Abstract
BackgroundPatients 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.MethodsA 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.ResultsMean (±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.ConclusionIn 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.
Highlights
Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease
In the current study we examined a panel of noninvasive candidate urine biomarkers of injury, which have been previously associated with inflammatory pathways, crystallization, and/or oxalate exposure in vitro or in vivo, in in order to determine if any correlated with urinary oxalate excretion, calcium oxalate supersaturation (CaOx SS), predicted proximal tubular oxalate concentration (PTOx), and estimated glomerular filtration rate
Our study population consisted of a cohort of 30 PH patients enrolled in the Rare Kidney Stone Consortium (RKSC) PH registry between 2004 and 2013 who had one or more biobanked urine specimens and no prior history of end stage renal disease (ESRD) or organ transplantation; among these, n = 24 were PH type 1, n = 4 were PH type 2, and n = 2 were PH type 3
Summary
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. Oxalate can combine with calcium within renal tubules leading to nephrocalcinosis and kidney stones. Strategies to reduce urine oxalate excretion and/or calcium oxalate crystallization have been the cornerstone of PH treatment [2]. In the current study we examined a panel of noninvasive candidate urine biomarkers of injury, which have been previously associated with inflammatory pathways, crystallization, and/or oxalate exposure in vitro or in vivo, in in order to determine if any correlated with urinary oxalate excretion, calcium oxalate supersaturation (CaOx SS), predicted proximal tubular oxalate concentration (PTOx), and estimated glomerular filtration rate (eGFR)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
