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Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria
Ellen R Brooks1, Bernd Hoppe, Dawn S Milliner
1Feinberg School of Medicine, Northwestern University, Department of Pediatrics, Chicago, Ill., USA.
Insights
Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) patients show distinct urine protein patterns. PH1 patients exhibit markers of inflammation and kidney injury, unlike IHC patients.
Area of Science:
- Nephrology
- Biochemistry
- Urology
Background:
- Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) are kidney stone diseases.
- These conditions can lead to nephrocalcinosis and chronic kidney disease (CKD).
- Clinical outcomes in PH1 correlate with urine oxalate, unlike IHC.
Purpose of the Study:
- To investigate differences in urine protein (PRO) patterns between PH1, IHC, and healthy controls (C).
- To identify specific urine protein profiles associated with higher urine oxalate levels in PH1.
Main Methods:
- Collected 24-hour urine samples from PH1 (n=47), IHC (n=35), and control (n=13) cohorts.
- Analyzed urine samples using targeted immunoassays for protein profiles and biochemical measurements for oxalate and calcium.
- Compared protein patterns across the three cohorts.
Main Results:
- Stone matrix proteins (osteopontin, calbindin, vitronectin) were lowest in PH1.
- Urine proteins related to inflammation (IL-10, MIP-1α), growth factors (EGF, IGF-1), and cell adhesion (VCAM-1) were elevated in PH1 compared to controls and IHC.
- Specific proteins like Fetuin A, IGF-1, MIP-1α, and VCAM-1 were significantly higher in PH1 versus IHC.
Conclusions:
- Urine protein profiles in PH1 indicate inflammation, oxidative stress, and altered tissue repair processes.
- These protein changes in PH1 are similar to those observed in CKD and acute kidney injury.
- Further analysis may reveal unique PH1 proteins or confirm links to poorer clinical outcomes.
Background:
Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) are stone-forming diseases that may result in the formation of calcium (Ca) oxalate (Ox) stones, nephrocalcinosis, and progressive chronic kidney disease (CKD). Poorer clinical outcome in PH1 is segregated by the highest urine (Ur)-Ox (UrOx), while IHC outcomes are not predictable by UrCa. We hypothesized that differences would be found in selected Ur-protein (PRO) patterns in PH1 and IHC, compared to healthy intra-familial sibling controls (C) of PH1 patients. We also hypothesized that the PRO patterns associated with higher UrOx levels would reflect injury, inflammation, biomineralization, and abnormal tissue repair processes in PH1.
Methods:
Twenty four-hour Ur samples were obtained from 3 cohorts: PH1 (n = 47); IHC (n = 35) and C (n = 13) and were analyzed using targeted platform-based multi-analyte profile immunoassays and for UrOx and UrCa by biochemical measurements.
Results:
Known stone matrix constituents, osteopontin, calbindin, and vitronectin were lowest in PH1 (C > IHC > PH1; p < 0.05). Ur-interleukin-10; chromogranin A; epidermal growth factor (EGF); insulin-like growth factor-1 (IGF-1), and macrophage inflammatory PRO-1α (MIP-1α) were higher in PH1 > C (p = 0.03 to p < 0.05). Fetuin A; IGF-1, MIP-1α, and vascular cell adhesion molecule-1 were highest in PH1 > IHC (p < 0.001 to p = 0.005).
Conclusion:
PH1 Ur-PROs reflected overt inflammation, chemotaxis, oxidative stress, growth factors (including EGF), and pro-angiogenic and calcification regulation/inhibition compared to the C and IHC cohorts. Many of the up- and downregulated PH1-PROs found in this study are also found in CKD, acute kidney injury, stone formers, and/or stone matrices. Further data analyses may provide evidence for PH1 unique PROs or demonstrate a poorer clinical outcome.
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