EFFECTS OF ACETATE DIALYSATE ON TRANSFORMING GROWTH-FACTOR BETA-1, INTERLEUKIN, AND BETA-2-MICROGLOBULIN PLASMA-LEVELS

To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1-alpha, IL-1-beta, IL-6), TNF-alpha, TGF-beta-1, and beta-2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF-beta-1, was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF-beta-1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P < 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P < 0. 10). Acutely. TGF-beta-1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac-free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70.52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57. 43 to 69 pg/ml; P < 0.05). beta-2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac-free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM VS. 1.05 mmol +/- 0.07 SEM; P < 0.05). Inflammatory cytokines may, therefore, not be detectable with standard ELISA assays even after HD. TGF-beta-1, which stimulates extracellular matrix and collagen synthesis and modulates other cytokines, could affect the progression of CRF and combined with acetate's possible effects on phosphate kinetics, could play a role in ectopic calcifications and renal bone disease. Finally, no effect of acetate on beta-2-microglobulin levels was found.