Kidney filter estimates that disagree may flag immune vulnerability in HIV

People living with HIV who show a specific pattern of disagreement between two common kidney-function estimates may carry a marker of deeper immune and viral vulnerability, according to a retrospective study of 409 treated people living with HIV published in AIDS Research and Therapy.

The pattern in question is negative creatinine–cystatin C eGFR discordance. Both estimates are influenced not only by actual filtration but also by non-GFR determinants, and when the cystatin C-based estimate falls more than 30 percent below the creatinine-based estimate, the person is classified as having negative discordance.

In the study cohort, this negative discordance occurred in 86 of 409 participants, a prevalence of 21.0 percent. The researchers used multivariable logistic regression to identify factors associated with the phenotype.

Immune dysfunction emerged as a central correlate. Negative discordance was associated with immune dysfunction overall, with an odds ratio of 3.33 (95 percent confidence interval 1.81–6.13). When examined by CD4 cell count, participants with fewer than 200 cells per microliter showed the strongest association, with an odds ratio of 7.15 (95 percent confidence interval 3.54–14.46). Detectable HIV RNA was also independently associated with negative discordance.

The study also followed the longitudinal evolution of the discordance among 172 participants who had repeat measurements. Over follow-up, negative discordance attenuated, with marked discordance decreasing from 26.7 percent to 10.5 percent, a change the authors report as statistically significant (p < 0.001).

Importantly, this convergence did not reflect a simple improvement in kidney function. The narrowing gap reflected a decline in the creatinine-based estimate and an increase in the cystatin C-based estimate, while the combined eGFR based on both markers remained stable. This divergent trajectory of the two estimates suggests that dynamic non-GFR determinants, factors that influence creatinine and cystatin C levels independently of filtration itself, contribute to the discordance phenotype.

Immunovirologic status improved during follow-up, but the picture was not uniform. Low CD4/CD8 ratios remained more frequent among participants who had shown negative discordance at baseline, indicating that some residual immunologic signature persisted even as the eGFR estimates converged.

The authors conclude that negative eGFRcr–eGFRcys discordance is common in people living with HIV and is associated with immunologic dysfunction and detectable HIV RNA. They suggest that discordance may provide a marker of residual immunovirologic vulnerability that goes beyond what measures of kidney function alone can offer.

As a retrospective study of treated people with HIV, the findings describe associations rather than causal effects, and the authors note that both eGFR estimates are subject to non-GFR determinants. Even so, the work points to a potentially useful signal: a routine comparison of two standard kidney-function estimates may reveal information about immune and viral status that neither estimate provides on its own.

Subject of Research: Creatinine–cystatin C eGFR discordance as a marker of immunovirologic vulnerability in people with HIV

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

Article References: Casas-Aparicio, G., León-Ortiz, A., Sánchez-Becerra, R., Schjetnan, M. G.-P., & Salgado Montes De Oca, G. (2026). Negative creatinine–cystatin C eGFR discordance is associated with immunovirologic vulnerability in people with HIV. AIDS Research and Therapy. https://doi.org/10.1186/s12981-026-00967-1

Image Credits: AI Generated

DOI: 10.1186/s12981-026-00967-1

Keywords: HIV, eGFR, cystatin C, creatinine, kidney function, CD4 count, immune dysfunction, viral load, retrospective study, biomarker, Negative, cystatin