Exploring the liver-kidney axis in the Ghanaian population: the RODAM prospective study.

Muhulo Muhau Mungamba, Felix Patience Chilunga, Eva L van der Linden, Erik Beune, Peter Henneman, Charles Frederick Hayfron-Benjamin, Karlijn Anna Catharina Meeks, Samuel Nkansah Darko, Sampson Twumasi-Ankrah, Ellis Owusu-Dabo, Adriaan Georgius Holleboom, Liffert Vogt, Bert-Jan van den Born, Benedicta Ngwenchi Nkeh-Chungag, Charles Agyemang

Journal: Journal of global health 2026;16():04252

PMID: 42495747

Abstract

BACKGROUND

The liver-kidney axis has been increasingly recognised as a potential pathway linking metabolic dysfunction to chronic kidney disease (CKD). However, longitudinal evidence from sub-Saharan African populations remains limited. We therefore aimed to prospectively investigate the association of baseline liver biomarkers with incident CKD and its components over six years in a transcontinental cohort of Ghanaians living in rural and urban Ghana and Amsterdam, the Netherlands.

METHODS

Using data from the prospective Research on Obesity and Diabetes among African Migrants cohort, we examined baseline liver biomarkers (gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the fatty liver index (FLI) in relation to incident CKD over approximately six years among Ghanaians in rural and urban Ghana and Amsterdam, The Netherlands. CKD was defined according to the Kidney Disease: Improving Global Outcomes 2021 criteria using race-free CKD-EPI equations. We used Poisson regression with robust standard errors to estimate adjusted incidence rate ratios (aIRRs) per standard deviation increases, adjusting for demographic, lifestyle, metabolic, and clinical factors. In fully adjusted models, we additionally accounted for longitudinal change (Δ) in liver biomarkers to isolate the association of baseline hepatic dysfunction with subsequent CKD risk.

RESULTS

Among 1,832 participants free of CKD at baseline (mean age of 45.9 years, 63% female), the incidence of CKD was 11%, the incidence of albuminuria was 9.7%, and the incidence of decreased estimated glomerular filtration rate (eGFR) was 2.3% over the follow-up period. Incident CKD was independently associated with higher baseline GGT (aIRR = 1.12; 95% confidence interval (CI) = 1.01-1.23), ALT (aIRR = 1.27; 95% CI = 1.04-1.50), and AST (aIRR = 1.20; 95% CI = 1.04-1.34). Associations were primarily driven by albuminuria, while we observed no significant associations for decreased eGFR. In exploratory analyses, elevated FLI was associated with incident CKD (aIRR = 1.92; 95% CI = 1.14-3.18 and albuminuria (aIRR = 2.15; 95% CI = 1.24-3.68), suggesting a broader metabolic-hepatic phenotype linked to early renal injury. Effect estimates remained materially consistent after inverse probability weighting to address differential follow-up.

CONCLUSIONS

In our study, markers of liver cell injury were associated with increased risk of CKD over six years in the African population. Our findings support a potential link between hepatic metabolic dysfunction and early renal injury, highlighting the need for integrated cardiometabolic risk assessment in sub-Saharan Africa.

© 2026 The Authors.

Address: Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Department of Human Biology, Nelson Mandela Drive, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa.; Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Department of Human Genetics and Epigenetics, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Department of Physiology and Anaesthesia/Critical Care, University of Ghana Medical School / Korle Bu Teaching Hospital, Accra, Ghana.; Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, USA.; Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of Statistics and Actuarial Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of Global and International Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Department of Internal Medicine, Section Nephrology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Department of Human Biology, Nelson Mandela Drive, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa.; Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, USA.
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