Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Drug-Induced Nephrotoxicity and Its Biomarkers

  • Kim, Sun-Young (College of Pharmacy, Duksung Women's University) ;
  • Moon, A-Ree (College of Pharmacy, Duksung Women's University)
  • Received : 2011.10.26
  • Accepted : 2011.11.09
  • Published : 2012.05.31
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Abstract

Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefits with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identified for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.

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References

  1. Alchi, B., Nishi, S., Kondo, D., Kaneko, Y., Matsuki, A., Imai, N., Ueno M., Iguchi, S., Sakatsume, M., Narita, I., Yamamoto, T. and Gejyo, F. (2005) Osteopontin expression in acute renal allograft rejection. Kidney Int. 67, 886-896. https://doi.org/10.1111/j.1523-1755.2005.00153.x
  2. Bailly, V., Zhang, Z., Meier, W., Cate, R., Sanicola, M. and Bonventre, J. V. (2002) Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J. Biol. Chem. 277, 39739-39748. https://doi.org/10.1074/jbc.M200562200
  3. Baron, S., Tyring, S. K., Fleischmann, W. R. Jr., Coppenhaver, D. H., Niesel, D. W., Klimpel, G. R., Stanton, G. J. and Hughes, T. K. (1991) The interferons. Mechanisms of action and clinical applications. JAMA 266, 1375-1383. https://doi.org/10.1001/jama.1991.03470100067035
  4. Bernard, A. M., Vyskocil, A. A., Mahieu, P. and Lauwerys, R. R. (1987) Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin. Chem. 33, 775-779.
  5. Bonventre, J. V., Vaidya, V. S., Schmouder, R., Feig, P. and Dieterle, F. (2010) Next-generation biomarkers for detecting kidney toxicity. Nat. Biotechnol. 28, 436-440. https://doi.org/10.1038/nbt0510-436
  6. Borregaard, N., Sehested, M., Nielsen, B. S., Sengeløv, H. and Kjeldsen, L. (1995) Biosynthesis of granule proteins in normal human bone marrow cells. Gelatinase is a marker of terminal neutrophil differentiation. Blood 85, 812-817.
  7. Coco, T. J. and Klasner, A. E. (2004) Drug-induced rhabdomyolysis. Curr. Opin. Pediatr. 16, 206-210. https://doi.org/10.1097/00008480-200404000-00017
  8. Conti, M., Moutereau, S., Zater, M., Lallali, K., Durrbach, A., Manivet, P., Eschwège, P. and Loric, S. (2006) Urinary cystatin C as a specific marker of tubular dysfunction. Clin. Chem. Lab. Med. 44, 288-291.
  9. Donovan, K. L., Coles, G. A. and Williams, J. D. (1994) An ELISA for the detection of type IV collagen in human urine--application to patients with glomerulonephritis. Kidney Int. 46, 1431-1437. https://doi.org/10.1038/ki.1994.415
  10. Emeigh Hart, S. G. (2005) Assessment of renal injury in vivo. J. Pharmacol. Toxicol. Methods 52, 30-45. https://doi.org/10.1016/j.vascn.2005.04.006
  11. Ferguson, M. A., Vaidya, V. S. and Bonventre, J. V. (2008) Biomarkers of nephrotoxic acute kidney injury. Toxicology 245, 182-193. https://doi.org/10.1016/j.tox.2007.12.024
  12. Finn, W. and Porter, G. (2003) Urinary biomarkers and nephrotoxicity. Clinical Nephrotoxins (2nd ed), pp. 621-655. Kluwer Academic Publishers, Massachusetts.
  13. Fored, C. M., Ejerblad, E., Lindblad, P., Fryzek, J. P., Dickman, P. W., Signorello, L. B., Lipworth, L., Elinder, C. G., Blot, W. J., McLaughlin, J. K., Zack, M. M. and Nyren, O. (2001) Acetaminophen, aspirin, and chronic renal failure. N. Engl. J. Med. 345, 1801-1808. https://doi.org/10.1056/NEJMoa010323
  14. Galley, H. F. (2000) Can acute renal failure be prevented? J. R. Coll. Surg. Edinb. 45, 44-50.
  15. Guder, W.G. and Hoffmann, W. (1992) Markers for the diagnosis and monitoring of renal tubular lesions. Clin. Nephrol. 38(Suppl 1), s3-7.
