Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women

Background: Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine. Design: Retrospective cohort analysis. Methods: Cystatin C and creatinine were measured from specimens taken and stored during the 1999-2000 examination among 908 HIV-infected participants in the Women's Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluated with multivariable linear regression. The associations of baseline categories (<60, 60-90, and >90 ml/min per 1.73m²) of creatinine estimated GFR (eGFR_cr), cystatin C eGFR (eGFR_cys), and combined creatinine-cystatin C eGFR (eGFR _cr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging. Results: CKD risk factors were associated with lower eGFR_cys and eGFR_cr-cys values compared with eGFR_cr. Relative to eGFR more than 90, the eGFR less than 60 category by eGFR_cys (Adjusted hazard ratio: 2.56; 95% confidence interval: 1.63-4.02), eGFR_cr-cys (3.11; 1.94-5.00), and eGFR_cr (2.34; 1.44-3.79) was associated with increased mortality risk. However, the eGFR 60-90 category was associated with increased mortality risk for eGFR_cys (1.80; 1.28-2.53) and eGFR_cr-cys (1.91; 1.38-2.66) but not eGFR_cr (1.20; 0.85-1.67). The overall NRI for mortality was 26% when reclassifying from eGFR_cr to eGFR _cys (P<0.001) and was 20% when reclassifying from eGFR _cr to eGFR_cr-cys (P<0.001). Conclusion: The addition of cystatin C may improve mortality risk prediction by stages of kidney function relative to creatinine. CKD risk factors are associated with an overestimate of GFR by serum creatinine relative to cystatin C.