Methylamine clearance by haemodialysis is low

Manish P. Ponda, Zhe Quan, Michal L. Melamed, Amanda C. Raff, Timothy W. Meyer, Thomas H. Hostetter

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. Dialysis adequacy is currently judged by measures of urea clearance. However, urea is relatively non-toxic and has properties distinct from large classes of other retained solutes. In particular, intracellularly sequestered solutes are likely to behave differently than urea.Methods. We studied an example of this class, the aliphatic amine monomethylamine (MMA), in stable haemodialysis outpatients (n = 10) using an HPLC-based assay.Results. Mean MMA levels pre-dialysis in end-stage renal disease subjects were 76 ± 15 μg/L compared to 32 ± 4 μg/L in normal subjects (n = 10) (P < 0.001). Mean urea reduction was 62% while the reduction ratio for MMA was 43% (P < 0.01). MMA levels rebounded in the 1 hour post-dialytic period to 85% of baseline, whereas urea levels rebounded only to 47% of baseline. MMA had a much larger calculated volume of distribution compared to urea, consistent with intracellular sequestration. Measures of intra-red blood cell (RBC) MMA concentrations confirmed greater levels in RBCs than in plasma with a ratio of 4.9:1. Because of the intracellular sequestration of MMA, we calculated its clearance using that amount removed from whole blood. Clearances for urea averaged 222 ± 41 ml/min and for MMA 121 ± 14 ml/min, while plasma clearance for creatinine was 162 ± 20 ml/min (P < 0.01, for all differences). Using in vitro dialysis, in the absence of RBCs, solute clearance rates were similar: 333 ± 6, 313 ± 8 and 326 ± 4 ml/min for urea, creatinine and MMA, respectively. These findings suggest that the lower MMA clearance relative to creatinine in vivo is a result of MMA movement into RBCs within the dialyser blood path diminishing its removal by dialysis.Conclusion. In conclusion, we find that, in conventional haemodialysis, MMA is not cleared as efficiently as urea or creatinine and raise the possibility that RBCs may limit its dialysis not merely by failing to discharge it, but by further sequestering it as blood passes through the dialyser.

Original languageEnglish (US)
Pages (from-to)1608-1613
Number of pages6
JournalNephrology Dialysis Transplantation
Volume25
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Renal Dialysis
Urea
Dialysis
Creatinine
methylamine
Artificial Kidneys
Chronic Kidney Failure
Amines
Outpatients
Erythrocytes
High Pressure Liquid Chromatography

Keywords

  • Haemodialysis
  • Uraemia

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Methylamine clearance by haemodialysis is low. / Ponda, Manish P.; Quan, Zhe; Melamed, Michal L.; Raff, Amanda C.; Meyer, Timothy W.; Hostetter, Thomas H.

In: Nephrology Dialysis Transplantation, Vol. 25, No. 5, 05.2010, p. 1608-1613.

Research output: Contribution to journalArticle

Ponda, Manish P. ; Quan, Zhe ; Melamed, Michal L. ; Raff, Amanda C. ; Meyer, Timothy W. ; Hostetter, Thomas H. / Methylamine clearance by haemodialysis is low. In: Nephrology Dialysis Transplantation. 2010 ; Vol. 25, No. 5. pp. 1608-1613.
@article{f9104410ba794630a6da9f1e4f0ad584,
title = "Methylamine clearance by haemodialysis is low",
abstract = "Background. Dialysis adequacy is currently judged by measures of urea clearance. However, urea is relatively non-toxic and has properties distinct from large classes of other retained solutes. In particular, intracellularly sequestered solutes are likely to behave differently than urea.Methods. We studied an example of this class, the aliphatic amine monomethylamine (MMA), in stable haemodialysis outpatients (n = 10) using an HPLC-based assay.Results. Mean MMA levels pre-dialysis in end-stage renal disease subjects were 76 ± 15 μg/L compared to 32 ± 4 μg/L in normal subjects (n = 10) (P < 0.001). Mean urea reduction was 62{\%} while the reduction ratio for MMA was 43{\%} (P < 0.01). MMA levels rebounded in the 1 hour post-dialytic period to 85{\%} of baseline, whereas urea levels rebounded only to 47{\%} of baseline. MMA had a much larger calculated volume of distribution compared to urea, consistent with intracellular sequestration. Measures of intra-red blood cell (RBC) MMA concentrations confirmed greater levels in RBCs than in plasma with a ratio of 4.9:1. Because of the intracellular sequestration of MMA, we calculated its clearance using that amount removed from whole blood. Clearances for urea averaged 222 ± 41 ml/min and for MMA 121 ± 14 ml/min, while plasma clearance for creatinine was 162 ± 20 ml/min (P < 0.01, for all differences). Using in vitro dialysis, in the absence of RBCs, solute clearance rates were similar: 333 ± 6, 313 ± 8 and 326 ± 4 ml/min for urea, creatinine and MMA, respectively. These findings suggest that the lower MMA clearance relative to creatinine in vivo is a result of MMA movement into RBCs within the dialyser blood path diminishing its removal by dialysis.Conclusion. In conclusion, we find that, in conventional haemodialysis, MMA is not cleared as efficiently as urea or creatinine and raise the possibility that RBCs may limit its dialysis not merely by failing to discharge it, but by further sequestering it as blood passes through the dialyser.",
keywords = "Haemodialysis, Uraemia",
author = "Ponda, {Manish P.} and Zhe Quan and Melamed, {Michal L.} and Raff, {Amanda C.} and Meyer, {Timothy W.} and Hostetter, {Thomas H.}",
year = "2010",
month = "5",
doi = "10.1093/ndt/gfp629",
language = "English (US)",
volume = "25",
pages = "1608--1613",
journal = "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Methylamine clearance by haemodialysis is low

AU - Ponda, Manish P.

