Healthy and Chronic Kidney Disease (CKD) Dogs Have Differences in Serum Metabolomics and Renal Diet May Have Slowed Disease Progression
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Animals and Study Design
4.2. Diet and Feeding Protocol
4.3. Sample Collection and Preparation
4.4. NMR Spectral Acquisition, Processing Parameters, and Identification of Serum Metabolites
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Polzin, D.J. Chronic Kidney Disease. In Nephrology and Urology of Small Animals; Bartges, J., Polzin, D., Eds.; Wiley-Blackwell: West Sussex, UK, 2011; pp. 433–471. [Google Scholar]
- Bartges, J.W. Chronic Kidney Disease in Dogs and Cats. Vet. Clin. N. Am. Small Anim. Pract. 2012, 42, 669–692. [Google Scholar] [CrossRef]
- Vanholder, R.; De Smet, R.; Hsu, C.; Vogeleere, P.; Ringoir, S. Uremic toxicity: The middle molecule hypothesis revisited. Semin. Nephrol. 1994, 14, 205–218. [Google Scholar]
- Vanholder, R.; De Smet, R. Pathophysiologic effects of uremic retention solutes. J. Am. Soc. Nephrol. 1999, 10, 1815–1823. [Google Scholar] [CrossRef]
- Go, A.S.; Chertow, G.M.; Fan, D.; McCulloch, C.E.; Hsu, C. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. N. Engl. J. Med. 2004, 351, 1296–1305. [Google Scholar] [CrossRef]
- Etgen, T.; Chonchol, M.; Förstl, H.; Sander, D. Chronic kidney disease and cognitive impairment: A systematic review and meta-analysis. Am. J. Nephrol. 2012, 35, 474–482. [Google Scholar] [CrossRef] [PubMed]
- Perlman, R.L.; Finkelstein, F.O.; Liu, L.; Roys, E.; Kiser, M.; Eisele, G.; Burrows-Hudson, S.; Messana, J.M.; Levin, N.; Rajagopalan, S.; et al. Quality of life in Chronic Kidney Disease (CKD): A cross-sectional analysis in the Renal Research Institute-CKD study. Am. J. Kidney Dis. 2005, 45, 658–666. [Google Scholar] [CrossRef]
- Hill, N.R.; Fatoba, S.T.; Oke, J.L.; Hirst, J.A.; O’Callaghan, C.A.; Lasserson, D.S.; Hobbs, F.D.R. Global Prevalence of Chronic Kidney Disease—A Systematic Review and Meta-Analysis. PLoS ONE 2016, 11, e0158765. [Google Scholar] [CrossRef] [PubMed]
- Polzin, D.; Osborne, C.; Hayden, D.; Stevens, J. Influence of reduced protein diets on morbidity, mortality, and renal function in dogs with induced chronic renal failure. Am. J. Vet. Res. 1984, 45, 506–517. [Google Scholar]
- Jacob, F.; Polzin, D.J.; Osborne, C.A.; Allen, T.A.; Kirk, C.A.; Neaton, J.D.; Lekcharoensuk, C.; Swanson, L.L. Clinical evaluation of dietary modification for treatment of spontaneous chronic renal failure in dogs. J. Am. Vet. Med. Assoc. 2002, 220, 1163–1170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chew, D.J.; Dibartola, S.P.; Schenck, P. Canine and Feline Nephrology and Urology, 2nd ed.; Elsevier Saunders: St. Louis, MO, USA, 2011; ISBN 978-0-7216-8178-8. [Google Scholar]
- Polzin, D.J. Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats. J. Vet. Emerg. Crit. Care 2013, 23, 205–215. [Google Scholar] [CrossRef]
- Yu, S.; Gross, K.; Allen, T. A renal food supplemented with vitamins E, C and beta-carotene reduces oxidative stress and improves kidney function in client-owned dogs with stages 2 or 3 kidney disease. J. Vet. Intern. Med. 2006, 20, 1537. [Google Scholar]
- Yu, S.; Paetau-Robinson, I. Dietary supplements of vitamins E and C and β-carotene reduce oxidative stress in cats with renal insufficiency. Vet. Res. Commun. 2006, 30, 403–413. [Google Scholar] [CrossRef]
- Brown, S.A. Oxidative Stress and Chronic Kidney Disease. Vet. Clin. N. Am. Small Anim. Pract. 2008, 38, 157–166. [Google Scholar] [CrossRef] [PubMed]
- Halfen, D.P.; Caragelasco, D.S.; De Souza Nogueira, J.P.; Jeremias, J.T.; Pedrinelli, V.; Oba, P.M.; Ruberti, B.; Pontieri, C.F.F.; Kogika, M.M.; Brunetto, M.A. Evaluation of electrolyte concentration and pro-inflammatory and oxidative status in dogs with advanced chronic kidney disease under dietary treatment. Toxins 2019, 12, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brown, S.A.; Brown, C.A.; Crowell, W.A.; Barsanti, J.A.; Allen, T.; Cowell, C.; Finco, D.R. Beneficial effects of chronic administration of dietary ω-3 polyunsaturated fatty acids in dogs with renal insufficiency. J. Lab. Clin. Med. 1998, 131, 447–455. [Google Scholar] [CrossRef]
- National Research Council (NRC) Nutrient Requirements of Dogs and Cats; National Academies Press: Washington, DC, USA, 2006; ISBN 0309086280.
