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Pathology of the Urinary System

  • Kendall S. FrazierEmail author
Chapter
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Abstract

The kidney is one of the most common organs for drug- or chemical-induced toxicities to occur, and nephrotoxicosis remains an important clinical concern in human patients. Laboratory animals utilized in clinical studies successfully predict human renal toxicosis and may develop similar renal pathology at appropriate doses. Histopathologic lesions in the kidney associated with nephrotoxic injury tend to fall into two major types: those affecting tubules (often by small molecules or chemical agents) and those affecting glomeruli (more often by biologic therapies). There are stereotypic morphologies in the kidney which can occur from a variety of toxic insults, and they often resemble one another. By understanding the nature of a lesion based on the nomenclature and the location provided by the pathologist, it is possible to glean some information regarding the severity, potential reversibility, and even mechanism of a particular renal toxin. Just as importantly, familiarity with common spontaneous background lesions in rodents and other laboratory animals used in toxicologic studies provides a basis to discount the clinical relevance of such lesions. Successful interpretation and translation of nonclinical kidney toxicity data depends on understanding dose and exposure relationships, renal clearance and absorption, and species selectivity related to a given test article, as well as comorbidities, and potential drug interactions associated with the patient or susceptible population. New experimental modalities and novel biomarkers are being utilized to augment traditional kidney-related endpoints in toxicity studies and explore potential pathophysiologic mechanisms of nephrotoxins to better inform the clinical safety of test articles and help drive decision-making.

Key words

Pathology Kidney Tubule Toxicity Glomerulonephritis Nephropathy 

References

  1. Abbas A, Mirza MM, Ganti AK, Tendulkar K (2015) Renal toxicities of targeted therapies. Target Oncol 10:487–499PubMedCrossRefPubMedCentralGoogle Scholar
  2. Adams LE, Roberts SM, Donovan-Brand R, Zimmer H, Hess EV (1993) Study of procainamide hapten-specific antibodies in rabbits and humans. Int J Immunopharmacol 15:887–897PubMedCrossRefPubMedCentralGoogle Scholar
  3. Almanzar MM, Frazier KS, Dube PH, Piqueras AI, Jones WK, Charette MF, Paredes AL (1998) Expression of OP-1 is selectively modified after acute ischemic renal injury. J Am Soc Nephrol 9:1456–1463PubMedPubMedCentralGoogle Scholar
  4. Anders MW (1980) Metabolism of drugs in kidney. Kidney Int 18:636–647PubMedCrossRefPubMedCentralGoogle Scholar
  5. Arts HH, Knoers VAM (2013) Current insights into renal ciliopathies: what can genetics teach us? Pediatr Nephrol 28:863–874PubMedCrossRefPubMedCentralGoogle Scholar
  6. Barthold SW (1998) Chronic progressive nephropathy, rat. In: Jones TC, Hard GC, Mohr U (eds) Monographs on pathology of laboratory animals. Urinary system, 2nd edn. Springer-Verlag, Berlin, pp 228–233Google Scholar
  7. Bendele AM, Buenger DA, Mcgrath JP, Schmalz CA, Hanasono GK (1994) Chronic toxicity, metabolism, and pharmacokinetics of the 5-HT3 receptor antagonist zatosetron (LY277359) in Fischer 344 rats. Fundam Appl Toxicol 22:494–504PubMedCrossRefPubMedCentralGoogle Scholar
  8. Bendele M (1988) Urologic syndrome, mouse. In: Jones TC, Hard GC, Mohr U (eds) Urinary system, 2nd edn. Springer-Verlag, Berlin, pp 456–462Google Scholar
  9. Bertani T, Poggi A, Pozzoni R, Delaini F, Sacchi G, Thoua Y, Mecca G, Remuzzi G, Donati MB (1982) Adriamycin-induced nephrotic syndrome in rats. Lab Investig 46:16–22PubMedPubMedCentralGoogle Scholar