AU - Quan, Zhe

AU - Melamed, Michal L.

AU - Raff, Amanda C.

AU - Meyer, Timothy W.

AU - Hostetter, Thomas H.

PY - 2010/5

Y1 - 2010/5

N2 - Background. Dialysis adequacy is currently judged by measures of urea clearance. However, urea is relatively non-toxic and has properties distinct from large classes of other retained solutes. In particular, intracellularly sequestered solutes are likely to behave differently than urea.Methods. We studied an example of this class, the aliphatic amine monomethylamine (MMA), in stable haemodialysis outpatients (n = 10) using an HPLC-based assay.Results. Mean MMA levels pre-dialysis in end-stage renal disease subjects were 76 ± 15 μg/L compared to 32 ± 4 μg/L in normal subjects (n = 10) (P < 0.001). Mean urea reduction was 62% while the reduction ratio for MMA was 43% (P < 0.01). MMA levels rebounded in the 1 hour post-dialytic period to 85% of baseline, whereas urea levels rebounded only to 47% of baseline. MMA had a much larger calculated volume of distribution compared to urea, consistent with intracellular sequestration. Measures of intra-red blood cell (RBC) MMA concentrations confirmed greater levels in RBCs than in plasma with a ratio of 4.9:1. Because of the intracellular sequestration of MMA, we calculated its clearance using that amount removed from whole blood. Clearances for urea averaged 222 ± 41 ml/min and for MMA 121 ± 14 ml/min, while plasma clearance for creatinine was 162 ± 20 ml/min (P < 0.01, for all differences). Using in vitro dialysis, in the absence of RBCs, solute clearance rates were similar: 333 ± 6, 313 ± 8 and 326 ± 4 ml/min for urea, creatinine and MMA, respectively. These findings suggest that the lower MMA clearance relative to creatinine in vivo is a result of MMA movement into RBCs within the dialyser blood path diminishing its removal by dialysis.Conclusion. In conclusion, we find that, in conventional haemodialysis, MMA is not cleared as efficiently as urea or creatinine and raise the possibility that RBCs may limit its dialysis not merely by failing to discharge it, but by further sequestering it as blood passes through the dialyser.

AB - Background. Dialysis adequacy is currently judged by measures of urea clearance. However, urea is relatively non-toxic and has properties distinct from large classes of other retained solutes. In particular, intracellularly sequestered solutes are likely to behave differently than urea.Methods. We studied an example of this class, the aliphatic amine monomethylamine (MMA), in stable haemodialysis outpatients (n = 10) using an HPLC-based assay.Results. Mean MMA levels pre-dialysis in end-stage renal disease subjects were 76 ± 15 μg/L compared to 32 ± 4 μg/L in normal subjects (n = 10) (P < 0.001). Mean urea reduction was 62% while the reduction ratio for MMA was 43% (P < 0.01). MMA levels rebounded in the 1 hour post-dialytic period to 85% of baseline, whereas urea levels rebounded only to 47% of baseline. MMA had a much larger calculated volume of distribution compared to urea, consistent with intracellular sequestration. Measures of intra-red blood cell (RBC) MMA concentrations confirmed greater levels in RBCs than in plasma with a ratio of 4.9:1. Because of the intracellular sequestration of MMA, we calculated its clearance using that amount removed from whole blood. Clearances for urea averaged 222 ± 41 ml/min and for MMA 121 ± 14 ml/min, while plasma clearance for creatinine was 162 ± 20 ml/min (P < 0.01, for all differences). Using in vitro dialysis, in the absence of RBCs, solute clearance rates were similar: 333 ± 6, 313 ± 8 and 326 ± 4 ml/min for urea, creatinine and MMA, respectively. These findings suggest that the lower MMA clearance relative to creatinine in vivo is a result of MMA movement into RBCs within the dialyser blood path diminishing its removal by dialysis.Conclusion. In conclusion, we find that, in conventional haemodialysis, MMA is not cleared as efficiently as urea or creatinine and raise the possibility that RBCs may limit its dialysis not merely by failing to discharge it, but by further sequestering it as blood passes through the dialyser.

KW - Haemodialysis

KW - Uraemia

UR - http://www.scopus.com/inward/record.url?scp=77951684644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951684644&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfp629

DO - 10.1093/ndt/gfp629

M3 - Article

VL - 25

SP - 1608

EP - 1613

JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

SN - 0931-0509

IS - 5

ER -