- Jones, D.P.; Park, Y.; Ziegler, T.R. Nutritional Metabolomics: Progress in Addressing Complexity in Diet and Health. Annu. Rev. Nutr. 2012, 32, 183–202. [Google Scholar] [CrossRef] [Green Version]
- Deng, P.; Jones, J.C.; Swanson, K.S. Effects of dietary macronutrient composition on the fasted plasma metabolome of healthy adult cats. Metabolomics 2014, 10, 638–650. [Google Scholar] [CrossRef]
- Rebholz, C.M.; Zheng, Z.; Grams, M.E.; Appel, L.J.; Sarnak, M.J.; Inker, L.A.; Levey, A.S.; Coresh, J. Serum metabolites associated with dietary protein intake: Results from the Modification of Diet in Renal Disease (MDRD) randomized clinical trial. Am. J. Clin. Nutr. 2019, 109, 517–525. [Google Scholar] [CrossRef]
- Fiehn, O. Metabolomics—The link between genotypes and phenotypes. Plant Mol. Biol. 2002, 48, 155–171. [Google Scholar] [CrossRef]
- German, J.B.; Hammockc, B.D.; Steven, M.W. Metabolomics: Building on a century of biochemistry to guide human health. Metabolomics 2005, 1, 3–9. [Google Scholar] [CrossRef]
- Xiao, J.F.; Zhou, B.; Ressom, H.W. Metabolite identification and quantitation in LC-MS/MS-based metabolomics. TrAC Trends Anal. Chem. 2012, 32, 1–14. [Google Scholar] [CrossRef] [Green Version]
- Coen, M.; Holmes, E.; Lindon, J.C.; Nicholson, J.K. NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chem. Res. Toxicol. 2008, 21, 9–27. [Google Scholar] [CrossRef] [PubMed]
- Qi, S.; Ouyang, X.; Wang, L.; Peng, W.; Wen, J.; Dai, Y. A Pilot Metabolic Profiling Study in Serum of Patients with Chronic Kidney Disease Based on 1H-NMR-Spectroscopy. Clin. Transl. Sci. 2012, 5, 379–385. [Google Scholar] [CrossRef] [Green Version]
- Savorani, F.; Rasmussen, M.A.; Mikkelsen, M.S.; Engelsen, S.B. A primer to nutritional metabolomics by NMR spectroscopy and chemometrics. Food Res. Int. 2013, 54, 1131–1145. [Google Scholar] [CrossRef] [Green Version]
- Shah, V.O.; Townsend, R.R.; Feldman, H.I.; Pappan, K.L.; Kensicki, E.; Vander Jagt, D.L. Plasma metabolomic profiles in different stages of CKD. Clin. J. Am. Soc. Nephrol. 2013, 8, 363–370. [Google Scholar] [CrossRef] [Green Version]
- Goraya, N.; Wesson, D.E. Dietary interventions to improve outcomes in chronic kidney disease. Curr. Opin. Nephrol. Hypertens. 2015, 24, 505–510. [Google Scholar] [CrossRef]
- Dossetor, J.B. The Relative Significance of Blood Urea Nitrogen and Serum Creatinine Concentrations in Azotemia. Ann. Intern. Med. 1966, 65, 1287–1299. [Google Scholar] [CrossRef]
- Kobayashi, T. Metabolomics and Stages of Chronic Kidney Disease. In Biomarkers in Kidney Disease; Patel, V.B., Preedy, V.R., Eds.; Springer: London, UK, 2015; pp. 69–82. ISBN 9789400776982. [Google Scholar]
- Braun, J.-P.; Lefebvre, H.P. Kidney Function and Damage. In Clinical Biochemistry of Domestic Animals; Kaneko, J.J., Harvey, J.W., Bruss, M.L., Eds.; Academic Press: Cambridge, MA, USA, 2008; pp. 485–528. ISBN 9780123704917. [Google Scholar]
- Park, R.; Rabinowitz, L. Effect of Reduced Glomerular Filtration Rate on the Fractional Excretion of Urea in the Dog. Exp. Biol. Med. 1969, 132, 27–29. [Google Scholar] [CrossRef] [PubMed]
- Hosten, A.O. BUN and Creatinine. In Clinical Methods: The History, Physical, and Laboratory; Walker, H., Hall, W., Hurst, J., Eds.; Butterworths: Boston, MA, USA, 1990; pp. 874–878. [Google Scholar]
