Longitudinal Estimated GFR Trajectories Among Workers at High Risk for CKD of Unknown Etiology

Abstract Introduction Chronic kidney disease of unknown etiology (CKDu) is a leading cause of mortality among young men in Nicaragua and El Salvador but longitudinal trends in kidney health and disease incidence remain poorly characterized. Methods We estimated glomerular filtration rate (eGFR) among young adult male workers in Nicaragua and El Salvador without known CKD (n=569), ages 18-45 years, with follow up every 6 months for three years. We estimated cumulative incidence of CKD, defined as ≥2 eGFR measurements of <60 mL/min/1.73 m², and incidence rate in person-years. We used a hierarchical clustering approach to identify latent patterns in longitudinal eGFR. Results Cumulative incidence was 4.5% (n=24). Incidence rate was 22.2 cases per 1,000 person-years (95%CI: 13.6 - 30.9). All incident cases experienced eGFR decline of >5 mL/min/1.73 m²/year. Mean annual decline in eGFR was -4.3 mL/min/1.73 m²/year (SE:0.3). Cluster analyses revealed four eGFR trajectories described as declining, stable and high, rapidly declining, and low and declining. Participants in the low and declining cluster (n=57; 10.9%) experienced mean annual eGFR decline of -8.2 mL/min/1.73 m²/year (SD: 0.7), with a pattern suggesting seasonal kidney stress and recovery. Participants in the rapidly declining cluster (n=10) were very young men (mean age: 23) who experienced a precipitous drop in eGFR (mean annual decline: -12.5 mL/min/1.73 m²/year (SD: 1.6)). Conclusion In this prospective cohort we observed declining eGFR including rapid decline in a young and apparently healthy subgroup. Relying on incidence measures alone may underestimate poor kidney health in the context of CKDu.