFR has shown that previous creatinine-based estimates significantly underestimated CKD burden in many African countries; in Malawi prevalence of eGFR \<90ml/min/1.73m2 may be 51%, and eGFR \<60ml/min/1.73m2 as high as 11.9% (6).
CKD has many causes, impacting on the public health strategies required to tackle it; however data on its underlying causes in Malawi and other countries of low-income Africa remain limited.
Cross-sectional data suggests risk is greater in older people with other LTCs (e.g. hypertension, HIV), however other causes are unaccounted for (11-14). No longitudinal research has been conducted in Malawi to explore the impact of traditional and non-traditional risk factors on CKD development and progression.
Evidence on proteinuria in Malawi is also sparse, a well-recognised predictor for progressive kidney disease, cardiovascular morbidity and mortality (15-17) and a therapeutic target of drugs mitigating progression (18-22).
Early detection and prevention of CKD and its risk factors, integrated with other LTCs, is vital to cost-effectively improve health outcomes within available resources, as recognised by the Malawi government's National Action Plan for NCDs (23-25). To guide this, more research is urgently needed on the risk factors for CKD development and progression in this setting, and on strategies for early detection and prevention and that may be effectively integrated with public health plans for other LTCs, without reliance on specialist nephrology input.
Aims and Objectives:
The overall work package has three main aims:
Aim 1: Determine (a) the mortality associated with CKD, and (b) the risk factors driving its development and progression in Malawian adults
Aim 2: Investigate the impacts of different models for integrating screening and prevention strategies for CKD and its risk factors into health services for other LTCs in LMICs.
Aim 3: With different stakeholder groups, qualitatively evaluate the feasibility and acceptability of different potential models for integrating CKD screening and prevention strategies into health services for high-risk patient groups in Malawi
The work described here relates to observational research which aims to address Aim 1. The specific objectives within Aim 1 are as follows:
Aim 1, Objective 1:
In Malawian adults aged ≥18 years living in MEIRU's rural +/- urban population cohorts, investigate the association between baseline kidney function and mortality outcomes (all-cause and cause-specific)
Aim 1, Objective 2:
In adults aged ≥18 years living in MEIRU's rural and urban population cohorts, determine the risk factors associated with development of impaired kidney function
Aim 1, Objective 3:
In adults aged ≥18 years living in MEIRU's rural and urban population cohorts, determine the risk factors associated with progression of impaired kidney function
Planned methods for Aim 1:
The proposed work for Aim 1 is nested within MEIRU rural (Karonga HDSS) and urban (Area 25, Lilongwe) open, population-based cohorts. These nationally representative cohort populations (n>50,000 adults ≥15 years) are situated in 135km2 of rural subsistence farming and fishing communities in northern Malawi and a township in the capital city. Population surveillance already includes annual censuses; births, deaths and migration registration, sociodemographic data and HIV-testing. This is ongoing in the rural cohort since 2002 and commenced in the urban cohort in 2022.26 For all deaths, a standardised WHO verbal autopsy (VA) tool is used to assign cause of death.
In both settings a comprehensive NCD survey was conducted 2013-2016. The currently ongoing Healthy Lives Malawi (HLM) survey is re-surveying long-term conditions (LTCs) in these populations. Available data from these two surveys includes household (SES, geolocators), interview (demographics, lifestyle factors, clinical history (prior diagnosis, screening and medications for chronic conditions), examination and measures (anthropometry, blood pressure, hand grip strength, peripheral arterial measures) and biological sample collection (serum, plasma and whole blood samples stored at -80 Celsius and other biological material).
Aim 1, objective 1
Aim 1, objective 2 - Investigate the risk factors for development of impaired kidney function in Malawian adults
Study design
Adults aged ≥18 years living within the demographic surveillance areas (Karonga HDSS +/- area 25, Lilongwe), who had had eGFRcreat ≥60ml/min/1.73m2 during their participation in the 2013-16 NCD survey, and who have also participated in the follow-up 2022-25 LTC survey Approach and methods
Aim 1, Objective 3
Study population
Approach and methods
An age-, sex- and site-stratified sample of n=1000-1100 adults with eGFRcystC \<90ml/min/1.73m2 at baseline (2013-16) will be selected (serum creatinine results will also be available for these individuals)
The participants will have already participated the 2022-25 LTC survey; serum and plasma samples are collected for storage in this survey and participants provide consent for testing of these in related and future studies.