  16. Herget-Rosenthal, S., Poppen, D., Husing, J., Marggraf, G., Pietruck, F., Jakob, H. G., Philipp, T. and Kribben, A. (2004) Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis. Clin. Chem. 50, 552-558. https://doi.org/10.1373/clinchem.2003.027763
  17. Horii, Y., Iwano, M., Hirata, E., Shiiki, M., Fujii, Y., Dohi, K. and Ishikawa, H. (1993) Role of interleukin-6 in the progression of mesangial proliferative glomerulonephritis. Kidney Int. 39(Suppl), S71-75.
  18. Huerta-Alardín, A. L., Varon, J. and Marik, P. E. (2005) Bench-tobedside review: Rhabdomyolysis -- an overview for clinicians. Crit. Care 9, 158-169. https://doi.org/10.1186/cc3221
  19. Ichimura, T., Bonventre, J. V., Bailly, V., Wei, H., Hession, C. A., Cate, R. L. and Sanicola, M. (1998) Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J. Biol. Chem. 273, 4135-4142. https://doi.org/10.1074/jbc.273.7.4135
  20. Isnard Bagnis, C., Deray, G., Baumelou, A., Le Quintrec, M. and Vanherweghem, J. L. (2004) Herbs and the kidney. Am. J. Kidney Dis. 44, 1-11.
  21. Kharasch, E. D., Schroeder, J. L., Bammler, T., Beyer, R. and Srinouanprachanh, S. (2006) Gene expression profiling of nephrotoxicity from the sevoflurane degradation product fluoromethyl-2,2-difl uoro- 1-(trifluoromethyl)vinyl ether ("compound A") in rats. Toxicol. Sci. 90, 419-431.
  22. Kirtane, A. J., Leder, D. M., Waikar, S. S., Chertow, G. M., Ray, K. K., Pinto, D. S., Karmpaliotis, D., Burger, A. J., Murphy, S. A., Cannon, C. P., Braunwald, E. and Gibson, C. M; TIMI Study Group. (2005) Serum blood urea nitrogen as an independent marker of subsequent mortality among patients with acute coronary syndromes and normal to mildly reduced glomerular filtration rates. J. Am. Coll. Cardiol. 45, 1781-1786. https://doi.org/10.1016/j.jacc.2005.02.068
  23. Kohli, H. S., Bhaskaran, M. C., Muthukumar, T., Thennarasu, K., Sud, K., Jha, V., Gupta, K. L. and Sakhuja. V. (2000) Treatment-related acute renal failure in the elderly: a hospital-based prospective study. Nephrol. Dial. Transplant. 15, 212-217. https://doi.org/10.1093/ndt/15.2.212
  24. Manor, S. M., Guillory, G. S. and Jain, S. P. (2004) Clopidogrel-induced thrombotic thrombocytopenic purpura-hemolytic uremic syndrome after coronary artery stenting. Pharmacotherapy 24, 664-667. https://doi.org/10.1592/phco.24.6.664.34732
  25. Markowitz, G. S., Fine, P. L., Stack, J. I., Kunis, C. L., Radhakrishnan, J., Palecki, W., Park, J., Nasr, S. H., Hoh, S., Siegel, D. S. and D'Agati, V. D. (2003) Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int. 64, 281-289. https://doi.org/10.1046/j.1523-1755.2003.00071.x
  26. Markowitz, G. S. and Perazella MA. (2005) Drug-induced renal failure: a focus on tubulointerstitial disease. Clin. Chim. Acta 351, 31-47. https://doi.org/10.1016/j.cccn.2004.09.005
  27. Mogensen, C. E. (1971) Urinary albumin excretion in early and longterm juvenile diabetes. Scand. J. Clin. Lab. Invest. 28, 101-109. https://doi.org/10.3109/00365517109090668
  28. Nagai, J. and Takano, M. (2010) Molecular-targeted approaches to reduce renal accumulation of nephrotoxic drugs. Expert Opin. Drug Metab. Toxicol. 6, 1125-1138. https://doi.org/10.1517/17425255.2010.497140