  10. Betton GR, Kenne K, Somers R, Marr A (2005) Protein biomarkers of nephrotoxicity; a review and findings with cyclosporin A, a signal transduction kinase inhibitor and N-phenylanthranilic acid. Cancer Biomark 1:59–67PubMedCrossRefPubMedCentralGoogle Scholar
  11. Boyce JT, Giddens WE Jr, Seifert R (1981) Spontaneous mesangioproliferative glomerulonephritis in pigtailed macaques (Macaca nemestrina). Vet Pathol 18(Suppl 6):82–88PubMedCrossRefPubMedCentralGoogle Scholar
  12. Cardesa A, Ribalta T (1998) Nephroblastoma, kidney, rat. In: Jones TC, Hard GC, Mohr U (eds) Monographs on pathology of laboratory animals. Urinary system, 2nd edn. Springer-Verlag, Berlin, pp 129–138Google Scholar
  13. Chebib FT, Sussman CR, Wang X, Harris PC, Torres VE (2015) Vasopressin and disruption of calcium signalling in polycystic kidney disease. Nat Rev Nephrol 11:451–464PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chen Y, Brott D, Luo W, Gangl E, Kamend H, Fikes J, Kinter L, Valentin J-P, Bialecki R (2013) Assessment of cisplatin-induced kidney injury using an integrated rodent platform. Toxicol Appl Pharmacol 268:352–361PubMedCrossRefPubMedCentralGoogle Scholar
  15. Choudhury D, Ahmed Z (2006) Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol 2:80–91PubMedCrossRefPubMedCentralGoogle Scholar
  16. Chow BS, Allen TJ (2015) Mouse models for studying diabetic nephropathy. Curr Protoc Mouse Biol 5:85–94PubMedCrossRefPubMedCentralGoogle Scholar
  17. Christensen S, Ottensen PD (1986) Lithium-induced uremia in rats. Survival and renal function and morphology after one year. Acta Pharmacol Toxicol (Copenh) 58:339–347CrossRefGoogle Scholar
  18. Cianciolo R, Yoon L, Krull D, Stokes A, Rodriguez A, Jordan H, Cooper D, Falls JG, Cullen J, Kimbrough C, Berridge B (2013) Gene expression analysis and urinary biomarker assays reveal activation of tubulointerstitial injury pathways in a rodent model of chronic proteinuria (Doxorubicin nephropathy). Nephron Exp Nephrol 124:1–10PubMedCrossRefPubMedCentralGoogle Scholar
  19. Clarke JB (2010) Mechanisms of adverse drug reactions to biologics. Handb Exp Pharmacol 196:453–474CrossRefGoogle Scholar
  20. Cohen SM (2002) Comparative pathology of proliferative lesions of the urinary bladder. Toxicol Pathol 30:663–671PubMedCrossRefPubMedCentralGoogle Scholar
  21. Cowley AW Jr, Ryan RP, Kurth T, Skelton MM, Schock-Kusch D, Gretz N (2013) Progression of glomerular filtration rate reduction determined in conscious dahl salt-sensitive hypertensive rats. Hypertension 62:85–90PubMedPubMedCentralCrossRefGoogle Scholar
  22. Crabbs TA, Frame SR, Laast VA, Patrick DJ, Thomas J, Zimmerman B, Hardisty JF (2013) Occurrence of spontaneous amphophilic-vacuolar renal tubular tumors in Sprague-Dawley rats from subchronic toxicity studies. Toxicol Pathol 41:866–871PubMedCrossRefPubMedCentralGoogle Scholar
  23. Davis MA, Ryan DH (1998) Apoptosis in the kidney. Toxicol Pathol 26:810–825PubMedCrossRefPubMedCentralGoogle Scholar
  24. Decker JH, Dochterman LW, Niquette AL, Brej M (2012) Association of renal tubular hyaline droplets with lymphoma in CD-1 mice. Toxicol Pathol 40:651–655PubMedCrossRefPubMedCentralGoogle Scholar
  25. Dereure O, Navarro R, Rossi JF, Guilhou JJ (2001) Rituximab induced vasculitis. Dermatology 203:83–84PubMedCrossRefPubMedCentralGoogle Scholar
  26. Dieterle F, Perentes E, Cordier A, Roth DR, Verdes P, Grenet O et al (2010a) Urinary clusterin, cystatin C, beta2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat Biotechnol 28:463–469PubMedCrossRefPubMedCentralGoogle Scholar
  27. Dieterle F, Sistare F, Goodsaid F, Papaluca M, Ozer JS, Webb CP et al (2010b) Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol 28:455–462PubMedCrossRefPubMedCentralGoogle Scholar
