Evaluation of the impact of delayed centrifugation on the diagnostic performance of serum creatinine as a baseline measure of renal function before antiretroviral treatment

Background: The measurement of serum creatinine is a standard requirement of the medical management of people living with HIV. Renal dysfunction is common, both as a complication of HIV-infection and as a result of its treatment. The detection of abnormal renal function before the start of antiretroviral therapy will impact patient management and the outcome of treatment. Objectives: This study aimed to determine if a time delay in the centrifugation of serum samples affected the creatinine level and the estimated glomerular filtration rate as recorded on the analytical platforms used in the laboratory. Methods: Twenty-two (n = 22) HIV-positive, newly diagnosed and treatment-naïve patients were randomly recruited from Alexandra Health Clinic, Johannesburg, South Africa. Serum samples were centrifuged at six time intervals following receipt of the sample viz. < 4 h (baseline), 6 h, 24 h, 48 h, 72 h and 96 h. Creatinine concentrations were measured on the Roche platform utilising the enzymatic and kinetic Jaffe methods. Whole blood samples were also analysed with the Abbott i-STAT point-of-care instrument. The estimated glomerular filtration rate was calculated using the Cockcroft Gault, CKD-Epidemiology Collaboration and Modified Diet and Renal Disease v3/4 equations. Results: At baseline (< 4 h) there was good agreement between the enzymatic and kinetic Jaffe methods: bias 1.7 μmol/l. The enzymatic and i-STAT creatinine concentrations were stable over 96 h viz. changes of 1.8% and 5.7%. However, from 24 h onwards agreement between the enzymatic and kinetic Jaffe methods was poor with the latter measuring 43.7 μmol/l higher than the enzymatic method at 96 h. Creatinine concentrations measured with the kinetic Jaffe method increased significantly in samples centrifuged after 6 h (p < 0.001, 61.7% change), and resulted in a 95% decline in eGFR at 96 h as determined with the CKD-Epidemiology Collaboration equation. Conclusion: The analysis of serum creatinine using the isotope dilution mass spectrometry traceable kinetic Jaffe method is unreliable if performed on samples centrifuged ≥ 6 h after collection. The raised creatinine concentration can affect clinical decisions such as renal functional assessment, choice of antiretroviral drug or regimen, and the dose and frequency of medication.