Abstract: FR-PO525
Specific Inflammatory and Renal Cellular Injury Markers Are Found in Urinary Extracellular Vesicles and Proteins Associated with Nephrocalcinosis and Stones in Type 1 Primary Hyperoxaluria Patients
Session Information
- Bone and Mineral Metabolism: Basic
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Jayachandran, Muthuvel, Mayo Clinic, Rochester, Minnesota, United States
- Yuzhakov, Stanislav, Mayo Clinic, Rochester, Minnesota, United States
- Rule, Andrew D., Mayo Clinic, Rochester, Minnesota, United States
- Milliner, Dawn S., Mayo Clinic, Rochester, Minnesota, United States
- Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
Background
Our previous study showed that specific inflammatory (MCP-1) and renal cell injury (NGAL) molecule associated urinary extracellular vesicles (EVs) were significantly lower in calcium oxalate (CaOx) stone formers compared matched controls. Primary hyperoxaluria type 1 (PH1) can cause nephrocalcinosis (NC), CaOx stones, and chronic kidney disease but specific populations of urinary EVs contribution in these disease processes are not well known.
Methods
Bio-banked urine from PH1 patients without (n=10) and with nephrocalcinosis (n=6) or stones (n=9) and age-/sex-matched (± 5 years) living kidney donors (n=25) was studied. All patients had an eGFR > 40 and no prior kidney or liver transplantation. Urinary EVs were analyzed by digital flow cytometry and analyzed as EVs/µL urine or EVs /mg creatinine. A customized protein array was used to identify specific proteins in urine.
Results
Compared to healthy controls, PH1 patients excreted significantly greater EVs and EVs with surface biomarkers of inflammation (ICAM-1, MCP-1, tissue factor, VCAM-1), renal injury (β2-microglobulin (β2-M), clusterin, KIM-1, Laminin α-5, NGAL), of glomerular origin (juxtaglomerular, mesangial, podocyte, and parietal cells), and of tubular origin (proximal and distal tubule, collecting duct) (all P<0.05). PH1 patients with NC had fewer total EVs than PH1 patients without NC or stones (P<0.05). PH1 patients with kidney stones had fewer total EVs, and subgroups of EVs with biomarkers of inflammation, renal injury, glomerular origin, specific renal tubular and papillary origin compared to PH1 patients without NC or stones (all P<0.05). Excretion of soluble urinary MCP-1, CRP, and osteopontin were all significantly lower in PH1 patients with NC compared to PH1 patients without either NC or stones, or patients with stones alone (P<0.05). A similar trend for decreased urinary excretion of soluble CD14, endoglin, E-selectin, ICAM-1, PDGFRβ, and osteoprotegrin was observed in PH1 patients with NC compared to the other groups.
Conclusion
This study suggests that inflammation-associated EVs and proteins released from specific populations of renal parenchyma of PH1 patients may contribute nephrocalcinosis and stone pathogenesis.
Funding
- NIDDK Support