  28. Donker AJ, Venuto RC, Vladutiu AO (1984) Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Brown Norway rats treated with D-penicillamine develop autoantibodies, circulating immune complexes, and disseminated intravascular coagulation. Clin Immunol Immunopathol 30:142–145PubMedCrossRefPubMedCentralGoogle Scholar
  29. Dorato MA, Engelhardt JA (2005) The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s). Regul Toxicol Pharmacol 42:265–274PubMedCrossRefPubMedCentralGoogle Scholar
  30. Elias AD, Eder JP, Shea T, Begg CB, Frei E 3rd, Antman KH (1990) High-dose ifosfamide with mesna uroprotection: a phase I study. J Clin Oncol 8:170–178PubMedCrossRefPubMedCentralGoogle Scholar
  31. Engelhardt JA (2016) Comparative renal toxicopathology of antisense oligonucleotides. Nucleic Acid Ther 26:199–209PubMedCrossRefPubMedCentralGoogle Scholar
  32. Engelhardt J, Fant P, Guionaud S, Henry SP, Leach M, Louden C, Scicchitano MS, Weaver JL, Zabka TS, Frazier KS (2015) Scientific and Regulatory Policy Committee Points-to-consider paper∗: Drug Induced Vascular Injury associated with non-small molecule therapeutics in preclinical development. Part II. Antisense oligonucleotides. Toxicol Pathol 43:935–944PubMedCrossRefPubMedCentralGoogle Scholar
  33. Ennulat D, Ringenberg M, Frazier KS (2018) Regulatory forum opinion piece: recommendations for a tiered approach to mechanistic toxicology studies of preclinical renal toxicity. Toxicol Pathol 46:636–646PubMedCrossRefPubMedCentralGoogle Scholar
  34. Everitt JI, Ross PW, Davis TW (1988) Urologic syndrome associated with wire caging in AKR mice. Lab Anim Sci 38:609–611PubMedPubMedCentralGoogle Scholar
  35. Frazier KS (2017) Species differences in renal development and associated developmental nephrotoxicity. Birth Defects Res 109:1243–1256PubMedCrossRefPubMedCentralGoogle Scholar
  36. Frazier KS, Obert LA (2018) Drug-induced glomerulonephritis: the spectre of biotherapeutic and antisense oligonucleotide immune activation in the kidney. Toxicol Pathol 46:904–917PubMedCrossRefPubMedCentralGoogle Scholar
  37. Frazier KS, Seely JC (2013) Urinary system. In: Sahota PS, Popp JA, Hardisty JF, Gopinath C (eds) Toxicologic pathology: preclinical safety assessment, 1st edn. CRC Press/Taylor & Francis Pub., Boca Raton, pp 421–484CrossRefGoogle Scholar
  38. Frazier KS, Dube P, Paredes A, Styer E (2002) Connective Tissue Growth Factor expression in the rat remnant kidney model and association with tubular epithelial cells undergoing transdifferentiation. Vet Pathol 37:328–335CrossRefGoogle Scholar
  39. Frazier KS, Seely JC, Hard GC, Betton GC, Burnett R, Nishikawa A, Nakatsuji S, Durchfeld-Meyer B, Bube A (2012) Proliferative and nonproliferative lesions in the rodent urinary system. Toxicol Pathol 40(4Sl):14–86CrossRefGoogle Scholar
  40. Frazier KS, Sobry C, Derr V, Adams MJ, Den Besten C, De Kimpe S, Francis I, Gales TL, Maguire SR, Mirabile RC, Mullins D, Palate B, Ponstein-Simarro Doorten Y, Ridings JE, Scicchitano MS, Silvano J, Woodfine J (2014) Species specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second generation antisense oligonucleotide. Toxicol Pathol 42:923–935PubMedCrossRefPubMedCentralGoogle Scholar
  41. Frazier KS, Obert LA (2018) Drug-Induced Glomerulonephritis: The Spectre of Biotherapeutic and Antisense Oligonucleotide Immune Activation in the Kidney. Toxicol Pathol 46: 904–917Google Scholar
  42. Frazier KS, Engelhardt J, Fant P, Guionaud S, Henry SP, Leach M, Louden C, Scicchitano MS, Weaver JL, Zabka TS (2015) Scientific and Regulatory Policy Committee Points-to-consider paper∗: Drug Induced Vascular Injury associated with non-small molecule therapeutics in preclinical development. Part I. biotherapeutics. Toxicol Pathol 43:915–934PubMedCrossRefPubMedCentralGoogle Scholar