- Maroni, B.J.; Steinman, T.I.; Mitch, W.E. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985, 27, 58–65. [Google Scholar] [CrossRef] [Green Version]
- Elliott, J.; Rawlings, J.M.; Markwell, P.J.; Barber, P.J. Survival of cats with naturally occurring chronic renal failure: Effect of dietary management. J. Small Anim. Pract. 2000, 41, 235–242. [Google Scholar] [CrossRef] [PubMed]
- Franch, H.A.; Mitch, W.E. Navigating Between the Scylla and Charybdis of Prescribing Dietary Protein for Chronic Kidney Diseases. Annu. Rev. Nutr. 2009, 29, 341–364. [Google Scholar] [CrossRef]
- Weiner, I.D.; Mitch, W.E.; Sands, J.M. Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion. Clin. J. Am. Soc. Nephrol. 2015, 10, 1444–1458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wyss, M.; Kaddurah-Daouk, R. Creatine and creatinine metabolism. Physiol. Rev. 2000, 80, 1107–1213. [Google Scholar] [CrossRef]
- Stevens, L.A.; Coresh, J.; Greene, T.; Levey, A.S. Assessing kidney function—Measured and estimated glomerular filtration rate. N. Engl. J. Med. 2006, 354, 2473–2483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- O’Connell, J.M.B.; Romeo, J.A.; Mudge, G.H. Renal tubular secretion of creatinine in the dog. Am. J. Physiol. Content 1962, 203, 985–990. [Google Scholar] [CrossRef]
- Stevens, L.A.; Levey, A.S. Measurement of kidney function. Med. Clin. N. Am. 2005, 89, 457–473. [Google Scholar] [CrossRef]
- Preiss, D.J.; Godber, I.M.; Lamb, E.J.; Dalton, R.N.; Gunn, I.R. The influence of a cooked-meat meal on estimated glomerular filtration rate. Ann. Clin. Biochem. 2007, 44, 35–42. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schutte, J.E.; Longhurst, J.C.; Gaffney, F.A.; Bastian, B.C.; Blomqvist, C.G. Total plasma creatinine: An accurate measure of total striated muscle mass. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 1981, 51, 762–766. [Google Scholar] [CrossRef] [PubMed]
- Levey, A.S. Measurement of renal function in chronic renal disease. Kidney Int. 1990, 38, 167–184. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.H.; Mitch, W.E. Mechanisms of muscle wasting in chronic kidney disease. Nat. Rev. Nephrol. 2014, 10, 504–516. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Laflamme, D. Development and Validation of a Body Condition Score System for Dogs. Canine Pract. 1997, 22, 10–15. [Google Scholar]
- Parker, V.; Freeman, L. Association between body condition and survival in dogs with acquired chronic kidney disease. J. Vet. Intern. Med. 2011, 25, 1306–1311. [Google Scholar] [CrossRef] [PubMed]
- Rudinsky, A.J.; Harjes, L.M.; Byron, J.; Chew, D.J.; Toribio, R.E.; Langston, C.; Parker, V.J. Factors associated with survival in dogs with chronic kidney disease. J. Vet. Intern. Med. 2018, 32, 1977–1982. [Google Scholar] [CrossRef] [Green Version]
- Walker, J.B. Creatine: Biosynthesis, Regulation, and Function. Adv. Enzymol. Relat. Areas Mol. Biol. 1979, 50, 177–242. [Google Scholar] [PubMed]
- Brosnan, J.T.; Brosnan, M.E. Creatine: Endogenous Metabolite, Dietary, and Therapeutic Supplement. Annu. Rev. Nutr. 2007, 27, 241–261. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Balsom, P.D.; Söderlund, K.; Ekblom, B. Creatine in Humans with Special Reference to Creatine Supplementation. Sports Med. 1994, 18, 268–280. [Google Scholar] [CrossRef] [PubMed]
