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Measurement of Glomerular Filtration Rate in Conscious Mice

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Kidney Research

Part of the book series: Methods in Molecular Biology ((MIMB,volume 466))

Abstract

Glomerular filtration rate (GFR) is an important index of renal function and routinely used in patient care and basic research to evaluate progression of renal diseases or test the efficacy of novel therapeutic strategies. Determination of GFR in mouse models has been mostly practiced in anesthetized animals, which is not suitable for serial monitoring of GFR in the individual mouse. In this chapter, we outline two approaches for determining GFR in conscious mice including 1) determination of urinary excretion of fluorescein-labelled inulin (FITC–inulin), and 2) determination of plasma FITC–inulin decay following a single bolus injection. The GFR values determined using these two methods are comparable. The sensitivity of the methods in reflecting renal function was validated in nephrectomized mice and early stage diabetic mice. The effects of inbred mouse genetic background on GFR values are also discussed in this chapter.

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References

  1. Coresh, Byrd-Holt, D., Astor, B. C., Briggs, J. P., Eggers, P. W., Lacher, D. A., and Hostetter, T. H. (2005). Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol 16, 180–188.

    Article  PubMed  Google Scholar 

  2. Hallan, S. I., Coresh, J., Astor, B. C., Asberg, A., Powe ,N. R., Romundstad, S., Hallan, H. A., Lydersen, S., and Holmen, J. (2006). International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. J Am Soc Nephrol 17, 2275–2284.

    Article  PubMed  Google Scholar 

  3. Fischer, P. A., Bogoliuk, C. B., Ramirez, A. J., Sanchez, R. A., and Masnatta, L. D. (2000). A new procedure for evaluation of renal function without urine collection in rat. Kidney Int 58, 1336–1341.

    Article  PubMed  CAS  Google Scholar 

  4. Prescott, L. F., Freestone, S., and McAuslane, J. A. (1991). Reassessment of the single intravenous injection method with inulin for measurement of the glomerular filtration rate in man. Clin Sci (Lond) 80, 167–176.

    CAS  Google Scholar 

  5. Levey, A. S. (1990). Measurement of renal function in chronic renal disease. Kidney Int 38, 167–184.

    Article  PubMed  CAS  Google Scholar 

  6. Ahloulay, M., Dechaux, M., Laborde, K., and Bankir, L. (1995). Influence of glucagon on GFR and on urea and electrolyte excretion: direct and indirect effects. Am J Physiol 269, F225–235.

    PubMed  CAS  Google Scholar 

  7. Bouby, N., Ahloulay, M., Nsegbe, E., Dechaux, M., Schmitt, F., and Bankir, L. (1996). Vasopressin increases glomerular filtration rate in conscious rats through its antidiuretic action. J Am Soc Nephrol 7, 842–851.

    PubMed  CAS  Google Scholar 

  8. Qi, Z., Whitt, I., Mehta, A., Jin, J., Zhao, M., Harris, R. C., Fogo, A. B., and Breyer, M. D. (2004). Serial determination of glomerular filtration rate in conscious mice using FITC–inulin clearance. Am J Physiol Renal Physiol 286, F590–596.

    Article  PubMed  CAS  Google Scholar 

  9. Lorenz, J. N. and Gruenstein, E. (1999). A simple, nonradioactive method for evaluating single-nephron filtration rate using FITC–inulin. Am J Physiol 276, F172–177.

    PubMed  CAS  Google Scholar 

  10. Catlin, D.H. (1983). Pharmacokinetics. In: Essentials of Pharmacology, C., edited by J.A. Bevan and J.H. Thompson. 3rd edn., Harper & Row, Publishers, Inc., Philadelphia.

    Google Scholar 

  11. Sturgeon, Sam, A. D., 2nd, and Law, W. R. (1998). Rapid determination of glomerular filtration rate by single-bolus inulin: a comparison of estimation analyses. J Appl Physiol 84, 2154–2162.