  43. Frith CH, Eighmy JJ, Fukushima S, Cohen SM, Squire RA, Chandra M (1995) Proliferative lesions of the lower urinary tract (urinary bladder, urethra and ureters) in rats. In: Guides for toxicologic pathology. STP/ARP/AFIP, Washington, DCGoogle Scholar
  44. Gautier JC, Riefke B, Walter J, Kurth P, Mylecraine L, Guilpin V et al (2010) Evaluation of novel biomarkers of nephrotoxicity in two strains of rat treated with cisplatin. Toxicol Pathol 38:943–956PubMedCrossRefPubMedCentralGoogle Scholar
  45. Goldstein RS, Tarloff JB, Hook JB (1988) Age-related nephropathy in laboratory rats. FASEB J 2:2241–2251PubMedCrossRefPubMedCentralGoogle Scholar
  46. Gopinath C, Mowat V (2014) The urinary system. In: Gopinath C, Mowat V (eds) Atlas of toxicological pathology. Springer, New York, pp 109–129CrossRefGoogle Scholar
  47. Gopinath C, Prentice DE, Lewis DJ (1987) The urinary system. In: Atlas of experimental toxicological pathology. MTP Press Limited, Lancaster, pp 77–90CrossRefGoogle Scholar
  48. Gray JE (1977) Chronic progressive nephrosis in the albino rat. CRC Crit Rev Toxicol 5:115–144PubMedCrossRefPubMedCentralGoogle Scholar
  49. Gray JE, van Zwieten MJ, Hollander CF (1982) Early light microscopic changes of chronic progressive nephrosis in several srains of aging laboratory rats. J Gerontol 37:142–150PubMedCrossRefPubMedCentralGoogle Scholar
  50. Groseclose MR, Laffan S, Frazier KS, Hughes-Earle A, Castellino S (2015) Imaging MS: an investigation of juvenile rat nephrotoxicity associated with dabrafenib administration. J Am Soc Mass Spectrom 6:887–898CrossRefGoogle Scholar
  51. Gruys E, Tooten PC, Kuijpers MH (1996) Lung, ileum and heart are predilection sites for AApoII amyloid deposition in CD-1 Swiss mice used for toxicity studies. Pulmonary amyloid indicates AApoAII. Lab Anim 30:28–34PubMedCrossRefPubMedCentralGoogle Scholar
  52. Hagiwara A, Asakawa E, Kurata Y, Sano M, Hirose M, Ito N (1992) Dose-dependent renal tubular renal tubular toxicity of Harman and norharman in male F344 rats. Toxicol Pathol 20:197–204PubMedCrossRefPubMedCentralGoogle Scholar
  53. Hard GC, Khan KN (2004) A contemporary overview of chronic progressive nephropathy in the laboratory rat, and its significance for human risk assessment. Toxicol Pathol 32:171–180PubMedCrossRefPubMedCentralGoogle Scholar
  54. Hard GC, Seely JC (2005) Recommendations for the interpretation of renal tubule proliferative lesions occurring in rat kidneys with advanced chronic progressive nephropathy (CPN). Toxicol Pathol 33:641–649PubMedCrossRefPubMedCentralGoogle Scholar
  55. Hard GC, Seely JC (2006) Histological investigation of diagnostically challenging tubule profiles in advanced chronic progressive nephropathy (CPN) in the Fischer 344 rat. Toxicol Pathol 34:941–948PubMedCrossRefPubMedCentralGoogle Scholar
  56. Hard GC, Snowden RT (1991) Hyaline droplet accumulation in rodent kidney proximal tubules: an association with histiocytic sarcoma. Toxicol Pathol 19:88–97PubMedCrossRefPubMedCentralGoogle Scholar
  57. Hard GC, Whysner J, English JC, Zang E, Williams GM (1997) Relationship of hydroquinone-associated rat renal tumors with spontaneous chronic progessisve nephropathy. Toxicol Pathol 25:132–143Google Scholar
  58. Hard GC, Alden CL, Bruner RH et al (1999) Non-proliferative lesions of the kidney and lower urinary tract in rats. In: Guides for toxicologic pathology. STP/ARP/AFIP, Washington, DC, pp 1–32Google Scholar
  59. Hard GC, Seely JC, Kissling GE, Betz LJ (2008) Spontaneous occurrence of a distinctive renal tubule tumor phenotype in rat carcinogenicity studies conducted by the National Toxicology Program. Toxicol Pathol 36:388–396PubMedPubMedCentralCrossRefGoogle Scholar