  29. Naughton, C. A. (2008) Drug-induced nephrotoxicity. Am. Fam. Physician. 78, 743-750.
  30. Nerlich, A. G., Schleicher, E. D., Wiest, I., Specks, U. and Timpl, R. (1994) Immunohistochemical localization of collagen VI in diabetic glomeruli. Kidney Int. 45, 1648-1656. https://doi.org/10.1038/ki.1994.216
  31. Nielsen, B. S., Borregaard, N., Bundgaard, J. R., Timshel, S., Sehested, M. and Kjeldsen, L. (1996) Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and infl ammatory bowel diseases. Gut 38, 414-420. https://doi.org/10.1136/gut.38.3.414
  32. Nomura, S., Wills, A. J., Edwards, D. R., Heath, J. K. and Hogan, B. L. (1988) Developmental expression of 2ar (osteopontin) and SPARC (osteonectin) RNA as revealed by in situ hybridization. J. Cell Biol. 106, 441-450. https://doi.org/10.1083/jcb.106.2.441
  33. Ohlsson, S., Wieslander, J. and Segelmark, M. (2003) Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. Clin. Exp. Immunol. 131, 528-535. https://doi.org/10.1046/j.1365-2249.2003.02083.x
  34. Oldberg, A., Franzen, A. and Heinegard, D. (1986) Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc. Natl. Acad. Sci. USA 83, 8819-8823. https://doi.org/10.1073/pnas.83.23.8819
  35. Olyaei, A. J., de Mattos, A. M. and Bennett, W. M. (1999) Immunosuppressant- induced nephropathy: pathophysiology, incidence and management. Drug Saf. 21, 471-488. https://doi.org/10.2165/00002018-199921060-00004
  36. Palmer, B. F. (2002) Renal dysfunction complicating the treatment of hypertension. N. Engl. J. Med. 347, 1256-1261. https://doi.org/10.1056/NEJMra020676
  37. Patarca, R., Freeman, G. J., Singh, R. P., Wei, F. Y., Durfee, T., Blattner, F., Regnier, D. C., Kojak, C. A., Mock, B. A., Morse, H. C., Jerrells, T. R. and Cantor, H. (1989) Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene: Definition of a novel T cell dependent response associated with genetic resistance to bacterial infection. J. Exp. Med. 170, 145-161. https://doi.org/10.1084/jem.170.1.145
  38. Perazella, M. A. (1999) Crystal-induced acute renal failure. Am. J. Med. 106, 459-465. https://doi.org/10.1016/S0002-9343(99)00041-8
  39. Perazella, M. A. (2005) Drug-induced nephropathy: an update. Expert Opin. Drug Saf. 4, 689-706. https://doi.org/10.1517/14740338.4.4.689
  40. Perneger, T. V., Whelton, P. K. and Klag, M. J. (1994) Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinfl ammatory drugs. N. Engl. J. Med. 331, 1675-1679. https://doi.org/10.1056/NEJM199412223312502
  41. Pisoni, R., Ruggenenti, P. and Remuzzi, G. (2001) Drug-induced thrombotic microangiopathy: incidence, prevention and management. Drug Saf. 24, 491-501. https://doi.org/10.2165/00002018-200124070-00002
  42. Prinsen, B. H., de Sain-van der Velden, M. G., Kaysen, G. A., Straver, H. W., van Rijn, H. J., Stellaard, F., Berger, R. and Rabelink, T. J. (2001) Transferrin synthesis is increased in nephrotic patients insuffi ciently to replace urinary losses. J. Am. Soc. Nephrol. 12, 1017-1025.
