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

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.