  60. Hard GC, Flake GP, Sills RC (2009) Re-evaluation of kidney histopathology from 13-week toxicity and two-year carcinogenicity studies of melamine in the F344 rat: morphologic evidence of retrograde nephropathy. Vet Pathol 46:1248–1257PubMedCrossRefPubMedCentralGoogle Scholar
  61. Hard GC, Seely JC, Betz LJ (2016) A survery of mesenchyme-related tumors of the rat kidney in the National Toxicology Program Archives, with particular reference to renal mesenchymal tumor. Toxicol Pathol 44:848–855PubMedCrossRefPubMedCentralGoogle Scholar
  62. Harpur E, Ennulat D, Hoffman D, Betton G, Gautier JC, Riefke B et al (2011) Biological qualification of biomarkers of chemical-induced renal toxicity in two strains of male rat. Toxicol Sci 122:235–252PubMedCrossRefPubMedCentralGoogle Scholar
  63. Hilliard LM, Denton KM (2016) Transcutaneous assessment of glomerular filtration rate in unanesthetized rats using a small animal imager: impact on arterial pressure, heart rate, and activity. Physiol Rep 4:e12723PubMedCentralCrossRefGoogle Scholar
  64. Hirokawa K (1975) Characterization of age-associated kidney disease in Wistar rats. Mech Ageing Dev 4:301–316PubMedCrossRefPubMedCentralGoogle Scholar
  65. Hoane JS, Johnson CL, Morrison JP, Elmore SA (2016) Comparison of renal amyloid and hyaline glomerulopathy in B6C3F1 mice. Toxicol Pathol 44:687–704PubMedPubMedCentralCrossRefGoogle Scholar
  66. Hoffmann D, Adler M, Vaidya VS, Rached E, Mulrane L, Gallagher WM et al (2010) Performance of novel kidney biomarkers in preclinical toxicity studies. Toxicol Sci 116:8–22PubMedPubMedCentralCrossRefGoogle Scholar
  67. Hook JB, McCormack KM, Kluwe WM (1979) Biochemical mechanisms of nephrotoxicity. In: Hodgson E, Bend JR, Philpot RM (eds) Review in biochemical toxicology, vol 1. Elsevier, New York, pp 58–73Google Scholar
  68. Ikeda H, Tauchi H, Shimasaki H (1999) Age and organ difference in amount and distribution of autofluorescent granules in rats. Mech Ageing Dev 31:139–146CrossRefGoogle Scholar
  69. Ito Y, Matsushita K, Tsuchiya T, Kohara Y, Yoshikawa T, Sato M, Kitaura K, Matsumoto S (2014) Spontaneous nephroblastoma with lung metastasis in a rat. J Toxicol Pathol 21:91–95CrossRefGoogle Scholar
  70. Jeppeson G, Skydsgaard M (2014) Spontaneous background pathology in Göttingen minipigs. Toxicol Pathol 42(2):257–266Google Scholar
  71. Karnik J, Chertow GM (2000) Analgesic-related renal disease: causes, patients at risk, management. J Crit Illn 15:49–58Google Scholar
  72. Katsanos KH, Tsianos V, Vagias I, Tsianos EV (2010) Patterns and clinical relevance of antibody responses during adalimumab therapy. Ann Gastroenterol 23:165–171Google Scholar
  73. Keller DA, Juberg DR, Catlin N, Farland WH, Hess FG, Wolf DC, Doerrer NG (2012) Identification and characterization of adverse effects in 21st century toxicology. Toxicol Sci 126:291–297PubMedPubMedCentralCrossRefGoogle Scholar
  74. Khan KNM, Alden CL (2002) Kidney. In: Haschek WG, Rousseaux CG, Wallig MA (eds) Handbook of toxicologic pathology, 2nd edn. Academic Press, San Diego, pp 255–336CrossRefGoogle Scholar
  75. Killary K, Diaz D, Argentieri G, Dugyala R, Bowenkamp K (2009) Kidney changes after daily slow-bolus IV injection of Polyoxyl 35 Castor oil/ethanol in 5% Dextrose for 2 weeks to Wistar rats. Microsc Microanal 15 suppl S2:968–969CrossRefGoogle Scholar
  76. Krabe E, Williams G, Lewis R, Kimber I, Foster P (2002) Distinguishing between adverse and non-adverse effects. Exp Toxicol Pathol 54:51–55. Urban & Fischer.Google Scholar
