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 . 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 , ex vivo HDF-IPIS at 500 mmol L demonstrated up to 50% higher IS removal. Haemolysis in sheep was low even at [Na ] of 600 mmol L (free Hb 0.016 ± 0.001 g dL ). In patients, compared to HD, a [Na ] of 240 mmol L 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 ), the dialytic clearance of free IS was 31.6 ± 12.8 mL min (P = 0.017) in HDF-IPIS, but [Na ] in arterial blood increased from 132 ± 2 to 136 ± 3 mmol L (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.