Risk factors for decline in estimated glomerular filtration rate amongst Malawian adults living in rural Karonga: Protocol for a prospective cohort study using cystatin C- and creatinine-based eGFR

BACKGROUND: The 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 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. METHODS: This protocol describes a prospective study being conducted in a general population Health and Demographic Surveillance Site in rural Karonga, Malawi (2024-2025). Eligible participants are adults aged 18 years and over who participated in two population-based surveys of long-term health conditions (2013-2016 and 2021-2025), with availability of baseline measures. New household-level data is being prospectively 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. DISCUSSION: This 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 health policies in Malawi for targeting CKD screening, prevention and treatment strategies to high-risk patient groups.