  77. Kumar G, Hota D, Nahar Saikia U, Pandhi P (2000) Evaluation of analgesic efficacy, gastrotoxicity and nephrotoxicity of fixed-dose combinations of nonselective, preferential and selective cyclooxygenase inhibitors with paracetamol in rats. Exp Toxicol Pathol 62:653–662CrossRefGoogle Scholar
  78. Kunze E (1992) Nonneoplastic and neoplastic lesions of the urinary bladder, ureter, and renal pelvis. In: Mohr U, Dungworth CC, Capen CC (eds) Pathobiology of the aging rat. ILSI Press, Washington, DC, pp 259–284Google Scholar
  79. Kunze E (1998) Hyperplasia, urinary bladder, rat. In: Jones TC, GC Hard UM (eds) Monographs on pathology of laboratory animals. Urinary system, 2nd edn. Springer-Verlag, Berlin, pp 332–366Google Scholar
  80. Lameire N (2005) The pathophysiology of acute renal failure. Crit Care Clin 21:197–210PubMedCrossRefPubMedCentralGoogle Scholar
  81. Leach MW, Rottman JB, Hock MB, Finco D, Rojko JL, Beyer JC (2014) Immunogenicity/hypersensitivity of biologics. Toxicol Pathol 42:293–300PubMedCrossRefPubMedCentralGoogle Scholar
  82. Lee HS, Song CY (2009) Differential role of mesangial cells and podocytes in TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease. Histol Histopathol 24:901–908PubMedPubMedCentralGoogle Scholar
  83. Lentini P, Zanoli L, Granata A, Signorelli SS, Castellino P, Dell’Aquila R (2017) Kidney and heavy metals – the role of environmental exposure (Review). Mol Med Rep 15:3413–3419PubMedCrossRefPubMedCentralGoogle Scholar
  84. Liebelt AG, Sass B, Sobel HJ, Werner RM (1989) Spontaneous nephroblastoma in a strain CE/J mouse. A case report. Toxicol Pathol 17:57–61PubMedCrossRefPubMedCentralGoogle Scholar
  85. Luke DR, Tomaszewski K, Damle B, Schlamm HT (2010) Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci 99:3291–3301PubMedCrossRefPubMedCentralGoogle Scholar
  86. Maak T, Johnson V, Kau ST, Figueiredo J, Sigulum D (1979) Renal filtration, transport and metabolism of low molecular weight proteins: a review. Kidney Int 16:251–270CrossRefGoogle Scholar
  87. Martínez-Salgado C, López-Hernández FJ, López-Novoa JM (2007) Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol 223:86–98PubMedCrossRefPubMedCentralGoogle Scholar
  88. Mattie DR, Alden CL, Newell TK, Gaworski CL, Flemming CD (1991) A 90-day continuous vapor inhalation toxicity study of JP-8 fuel followed by 20 ro 21 months of recovery in Fischer 344 rats and C57BL/6 mice. Toxicol Pathol 19:77–87PubMedCrossRefPubMedCentralGoogle Scholar
  89. McDill BW, Li SZ, Kovach PA, Ding L, Chen F (2006) Congenital progressive hydronephrosis (CPH) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. Proc Natl Acad Sci U S A 103:6952–6957PubMedPubMedCentralCrossRefGoogle Scholar
  90. McInnes EF, Ernst H, Germann P-G (2015) Spontaneous nonneoplastic lesions in control Syrian hamsters in three 24-month long-term carcinogenicity studies. Toxicol Pathol 43:272–281PubMedCrossRefPubMedCentralGoogle Scholar
  91. Melnick RL, Burns KM, Ward JM, Huff J (2013) Chemically exacerbated chronic progressive nephropathy not associated with renal tubular tumor induction in rats: an evaluation based on 60 carcinogenicity studies by the National Toxicology Program. Toxicol Sci 128:346–356CrossRefGoogle Scholar
  92. Molon-Noblot S, Boussiquet-Leroux C, Owen RA et al (1992) Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitiors. Toxicol Pathol 20:93–102PubMedCrossRefPubMedCentralGoogle Scholar
  93. Montgomery CA, Seely JC (1990) Kidney. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF (eds) Pathology of the Fisher rat. Reference and atlas. Academic press, San Diego, pp 127–153Google Scholar
  94. Moore KL, Persaud TVN (eds) (2003) The developing human: clinically oriented embryology. WB Saunders, PhiladelphiaGoogle Scholar
