Negative creatinine–cystatin C eGFR discordance is associated with immunovirologic vulnerability in people with HIV

People living with HIV (PLWH) remain at risk of kidney dysfunction, making the assessment of glomerular filtration an component of HIV care. However, both creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR) are influenced by non-GFR determinants, and discordance between these estimates may provide information beyond kidney function. We evaluated the prevalence, immunovirologic correlates, and longitudinal evolution of eGFRcr–eGFRcys discordance in PLWH. We conducted a retrospective study of 409 treated PLWH. Negative discordance was defined as eGFRcys > 30% lower than eGFRcr. Multivariable logistic regression evaluated factors associated with negative discordance. Longitudinal analyses examined changes in eGFR estimates and immunovirologic parameters among 172 participants with measurements. Negative discordance occurred in 86 participants (21.0%). Immune dysfunction was associated with negative discordance (OR 3.33, 95% CI 1.81–6.13), with CD4 < 200 cells/µL showing the association (OR 7.15, 95% CI 3.54–14.46). Detectable HIV RNA was independently associated with negative discordance. Negative discordance attenuated, with marked discordance decreasing from 26.7% to 10.5% ( p < 0.001). This convergence reflected a decline in eGFRcr and an increase in eGFRcys, while combined eGFRcr-cys remained stable. Immunovirologic status improved, but low CD4/CD8 ratios remained more frequent among participants with baseline negative discordance. Negative eGFRcr–eGFRcys discordance is common in PLWH and is associated with immunologic dysfunction and detectable HIV RNA. Its attenuation during follow-up, together with divergent trajectories of eGFR estimates, suggests that dynamic non-GFR determinants contribute to this phenotype. Discordance may provide a marker of residual immunovirologic vulnerability beyond measures of kidney function.