Division of Nephrology

Intracellularly Sequestered Solutes in Conventional Hemodialysis

Manish P. Ponda, Zhe Quan, Michal Melamed, Amanda C. Raff, Timothy Meyer, Thomas H. Hostetter. Medicine/Nephrology, Albert Einstein College of Medicine, Bronx, NY; Medicine/Nephrology, Stanford University School of Medicine, Stanford, CA

Currently dialysis adequacy is judged by measures of urea clearance. However, urea is relatively non-toxic and has properties distinct from large classes of retained solutes. In addition to protein bound solutes, another class of non-urea type solutes is the aliphatic amines, which are believed to be intracellularly sequestered.

We studied two representative aliphatic amines, monomethylamine (MMA) and ethyl amine (EtA), in stable hemodialysis outpatients (n = 10) using an HPLC-based assay. Mean MMA and EtA levels were 75.7 g/L and 69.1 g/L, respectively. Values in 10 normal subjects were 31.6 g/L and 32.8 g/L for MMA and EtA respectively. Mean urea reduction was 62% while reduction ratios for MMA and EtA were 43% and 40% (P < 0.01 vs. urea). Mean urea clearance was 225 ml/min by blood side calculations, whereas MMA and EtA clearances were 52 ml/min and 49 ml/min (P < 0.001 vs. urea). Both aliphatic amines displayed large rebound in the 1 hour post-dialytic period. MMA returned to 85% and ETA 84% of baseline, whereas urea rebounded only to 47% of baseline. MMA had a much larger calculated Vd compared to urea, consistent with intracellular sequestration. Measures of intra-RBC amine concentrations confirmed greater levels in RBCs than in plasma with a ratio of 4.1:1 for MMA and 3.5:1 for EtA. MMA and EtA removal may be impaired further by changes in pH, PCO2 and PO2 within the dialyzer.

We confirmed that plasma pH falls by 0.1 units, plasma PCO2 increases by 20 mm Hg and that plasma PO2 increases by 12 mm Hg from dialyzer inlet to outlet. These changes should accentuate even further the sequestration of MMA and EtA within RBCs as they flow though the dialyzer. This would decrease the diffusion from plasma to dialysate impairing their removal. In conclusion, these first detailed descriptions of aliphatic amines in conventional hemodialysis show they are not handled as efficiently as urea. Efforts to improve dialysis adequacy should include further study of non-urea type solutes.

Disclosure - Consultant: Wyeth Pharmaceuticals

Presented at the American Society of Nephrology Renal Week 2007, San Francisco, California

Division Chief

Michael RossMichael Ross, MD (bio)
Chief, Division of Nephrology
Albert Einstein College of Medicine
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