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Cystatin C in HIV Infection: A Marker of Pre-clinical Kidney Disease
Michelle Odden*1, R Scherzer1, L Szczech2, S Sidney3, P Bacchetti1,4, P Bacchetti1,4, C Grunfeld1,4, C Grunfeld1,4, M Shlipak1,4, and M Shlipak1,4
1San Francisco VAMC, CA, US; 2Duke Univ Med Ctr, Durham, NC, US; 3Kaiser Permanente, Oakland, CA, US; and 4Univ of California, San Francisco Sch of Med, US
Background: Kidney disease has been identified as an
important complication of human HIV infection, but the majority of studies of
HIV and kidney function have focused on severe kidney disease or HIV-associated
nephropathy. Cystatin C is an alternative measure of
kidney function that may be more sensitive compared with creatinine
in the setting of chronic disease.
Methods: We compared kidney
function in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM)
cohort, a nationally representative sample in the United States, studying 1008 HIV-infected
participants and 290 population-based controls from the CARDIA study. Analyses
comparing HIV-infected participants with controls were restricted to 519 HIV-infected
participants in the same age-range as the controls. Kidney function was measured using cystatin C, creatinine, and estimated glomerular
filtration rate (eGFR) by the abbreviated modification
of diet in renal disease (MDRD) equation. Elevated cystatin
C was defined as >1.0 mg/L, a threshold demonstrated to be associated with
increased risk for kidney and cardiovascular disease and death. A
comparable creatinine-based endpoint was an eGFR
<75 mL/minute/1.73 m2, which also corresponded to the fourth
percentile in the control population.
Results: Cystatin C was
higher in HIV-infected individuals; mean cystatin C
was 0.92±0.22 mg/L in HIV-infected and
0.76±0.15 mg/L in controls, p <0.0001. In contrast, mean
creatinine levels and eGFR were similar in HIV-infected
and controls (0.87±0.21
vs 0.85±0.19, p = 0.35
and 110±26 vs
106±23, p = 0.06, respectively). In
HIV-infected participants, cystatin C was not
correlated with lean body mass (r = –0.01,
95%CI –0.08 to 0.06, p = 0.87), whereas creatinine
was positively correlated (r = 0.34,
95%CI 0.28 to 0.40, p <0.0001).
After adjustment for demographic characteristics and clinical factors, HIV
infection was associated with a greater odds for cystatin
C >1.0 mg/dL (odds ratio = 9.8, 95%CI 4.4 to 22.0,
p <0.0001). HIV infection was not
associated with significantly increased odds for lower eGFR
(OR = 1.28, 95%CI 0.56 to 2.92, p = 0.55).
Conclusions: Despite similar mean creatinine
levels in HIV-infected persons and controls, HIV infection was associated with
elevated cystatin C, a sensitive marker of impaired
kidney function. Cystatin C could be a useful
clinical tool to identify HIV-infected persons at increased risk for kidney and
cardiovascular disease.
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