Skip to main content
SpringerLink
Log in

Mouse Models and Methods for Studying Human Disease, Acute Kidney Injury (AKI)

  • Protocol
  • First Online:
Mouse Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1194))

Abstract

Acute kidney injury (AKI) is serious complication in hospitalized patients with high level of mortality. There is not much progress made for the past 50 years in reducing the mortality rate despite advances in understanding disease pathology. Using variety of animal models of acute kidney injury, scientist studies the pathogenic mechanism of AKI and to test therapeutic drugs, which may reduce renal injury. Among them, renal pedicle clamping and cisplatin induced nephrotoxicity in mice are most prominently used, mainly due to the availability of gene knockouts to study specific gene functions, inexpensive and availability of the inbred strain with less genetic variability. However, ischemic mouse model is highly variable and require excellent surgical skills to reduce variation in the observation. In this chapter, we describe a detailed protocol of the mouse model of bilateral renal ischemia–reperfusion and cisplatin induced nephrotoxicity. We also discuss the protocol for the isolation and analysis of infiltrated inflammatory cell into the kidney by flow cytometry. Information provided in this chapter will help scientist who wants to start research on AKI and want to establish the mouse model for ischemic and toxic kidney injury.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT (1983) Hospital-acquired renal insufficiency: a prospective study. Am J Med 74:243–248

    Article  CAS  PubMed  Google Scholar 

  2. Shusterman N, Strom BL, Murray TG, Morrison G, West SL, Maislin G (1987) Risk factors and outcome of hospital-acquired acute renal failure. Clinical epidemiologic study. Am J Med 83:65–71

    Article  CAS  PubMed  Google Scholar 

  3. Liano F, Junco E, Pascual J, Madero R, Verde E (1998) The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney Int Suppl 66:S16–S24

    CAS  PubMed  Google Scholar 

  4. Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J (1998) Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104:343–348

    Article  CAS  PubMed  Google Scholar 

  5. Levy EM, Viscoli CM, Horwitz RI (1996) The effect of acute renal failure on mortality. A cohort analysis. JAMA 275:1489–1494

    Article  CAS  PubMed  Google Scholar 

  6. Li X, Hassoun HT, Santora R, Rabb H (2009) Organ crosstalk: the role of the kidney. Curr Opin Crit Care 15:481–487

    Article  PubMed  Google Scholar 

  7. Klein CL, Hoke TS, Fang WF, Altmann CJ, Douglas IS, Faubel S (2008) Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int 74:901–909

    Article  CAS  PubMed  Google Scholar 

  8. Himmelfarb J, Joannidis M, Molitoris B, Schietz M, Okusa MD, Warnock D, Laghi F, Goldstein SL, Prielipp R, Parikh CR, Pannu N, Lobo SM, Shah S, D’Intini V, Kellum JA (2008) Evaluation and initial management of acute kidney injury. Clin J Am Soc Nephrol 3(4):962–967

    Article  PubMed Central  PubMed  Google Scholar 

  9. Waikar SS, Liu KD, Chertow GM (2008) Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol 3:844–861

    Article  PubMed  Google Scholar 

  10. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212

    Article  PubMed Central  PubMed  Google Scholar 

  11. Liangos O, Wald R, O’Bell JW, Price L, Pereira BJ, Jaber BL (2006) Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol 1:43–51

    PubMed  Google Scholar 

  12. Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, Hiesmayr M (2004) Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 15:1597–1605

    Article  CAS  PubMed  Google Scholar 

  13. Al Ghonaim M, Pannu N (2006) Prevention and treatment of contrast-induced nephropathy. Tech Vasc Interv Radiol 9:42–49

    Article  PubMed  Google Scholar 

  14. Dangas G, Iakovou I, Nikolsky E, Aymong ED, Mintz GS, Kipshidze NN, Lansky AJ, Moussa I, Stone GW, Moses JW, Leon MB, Mehran R (2006) Radiocontrast-induced acute renal failure–impact beyond the acute phase: contrast-induced nephropathy after percutaneous coronary interventions in relation to chronic kidney disease and hemodynamic variables. Am J Cardiol 95: 13-19, 2005. J Am Soc Nephrol 17:595–599

    Article  Google Scholar 

  15. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB (2010) Mechanisms of cisplatin nephrotoxicity. Toxins (Basel) 2:2490–2518

    Article  CAS  Google Scholar 

  16. Baliga R, Ueda N, Walker PD, Shah SV (1999) Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev 31:971–997

    Article  CAS  PubMed  Google Scholar 

  17. Pabla N, Dong Z (2008) Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 73:994–1007

    Article  CAS  PubMed  Google Scholar 

  18. Bennett WM (1997) Drug nephrotoxicity: an overview. Ren Fail 19:221–224

    Article  CAS  PubMed  Google Scholar 

  19. LeBrun M, Grenier L, Gourde P, Bergeron MG, Labrecque G, Beauchamp D (1996) Nephrotoxicity of amphotericin b in rats: effects of the time of administration. Life Sci 58:869–876