- Harris, R.C.; Lowe, J.A.; Warnes, K.; Orme, C.E. The concentration of creatine in meat, offal and commercial dog food. Res. Vet. Sci. 1997, 62, 58–62. [Google Scholar] [CrossRef]
- Dobenecker, B.; Braun, U. Creatine and creatinine contents in different diet types for dogs—Effects of source and processing. J. Anim. Physiol. Anim. Nutr. 2015, 99, 1017–1024. [Google Scholar] [CrossRef] [PubMed]
- Laing, C.M.; Toye, A.M.; Capasso, G.; Unwin, R.J. Renal tubular acidosis: Developments in our understanding of the molecular basis. Int. J. Biochem. Cell Biol. 2005, 37, 1151–1161. [Google Scholar] [CrossRef]
- Choi, J.Y.; Yoon, Y.J.; Choi, H.J.; Park, S.H.; Kim, C.D.; Kim, I.S.; Kwon, T.H.; Do, J.Y.; Kim, S.H.; Ryu, D.H.; et al. Dialysis modality-dependent changes in serum metabolites: Accumulation of inosine and hypoxanthine in patients on haemodialysis. Nephrol. Dial. Transplant. 2011, 26, 1304–1313. [Google Scholar] [CrossRef] [Green Version]
- Psihogios, N.G.; Kalaitzidis, R.G.; Dimou, S.; Seferiadis, K.I.; Siamopoulos, K.C.; Bairaktari, E.T. Evaluation of tubulointerstitial lesions’ severity in patients with glomerulonephritides: An NMR-based metabonomic study. J. Proteome Res. 2007, 6, 3760–3770. [Google Scholar] [CrossRef]
- Jia, L.; Wang, C.; Zhao, S.; Lu, X.; Xu, G. Metabolomic identification of potential phospholipid biomarkers for chronic glomerulonephritis by using high performance liquid chromatography-mass spectrometry. J. Chromatogr. B 2007, 860, 134–140. [Google Scholar] [CrossRef]
- Vaziri, N.D. Dyslipidemia of chronic renal failure: The nature, mechanisms, and potential consequences. Am. J. Physiol. Ren. Physiol. 2006, 290, 262–272. [Google Scholar] [CrossRef]
- Behling-Kelly, E. Serum Lipoprotein Changes in Dogs with Renal Disease. J. Vet. Intern. Med. 2014, 28, 1692–1698. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vaziri, N.D.; Norris, K. Lipid disorders and their relevance to outcomes in chronic kidney disease. Blood Purif. 2011, 31, 189–196. [Google Scholar] [CrossRef] [PubMed]
- Leal-Pinto, E.; Park, H.; King, F.; MacLeod, M.; Pitts, R. Metabolism of lactate by the intact functioning kidney of the dog. Am. J. Physiol. 1973, 224, 1463–1467. [Google Scholar] [CrossRef] [Green Version]
- Bellomo, R.; Kellum, J.A.; Pinsky, M.R. Transvisceral lactate fluxes during early endotoxemia. Chest 1996, 110, 198–204. [Google Scholar] [CrossRef] [PubMed]
- Bartlett, S.; Espinal, J.; Janssens, P.; Ross, B.D. The influence of renal function on lactate and glucose metabolism. Biochem. J. 1984, 219, 73–78. [Google Scholar] [CrossRef] [Green Version]
- Kopple, J.D.; Swendseid, M.E. Protein and amino acid metabolism in uremic patients undergoing maintenance hemodialysis. Kidney Int. Suppl. 1975, 2, 64–72. [Google Scholar]
- May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E. Branched-chain amino acid metabolism in rat muscle: Abnormal regulation in acidosis. Am. J. Physiol. Endocrinol. Metab. 1987, 252, E712–E718. [Google Scholar] [CrossRef]
- Busque, S.M.; Wagner, C.A. Potassium restriction, high protein intake, and metabolic acidosis increase expression of the glutamine transporter SNAT3 (Slc38a3) in mouse kidney. Am. J. Physiol. Ren. Physiol. 2009, 297, 440–450. [Google Scholar] [CrossRef] [PubMed]
- IRIS Staging of CKD. Available online: http://www.iris-kidney.com/guidelines/ (accessed on 27 August 2020).
