Abstract: TH-PO857

The Effects of Peritoneal Dialysis and Intraperitoneal Amino Acids on Protein Carbamylation

Session Information

  • Peritoneal Dialysis - I
    November 02, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis

Authors

  • Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Perl, Jeffrey, St. Michael's Hospital, Toronto, Ontario, Canada
  • Freeman, Megan Jolie, St. Michael's Hospital, Toronto, Ontario, Canada
  • Trottier, Caitlin A., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Berg, Anders H., Beth Israel Deaconess Medical Center , Boston, Massachusetts, United States
Background

Protein carbamylation is a urea-driven post translational protein modification associated with mortality in hemodialysis (HD) patients. Free amino acids (AA) competitively inhibit protein carbamylation and parenteral AA therapy reduces carbamylation in HD patients. Peritoneal dialysis (PD) yields differences in urea clearance and AA balance compared to HD, but its effects on carbamylation are unclear. We assessed carbamylation burden in PD patients and determined the effects of AA enriched PD solutions on carbamylation.

Methods

We measured carbamylated albumin levels (C-Alb; a marker of total body carbamylation load) in 100 diabetic HD subjects, matched by age, sex, and race to 98 PD subjects with available plasma samples from the IMPENDIA trial. The IMPENDIA randomized trial (n=180) examined whether low-glucose PD solutions (combination of dextrose, icodextrin, and amino acids) improved metabolic control in diabetic PD patients compared to a control group (dextrose only solutions; 48 treated and 50 control subjects had samples available). C-Alb was compared between HD and PD groups and within IMPENDIA by treatment allocation.

Results

PD patients had a higher baseline C-Alb level compared to HD patients (Table). There were no major differences in basic clinical parameters between the complete IMPENDIA group and the subset with available samples. Among the IMPENDIA participants analyzed, there was no significant difference in C-Alb change from baseline to 6 months in either arm, but treated subjects showed a trend to increased carbamylation (Table). The intervention arm demonstrated a greater change in blood urea nitrogen, possibly explaining the trend for increased carbamylation (Table).

Conclusion

For the first time, we show that carbamylation levels in PD patients run higher than matched HD patients. Incorporating intraperitoneal AA solutions was associated with an increase in urea levels and a marginal increase in C-Alb. PD outcomes may improve if carbamylation burden can be reduced. However, unlike HD where parenteral AA therapy reduces carbamylation, AA-based intraperitoneal solutions as part of the IMPENDIA treatment arm were not effective at reducing carbamylation.

Table
VariableHemodialysis baseline
(n=100)
All
peritoneal dialysis
baseline
(n=98)
P-valueControl
peritoneal dialysis
baseline
(n= 50)
Control
peritoneal dialysis
6 months
(n=50)
Intervention
peritoneal dialysis
baseline
(n=48)
Intervention
peritoneal dialysis
6 months
(n=48)
P-value for treatment difference (control – intervention)
Carbamylated albumin (mmol/mol, mean±SD )11.5±4.510.1±4.20.0311.8±4.611.3±3.711.1±4.212.3±4.80.09
Blood urea nitrogen (mg/dL, mean±SD )47.7±14.759.2±16.7<0.0159.1±16.861.6±16.856.3±14.069.7±16.8<0.01

Funding

  • NIDDK Support