Haemodiafiltration at increased plasma ionic strength for improved protein-bound toxin removal

Aim: Protein-bound uraemic toxin accumulation causes uraemia-associated cardiovascular morbidity. Enhancing the plasma ionic strength releases toxins from protein binding and makes them available for removal during dialysis. This concept was implemented through high sodium concentrations ([Na⁺ ]) in the substituate of pre-dilution haemodiafiltration at increased plasma ionic strength (HDF-IPIS).

Methods: Ex vivo HDF-IPIS with blood tested increasing [Na⁺ ] to demonstrate efficacy and haemocompatibility. Haemocompatibility was further assessed in sheep using two different HDF-IPIS set-ups and [Na⁺ ] between 350 and 600 mmol L^-1 . Safety and efficacy of para-cresyl sulphate (pCS) and indoxyl sulphate (IS) removal was further investigated in a randomized clinical pilot trial comparing HDF-IPIS to HD and HDF.

Results: Compared to [Na⁺ ] of 150 mmol L^-1 , ex vivo HDF-IPIS at 500 mmol L^-1 demonstrated up to 50% higher IS removal. Haemolysis in sheep was low even at [Na⁺ ] of 600 mmol L^-1 (free Hb 0.016 ± 0.001 g dL^-1 ). In patients, compared to HD, a [Na⁺ ] of 240 mmol L^-1 in HDF-IPIS resulted in 40% greater reduction (48.7 ± 23.6 vs. 67.8 ± 7.9%; P = 0.013) in free IS. Compared to HD and HDF (23.0 ± 14.8 and 25.4 ± 10.5 mL min^-1 ), the dialytic clearance of free IS was 31.6 ± 12.8 mL min^-1 (P = 0.017) in HDF-IPIS, but [Na⁺ ] in arterial blood increased from 132 ± 2 to 136 ± 3 mmol L^-1 (0 vs. 240 min; P < 0.001).

Conclusion: HDF-IPIS is technically and clinically feasible. More effective HDF-IPIS requires higher temporary plasma [Na⁺ ], but dialysate [Na⁺ ] has to be appropriately adapted to avoid sodium accumulation.