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
N1 - Funding Information:
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.
Publisher Copyright:
© 2020 The Author(s).
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
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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 -