Background: Inulin clearance is the most accurate test for GFR measurement. Recently, we have shown that in patients with β-thalassemia major, Inulin clearance measurements were 40% lower than estimated GFR (eGFR), calculated by different creatinine-based equations, when creatinine was measured by the Jaffe reaction (Creat-J). Since inulin clearance cannot be routinely used, the present study examines whether serum creatinine measurement using enzymatic method (Creat-E) or Cystatin C could provide a better assessment of kidney function than Creat-J.
Methods: During routine outpatient clinic visits, blood samples were drawn from β-thalassemia major patients for serum Creat-E and Creat-J calibrated to isotope-dilution mass spectrometry traceable, Cystatin C, and thyroid function tests. To calculate eGFR, creatinine and Cystatin C values were placed in the following equations: Cockcroft-Gault (CG), MDRD study, 2009 CKD-EPI creatinine, 2012 CKD-EPI creatinine-cystatin C, and 2012 CKD-EPI cystatin C. Statistical analysis was performed using Spearman's correlation test and Wilcoxon non-parametric paired test. Data are presented as means ± SD. P≤0.05 was considered to be statistically significant.
Results: A total of 22 adult patients were included. The mean age of all patients was 38±10 yrs, of whom 45% were above 50 yrs and 59% were females. All patients received iron chelating agents and had normal thyroid function tests. The results demonstrated a significant difference between paired values of creatinine. Mean Creat-J was 0.45±0.3 mg/dl, median 0.37 mg/dl (0.18-1.23 mg/dl); mean Creat-E was 0.63±0.3 mg/dl, median 0.55 mg/dl (0.27-1.35 mg/dl), p<0.001, which comprises a 32±18% and 33% lower mean and median Creat-J vs. Creat-E, respectively. Using Spearman's test, correlation between Creat-E and Creat-J was 0.75 (p<0.001). Then, eGFR was calculated. Using 2009 CKD-EPI Creat-E eGFR as a reference, most equations showed statistically significant overestimation of eGFRs. Correlation coefficients showed best agreement of eGFR values based on CKD-EPI Creat-E and MDRD Creat-E, =0.954 and between CKD-EPI Creat-E and CKD-EPI Creat-J = 0.854, p<0.01. eGFR based on Cystatin C did not improve correlation vs. CKD-EPICreat-E (0.733), yet when combined with Creat-E, in 2012 CKD-EPI creatinine-cystatin C formula, the coefficient was 0.892, p<0.01.
Conclusions: Our results suggest that in thalassemia major patients, creatinine should be measured using a standardized enzymatic method. Furthermore, based on correlation and paired evaluation results, we suggest applying the 2009 CKD-EPICreat-E or 2012 CKD-EPI Creatinine E-cystatin C equations to estimate GFR in this subset of hematologic patients.