  95. Morgan WA, Kaler B, Bach PH (1998) The role of reactive oxygen species in adriamycin and menadione-induced glomerular toxicity. Toxicol Lett 94:209–215PubMedCrossRefPubMedCentralGoogle Scholar
  96. Moriguchi T, Motohashi H, Hosoya T, Nakajima O, Takahashi S, Ohsako S, Aoki Y, Nishimura N, Tohyama C, Fujii-Kuriyama Y, Yamamoto M (2003) Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse. Proc Natl Acad Sci U S A 100:5652–5657PubMedPubMedCentralCrossRefGoogle Scholar
  97. Mutsuga M, Asaoka Y, Togashi Y, Imura N, Miyoshi T, Miyamoto Y (2013) Spontaneous accumulation of globotriaosylceramide (Gb3) in proximal renal tubules in an ICR mouse. J Toxicol Pathol 26:429–432PubMedPubMedCentralCrossRefGoogle Scholar
  98. Nakanuma Y, Harada K, Sato Y, Ikeda H (2010) Recent progress in the etiopathogenesis of pediatric biliary disease, particularly Caroli’s disease with congenital hepatic fibrosis and biliary atresia. Histol Histopathol 25:223–235PubMedPubMedCentralGoogle Scholar
  99. Neugarten J, Kasiske B, Silbiger SR et al (2002) Effects of sex on renal structure. Nephron 90:139–144PubMedCrossRefPubMedCentralGoogle Scholar
  100. Nicoletta JA, Schwartz GJ (2004) Distal renal tubular acidosis. Curr Opin Pediatr 16:194–198PubMedCrossRefPubMedCentralGoogle Scholar
  101. Nigam SK, Wu W, Bush KT, Hoenig MP, Blantz RB, Bhatnagar V (2015) Handling of drugs, metabolites, and uremic toxins by kidney proximal tubule drug transporters. Clin J Am Soc Nephrol 10:2039–2049PubMedPubMedCentralCrossRefGoogle Scholar
  102. Nishimura N, Matsumura F, Vogel CFA, Nishimura H, Yonemoto J, Yoshioka W, Tohyama C (2008) Critical role of cyclooxygenase-2 activation in pathogenesis of hydronephrosis caused by lactational exposure of mice to dioxin. Toxicol Appl Pharmacol 231:374–383PubMedCrossRefPubMedCentralGoogle Scholar
  103. Owen G, Smith THF, Agersborg HPK Jr (1970) Toxicity of some benzodiazepine compounds with CNS activity. Toxicol Appl Pharmacol 16:556–570PubMedCrossRefPubMedCentralGoogle Scholar
  104. Owen RA, Heywood R (1986) Age-related variations in renal structure and function in Sprague-Dawley rats. Toxicol Pathol 14:158–167PubMedCrossRefPubMedCentralGoogle Scholar
  105. Ozer JS, Dieterle F, Troth S, Perentes E, Cordier A, Verdes P et al (2010) A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol 28:486–494PubMedCrossRefPubMedCentralGoogle Scholar
  106. Pabla N, Dong Z (2008) Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 73:994–1007PubMedCrossRefPubMedCentralGoogle Scholar
  107. Palmer BF, Heinrich WL (2004) Toxic nephropathy. In: Brenner and Rector’s the kidney, 7th edn. W.B. Saunders, Philadelphia, pp 1625–1658Google Scholar
  108. Perazella MA (2009) Renal vulnerability to drug toxicity. Clin J Am Soc Nephrol 4:1275–1283PubMedCrossRefPubMedCentralGoogle Scholar
  109. Perey DYE, Herdman RC, Good RA (1967) Polycystic renal disease: a new experimental model. Science 158:494–496PubMedCrossRefPubMedCentralGoogle Scholar
  110. Peter CP, Burek JD, van Zwieten MJ (1986) Spontaneous nephropathies in rats. Toxicol Pathol 14:91–100PubMedCrossRefPubMedCentralGoogle Scholar
  111. Polichnowski AJ, Griffin KA, Long J, Williamson GA, Bidani AK (2013) Blood pressure-renal blood flow relationships in conscious angiotensin II- and phenylephrine-infused rats. Am J Physiol Renal Physiol 305:F1074–F1084PubMedPubMedCentralCrossRefGoogle Scholar
  112. Quiros Y, Vicente-Vicente L, Morales AI, Lo’pez-Novoa JM, Lopez-Hernandez FJ (2011) An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicol Sci 119:245–256PubMedCrossRefPubMedCentralGoogle Scholar
  113. Ritskes-Hoitinga J, Beynen AC (1992) Nephrocalcinosis in the rat: a literature review. Prog Food Nutr Sci 16:85–124PubMedPubMedCentralGoogle Scholar