  43. Rached E., Hoffmann, D., Blumbach, K., Weber, K., Dekant, W. and Mally, A. (2008) Evaluation of putative biomarkers of nephrotoxicity after exposure to ochratoxin A in vivo and in vitro. Toxicol. Sci. 103, 371-381. https://doi.org/10.1093/toxsci/kfn040
  44. Rodriguez-Iturbe, B. and Garcia Garcia, G. (2010) The role of tubulointerstitial infl ammation in the progression of chronic renal failure. Nephron. Clin. Pract. 116, c81-c88. https://doi.org/10.1159/000314656
  45. Rossert, J. (2001) Drug-induced acute interstitial nephritis. Kidney Int. 60, 804-817. https://doi.org/10.1046/j.1523-1755.2001.060002804.x
  46. Schaub, S., Wilkins, J. A., Antonovici, M., Krokhin, O., Weiler, T., Rush, D. and Nickerson, P. (2005) Proteomic-based identifi cation of cleaved urinary beta2-microglobulin as a potential marker for acute tubular injury in renal allografts. Am. J. Transplant. 5, 729-738. https://doi.org/10.1111/j.1600-6143.2005.00766.x
  47. Schetz, M., Dasta, J., Goldstein, S. and Golper, T. (2005) Drug-induced acute kidney injury. Curr. Opin. Crit. Care 11, 555-565. https://doi.org/10.1097/01.ccx.0000184300.68383.95
  48. Schnellmann, R.G. and Kelly, K.J. (1999). Pathophysiology of nephrotoxic acute renal failure, in atlas of diseases of the kidney vol 1. (R. W. Schrier, Ed.), pp 15.1-15.14. Blackwell Science (Wash DC) Ltd., Oxford.
  49. Schoolwerth, A. C., Sica, D. A., Ballermann, B. J. and Wilcox, C. S; Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. (2001) Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation 104, 1985-1991. https://doi.org/10.1161/hc4101.096153
  50. Schurek, H. J., Neumann, K. H., Flohr, H., Zeh, M.and Stolte, H. (2000) Diagnostic and prognostic signifi cance of proteinuria selectivity index in glomerular diseases. Clin. Chim. Acta 297, 73-83. https://doi.org/10.1016/S0009-8981(00)00235-7
  51. Shao, C., Li, M., Li, X., Wei, L., Zhu, L., Yang, F., Jia, L., Mu, Y., Wang, J., Guo, Z., Zhang, D., Yin, J., Wang, Z., Sun, W., Zhang, Z. and Gao, Y. (2011) A tool for biomarker discovery in the urinary proteome: a manually curated human and animal urine protein biomarker database. Mol. Cell Proteomics 10, M111.010975.
  52. Shiraga, H., Min, W., Van Dusen, W.J., Clayman, M.D., Miner, D., Terrell, C. H., Sherbotie, J. R., Foreman, J. W., Przysiecki, C., Neilson, E. G. and Hoyer, J. R. (1992) Inhibition of calcium oxalate crystal growth in vitro by uropontin: Another member of the aspartic acidrich protein superfamily. Proc. Natl. Acad. Sci. USA 89, 426-430. https://doi.org/10.1073/pnas.89.1.426
  53. Vaidya, V. S., Ferguson, M. A. and Bonventre, J. V. (2008) Biomarkers of acute kidney injury. Annu. Rev. Pharmacol. Toxicol. 48, 463-493. https://doi.org/10.1146/annurev.pharmtox.48.113006.094615
  54. Vaidya, V. S., Ramirez, V., Ichimura, T., Bobadilla, N. A. and Bonventre, J. V. (2006) Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am. J. Physiol. Renal. Physiol. 290, F517-529. https://doi.org/10.1152/ajprenal.00291.2005
  55. Wada, T., Yokoyama, H., Tomosugi, N., Hisada, Y., Ohta, S., Naito, T., Kobayashi, K., Mukaida, N. and Matsushima, K. (1994) Detection of urinary interleukin-8 in glomerular diseases. Kidney Int. 46, 455-460. https://doi.org/10.1038/ki.1994.293
  56. Wu, Y., Yang, L., Su, T., Wang, C., Liu, G. and Li, X. M. (2010) Pathological signifi cance of a panel of urinary biomarkers in patients with drug-induced tubulointerstitial nephritis. Clin. J. Am. Soc. Nephrol. 5, 1954-1959. https://doi.org/10.2215/CJN.02370310
  57. Xu, S. Y., Pauksen, K. and Venge, P. (1995) Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand. J. Clin. Lab. Invest. 55, 125-131. https://doi.org/10.3109/00365519509089604
