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



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.



Compared to [Na+] of 150 mmol L-1, ex vivo HDF-IPIS at 500 mmol L-1demonstrated 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-1in 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).



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.
Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany.
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DH
Krieter
eXcorLab GmbH, Obernburg, Germany.
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E
Devine
Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany.
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T
Körner
eXcorLab GmbH, Obernburg, Germany.
M
M
Rüth
Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany.
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C
Wanner
eXcorLab GmbH, Obernburg, Germany.
M
M
Raine
Institute of Molecular Cardiovascular Research, University Hospital RWTH Aachen, Aachen, Germany.
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J
Jankowski
eXcorLab GmbH, Obernburg, Germany.
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HD
Lemke
D000368:Aged; D000818:Animals; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012756:Sheep; D014511:Uremia / Q000517:prevention & control
end-stage renal disease; haemodiafiltration; haemodialysis; ionic strength; maintenance dialysis; protein-bound toxins