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.