High serum creatinine concentration is associated with metabolic perturbations in dogs

Abstract Background The kidneys have many essential metabolic functions, and metabolic disturbances during decreased renal function have not been studied extensively. Objectives To identify metabolic changes in blood samples with increased serum creatinine concentration, indicating decreased glomeru...

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Main Authors: Claudia Ottka, Katariina Vapalahti, Ann‐Marie Määttä, Nanna Huuskonen, Sinikka Sarpanen, Liisa Jalkanen, Hannes Lohi
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Veterinary Internal Medicine
Subjects:
Online Access:https://doi.org/10.1111/jvim.16011
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author Claudia Ottka
Katariina Vapalahti
Ann‐Marie Määttä
Nanna Huuskonen
Sinikka Sarpanen
Liisa Jalkanen
Hannes Lohi
author_facet Claudia Ottka
Katariina Vapalahti
Ann‐Marie Määttä
Nanna Huuskonen
Sinikka Sarpanen
Liisa Jalkanen
Hannes Lohi
author_sort Claudia Ottka
collection DOAJ
description Abstract Background The kidneys have many essential metabolic functions, and metabolic disturbances during decreased renal function have not been studied extensively. Objectives To identify metabolic changes in blood samples with increased serum creatinine concentration, indicating decreased glomerular filtration. Animals Clinical samples analyzed using a nuclear magnetic resonance (NMR) based metabolomics platform. The case group consisted of 23 samples with serum creatinine concentration >125 μmol/L, and the control group of 873 samples with serum creatinine concentration within the reference interval. Methods Biomarker association with increased serum creatinine concentration was evaluated utilizing 3 statistical approaches: Wilcoxon rank‐sum test, logistic regression analysis (false discovery rate (FDR)‐corrected P‐values), and random forest classification. Medians of the biomarkers were compared to reference intervals. A heatmap and box plots were used to represent the differences. Results All 3 statistical approaches identified similar analytes associated with increased serum creatinine concentrations. The percentages of citrate, tyrosine, branched‐chain amino acids, valine, leucine, albumin, linoleic acid and the ratio of phenylalanine to tyrosine differed significantly using all statistical approaches, acetate differed using the Wilcoxon test and random forest, docosapentaenoic acid percentage only using logistic regression (P < .05), and alanine only using random forest. Conclusions and Clinical Importance We identified several metabolic changes associated with increased serum creatinine concentrations, including prospective diagnostic markers and therapeutic targets. Further research is needed to verify the association of these changes with the clinical state of the dog. The NMR metabolomics test is a promising tool for improving diagnostic testing and management of renal diseases in dogs.
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spelling doaj.art-44679c0ab1004e9385471d1e329813662022-12-22T04:06:51ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762021-01-0135140541410.1111/jvim.16011High serum creatinine concentration is associated with metabolic perturbations in dogsClaudia Ottka0Katariina Vapalahti1Ann‐Marie Määttä2Nanna Huuskonen3Sinikka Sarpanen4Liisa Jalkanen5Hannes Lohi6PetMeta Labs Ltd Helsinki FinlandPetMeta Labs Ltd Helsinki FinlandMovet Ltd Kuopio FinlandMovet Ltd Kuopio FinlandKuopion Eläinlääkärikeskus Ltd Kuopio FinlandPieneläinvastaanotto Punaturkki Ltd Kuopio FinlandPetMeta Labs Ltd Helsinki FinlandAbstract Background The kidneys have many essential metabolic functions, and metabolic disturbances during decreased renal function have not been studied extensively. Objectives To identify metabolic changes in blood samples with increased serum creatinine concentration, indicating decreased glomerular filtration. Animals Clinical samples analyzed using a nuclear magnetic resonance (NMR) based metabolomics platform. The case group consisted of 23 samples with serum creatinine concentration >125 μmol/L, and the control group of 873 samples with serum creatinine concentration within the reference interval. Methods Biomarker association with increased serum creatinine concentration was evaluated utilizing 3 statistical approaches: Wilcoxon rank‐sum test, logistic regression analysis (false discovery rate (FDR)‐corrected P‐values), and random forest classification. Medians of the biomarkers were compared to reference intervals. A heatmap and box plots were used to represent the differences. Results All 3 statistical approaches identified similar analytes associated with increased serum creatinine concentrations. The percentages of citrate, tyrosine, branched‐chain amino acids, valine, leucine, albumin, linoleic acid and the ratio of phenylalanine to tyrosine differed significantly using all statistical approaches, acetate differed using the Wilcoxon test and random forest, docosapentaenoic acid percentage only using logistic regression (P < .05), and alanine only using random forest. Conclusions and Clinical Importance We identified several metabolic changes associated with increased serum creatinine concentrations, including prospective diagnostic markers and therapeutic targets. Further research is needed to verify the association of these changes with the clinical state of the dog. The NMR metabolomics test is a promising tool for improving diagnostic testing and management of renal diseases in dogs.https://doi.org/10.1111/jvim.16011acute renal failurechronic renal failuremetabolomicsNMR
spellingShingle Claudia Ottka
Katariina Vapalahti
Ann‐Marie Määttä
Nanna Huuskonen
Sinikka Sarpanen
Liisa Jalkanen
Hannes Lohi
High serum creatinine concentration is associated with metabolic perturbations in dogs
Journal of Veterinary Internal Medicine
acute renal failure
chronic renal failure
metabolomics
NMR
title High serum creatinine concentration is associated with metabolic perturbations in dogs
title_full High serum creatinine concentration is associated with metabolic perturbations in dogs
title_fullStr High serum creatinine concentration is associated with metabolic perturbations in dogs
title_full_unstemmed High serum creatinine concentration is associated with metabolic perturbations in dogs
title_short High serum creatinine concentration is associated with metabolic perturbations in dogs
title_sort high serum creatinine concentration is associated with metabolic perturbations in dogs
topic acute renal failure
chronic renal failure
metabolomics
NMR
url https://doi.org/10.1111/jvim.16011
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