Ignite Creation Date:
2024-05-06 @ 8:16 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06312072
Status:
RECRUITING
Last Update Posted:
2024-03-15
First Post:
2023-04-11
Brief Title:
Understanding Risk Factors for Progressive Chronic Kidney Disease in Malawi
Sponsor:
Liverpool School of Tropical Medicine
Organization:
Liverpool School of Tropical Medicine
Study Overview
Official Title:
Understanding Risk Factors for Progressive Chronic Kidney Disease in Malawi to Inform Interventions for Earlier Detection and Prevention Impso Study
Status:
RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
1 Determine the mortality associated with CKD and the risk factors driving its development and progression in Malawian adults 2 Investigate the impacts of different models for integrating screening and prevention strategies for CKD and its risk factors into health services for other long-term conditions in low- and middle-income countries 3 With patients carers healthcare workers and policy makers 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
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
1 Determine the mortality associated with CKD and the risk factors driving its development and progression in Malawian adults 2 Investigate the impacts of different models for integrating screening and prevention strategies for CKD and its risk factors into health services for other long-term conditions in low- and middle-income countries 3 With patients carers healthcare workers and policy makers 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
Detailed Description:
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 89
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 90mlmin173m2 may be 51 and eGFR 60mlmin173m2 as high as 119 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 eg 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 governments 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 MEIRUs 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 MEIRUs 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 MEIRUs 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 n50000 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 202226 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
Investigate the association between baseline kidney function and mortality outcomes all-cause and cause-specific in Malawian adults Study design
Survival analysis using secondary data Study population
Adults aged 18 years living within the demographic surveillance areas Karonga HDSS - area 25 Lilongwe depending on availability of longitudinal data for the urban site who participated in the 2013-16 NCD survey Approach and methods
eGFRcreat and eGFRcystC will be calculated for adults living in the rural - urban site who have had serum creatinine estimated n5000 - cystatin C estimated n2500 tested on historical serum samples collected during their participation in the 2013-16 NCD survey and for whom longitudinal demographic surveillance data is available
Existing sociodemographic and comorbidity data will be available for these individuals
Existing mortality data physician assigned cause of death from verbal autopsy reports will be analysed to for adults in different baseline eGFR categories
Participants will be included until last point of follow-up
Aim 1 objective 2 - Investigate the risk factors for development of impaired kidney function in Malawian adults
Study design
Retrospective cohort study Study population
Adults aged 18 years living within the demographic surveillance areas Karonga HDSS - area 25 Lilongwe who had had eGFRcreat 60mlmin173m2 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
A sample of n4000 adults with eGFRcreat 60mlmin173m2 at baseline 2013-16 will be randomly selected within age and sex strata these creatinine results are already available from which eGFR can be calculated
The participants will have already participated in the 2022-25 LTC survey serum and plasma samples are collected for storage in this survey and participants provide consent for testing of these samples in future studies
Creatinine will be tested on the 2022-25 LTC serum samples such that each participant has individual-level paired creatinine results from the two surveys
Extensive sociodemographic and comorbidity data from both surveys already exists for all participants These will be used to analyse associations between risk factors of interest and development of kidney disease outcome measures
Aim 1 Objective 3
Investigate the risk factors for progression of impaired kidney function in Malawian adults Study design
Prospective cohort study
Study population
- Adults aged 18 years living within the demographic surveillance areas Karonga HDSS - area 25 Lilongwe with persistent eGFRcystC 90mlmin173m2 during their participation in both the 2013-16 NCD and 2022-25 LTC surveys
Approach and methods
An age- sex- and site-stratified sample of n1000-1100 adults with eGFRcystC 90mlmin173m2 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
1 A medical interview containing questions on potential risk factors for kidney disease not already captured in the LTC survey specific medical history specific medications family history
2 Health-related quality of life data
3 HIV rapid test and counselling will be offered to individuals with unknown HIV status
4 Venepuncture for blood tests - creatinine and cystatin C taken 90 days after LTC sample confirming chronicity and for storage
5 Early morning mid-stream urine MSU collection - for point of care dipstick urinalysis and laboratory tests including microscopy gram stain filtration and centrifugation for Schistosoma ova and urine albumin-creatinine ratio uACR
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 andor 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
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 89
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 90mlmin173m2 may be 51 and eGFR 60mlmin173m2 as high as 119 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 eg 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 governments 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 MEIRUs 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 MEIRUs 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 MEIRUs 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 n50000 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 202226 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
Investigate the association between baseline kidney function and mortality outcomes all-cause and cause-specific in Malawian adults Study design
Survival analysis using secondary data Study population
Adults aged 18 years living within the demographic surveillance areas Karonga HDSS - area 25 Lilongwe depending on availability of longitudinal data for the urban site who participated in the 2013-16 NCD survey Approach and methods
eGFRcreat and eGFRcystC will be calculated for adults living in the rural - urban site who have had serum creatinine estimated n5000 - cystatin C estimated n2500 tested on historical serum samples collected during their participation in the 2013-16 NCD survey and for whom longitudinal demographic surveillance data is available
Existing sociodemographic and comorbidity data will be available for these individuals
Existing mortality data physician assigned cause of death from verbal autopsy reports will be analysed to for adults in different baseline eGFR categories
Participants will be included until last point of follow-up
Aim 1 objective 2 - Investigate the risk factors for development of impaired kidney function in Malawian adults
Study design
Retrospective cohort study Study population
Adults aged 18 years living within the demographic surveillance areas Karonga HDSS - area 25 Lilongwe who had had eGFRcreat 60mlmin173m2 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
A sample of n4000 adults with eGFRcreat 60mlmin173m2 at baseline 2013-16 will be randomly selected within age and sex strata these creatinine results are already available from which eGFR can be calculated
The participants will have already participated in the 2022-25 LTC survey serum and plasma samples are collected for storage in this survey and participants provide consent for testing of these samples in future studies
Creatinine will be tested on the 2022-25 LTC serum samples such that each participant has individual-level paired creatinine results from the two surveys
Extensive sociodemographic and comorbidity data from both surveys already exists for all participants These will be used to analyse associations between risk factors of interest and development of kidney disease outcome measures
Aim 1 Objective 3
Investigate the risk factors for progression of impaired kidney function in Malawian adults Study design
Prospective cohort study
Study population
- Adults aged 18 years living within the demographic surveillance areas Karonga HDSS - area 25 Lilongwe with persistent eGFRcystC 90mlmin173m2 during their participation in both the 2013-16 NCD and 2022-25 LTC surveys
Approach and methods
An age- sex- and site-stratified sample of n1000-1100 adults with eGFRcystC 90mlmin173m2 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
1 A medical interview containing questions on potential risk factors for kidney disease not already captured in the LTC survey specific medical history specific medications family history
2 Health-related quality of life data
3 HIV rapid test and counselling will be offered to individuals with unknown HIV status
4 Venepuncture for blood tests - creatinine and cystatin C taken 90 days after LTC sample confirming chronicity and for storage
5 Early morning mid-stream urine MSU collection - for point of care dipstick urinalysis and laboratory tests including microscopy gram stain filtration and centrifugation for Schistosoma ova and urine albumin-creatinine ratio uACR
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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None