- FEDIAF—European Pet Food Industry Federation. Nutritional Guidelines for Complete and Complementary Pet Food for Cats and Dogs; FEDIAF: Brussels, Belgium, 2019. [Google Scholar]
- Beckonert, O.; Keun, H.C.; Ebbels, T.M.D.; Bundy, J.; Holmes, E.; Lindon, J.C.; Nicholson, J.K. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc. 2007, 2, 2692–2703. [Google Scholar] [CrossRef] [PubMed]
Nutrients | ||
---|---|---|
Per 100 g of Diet (as Fed) | Per 1000 kcal | |
Dry matter (g) | 90.00 | − |
Protein (g) | 14.50 | 35.60 |
Fat (g) | 18.00 | 44.20 |
Ash (g) | 5.50 | 13.50 |
Crude fiber (g) | 3.50 | 8.60 |
Minimum calcium (g) | 0.40 | 0.98 |
Maximum calcium (g) | 0.90 | 2.21 |
Phosphorus (g/kg) | 0.30 | 0.74 |
Potassium (g/kg) | 0.60 | 1.47 |
Omega 6 (g) | 2.00 | 4.91 |
Omega 3 (g) | 0.52 | 1.27 |
EPA + DHA (g) | 0.35 | 0.86 |
Food base excess (mEq) | 11.30 | 27.75 |
Metabolizable energy (kcal/g) | 4.072 b |
Nutrients | ||
---|---|---|
Per 100 g of Diet (as Fed) | Per 1000 kcal | |
Dry matter (g) | 90.00 | − |
Protein (g) | 23.00 | 60.61 |
Fat (g) | 12.00 | 31.62 |
Ash (g) | 7.50 | 19.76 |
Crude fiber (g) | 3.00 | 7.91 |
Minimum calcium (g) | 0.80 | 2.11 |
Maximum calcium (g) | 1.60 | 4.22 |
Phosphorus (g/kg) | 0.70 | 1.84 |
Potassium (g/kg) | 0.50 | 1.32 |
Omega 6 (g) | 2.00 | 5.27 |
Omega 3 (g) | 0.22 | 0.58 |
Metabolizable energy (kcal/g) | 3.795 b |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Brunetto, M.A.; Ruberti, B.; Halfen, D.P.; Caragelasco, D.S.; Vendramini, T.H.A.; Pedrinelli, V.; Macedo, H.T.; Jeremias, J.T.; Pontieri, C.F.F.; Ocampos, F.M.M.; et al. Healthy and Chronic Kidney Disease (CKD) Dogs Have Differences in Serum Metabolomics and Renal Diet May Have Slowed Disease Progression. Metabolites 2021, 11, 782. https://doi.org/10.3390/metabo11110782
Brunetto MA, Ruberti B, Halfen DP, Caragelasco DS, Vendramini THA, Pedrinelli V, Macedo HT, Jeremias JT, Pontieri CFF, Ocampos FMM, et al. Healthy and Chronic Kidney Disease (CKD) Dogs Have Differences in Serum Metabolomics and Renal Diet May Have Slowed Disease Progression. Metabolites. 2021; 11(11):782. https://doi.org/10.3390/metabo11110782
Chicago/Turabian StyleBrunetto, Marcio Antonio, Bruna Ruberti, Doris Pereira Halfen, Douglas Segalla Caragelasco, Thiago Henrique Annibale Vendramini, Vivian Pedrinelli, Henrique Tobaro Macedo, Juliana Toloi Jeremias, Cristiana Fonseca Ferreira Pontieri, Fernanda Maria Marins Ocampos, and et al. 2021. "Healthy and Chronic Kidney Disease (CKD) Dogs Have Differences in Serum Metabolomics and Renal Diet May Have Slowed Disease Progression" Metabolites 11, no. 11: 782. https://doi.org/10.3390/metabo11110782