Uremic toxin development in living kidney donors: a longitudinal study

Megan Rossi, Katrina L Campbell, David W Johnson, Tony Stanton, Brian A Haluska, Carmel M Hawley, Goce Dimeski, Brett C McWhinney, Jacobus P J Ungerer, Omar M Kaisar, Nicole M Isbel

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Abstract

BACKGROUND: Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known.

METHODS: Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques.

RESULTS: Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03).

CONCLUSION: This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.

Original languageEnglish
Pages (from-to)548-54
Number of pages7
JournalTransplantation
Volume97
Issue number5
DOIs
Publication statusPublished - 15 Mar 2014
Externally publishedYes

Fingerprint

Living Donors
Indican
Nephrectomy
Longitudinal Studies
Kidney
Sulfates
Uric Acid
Carotid Intima-Media Thickness
Brachial Artery
C-Reactive Protein
Glycerol
Cystatin C
Vascular Stiffness
Kidney Diseases
Serum
Glomerular Filtration Rate
Chronic Renal Insufficiency
Liquid Chromatography
Observational Studies
Dilatation

Cite this

Rossi, M., Campbell, K. L., Johnson, D. W., Stanton, T., Haluska, B. A., Hawley, C. M., ... Isbel, N. M. (2014). Uremic toxin development in living kidney donors: a longitudinal study. Transplantation, 97(5), 548-54. https://doi.org/10.1097/01.tp.0000436906.48802.c4
Rossi, Megan ; Campbell, Katrina L ; Johnson, David W ; Stanton, Tony ; Haluska, Brian A ; Hawley, Carmel M ; Dimeski, Goce ; McWhinney, Brett C ; Ungerer, Jacobus P J ; Kaisar, Omar M ; Isbel, Nicole M. / Uremic toxin development in living kidney donors : a longitudinal study. In: Transplantation. 2014 ; Vol. 97, No. 5. pp. 548-54.
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abstract = "BACKGROUND: Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known.METHODS: Forty-two living kidney donors (Caucasian; 76{\%} female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques.RESULTS: Kidney function decreased by 30{\%} after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44{\%} to 100{\%}, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03).CONCLUSION: This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.",
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Rossi, M, Campbell, KL, Johnson, DW, Stanton, T, Haluska, BA, Hawley, CM, Dimeski, G, McWhinney, BC, Ungerer, JPJ, Kaisar, OM & Isbel, NM 2014, 'Uremic toxin development in living kidney donors: a longitudinal study' Transplantation, vol. 97, no. 5, pp. 548-54. https://doi.org/10.1097/01.tp.0000436906.48802.c4

Uremic toxin development in living kidney donors : a longitudinal study. / Rossi, Megan; Campbell, Katrina L; Johnson, David W; Stanton, Tony; Haluska, Brian A; Hawley, Carmel M; Dimeski, Goce; McWhinney, Brett C; Ungerer, Jacobus P J; Kaisar, Omar M; Isbel, Nicole M.

In: Transplantation, Vol. 97, No. 5, 15.03.2014, p. 548-54.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Uremic toxin development in living kidney donors

T2 - a longitudinal study

AU - Rossi, Megan

AU - Campbell, Katrina L

AU - Johnson, David W

AU - Stanton, Tony

AU - Haluska, Brian A

AU - Hawley, Carmel M

AU - Dimeski, Goce

AU - McWhinney, Brett C

AU - Ungerer, Jacobus P J

AU - Kaisar, Omar M

AU - Isbel, Nicole M

PY - 2014/3/15

Y1 - 2014/3/15

N2 - BACKGROUND: Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known.METHODS: Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques.RESULTS: Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03).CONCLUSION: This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.

AB - BACKGROUND: Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known.METHODS: Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques.RESULTS: Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03).CONCLUSION: This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.

U2 - 10.1097/01.tp.0000436906.48802.c4

DO - 10.1097/01.tp.0000436906.48802.c4

M3 - Article

VL - 97

SP - 548

EP - 554

JO - Transplantation bulletin

JF - Transplantation bulletin

SN - 0041-1337

IS - 5

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Rossi M, Campbell KL, Johnson DW, Stanton T, Haluska BA, Hawley CM et al. Uremic toxin development in living kidney donors: a longitudinal study. Transplantation. 2014 Mar 15;97(5):548-54. https://doi.org/10.1097/01.tp.0000436906.48802.c4