    Article  CAS  PubMed  Google Scholar 

  20. Timmer RT, Sands JM (1999) Lithium intoxication. J Am Soc Nephrol 10:666–674

    CAS  PubMed  Google Scholar 

  21. Bonventre JV (1993) Mechanisms of ischemic acute renal failure. Kidney Int 43:1160–1178

    Article  CAS  PubMed  Google Scholar 

  22. Sheridan AM, Bonventre JV (2001) Pathophysiology of ischemic acute renal failure. Contrib Nephrol 132:7–21

    Article  CAS  PubMed  Google Scholar 

  23. Brezis M, Rosen S (1995) Hypoxia of the renal medulla–its implications for disease. N Engl J Med 332:647–655

    Article  CAS  PubMed  Google Scholar 

  24. Heyman SN, Rosen S, Rosenberger C (2008) Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy. Clin J Am Soc Nephrol 3:288–296

    Article  PubMed  Google Scholar 

  25. Rosenberger C, Rosen S, Heyman SN (2006) Renal parenchymal oxygenation and hypoxia adaptation in acute kidney injury. Clin Exp Pharmacol Physiol 33:980–988

    Article  CAS  PubMed  Google Scholar 

  26. Harvig B, Engberg A, Ericsson JL (1980) Effects of cold ischemia on the preserved and transplanted rat kidney. Structural changes of the loop of Henle, distal tubule and collecting duct. Virchows Arch B Cell Pathol Incl Mol Pathol 34:173–192

    Article  CAS  PubMed  Google Scholar 

  27. Doi K, Leelahavanichkul A, Yuen PS, Star RA (2009) Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest 119:2868–2878

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Miyaji T, Hu X, Yuen PS, Muramatsu Y, Iyer S, Hewitt SM, Star RA (2003) Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice. Kidney Int 64:1620–1631

    Article  CAS  PubMed  Google Scholar 

  29. Dear JW, Yasuda H, Hu X, Hieny S, Yuen PST, Hewitt SM, Sher A, Star RA (2006) Sepsis-induced organ failure is mediated by different pathways in the kidney and liver: Acute renal failure is dependent on MyD88 but not renal cell apoptosis. Kidney Int 69:832–836

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Cordier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV (2010) Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 28:478–485

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Grgic I, Campanholle G, Bijol V, Wang C, Sabbisetti VS, Ichimura T, Humphreys BD, Bonventre JV (2012) Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis. Kidney Int 82:172–183

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, Chadban SJ (2010) HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol 21:1878–1890

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Weight SC, Furness PN, Nicholson ML (1998) New model of renal warm ischaemia-reperfusion injury for comparative functional, morphological and pathophysiological studies. Br J Surg 85:1669–1673

    Article  CAS  PubMed  Google Scholar 

  34. Ramesh G, Reeves WB (2002) TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 110:835–842

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Ramesh G, Reeves WB (2004) Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha. Kidney Int 65:490–499

    Article  CAS  PubMed  Google Scholar 

  36. Ramesh G, Reeves WB (2005) p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice. Am J Physiol Renal Physiol 289:F166–F174

    Article  CAS  PubMed  Google Scholar 

  37. Singh AP, Junemann A, Muthuraman A, Jaggi AS, Singh N, Grover K, Dhawan R (2012) Animal models of acute renal failure. Pharmacol Rep 64:31–44

    Article  CAS  PubMed  Google Scholar 

  38. Coca SG, Yalavarthy R, Concato J, Parikh CR (2008) Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int 73(9):1008–1016

    Article  CAS  PubMed  Google Scholar 

  39. Edelstein CL (2008) Biomarkers of acute kidney injury. Adv Chronic Kidney Disease 15:222–234

    Article  Google Scholar 

  40. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV (2002) Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62:237–244

    Article  CAS  PubMed  Google Scholar 

  41. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238

    Article  CAS  PubMed  Google Scholar 

  42. Ramesh G, Krawczeski CD, Woo JG, Wang Y, Devarajan P (2010) Urinary netrin-1 is an early predictive biomarker of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 5:395–401

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Noiri E, Doi K, Negishi K, Tanaka T, Hamasaki Y, Fujita T, Portilla D, Sugaya T (2008) Urinary fatty acid binding protein 1: an early predictive biomarker of kidney injury. Am J Physiol Renal Physiol 296(4):F669–F679

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and Vascular Biology Center, CB-3330, Georgia Health Sciences University, 1459 Laney-Walker Blvd, Augusta, GA, 30912, USA

    Ganesan Ramesh Ph.D.

  2. Department of Medicine and Vascular Biology Center, Georgia Health Sciences University, Augusta, GA, 30912, USA

    Punithavathi Ranganathan

Authors
  1. Ganesan Ramesh Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Punithavathi Ranganathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ganesan Ramesh Ph.D. .

Editor information

Editors and Affiliations

  1. Stem Cell Regulation and Animal Aging Section, Basic Research Laboratory,, National Cancer Institute, National Institutes of Health, Frederick, MD, USA

    Shree Ram Singh

  2. Genetically Engineered Mouse Modeling Core/Department of Molecular Virology, Immunology and Medical Genetics, Wexner Medical Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    Vincenzo Coppola

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Ramesh, G., Ranganathan, P. (2014). Mouse Models and Methods for Studying Human Disease, Acute Kidney Injury (AKI). In: Singh, S., Coppola, V. (eds) Mouse Genetics. Methods in Molecular Biology, vol 1194. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1215-5_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1215-5_24

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1214-8

  • Online ISBN: 978-1-4939-1215-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation