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Updated: May 4, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
HIV viremia and T-cell activation differentially affect the performance of glomerular filtration rate equations based
Bhavna Bhasin1, Bryan Lau2, Mohamed G Atta1
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Insights
Serum creatinine and cystatin C are common markers for kidney function. In HIV-positive individuals, cystatin C-based estimates of kidney function are less accurate and more biased, potentially limiting their use.
Area of Science:
- Nephrology
- Infectious Diseases
- Immunology
Background:
- Serum creatinine and cystatin C are established markers for estimating glomerular filtration rate (GFR).
- The comparative performance of these endogenous markers against measured GFR (mGFR) in HIV-positive individuals remains incompletely understood.
Purpose of the Study:
- To evaluate the accuracy and bias of estimated GFR equations (eGFRcr, eGFRcys, eGFRcr-cys) compared to mGFR in HIV-positive and HIV-negative individuals.
- To investigate the association of HIV-related factors and T-cell activation with the performance of these GFR markers.
Main Methods:
- Assessed eGFRcr, eGFRcys, and eGFRcr-cys performance against plasma iohexol clearance (mGFR) in 187 HIV-positive and 98 HIV-negative participants.
- Defined bias as eGFR-mGFR difference and accuracy as the percentage of eGFR within 30% of mGFR.
- Measured activated CD4 and CD8 T-cells using flow cytometry and assessed hepatitis C seropositivity.
Main Results:
- All eGFR equations showed reduced accuracy in HIV-positive compared to HIV-negative individuals; eGFRcr-cys was the most accurate overall.
- In HIV-positive individuals, eGFRcys demonstrated significantly lower accuracy and higher bias, associated with antiretroviral therapy, HIV RNA suppression, and T-cell activation.
- Hepatitis C seropositivity increased eGFRcys bias in both groups, while eGFRcr performance was not affected by HIV-related factors or T-cell activation.
Conclusions:
- The performance of cystatin C-based GFR estimation in HIV-positive individuals is significantly influenced by HIV treatment status and immune activation markers.
- These associations may compromise the reliability of eGFRcys as a GFR marker in this specific population.
- Creatinine-based eGFR equations showed more consistent performance irrespective of HIV-related factors.
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.
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