Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria

Xiangling Wang; Gauri Bhutani; Lisa E. Vaughan; Felicity T. Enders; Zejfa Haskic; Dawn Milliner; John C. Lieske; Dean Assimos; Michelle Baum; Michael Somers; Lawrence Copelovitch; Prasad Devarajan; David Goldfarb; Elizabeth Harvey; Lisa Robinson; William Haley; Mini Michael; Craig Langman

doi:10.1186/s12882-020-01783-z

Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria

Xiangling Wang, Gauri Bhutani, Lisa E. Vaughan, Felicity T. Enders, Zejfa Haskic, Dawn Milliner, John C. Lieske^*, Dean Assimos, Michelle Baum, Michael Somers, Lawrence Copelovitch, Prasad Devarajan, David Goldfarb, Elizabeth Harvey, Lisa Robinson, William Haley, Mini Michael, Craig Langman

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Background: Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. Methods: A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and EGFR. Results: Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (EGFR) of 68.4 ± 21.0 ml/min/1.73m². After adjustment for age, sex, and EGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher EGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. Conclusion: In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

Original language	English (US)
Article number	133
Journal	BMC nephrology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12882-020-01783-z
State	Published - Apr 15 2020

Funding

This study was supported by the Rare Kidney Stone Consortium (U54DK083908), a part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences’ (NCATS). This consortium is funded through collaboration between NCATS, and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Oxalosis and Hyperoxaluria Foundation and the Mayo Foundation. OxThera, Inc. also provided partial funding for this study. The investigators had full responsibility for the study design, data collection, data interpretation, and preparation of the manuscript.

Keywords

Crystallization
Glomerular filtration rate
Monocyte-chemoattractant protein 1
Primary hyperoxaluria
Renal damage

ASJC Scopus subject areas

Nephrology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12882-020-01783-z

Cite this

Wang, X., Bhutani, G., Vaughan, L. E., Enders, F. T., Haskic, Z., Milliner, D., Lieske, J. C., Assimos, D., Baum, M., Somers, M., Copelovitch, L., Devarajan, P., Goldfarb, D., Harvey, E., Robinson, L., Haley, W., Michael, M., & Langman, C. (2020). Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria. BMC nephrology, 21(1), Article 133. https://doi.org/10.1186/s12882-020-01783-z

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title = "Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria",

abstract = "Background: Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. Methods: A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and EGFR. Results: Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (EGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and EGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher EGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. Conclusion: In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.",

keywords = "Crystallization, Glomerular filtration rate, Monocyte-chemoattractant protein 1, Primary hyperoxaluria, Renal damage",

author = "Xiangling Wang and Gauri Bhutani and Vaughan, \{Lisa E.\} and Enders, \{Felicity T.\} and Zejfa Haskic and Dawn Milliner and Lieske, \{John C.\} and Dean Assimos and Michelle Baum and Michael Somers and Lawrence Copelovitch and Prasad Devarajan and David Goldfarb and Elizabeth Harvey and Lisa Robinson and William Haley and Mini Michael and Craig Langman",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = apr,

day = "15",

doi = "10.1186/s12882-020-01783-z",

language = "English (US)",

volume = "21",

journal = "BMC nephrology",

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Wang, X, Bhutani, G, Vaughan, LE, Enders, FT, Haskic, Z, Milliner, D, Lieske, JC, Assimos, D, Baum, M, Somers, M, Copelovitch, L, Devarajan, P, Goldfarb, D, Harvey, E, Robinson, L, Haley, W, Michael, M & Langman, C 2020, 'Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria', BMC nephrology, vol. 21, no. 1, 133. https://doi.org/10.1186/s12882-020-01783-z

TY - JOUR

T1 - Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria

AU - Wang, Xiangling

AU - Bhutani, Gauri

AU - Vaughan, Lisa E.

AU - Enders, Felicity T.

AU - Haskic, Zejfa

AU - Milliner, Dawn

AU - Lieske, John C.

AU - Assimos, Dean

AU - Baum, Michelle

AU - Somers, Michael

AU - Copelovitch, Lawrence

AU - Devarajan, Prasad

AU - Goldfarb, David

AU - Harvey, Elizabeth

AU - Robinson, Lisa

AU - Haley, William

AU - Michael, Mini

AU - Langman, Craig

PY - 2020/4/15

Y1 - 2020/4/15

N2 - Background: Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. Methods: A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and EGFR. Results: Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (EGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and EGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher EGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. Conclusion: In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

AB - Background: Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. Methods: A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and EGFR. Results: Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (EGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and EGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher EGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. Conclusion: In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

KW - Crystallization

KW - Glomerular filtration rate

KW - Monocyte-chemoattractant protein 1

KW - Primary hyperoxaluria

KW - Renal damage

UR - https://www.scopus.com/pages/publications/85083409890

UR - https://www.scopus.com/inward/citedby.url?scp=85083409890&partnerID=8YFLogxK

U2 - 10.1186/s12882-020-01783-z

DO - 10.1186/s12882-020-01783-z

M3 - Article

C2 - 32293313

AN - SCOPUS:85083409890

SN - 1471-2369

VL - 21

JO - BMC nephrology

JF - BMC nephrology

IS - 1

M1 - 133

ER -

Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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