Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiologic mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of beta-hydroxybuyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In Study 1 (n=10), patients became alkalemic using 37 mEq/L dialysate bicarbonate; in contrast, using 27 mEq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 mEq/L dialysate bicarbonate (50.9 versus 49.1 mEq using 27 mEq/L, p=0.66); serum BHB increased in both treatments similarly (p=0.27); and blood lactate was only slightly higher using 37 mEq/L dialysate (p=0.048), differing by 0.2 mEq/L at the end of hemodialysis. In Study 2 (n=7), patients achieved steady-state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 mEq/L bicarbonate dialysate compared with 35 mEq/L, and as in Study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to Study 1 and again did not differ between treatments (38.9 versus 43.5 mEq, p=0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r=0.81, p <0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis nor modify organic anion losses into dialysate.