    PubMed  CAS  Google Scholar 

  12. Ma, L. J. and Fogo, A. B. (2003). Model of robust induction of glomerulosclerosis in mice: importance of genetic background. Kidney Int 64, 350–355.

    Article  PubMed  Google Scholar 

  13. Goldfarb, D. A., Matin, S. F., Braun, W. E., Schreiber, M. J., Mastroianni, B., Papajcik, D., Rolin, H. A., Flechner, S., Goormastic, M., and Novick, A. C. (2001). Renal outcome 25 years after donor nephrectomy. J Urol 166, 2043–2047.

    Article  PubMed  CAS  Google Scholar 

  14. Hammond, K. A. and Janes, D. N. (1998). The effects of increased protein intake on kidney size and function. J Exp Biol 201 (Pt 13), 2081–2090.

    PubMed  CAS  Google Scholar 

  15. Messow, C., Gartner, K., Hackbarth, H., Kangaloo, M., and Lunebrink, L. (1980). Sex differences in kidney morphology and glomerular filtration rate in mice. Contrib Nephrol 19, 51–55.

    PubMed  CAS  Google Scholar 

  16. Noonan, W. T. and Banks, R. O. (2000). Renal function and glucose transport in male and female mice with diet-induced type II diabetes mellitus. Proc Soc Exp Biol Med 225, 221–230.

    Article  PubMed  CAS  Google Scholar 

  17. Hackbarth, H. and Hackbarth, D. (1981). Genetic analysis of renal function in mice. 1. Glomerular filtration rate and its correlation with body and kidney weight. Lab Anim 15, 267–272.

    Article  PubMed  CAS  Google Scholar 

  18. Cohen, M. P., Clements, R. S., Hud, E., Cohen, J. A., and Ziyadeh, F. N. (1996). Evolution of renal function abnormalities in the db/db mouse that parallels the development of human diabetic nephropathy. Exp Nephrol 4, 166–171.

    PubMed  CAS  Google Scholar 

  19. Gartner, K. (1978). Glomerular hyperfiltration during the onset of diabetes mellitus in two strains of diabetic mice (c57bl/6j db/db and c57bl/ksj db/db). Diabetologia 15, 59–63.

    Article  PubMed  CAS  Google Scholar 

  20. Breyer, M. D., Bottinger, E., Brosius, F. C., 3rd, Coffman, T. M., Harris, R. C., Heilig, C. W., and Sharma, K. (2005). Mouse models of diabetic nephropathy. J Am Soc Nephrol 16, 27–45.

    Article  PubMed  Google Scholar 

  21. Dunn, S. R., Qi, Z., Bottinger, E. P., Breyer, M. D., and Sharma, K. (2004). Utility of endogenous creatinine clearance as a measure of renal function in mice. Kidney Int 65, 1959–1967.

    Article  PubMed  CAS  Google Scholar 

  22. Jung, K., Wesslau, C., Priem, F., Schreiber, G., and Zubek, A. (1987). Specific creatinine determination in laboratory animals using the new enzymatic test kit “Creatinine-PAP.” J Clin Chem Clin Biochem 25, 357–361.

    PubMed  CAS  Google Scholar 

  23. Takahashi, N., Boysen, G., Li, F., Li, Y., and Swenberg, J. A. (2007). Tandem mass spectrometry measurements of creatinine in mouse plasma and urine for determining glomerular filtration rate. Kidney Int 71, 266–271.

    Article  PubMed  CAS  Google Scholar 

  24. Haines, H. and Farmer, J. N. (1991). Glomerular filtration rate and plasma solutes in BALB/c mice infected with Plasmodium berghei. Parasitol Res 77, 411–414.

    Article  PubMed  CAS  Google Scholar 

  25. Aizman, R., Asher, C., Fuzesi, M., Latter, H., Lonai, P., Karlish, S. J., and Garty, H. (2002). Generation and phenotypic analysis of CHIF knockout mice. Am J Physiol Renal Physiol 283, F569–577.

