Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-19T08:49:02.615Z Has data issue: false hasContentIssue false
  • English
  • Français

Four- and six-hour urinary albumin excretion is a valuable alternative to 24-h urinary albumin excretion in male db/db mice

Published online by Cambridge University Press:  01 January 2023

SA Nørgaard ,
FW Sand ,
DB Sørensen  and
H Søndergaard
SA Nørgaard*
Affiliation:
Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 2 Sal, 1870 Frederiksberg C, 1-62 Denmark
FW Sand
Affiliation:
Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark
DB Sørensen
Affiliation:
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 2 Sal, 1870 Frederiksberg C, 1-62 Denmark
H Søndergaard
Affiliation:
Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark
*
* Contact for correspondence: [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic cages on wire mesh without enrichment. This is known to be stressful for the mice. Therefore, it was investigated if shorter urine collections would be sufficient to get reliable assessments of albuminuria. Twenty-one diabetic (C57BLKS-Leprdb/ db) and ten non-diabetic mice (C57BLKS-Leprdb/+) were placed in metabolic cages at 15 and 20 weeks of age (WoA) for 24 h. Urine samples were taken at 4, 6, 18 and 24 h and albumin and creatinine concentration were measured. Four- and 6-h UAE was found to correlate significantly with 24-h UAE. Furthermore, a significant correlation was found between 24-h UAE and albumin:creatinine ratio (ACR) in the 4-h sample. However, the strength of the correlation between ACR and 24-h UAE was weaker than between the 4- and 24-h UAE. This suggests that normalising to creatinine may not provide additional value to the 4-h urine collection. In conclusion, the strong correlation between 4- and 6-h UAE and 24-h UAE indicates that the collection period can be considerably reduced. This refinement could reduce stress and increase welfare of the db/db model and potentially be applied to other DN models.

Keywords

albuminuriaanimal welfaredb/db micediabetic nephropathymetabolic cagesrefinement
Type
Research Article
Information
Animal Welfare , Volume 29 , Issue 2 , May 2020 , pp. 143 - 149
Copyright
© 2020 Universities Federation for Animal Welfare

References

Azushima, K, Gurley, SB and Coffman, TM 2018 Modelling diabetic nephropathy in mice. Nature Reviews Nephrology 14: 48–56. https://doi.org/10.1038/nrneph.2017.142 BangsgaardCrossRefGoogle ScholarPubMed
Bendtsen, KM, Krych, L, Sørensen, DB, Pang, W, Nielsen, DS, Josefsen, K, Hansen, LH, Sørensen, SJ and Hansen, AK 2012 Gut microbiota composition is correlated to grid floor induced stress and behaviour in the BALB/c mouse. PLoS One 7: e46231. https://doi.org/10.1371/journal.pone.0046231CrossRefGoogle Scholar
Bartolomucci, A, Palanza, P, Sacerdote, P, Ceresini, G, Chirieleison, A, Panerai, AE and Parmigiani, S 2003 Individual housing induces altered immuno-endocrine responses to psychological stress in male mice. Psychoneuroendocrinology 28:540–558. https://doi.org/10.1016/S0306-4530(02)00039-2CrossRefGoogle ScholarPubMed
Birn, H and Christensen, EI 2006 Renal albumin absorption in physiology and pathology. Kidney International 69: 440–449. https://doi.org/10.1038/sj.ki.5000141CrossRefGoogle ScholarPubMed
Breyer, MD, Bottinger, E, Brosius, FC, Coffman, TM, Harris, RC, Heilig, CW and Sharma, K 2005 Mouse models of diabet-ic nephropathy. Journal of the American Society of Nephrology 16:27–45. https://doi.org/10.1681/ASN.2004080648CrossRefGoogle Scholar
Brosius FC, III, Alpers, CE, Bottinger, EP, Breyer, MD, Coffman, TM, Gurley, SB, Harris, RC, Kakoki, M, Kretzler, M, Leiter, EH, Levi, M, McIndoe, RA, Sharma, K, Smithies, O, Susztak, K, Takahashi, N and Takahashi, T 2009 Mouse models of diabetic nephropathy. Journal of the American Society of Nephrology 20: 2503–2512. https://doi.org/10.1681/ASN.2009070721CrossRefGoogle ScholarPubMed
Cambar, J, Toussaint, C, Le Moigne, F, Cales, P and Crockett, R 1981 Circadian rhythms in rat and mouse urinary electrolytes and nitrogen derivatives excretion. Journal de Physiologie 77: 887–890Google ScholarPubMed
Grosbellet, E, Dumont, S, Schuster-Klein, C, Guardiola-Lemaitre, B, Pevet, P, Criscuolo, F and Challet, E 2016 Circadian phenotyping of obese and diabetic db/db mice. Biochimie 124: 198–206. https://doi.org/10.1016/j.biochi.2015.06.029CrossRefGoogle ScholarPubMed
Gross, JL, de Azevedo, MJ, Silveiro, SP, Canani, LH, Caramori, ML and Zelmanovitz, T 2005 Diabetic nephropa-thy: diagnosis, prevention, and treatment. Diabetes Care 28: 164–176. https://doi.org/10.2337/diacare.28.1.164CrossRefGoogle Scholar
Hoffman, JF, Fan, AX, Neuendorf, EH, Vergara, VB and Kalinich, JF 2018 Hydrophobic sand versus metabolic cages: A com-parison of urine collection methods for rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science 57: 51–57Google Scholar
Hoppe, CC, Moritz, KM, Fitzgerald, SM, Bertram, JF and Evans, RG 2009 Transient hypertension and sustained tachycar-dia in mice housed individually in metabolism cages. Physiological Research 58: 69–75CrossRefGoogle Scholar
Kalliokoski, O, Jacobsen, KR, Darusman, HS, Henriksen, T, Weimann, A, Poulsen, HE, Hau, J and Abelson, KS 2013 Mice do not habituate to metabolism cage housing-a three week study of male BALB/c mice. PLoS One 8: e58460. https://doi.org/10.1371/journal.pone.0058460CrossRefGoogle ScholarPubMed
Kurien, BT, Everds, NE and Scofield, RH 2004 Experimental animal urine collection: a review. Laboratory Animals 38: 333–361. https://doi.org/10.1258/0023677041958945CrossRefGoogle ScholarPubMed
Manser, CE, Morris, TH and Broom, DM 1995 An investigation into the effects of solid or grid cage flooring on the welfare of laboratory rats. Laboratory Animals 29: 353–363. https://doi.org/10.1258/002367795780740023CrossRefGoogle ScholarPubMed
Moresco, RN, Sangoi, MB, De Carvalho, JA, Tatsch, E and Bochi, GV 2013 Diabetic nephropathy: traditional to proteomic markers. Clinica Chimica Acta 421: 17–30. https://doi.org/10.1016/j.cca.2013.02.019CrossRefGoogle ScholarPubMed
Nørgaard, SA, Sand, FW, Sørensen, DB, Abelson, KS and Søndergaard, H 2018 Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropa-thy. Laboratory Animals 52: 373–383. https://doi.org/10.1177/0023677217747915CrossRefGoogle Scholar
Qi, Z, Fujita, H, Jin, J, Davis, LS, Wang, Y, Fogo, AB and Breyer, MD 2005 Characterisation of susceptibility of inbred mouse strains to diabetic nephropathy. Diabetes 54: 2628–2637. https://doi.org/10.2337/diabetes.54.9.2628CrossRefGoogle ScholarPubMed