Open AccessUrinary UDP-Glucose as a Novel Actionable Biomarker of Dehydration-Induced Acute Kidney Injury
Author(s) -
María Agustina Battistone,
Alexandra C. Mendelsohn,
Dennis Brown,
Sylvie Breton
Publication year - 2021
Publication title -
annals of nutrition and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.926
H-Index - 81
eISSN - 1421-9697
pISSN - 0250-6807
DOI - 10.1159/000520566
Subject(s) - acute kidney injury , creatinine , kidney , dehydration , blood urea nitrogen , inflammation , renal function , urinary system , chemistry , medicine , endocrinology , biochemistry
Background: People working in “extreme” conditions termed as sugar cane workers, firefighters and military personnel are subjected to significant dehydration. Prolonged episodes of dehydration may result in acute kidney Injury (AKI). AKI is associated with inflammation and is usually diagnosed only after the kidneys have gone through significant and often irreversible damage. We showed that the P2Y14 receptor mediates renal inflammation, leading to AKI following ischemia-reperfusion-injury [ 1 ]. P2Y14 is activated by the danger molecule UDP-glucose (UDP-Glc). Here we hypothesized that UDP-Glc is released by cells throughout the body after dehydration-induced stress. UDP-Glc is filtered by the kidney and concentrated in collecting ducts where it activates P2Y14 in intercalated cells. This would trigger renal inflammation and contribute to dehydration-associated AKI. Objective: The aim of this study was to characterize the participation of UDP-Glc in pro-inflammatory cell recruitment and renal dysfunction following dehydration. Method: Mice were subjected to water deprivation for 24, 48, and 72 h. Kidney function was assessed via serum creatinine (SCr), blood urea nitrogen (BUN), and urine albumin. To study proximal tubule (PT) damage, aquaporin 1 (AQP1) localization was analyzed by immunofluorescence (IF). Urinary UDP-Glc concentration was measured by LC-MS, and renal recruitment of immune cells by flow cytometry and IF. Results: Water deprivation induced elevations in SCr and BUN after 48 h and 72 h, relative to control. Dehydration also induced albuminuria and the redistribution of AQP1 from the plasma membrane into the PT cell body indicating PT injury. An increase in urinary UDP-Glc concentration and renal recruitment of macrophages were detected at 48 h and 72 h of dehydration. Conclusion: This study supports the hypothesis that UDP-Glc, released by damaged cells during severe dehydration, induces the renal recruitment of inflammatory macrophages leading to PT injury and kidney dysfunction (Fig. 1). Blocking the UDP-Glc/P2Y14 pathway represents, therefore, a new therapeutic avenue for the attenuation of dehydration-induced renal inflammation and injury. In this context, urinary UDP-Glc is a promising actionable biomarker for dehydration-induced AKI.