Coagulation is associated with renal function decline and chronic kidney disease in people living with HIV in South Africa

Abstract

Background Chronic inflammation is a well-documented feature of human immunodeficiency virus (HIV) infection and is implicated in the progression of several comorbidities, including chronic kidney disease (CKD). Notably, chronic coagulation activation is another common phenomenon mediated by chronic inflammation among people living with HIV (PLWH) and has also been linked to CKD progression. However, the relationship between inflammation, coagulation and renal dysfunction remains underexplored in African populations with high HIV prevalence. This study investigated the association between systemic inflammation, coagulation activation and renal function among PLWH, particularly those receiving antiretroviral therapy (ART). Methods In this cross-sectional study, 151 adults were enrolled, comprising 80 PLWH on ART, 27 PLWH not on ART, and 44 people not living with HIV (PNLWH). Inflammatory marker, C-reactive protein (CRP) and coagulation markers including fibrinogen and D-dimer, were measured and CKD stages were determined using estimated glomerular filtration rate (eGFR), which was calculated based on cystatin C (cystC) levels (eGFR cystC ). Results In the overall PLWH cohort, D-dimer was significantly associated with reduced eGFR cystC in both crude ( p = 0.004) and adjusted analyses ( p = 0.014), indicating poorer kidney function. Fibrinogen showed a significant association with reduced eGFR cystC only after adjusting for confounders ( p = 0.048). Among PLWH on ART, D-dimer remained independently associated with reduced eGFR cystC , while fibrinogen showed an independent association after adjustment (β = -1.54, p = 0.031). Elevated fibrinogen levels were associated with an increased odds of CKD in the overall PLWH group (AOR = 1.12, 95% CI 1.00–1.23, p = 0.0 41), and elevated D-dimer levels were associated with increased odds of CKD among those on ART (AOR = 1.01, 95% CI 1.00–1.03, p = 0.045). Conclusion The study reveals that both D-dimer and fibrinogen, key markers of coagulation are independently associated with renal function decline and risk of CKD in PLWH, particularly those on ART. These findings suggest that coagulation activation may be an early indicator of declining kidney function and increased risk of CKD in PLWH, potentially preceding overt systemic inflammation.