    PubMed  CAS  Google Scholar 

  26. Park, K. M., Chen, A., and Bonventre, J. V. (2001). Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem 276, 11870–11876.

    Article  PubMed  CAS  Google Scholar 

  27. Wang, W., Jittikanont, S., Falk, S. A., Li, P., Feng, L., Gengaro, P. E., Poole, B. D., Bowler, R. P., Day, B. J., Crapo, J. D., and Schrier, R. W. (2003). Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure. Am J Physiol Renal Physiol 284, F532–537.

    PubMed  CAS  Google Scholar 

  28. O’Donnell, M. P., Burne, M., Daniels, F., and Rabb, H. (2002). Utility and limitations of serum creatinine as a measure of renal function in experimental renal ischemia-reperfusion injury. Transplantation 73, 1841–1844.

    Article  PubMed  Google Scholar 

  29. Kawada, N., Imai, E., Karber, A., Welch, W. J., and Wilcox, C. S. (2002). A mouse model of angiotensin II slow pressor response: role of oxidative stress. J Am Soc Nephrol 13, 2860–2868.

    Article  PubMed  CAS  Google Scholar 

  30. Cervenka, L., Mitchell, K. D., and Navar, L. G. (1999). Renal function in mice: effects of volume expansion and angiotensin II. J Am Soc Nephrol 10, 2631–2636.

    PubMed  CAS  Google Scholar 

  31. Luippold, G., Pech, B., Schneider, S., Osswald, H., and Muhlbauer, B. (2002). Age dependency of renal function in CD-1 mice. Am J Physiol Renal Physiol 282, F886–890.

    PubMed  CAS  Google Scholar 

  32. Cullen-McEwen, L. A., Kett, M. M., Dowling, J., Anderson, W. P., and Bertram, J. F. (2003). Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice. Hypertension 41, 335–340.

    Article  PubMed  CAS  Google Scholar 

  33. Wulff, P., Vallon, V., Huang, D. Y., Volkl, H., Yu, F., Richter, K., Jansen, M., Schlunz, M., Klingel, K., Loffing, J., Kauselmann, G., Bosl, M. R., Lang, F., and Kuhl, D. (2002). Impaired renal Na(+) retention in the sgk1-knockout mouse. J Clin Invest 110, 1263–1268.

    PubMed  CAS  Google Scholar 

  34. Brown, R., Ollerstam, A., Johansson, B., Skott, O., Gebre-Medhin, S., Fredholm, B., and Persson, A. E. (2001). Abolished tubuloglomerular feedback and increased plasma renin in adenosine A1 receptor-deficient mice. Am J Physiol Regul Integr Comp Physiol 281, R1362–1367.

    PubMed  CAS  Google Scholar 

  35. Lorenz, J. N., Baird, N. R., Judd, L. M., Noonan, W. T., Andringa, A., Doetschman, T., Manning, P. A., Liu, L. H., Miller, M. L., and Shull, G. E. (2002). Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter’s syndrome. J Biol Chem 277, 37871–37880.

    Article  PubMed  CAS  Google Scholar 

  36. Sun, D., Samuelson, L. C., Yang, T., Huang, Y., Paliege, A., Saunders, T., Briggs, J., and Schnermann, J. (2001). Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci U S A 98, 9983–9988.

    Article  PubMed  CAS  Google Scholar 

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Qi, Z., Breyer, M.D. (2009). Measurement of Glomerular Filtration Rate in Conscious Mice. In: Becker, G., Hewitson, T. (eds) Kidney Research. Methods in Molecular Biology, vol 466. Humana Press. https://doi.org/10.1007/978-1-59745-352-3_5

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  • DOI: https://doi.org/10.1007/978-1-59745-352-3_5

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-945-1

  • Online ISBN: 978-1-59745-352-3

  • eBook Packages: Springer Protocols

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