Abstract

Abstract Background and Aims Serum creatinine is mainly used to estimate GFR in a patient with steady state kidney function. In ESKD patients on HD therapy however it may be used as a surrogate muscle mass indicator The predialysis serum creatinine decreases in time with HD therapy duration and low pre dialysis concentrations have been associated with increased all cause and cardiovascular mortality probably related to protein energy wasting. Under these conditions our working hypothesis was that exploring blood cytokine biomarkers (BM) and their significance in HD patients the correction of BM blood values to a prognosis marker (as pre dialysis serum creatinine) may change the results of our findings. Method 63 G5D patients (21 female and 42 male median age 61years.) have been included in a prospective study concerning assessment of 5 blood cytokine biomarkers (KIM-1,TGF beta, IL-6, soluble Klotho and VEGF) and their prognosis significance. At inclusion, the median duration of HD therapy was 3.2 years. Patients have been assessed for cardiovascular disease (including history, EKG and cardiac ultrasound, PVW). Standard blood biochemistry and blood count have been performed. Enzyme- linked immunosorbent assays were used for the assessment of blood BM. Statistical correlations of cytokine values and cytokine/predialysis serum creatinine with the collected data were performed Results The average plasma levels of the investigated biomarkers were: KIM-1 267.1+/-482.9 pg/ml, IL-6 7.3+/-5.1 pg/ml, TGFβ 298.9+/-609.5 pg/ml, VEGF 1371.3+/-787.5 pg/ml, Soluble Klotho 305.7+/-341.6 pg/ml. The average predialysis serum creatinine (SCr) was 8.4+/-1.9 mg/dl. KIM-1 levels correlated with CRP (r=0.28, p=0.028) and Left Ventricular Hypertrophy (LVH) (r= - 0.28, p=0.026). The correlations of KIM-1/SCr did not significantly differ (with CRP r= 0.29, p=0.023 and LVH r= - 0.25, p= 0.047). IL-6 levels correlated with sKlotho (r=0.37, p=0.003), IL-6/SCr however correlated with iPTH (r=0.26, p=0.045), sKlotho (r=0.90, p=0.001), Alc.P (r=0.32, p=0.012), Ferritin (r= - 0.28, p=0.029), monthly EPO dose (r= - 0.26, p=0.044), TGFβ (r=0.36, p=0.023), VEGF/SCr (r=0.43, p= 0.000). TGFβ correlated with SCr levels (r= - 0.32, p=0.047) but TGFβ/SCr correlated with sKlotho (r=0.36, p=0.005), IL-6 (r=0.98, p=0.000), Ferritin levels (r= - 0.28, p=0.027). VEGF did not correlate with any of our investigated data however when reported to SCr, VEGF/SCr correlated with sKlotho (r=0.34, p=0.008), monthly EPO dose (r= - 0.27, p=0.035), PWW results (r= - 0.33, p=0.034), IL-6/SCr (r= 0.43, p=0.000), sKloto/SCr (r=0.39, p=0.002). sKlotho correlated with IL-6 (see above), daily EPO dose (r= - 0.31, p=0.013). sKlotho/SCr correlated with eKt/V (r=0.25, p=0.048), TGFβ (r=0.34, p=0.034), IL-6 (as above), iPTH (r=0.26, p=0.043), Ferritin (r= - 0.27, p=0.024). Conclusion With the exception of KIM-1 our working hypothesis was confirmed and it seems that in HD patients statistics are modified if blood biomarkers (BM) are referred to predialysis serum creatinine. More research is needed in order to verify the validity and significance of our observations.

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