Understanding Risk Factors for Progressive Chronic Kidney Disease in Malawi

NCT06312072 | Unknown

• 1 other identifier: 23-019
• Study Type: observational
• Target: 1,100
• Locations: 1 country
• Sites: 1

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

Conditions

Chronic Kidney Diseases; Non-Communicable Chronic Diseases; Non-communicable Disease; Kidney Diseases

Outcome Measures

Primary Outcomes (3)

• Aim 1, objective 3 primary outcome measure

  25% reduction in eGFRcystC from baseline AND change in eGFRcystC category

  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

  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)

  Deaths reported over maximum 10 year time period (time of inclusion in NCD study, 2013-16, to time of analysis, 2023)

Secondary Outcomes (8)

• Aim 1, objective 3 secondary outcome measure 1:

  Over duration of follow-up (2013 to 2025, average around 7.5 years)

• Aim 1, objective 3 secondary outcome measure 2:

  Over duration of follow-up (2013 to 2025, average around 7.5 years)

• Aim 1, objective 3 secondary outcome measure 3:

  Over duration of follow-up (2013 to 2025, average around 7.5 years)

• Aim 1, objective 3 secondary outcome measure 4:

  Over duration of follow-up (2013 to 2025, average around 7.5 years)

• Aim 1, objective 3 secondary outcome measure 5:

  Over duration of follow-up (2013 to 2025, average around 7.5 years)

Study Arms (2)

MEIRU rural population cohort

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

MEIRU urban population cohort

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

Interventions

No intervention; observational study OTHER

No intervention; observational study

MEIRU rural population cohort; MEIRU urban population cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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).

You may qualify if:

• Adult ≥ 18 years at time of participation in 2013-16 NCD survey
• Living in one of the demographic surveillance sites (Chilumba, Karonga or Lilongwe area 25)
• Creatinine +/- cystatin C result available from serum sample taken in 2013-16 NCD survey

You may not qualify if:

• Child (age \<18 years)
• Not living in one of the study areas
• Aim 1, Objective 2 (retrospective cohort study)
• eGFRcreat ≥60ml/min/1.73m3 at baseline (using creatinine tested on serum sample from 2013-16 survey)
• Participated and provided blood (serum) sample in 2022-25 long-term conditions (LTC) survey i.e. individual-level longitudinal paired serum samples available, including consent already given for testing of stored samples in future studies
• Child (age \<18 years)
• Not living in one of the study areas
• Not consented previously to storage of blood samples and use of samples in future studies
• Aim 1, Objective 3
• As for Objective 1, PLUS:
• eGFRcystC \<90ml/min/1.73m3 at baseline (using cystatin C tested on 2013-16 serum sample)
• Participated and provided serum sample in 2022-25 long-term conditions (LTC) survey i.e. individual-level longitudinal paired serum samples available
• Still alive and living in one of the demographic surveillance sites
• Able to provide consent or assent with consent from an appropriate nominated guardian
• Exlusion criteria:

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead
• Wellcome Trust: collaborator
• Malawi Epidemiology and Intervention Research Unit: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• University of Glasgow: collaborator
• Malawi-Liverpool-Wellcome Trust Clinical Research Programme: collaborator

Study Sites (1)

Malawi Epidemiology and Intervention Research Unit

Chilumba, Karonga, P.O. Box 46, Malawi

RECRUITING

Related Publications (26)

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• Levin A, Tonelli M, Bonventre J, Coresh J, Donner JA, Fogo AB, Fox CS, Gansevoort RT, Heerspink HJL, Jardine M, Kasiske B, Kottgen A, Kretzler M, Levey AS, Luyckx VA, Mehta R, Moe O, Obrador G, Pannu N, Parikh CR, Perkovic V, Pollock C, Stenvinkel P, Tuttle KR, Wheeler DC, Eckardt KU; ISN Global Kidney Health Summit participants. Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet. 2017 Oct 21;390(10105):1888-1917. doi: 10.1016/S0140-6736(17)30788-2. Epub 2017 Apr 20.

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• Stanifer JW, Jing B, Tolan S, Helmke N, Mukerjee R, Naicker S, Patel U. The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2014 Mar;2(3):e174-81. doi: 10.1016/S2214-109X(14)70002-6. Epub 2014 Feb 10.

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• Kaze AD, Ilori T, Jaar BG, Echouffo-Tcheugui JB. Burden of chronic kidney disease on the African continent: a systematic review and meta-analysis. BMC Nephrol. 2018 Jun 1;19(1):125. doi: 10.1186/s12882-018-0930-5.

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• Fabian J, Kalyesubula R, Mkandawire J, Hansen CH, Nitsch D, Musenge E, Nakanga WP, Prynn JE, Dreyer G, Snyman T, Ssebunnya B, Ramsay M, Smeeth L, Tollman S, Naicker S, Crampin A, Newton R, George JA, Tomlinson L; African Research on Kidney Disease Consortium. Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study. Lancet Glob Health. 2022 Aug;10(8):e1159-e1169. doi: 10.1016/S2214-109X(22)00239-X.

  PMID: 35839814 BACKGROUND

• Luyckx VA, Moosa MR. Priority Setting as an Ethical Imperative in Managing Global Dialysis Access and Improving Kidney Care. Semin Nephrol. 2021 May;41(3):230-241. doi: 10.1016/j.semnephrol.2021.05.004.

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• Dreyer G, Dobbie H, Banks R, Allain T, Gonani A, Turner NLV. Supporting Malawi's dialysis services in the international community. Br J Ren Med. 2012;17:24-6.

