HIV viremia and T-cell activation differentially affect the performance of glomerular filtration rate equations based on creatinine and cystatin C

Abstract

Background: Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established.

Methods: We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry.

Results: The median mGFR was >100 ml/min/1.73 m(2) in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C.

Conclusions: The performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.

Figure 1. Bland-Altman plots for estimated and measured glomerular filtration rate (GFR) in HIV-positive participants using the CKD-EPI equations for serum creatinine (A), cystatin C (B), or both biomarkers (C).

The average GFR (measured and estimated) is shown on the X axes. Bias, defined as the difference between estimated and measured GFR, is displayed on the Y axes. The average biases are represented by the horizontal solid lines and the horizontal dashed lines represent 2 standard deviations above and below the averages.

Figure 2. Bland-Altman plots for estimated and measured glomerular filtration rate (GFR) in HIV-negative participants using the CKD-EPI equations for serum creatinine (A), cystatin C (B), or both biomarkers (C).

The average GFR (measured and estimated) is shown on the X axes. Bias, defined as the difference between estimated and measured GFR, is displayed on the Y axes. The average biases are represented by the horizontal solid lines and the horizontal dashed lines represent 2 standard deviations above and below the averages.

Figure 3. Correlation of estimated glomerular filtration rate (eGFR) bias, defined as the difference between eGFR and measured GFR, with percentage of activated CD8 T cells (CD38+ and HLA-DR+) using the creatine-based CKD-EPI equation in HIV-negative (A) and HIV-positive (B) subjects, and the cystatin C-based CKD-EPI equation in HIV negative (C) and HIV-positive (D) subjects.

The percentage of CD8+ T cells with an activated phenotype is shown on the X axes (note, different scales for HIV-positive and HIV-negative groups). Rho is the spearman rank correlation coefficient, which may vary between −1 and 1. The dashed lines represent least-squares regression lines.