Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.
Abstract: Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts ( = 0.001; estimate = 135) and uGGT/Cr ( = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr ( = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.
Publication Date: 2023-12-07 PubMed ID: 38136813PubMed Central: PMC10741069DOI: 10.3390/ani13243776Google Scholar: Lookup
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Summary
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The study examines the role of matrix metalloproteinase-9 as a biomarker for kidney disease in dehydrated horses. It found that this protein was higher in these horses upon arrival compared to later measurements, indicating its potential influence in initial stages of dehydration-related kidney complications.
Introduction and Study Objective
- Matrix metalloproteinase-9 (MMP-9) is a protein that plays a role in breaking down the extracellular matrix during tissue rebuilding and remodeling. It has been found to be elevated in kidney disease, specifically in the renal tissue of humans.
- However, its role as a potential biomarker for kidney disease in veterinary medicine and in particular in horses has not been significantly explored or validated.
- The objective of this research was to examine the levels of serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) in dehydrated horses. The reason for this is to better understand if there is a correlation between dehydration (which can lead to kidney issues) and the levels of this protein.
Methodology
- The study included 40 horses that were diagnosed with varying levels of dehydration. Blood and urine samples were taken at different time points: upon admission (t0), and after 12 (t12), 24 (t24), and 48 hours (t48).
- A specific type of test (Anti-equine MMP-9 sandwich ELISA) was used to detect the presence and quantity of MMP-9 in the samples.
- The study also controlled for other factors such as serum creatinine, urea and symmetric dimethylarginine, urine-specific gravity, urinary protein concentration, fractional sodium excretion, and a specific urinary biomarker ratio (uGGT/Cr).
Findings and Conclusion
- The MMP-9 levels in the serum (sMMP-9) were significantly higher upon admission than in any of the subsequent measurements. This suggests that this protein could be more active or released into the blood during the initial stages of dehydration-related renal complications.
- However, no significant differences were seen in the urinary MMP-9 or the urinary MMP-9/creatinine ratio in comparison to the control group. It implies that the urinary values of these biomarkers might not be indicative of dehydration or renal issues in horses.
- Furthermore, no considerable variations were seen between different dehydration groups, suggesting that the severity of dehydration might not impact the MMP-9 levels.
- Notably, correlations were found between the serum MMP-9 and urinary biomarkers like uGGT/Cr and urinary casts, signifying a potential interconnection between these variables which needs further exploration.
- In conclusion, the MMP-9 protein was found to be elevated in the serum of dehydrated horses on arrival, which then decreased over subsequent measurements. This suggests its potential role as a biomarker in initial dehydration-related renal complications, but further study is needed to cement this theory.
Cite This Article
APA
van Spijk JN, Lo HC, Merle R, Richter IG, Diemar A, Stoeckle SD, Gehlen H.
(2023).
Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.
Animals (Basel), 13(24), 3776.
https://doi.org/10.3390/ani13243776 Publication
Researcher Affiliations
- Equine Clinic, Free University of Berlin, 14163 Berlin, Germany.
- Vetsuisse Faculty, Equine Department, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
- Equine Clinic, Free University of Berlin, 14163 Berlin, Germany.
- Institute for Veterinary Epidemiology and Biostatistics, Free University of Berlin, 14163 Berlin, Germany.
- Research Centre of Medical Technology and Biotechnology, Department of Cell Biology, 99947 Bad Langensalza, Germany.
- Research Centre of Medical Technology and Biotechnology, Department of Cell Biology, 99947 Bad Langensalza, Germany.
- Equine Clinic, Free University of Berlin, 14163 Berlin, Germany.
- Equine Clinic, University of Leipzig, An den Tierkliniken 11a, 04103 Leipzig, Germany.
- Equine Clinic, Free University of Berlin, 14163 Berlin, Germany.
Conflict of Interest Statement
We declare I.-G. Richter and A. Diemar employed by the Research Center of Medical Technology and Biotechnology, Bad Langensalza, Germany, which developed and offered the ELISA kit to measure MMP-9 in this study. There are no other financial or personal relationships that could have appeared to influence the work reported in this paper.
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