Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals

HIV Med. 2014 Feb;15(2):116-23. doi: 10.1111/hiv.12087. Epub 2013 Sep 11.


Objectives: The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFR(cr)), cystatin C (GFR(cys)) and the combination of these markers (GFR(cr-cys)) have recently been assessed in HIV-infected individuals. We assessed the associations of GFR, estimated by these three equations, with clinical events in HIV-infected individuals.

Methods: We compared the associations of baseline GFR(cr), GFR(cys) and GFR(cr-cys) [using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations] with mortality, cardiovascular events (CVEs) and opportunistic diseases (ODs) in the Strategies for the Management of Antiretroviral Therapy (SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation (SD) change in GFR.

Results: A total of 4614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFR(cys) was weakly to moderately correlated with HIV RNA, CD4 cell count, high-sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFR(cr) had little or no correlation with these factors. GFR(cys) had the strongest associations with the three clinical outcomes, followed closely by GFR(cr-cys), with GFR(cr) having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors and inflammation markers, a 1-SD lower GFR(cys) was associated with a 55% [95% confidence interval (CI) 27-90%] increased risk of mortality, a 21% (95% CI 0-47%) increased risk of CVE, and a 22% (95% CI 0-48%) increased risk of OD.

Conclusions: Of the three CKD-EPI GFR equations, GFR(cys) had the strongest associations with mortality, CVE and OD.

Trial registration: NCT00027352.

Keywords: HIV-1; cardiovascular disease; creatinine; cystatin C; glomerular filtration rate; mortality; opportunistic disease.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS-Related Opportunistic Infections / blood*
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Biomarkers / blood
  • Cardiovascular Diseases / blood*
  • Creatinine / blood*
  • Cystatin C / blood*
  • Female
  • Glomerular Filtration Rate*
  • HIV Infections / blood*
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / mortality
  • HIV-1*
  • Humans
  • Kidney Diseases / diagnosis
  • Kidney Diseases / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • RNA, Viral / blood


  • Anti-HIV Agents
  • Biomarkers
  • Cystatin C
  • RNA, Viral
  • Creatinine

Associated data