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Risk factors for long-term decline in kidney function amongst Malawian adults living in rural Karonga: protocol for a prospective cohort study

Snead, C. M.; Mkandawire, C.; Kambiya, P.; Munthali-Mkandawire, S.; Kalobekamo, F.; Dube, A.; Nkosi-Gondwe, T.; Mtenga, B. B.; Nzundah, D.; Kwamkwanya, L.; Bellings, D.; Nakanga, W.; Fabian, J.; Kalyesubula, R.; Phiri, C.; Limbani, F.; Taylor, D. M.; Crampin, A. C.; Mwandumba, H. C.; Price, A. J.

2025-08-05 epidemiology
10.1101/2025.08.01.25332688 medRxiv
Show abstract

BackgroundThe global burden of chronic kidney disease (CKD) is rising, disproportionately impacting on low- and middle-income countries. In African populations, use of serum creatinine to estimate glomerular filtration rate (GFR) significantly underestimates CKD prevalence, contributing to its under-recognition as a health problem. Serum cystatin C provides more accurate estimates of Iohexol measured GFR than creatinine. Early diagnosis and treatment of CKD, targeted towards high-risk individuals, is essential to reduce premature morbidity and mortality. However, little is known about risk factors for CKD development and progression in Africa owing to limited longitudinal data. This study aims to determine risk factors for progressive kidney function decline among adults living in rural, northern Malawi. MethodsThis protocol describes an ongoing prospective study being conducted in a general population cohort in rural Karonga, Malawi. We are recruiting adults aged 18 years and over who participated in two previous population-based surveys of long-term health conditions, over five years apart. New household-level data is being collected on CKD risk factors, alongside blood and urine samples. Cystatin C and creatinine will be tested on individual-level paired, stored serum samples collected at three longitudinal time points. Urine will undergo dipstick urinalysis, microscopy and testing for albumin and creatinine to quantify proteinuria. The primary outcome will be sustained 25% reduction in estimated GFR (eGFR) from baseline and change in eGFR category, determined using serum cystatin C. Multivariable logistic regression will be used to determine effect size estimates of key risk factors for kidney function decline. DiscussionThis study will provide important data on risk factors for eGFR decline and CKD progression amongst Malawian adults. The findings will inform future research into important context-specific risk factors, and could directly inform future health policies in Malawi for targeting CKD screening, prevention and treatment strategies to the highest risk patient groups.

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