Uremic Toxins Overview

Uremic Toxins Christos Argyropoulos Renal Grand Rounds 15/10/2007

General Outline ,[object Object],[object Object],[object Object],[object Object]

The “Chosen” Ones ,[object Object],[object Object],[object Object],[object Object]

Uremia ,[object Object],[object Object],[object Object],[object Object]

Uremia ,[object Object],[object Object]

Of theories, measurements and experiments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

The “Residual” Syndrome ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Clinical Manifestations of the “Residual” Syndrome ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Possible Causes of the “Residual” Syndrome ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Semin. Dial. (2001) 14(4):246-251

Possible Causes of the “Residual” Syndrome ,[object Object]

Uremic Solutes (The NEMJ view) N Engl J Med 357:1316, September 27, 2007

A Systematic Approach To Uremic Retention Solutes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],http://www.uremic-toxins.org/

A Systematic Approach To Uremic Retention Solutes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],KI, 63 (2003) 1934-1943

A Systematic Approach To Uremic Retention Solutes http://www.nephro-leipzig.de/eutoxdb/index.php

A Systematic Approach To Uremic Retention Solutes ,[object Object],[object Object],KI, 63 (2003) 1934-1943

A Systematic Approach To Uremic Retention Solutes ,[object Object],[object Object],[object Object],[object Object],[object Object],KI, 63 (2003) 1934-1943

Causes and Consequences of Variability ,[object Object],[object Object],[object Object],[object Object],[object Object],Nephrology Dialysis Transplantation July 15 2007 , doi:10.1093/ndt/gfm151

Clinical Implications of Solute Accumulation ,[object Object],[object Object],[object Object]

Clinical Implications of Solute Accumulation ,[object Object],[object Object],[object Object],[object Object],[object Object]

Urea ,[object Object],[object Object],[object Object]

Guanidines ,[object Object],[object Object],[object Object],[object Object]

Guanidines - Creatinine ,[object Object],[object Object],[object Object],[object Object]

Guanidines – Non Creatinine ,[object Object],[object Object],[object Object]

Memory, Emotions, Seizures: Kidney v.s. Brain ,[object Object],[object Object],[object Object]

Memory, Emotions, Seizures: Kidney v.s. Brain ,[object Object],[object Object],Neuropsychopharmacology (2004) 29, 952–959

Memory, Emotions, Seizures: Kidney v.s. Brain ,[object Object],[object Object],[object Object],[object Object],[object Object],Physiology and Behaviour 84(2) , 15 February 2005, Pages 251-264

Memory, Emotions, Seizures: Kidney v.s. Hippocampus http://en.wikipedia.org/wiki/Morris_water_maze Physiology and Behaviour 84(2) , 15 February 2005, Pages 251-264

Memory, Emotions, Seizures: Kidney v.s. Hippocampus ,[object Object],http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.TOC&depth=2

Memory, Emotions, Seizures: Kidney v.s. Hippocampus KI (2001) 59(S78): 77-83 GSA competes for the Mg2+ binding site of the NMDA channel leading to over-activation of the channel, Ca2+ influx, neurotoxicity and cell death

Guanidines – Other Effects ,[object Object],[object Object],[object Object],[object Object]

P-Cresol and Conjugates ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

3-carboxy-4-methyl-5-propyl-2-furanpropionic acid ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Homocysteine (Hcy) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JAMA. 2006;296:2720-2726 http://www.medscape.com/viewarticle/548317

Homocysteine (Hcy) ,[object Object],[object Object],[object Object],[object Object],[object Object],Nephrology Dialysis Transplantation 2006 21(5):1161-1166

Small molecular toxins and the dose of dialysis ,[object Object],[object Object],[object Object],[object Object],[object Object],Am J Kidney Dis. 2007 Aug;50(2):279-88.

Beyond small molecules ,[object Object],[object Object],[object Object],[object Object]

Proteomics and the Quest for Middle Molecules ,[object Object],[object Object],[object Object],[object Object]

Proteomics and the Quest for Middle Molecules Nephrology Dialysis Transplantation 2004 19(12):3068-3077; doi:10.1093/ndt/gfh509 http://www.decodon.com/

Effect of Membrane Flux in Maintenance Hemodialysis Nephrology Dialysis Transplantation 2004 19(12):3068-3077; doi:10.1093/ndt/gfh509

Effect of Membrane Flux in Maintenance Hemodialysis ,[object Object],[object Object],[object Object],[object Object],[object Object],Nephrology Dialysis Transplantation 2004 19(12):3068-3077; doi:10.1093/ndt/gfh509

Clinical Application of Proteomics : Defining the Problem ,[object Object],[object Object],[object Object]

Clinical Application of Proteomics : Proposing an Intervention ,[object Object],[object Object],Nephrology Dialysis Transplantation 2007 22(Supplement 5):v8-v12; doi:10.1093 /ndt/gfm293

Clinical Application of Proteomics : Why does the intervention work? ,[object Object],[object Object],[object Object],Nephrology Dialysis Transplantation 2007 22(Supplement 5):v13-v19; doi:10.1093/ndt/gfm295

Clinical Application of Proteomics : Why does the intervention work? Nephrology Dialysis Transplantation 2007 22(Supplement 5):v13-v19; doi:10.1093/ndt/gfm295

Clinical Application of Proteomic Research: PD ,[object Object],[object Object],[object Object],[object Object],[object Object],J. Proteome Res., ASAP Article 10.1021/ pr0702969 S1535-3893(07)00296-5

Low – Molecular Weight Proteins that accumulate in ESRD J Am Soc Nephrol 13:S41-S47, 2002

Accumulation of solutes v.s. Cumulative Protein Damage ,[object Object],[object Object]

Accumulation of solutes v.s. Cumulative Protein Damage ,[object Object],[object Object],[object Object]

Major Classes of Irreversible Protein Damage Products ,[object Object],[object Object],[object Object],[object Object],Nephrology Dialysis Transplantation 2007 22(Supplement 5):v20-v36; doi:10.1093/ndt/gfm294 J Am Soc Nephrol 16: 3687-3693, 2005

Tissue AGEs and mortality in ESRD

Putting it all together ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Nephrology Dialysis Transplantation 2007 22(Supplement 5):v20-v36

Putting it all together Nephrology Dialysis Transplantation 2007 22(Supplement 5):v20-v36

Knowing is not enough, we must apply. Willing is not enough, we must do. Goethe

What do we know? ,[object Object],[object Object],[object Object],[object Object]

What can we do? ,[object Object],[object Object],[object Object]

What can we do? ,[object Object],[object Object],[object Object],[object Object]

What can we do? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

If you are interested to find out more … ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Uremic Toxins Overview

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Uremic Toxins Overview