  BACKGROUND

• https://www.theisn.org/blog/2014/11/24/caring-for-kidney-patients-in-malawi/

  BACKGROUND

• Fabian J, George JA, Etheredge HR, van Deventer M, Kalyesubula R, Wade AN, Tomlinson LA, Tollman S, Naicker S. Methods and reporting of kidney function: a systematic review of studies from sub-Saharan Africa. Clin Kidney J. 2019 Aug 19;12(6):778-787. doi: 10.1093/ckj/sfz089. eCollection 2019 Dec.

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• Nakanga WP, Prynn JE, Banda L, Kalyesubula R, Tomlinson LA, Nyirenda M, Crampin AC. Prevalence of impaired renal function among rural and urban populations: findings of a cross-sectional study in Malawi. Wellcome Open Res. 2019 Jun 10;4:92. doi: 10.12688/wellcomeopenres.15255.1. eCollection 2019.

  PMID: 31656860 BACKGROUND

• Muiru AN, Charlebois ED, Balzer LB, Kwarisiima D, Elly A, Black D, Okiror S, Kabami J, Atukunda M, Snyman K, Petersen M, Kamya M, Havlir D, Estrella MM, Hsu CY. The epidemiology of chronic kidney disease (CKD) in rural East Africa: A population-based study. PLoS One. 2020 Mar 4;15(3):e0229649. doi: 10.1371/journal.pone.0229649. eCollection 2020.

  PMID: 32130245 BACKGROUND

• Kalyesubula R, Nankabirwa JI, Ssinabulya I, Siddharthan T, Kayima J, Nakibuuka J, Salata RA, Mondo C, Kamya MR, Hricik D. Kidney disease in Uganda: a community based study. BMC Nephrol. 2017 Apr 3;18(1):116. doi: 10.1186/s12882-017-0521-x.

  PMID: 28372551 BACKGROUND

• Stanifer JW, Maro V, Egger J, Karia F, Thielman N, Turner EL, Shimbi D, Kilaweh H, Matemu O, Patel UD. The epidemiology of chronic kidney disease in Northern Tanzania: a population-based survey. PLoS One. 2015 Apr 17;10(4):e0124506. doi: 10.1371/journal.pone.0124506. eCollection 2015.

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• Ruggenenti P, Perna A, Mosconi L, Matalone M, Pisoni R, Gaspari F, Remuzzi G. Proteinuria predicts end-stage renal failure in non-diabetic chronic nephropathies. The "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN). Kidney Int Suppl. 1997 Dec;63:S54-7.

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• Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995 Nov 15;123(10):754-62. doi: 10.7326/0003-4819-123-10-199511150-00003.

  PMID: 7574193 BACKGROUND

• Agrawal V, Marinescu V, Agarwal M, McCullough PA. Cardiovascular implications of proteinuria: an indicator of chronic kidney disease. Nat Rev Cardiol. 2009 Apr;6(4):301-11. doi: 10.1038/nrcardio.2009.11.

  PMID: 19352334 BACKGROUND

• Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group. Lancet. 1997 Jun 21;349(9068):1787-92.

  PMID: 9269212 BACKGROUND

• Ruggenenti P, Perna A, Remuzzi G. ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy. J Am Soc Nephrol. 2001 Dec;12(12):2832-2837. doi: 10.1681/ASN.V12122832.

  PMID: 11729254 BACKGROUND

• Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. Epub 2020 Oct 23.

  PMID: 33264825 BACKGROUND

• Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.

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• The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4.

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• Okpechi IG, Bello AK, Ameh OI, Swanepoel CR. Integration of Care in Management of CKD in Resource-Limited Settings. Semin Nephrol. 2017 May;37(3):260-272. doi: 10.1016/j.semnephrol.2017.02.006.

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• World Health Organization. Strengthening Health Systems to Improve Health Outcomes. https://www.who.int/healthsystems/ strategy/en/. 2007. Accessed February 26, 2021

  BACKGROUND

• Commission NP. The Malawi Noncommunicable Diseases & Injuries Poverty Commission Report. Lilongwe: Malawi Ministry of Health, 2018. http://www.ncdipoverty.org/malawi-report

  BACKGROUND

• Crampin AC, Dube A, Mboma S, Price A, Chihana M, Jahn A, Baschieri A, Molesworth A, Mwaiyeghele E, Branson K, Floyd S, McGrath N, Fine PE, French N, Glynn JR, Zaba B. Profile: the Karonga Health and Demographic Surveillance System. Int J Epidemiol. 2012 Jun;41(3):676-85. doi: 10.1093/ije/dys088. Epub 2012 Jun 22.

  PMID: 22729235 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum (blood) samples will be stored in MEIRU's biorepository for use in future longitudinal studies

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Noncommunicable Diseases; Kidney Diseases

Interventions

Observation

Condition Hierarchy (Ancestors)

Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Charlotte Snead, BM BCh

  Liverpool School of Tropical Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurence Tembo

CONTACT

+265 888 348 705; laurence.tembo@meiru.mw

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: March 15, 2024
• Study Start: February 14, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 15, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: The MEIRU data access management committee is responsible for deciding on data to be made publicly available, and time frames.
• Access Criteria: The MEIRU data access management committee is responsible for deciding on data to be made publicly available, and time frames. Additionally, through a systematised data access requests, the committee will authorize access to more highly resolved data sets. The Biorepository Access Management Committee will approve sample access plans.

Locations

MA (1)