How to estimate glomerular filtration rate in sub-Saharan Africa: design and methods of the African Research into Kidney Diseases (ARK) study

Abstract

Background: Chronic kidney disease (CKD) is a substantial cause of morbidity and mortality worldwide with disproportionate effects in sub-Saharan Africa (SSA). The optimal methods to estimate glomerular filtration rate (GFR) and therefore to determine the presence of CKD in SSA are uncertain. We plan to measure iohexol excretion to accurately determine GFR in Malawi, South Africa and Uganda. We will then assess the performance of existing equations to estimate GFR and determine whether a modified equation can better improve estimation of GFR in sub-Saharan Africa. Methods: The African Research on Kidney Disease (ARK) study is a three-country study embedded within existing cohorts. We seek to enrol 3000 adults > 18 years based on baseline serum creatinine. Study procedures include questionnaires on socio-demographics and established risk factors for kidney disease along with anthropometry, body composition, blood pressure, blood chemistry and urine microscopy and albuminuria. We will measure GFR (mGFR) by plasma clearance of iohexol at 120, 180 and 240 min. We will compare eGFR determined by established equations with mGFR using Bland-Altman plots. We will use regression methods to estimate GFR and compare the newly derived model with existing equations. Discussion: Through the ARK study, we aim to establish the optimal approach to estimate GFR in SSA. The study has the advantage of drawing participants from three countries, which will increase the applicability of the findings across the region. It is also embedded within established cohorts that have longitudinal information and serial measures that can be used to characterize kidney disease over a period of time. This will help to overcome the limitations of previous research, including small numbers, selected population subgroups , and lack of data on proteinuria. The ARK collaboration provides an opportunity for close working partnerships across different centres, using standardized protocols and measurements, and shared bio-repositories. We plan to build on the collaboration for this study for future work on kidney disease in sub-Saharan Africa, and welcome additional partners from across the continent.

Methods to estimate baseline creatinine and define acute kidney injury in lean Ugandan children with severe malaria: a prospective cohort study

“…This emphasizes the importance of nutritional status and body habitus when selecting methods to estimate bSCr and the need for evaluating and validating a range of equations. Efforts are underway to evaluate eGFR equations in adults across sub-Saharan Africa [15], and parallel efforts in children would be advantageous to better understand how measured GFR and estimated bSCr relate in this setting.…”

“…As such, the development of validated height-independent approaches to estimate bSCr in LMIC would simplify AKI diagnosis. Recently, there have been efforts to measure creatinine and evaluate the burden of kidney disease in adults in sub-Saharan Africa [13][14][15][16], but data from pediatric populations are lacking [17].…”

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

“…In the past few years, there have been efforts to validate GFR estimating equations within adult populations in sub-Saharan Africa, [33][34][35] but data from pediatric populations are lacking. 36 Additional studies to evaluate and standardize approaches to estimate baseline AKI across the pediatric age-spectrum for low-and-middle-income countries are needed to facilitate comparisons across populations and age groups in LMIC and high-income countries (HIC).…”

Diagnostic accuracy of semiquantitative point of care urine albumin to creatinine ratio and urine dipstick analysis in a primary care resource limited setting in South Africa

“…Our sub-study comprised part of the prospective African Research on Kidney (ARK) study, the methods of which have been published [ 23 ]. To summarise, the ARK study was conducted in the Agincourt Health and Demographic Surveillance Site, Mpumalanga province, SA.…”