Cystatin C and creatinine will be tested on the 2022-25 LTC serum samples such that each participant has individual-level paired kidney function results from the two previous surveys.
At ≥90 days following the LTC sample collection, a medical fieldworker will visit the household of each eligible participant to invite participation and consent (or assent) to participate in data collection for kidney disease and its risk factors, using standardised procedures for recording, collecting measurements and coding.
The data collected on kidney disease and its risk factors will include:
The medical interview and health-related quality of life questionnaire data will be collected at the first household visit following the patient information and consent process; blood and urine samples will then be collected at a second, early morning household visit. Screening questions about menstruation (for females) and symptoms of urinary tract infection will be asked prior to scheduling the second household visit. Participants with symptoms of urine infection will be referred for clinical assessment. Participants with new urine symptoms or with particular urine dipstick abnormalities (leucocytes, nitrites and/or blood) at the point of urine collection at the second household visit will receive a third household visit for collection of a second, confirmatory urine sample.
Schistosoma IgG ELISA and CRP, new risk factors of interest, will be tested on participants' stored serum samples (from 2013-16).
Data on these new risk factors of interest will be analysed for association with kidney disease progression outcomes.
The proposed work for Aim 1 is nested within MEIRU rural (Karonga HDSS) and urban (Area 25, Lilongwe) open, population-based cohorts. These nationally representative cohort populations are situated in 135km2 of rural subsistence farming and fishing communities in northern Malawi and a township in the capital city. Population surveillance already includes annual censuses; births, deaths and migration registration, sociodemographic data and HIV-testing. This is ongoing in the rural cohort since 2002 and commenced in the urban cohort in 2022 (26). Detailed sociodemographic and risk factor data is available from two surveys (2013-16 non-communicable disease survey and 2022-25 long-term conditions survey).
Aim 1, Objective 1 (survival analysis):
Inclusion Criteria:
Exclusion Criteria:
Aim 1, Objective 2 (retrospective cohort study)
Inclusion criteria:
Exclusion Criteria:
Aim 1, Objective 3
Inclusion criteria:
As for Objective 1, PLUS:
Exlusion criteria:
Adults aged \>=18 living in MEIRU's rural health demographic surveillance area (Karonga district) No interventions to be administered; observational study only, with collection of survey data, blood samples and urine samples.
Other: No intervention; observational study
Adults aged \>=18 living in MEIRU's urben demographic surveillance area (Lilongwe Area 25) No interventions to be administered; observational study only, with collection of survey data, blood samples and urine samples.
Other: No intervention; observational study
No intervention; observational study
Aim 1, objective 3 primary outcome measure
25% reduction in eGFRcystC from baseline AND change in eGFRcystC category
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 2 primary outome measure
Development of eGFRcreat \<60ml/min/1.72m2
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 1 primary outcome measure:
• All-cause mortality rate per 1000 person-years at risk (adjusted for age, sex, key comorbidities)
Time frame: Deaths reported over maximum 10 year time period (time of inclusion in NCD study, 2013-16, to time of analysis, 2023)
Aim 1, objective 3 secondary outcome measure 1:
25% reduction in eGFRcreat from baseline AND change in eGFRcreat category
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 3 secondary outcome measure 2:
57% decline in eGFR
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 3 secondary outcome measure 3:
40% decline in eGFR
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 3 secondary outcome measure 4:
30% decline in eGFR
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 3 secondary outcome measure 5:
20% decline in eGFR
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 3 secondary outcome measure 6:
Kidney failure, defined by: * eGFR\<15ml/min/1.73m2 * Commencement of maintenance KRT (≥4 weeks duration)
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 2 secondary outcome measure:
Development of eGFRcreat \<90ml/min/1.72m2
Time frame: Over duration of follow-up (2013 to 2025, average around 7.5 years)
Aim 1, objective 1 secondary outcome measure:
Cause-specific mortality per 1000 person-years at risk (physician-assigned)
Time frame: Deaths reported over maximum 10 year time period (time of inclusion in NCD study, 2013-16, to time of analysis, 2023)
Plan to share: Yes — This study will contribute data to the MEIRU data repository. MEIRU has a data access management committee which will approve any requested access to MEIRU data repository.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Liverpool School of Tropical Medicine