  58. Zager, R. A. (1997) Pathogenetic mechanisms in nephrotoxic acute renal failure. Semin. Nephrol. 17, 3-14.

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  44. A Review on Drug‐Induced Nephrotoxicity: Pathophysiological Mechanisms, Drug Classes, Clinical Management, and Recent Advances in Mathematical Modeling and Simulation Approaches vol.9, pp.8, 2012, https://doi.org/10.1002/cpdd.879
  45. Nanotoxic Effects of Silver Nanoparticles on Normal HEK-293 Cells in Comparison to Cancerous HeLa Cell Line vol.16, pp.None, 2012, https://doi.org/10.2147/ijn.s289008
  46. Toxicological Profile of the Aqueous Extract of Tectona grandis L.F. (Verbenaceae) Leaves: A Medicinal Plant Used in the Treatment of Typhoid Fever in Traditional Cameroonian Medicine vol.2021, pp.None, 2012, https://doi.org/10.1155/2021/6646771
  47. Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]Pyridazinone Exert Anti-Inflammatory Activity without Acute Gastrotoxicity in the Carrageenan-Induced Rat Paw Edema Test vol.14, pp.None, 2021, https://doi.org/10.2147/jir.s330614
  48. The Cytotoxicity and Nephroprotective Activity of the Ethanol Extracts of Angelica keiskei Koidzumi Stems and Leaves against the NAPQI-Induced Human Embryonic Kidney (HEK293) Cell Line vol.2021, pp.None, 2012, https://doi.org/10.1155/2021/6458265
  49. Predicting changes in renal metabolism after compound exposure with a genome-scale metabolic model vol.412, pp.None, 2012, https://doi.org/10.1016/j.taap.2020.115390
  50. Single-dose and 4-week repeated dose Toxicity of Aconitum Sinomontanum Nakai Pharmacopuncture: An Experimental Study vol.38, pp.1, 2012, https://doi.org/10.13045/jar.2020.00332
  51. Umbelliferone attenuates gentamicin-induced renal toxicity by suppression of TLR-4/NF-κB-p65/NLRP-3 and JAK1/STAT-3 signaling pathways vol.28, pp.9, 2012, https://doi.org/10.1007/s11356-020-11416-5
  52. Rebamipide potentially mitigates methotrexate‐induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study vol.304, pp.3, 2021, https://doi.org/10.1002/ar.24482
  53. Amphora algae with low‐level ionizing radiation exposure ameliorate D‐galactosamine‐induced inflammatory impairment in rat kidney vol.36, pp.4, 2021, https://doi.org/10.1002/tox.23050
  54. Incidence and Risk Factors for Acute Kidney Injury during the Treatment of Methicillin-Sensitive Staphylococcus aureus Infections with Cloxacillin Based Antibiotic Regimens: A French Retrospective Stu vol.10, pp.12, 2012, https://doi.org/10.3390/jcm10122603
  55. Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway vol.26, pp.21, 2021, https://doi.org/10.3390/molecules26216647
  56. Identification of Renoprotective Phytosterols from Mulberry (Morus alba) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells vol.10, pp.11, 2021, https://doi.org/10.3390/plants10112481
  57. Use of in vitro metabolomics in NRK cells to help predicting nephrotoxicity and differentiating the MoA of nephrotoxicants vol.353, pp.None, 2012, https://doi.org/10.1016/j.toxlet.2021.09.011
  58. Preliminary sub-acute toxicological assessment of methanol leaves extract of Culcasia angolensis (Araceae) in Wistar rats vol.45, pp.1, 2012, https://doi.org/10.1186/s42269-021-00686-9
  59. Using intracellular metabolic profiling to identify novel biomarkers of cisplatin-induced acute kidney injury in NRK-52E cells vol.85, pp.1, 2012, https://doi.org/10.1080/15287394.2021.1969305
  60. Safety assessment of the ethanolic extract from Piper vicosanum yunck leaves in male rats vol.2, pp.1, 2022, https://doi.org/10.1016/j.phyplu.2021.100165