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

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Biochemistry

Background:

• Protein-bound uremic toxins contribute to cardiovascular complications in patients with kidney failure.
• Increasing plasma ionic strength can release these toxins from protein binding, enhancing their removal during dialysis.

Purpose of the Study:

• To evaluate the efficacy and safety of pre-dilution hemodiafiltration at increased plasma ionic strength (HDF-IPIS) using high sodium concentrations.
• To assess the removal of specific protein-bound toxins, para-cresyl sulfate (pCS) and indoxyl sulfate (IS).

Main Methods:

• Ex vivo testing of HDF-IPIS with varying sodium concentrations ([Na+]) to assess toxin removal and hemocompatibility.
• In vivo assessment of hemocompatibility in sheep using HDF-IPIS with high [Na+].
• A randomized clinical pilot trial comparing HDF-IPIS to standard hemodialysis (HD) and hemodiafiltration (HDF) in patients.

Main Results:

• Ex vivo HDF-IPIS at 500 mmol/L [Na+] showed up to 50% higher IS removal compared to 150 mmol/L [Na+].
• Hemolysis in sheep was minimal even at 600 mmol/L [Na+].
• In patients, HDF-IPIS with 240 mmol/L [Na+] achieved a 40% greater reduction in free IS compared to HD and significantly higher dialytic clearance of free IS.

Conclusions:

• HDF-IPIS is a technically and clinically feasible dialysis method.
• Higher temporary plasma [Na+] enhances HDF-IPIS effectiveness, but careful dialysate [Na+] management is crucial to prevent sodium overload.