  114. Rojko JL, Price-Schiavi S (2008) Physiologic IgG biodistribution, transport, and clearance: implications for monoclonal antibody products. In: Cavagnaro JA (ed) Preclinical safety evaluation of biopharmaceuticals: a science-based approach to facilitating clinical trials. Wiley, New York, pp 241–276CrossRefGoogle Scholar
  115. Rojko JL, Evans M, Price SA, Han B, Waine G, DeWitte M, Haynes J et al (2014) Formation, clearance, deposition, pathogenicity, and identification of biopharmaceutical-related immune complexes: review and case studies. Toxicol Pathol 42:725–764PubMedCrossRefPubMedCentralGoogle Scholar
  116. Romen W, Bannasch P, Aterman K (1975) Toxic glomerulosclerosis. Morphology and pathogenesis. Light and electron microscopic studies of the glomerular changes in the kidney of rats poisoned by N nitrosomorpholine. Virchows Arch B Cell Pathol 19:205–219PubMedPubMedCentralGoogle Scholar
  117. Rosenberg AS (2006) Effects of protein aggregates: an immunologic perspective. AAPS J 8:501–507CrossRefGoogle Scholar
  118. Rouse RL, Zhang J, Stewart SR, Rosenzweig BA, Espandiari P, Sadrieh NK (2011) Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats. Kidney Int 79:1186–1197PubMedCrossRefPubMedCentralGoogle Scholar
  119. Schetz M, Dasta J, Goldstein S, Golper T (2005) Drug-induced acute kidney injury. Curr Opin Crit Care 11:555–565PubMedCrossRefPubMedCentralGoogle Scholar
  120. Seely JC (1999) Kidney. In: Maronpot RR, Boorman GA, Gaul BW (eds) Pathology of the mouse. Reference and atlas. Cache River Press, Vienna, pp 207–234Google Scholar
  121. Seely JC, Frazier KS (2015) Regulatory forum opinion piece: dispelling confusing pathology terminology; recognition and interpretation of selected rodent renal tubule lesions. Toxicol Pathol 43:457–463PubMedCrossRefPubMedCentralGoogle Scholar
  122. Sellers RS, Khan KNM (2005) Age, sex, species differences in nephrotoxic response. In: Tarloff JB, Lash LH (eds) Toxicology of the kidney. CRC Press, Boca Raton, pp 1059–1097Google Scholar
  123. Short BG, Goldstein RS (1992) Nonneoplastic lesions in the kidney. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat. ILSI Press, Washington, DC, pp 211–225Google Scholar
  124. Short BG, Burnett VL, Swenberg JM (1989) Elevated proliferation of proximal tubule cells and localization of accumulated α2u-globulin in F344 rats during exposure to unleaded gasoline or 2,2,4-trimethylpentane. Toxicol Appl Pharmacol 101:414–431PubMedCrossRefPubMedCentralGoogle Scholar
  125. Slaughter TN, Paige A, Spires D, Kojima N, Kyle PB, Garrett MR, Roman RJ, Williams JM (2013) Characterization of the development of renal injury in Type-1 diabetic Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol 305:R727–R734PubMedPubMedCentralCrossRefGoogle Scholar
  126. Stills HF Jr, Bullock BC, Clarkson TB (1983) Increased atherosclerosis and glomerulonephritis in cynomolgus monkeys (Macaca fascicularis) given injections of BSA over an extended period of time. Am J Pathol 113:222–234PubMedPubMedCentralGoogle Scholar
  127. Slausen DO, Lewis RM (1979) Comparative pathology of glomerulonephritis in animals. Vet Pathol 16:135–164Google Scholar
  128. Suzuki S, Arnold LL, Muirhead D et al (2008) Inorganic arsenic-induced intramitochondrial granules in mouse urothelium. Toxicol Pathol 36:999–1005PubMedCrossRefPubMedCentralGoogle Scholar
  129. Swenberg JA (1993) Alpha 2u-globulin nephropathy: review of the cellular and molecular mechanisms involved and their implications for human risk assessment. Environ Health Perspect 101(Suppl 6):39–44PubMedPubMedCentralCrossRefGoogle Scholar
  130. Swenberg JA, Short B, Borghoff S, Strasser J, Charbonneau M (1989) The comparative pathobiology of α2u-globulin nephropathy. Toxicol Appl Pharmacol 97:35–46PubMedCrossRefPubMedCentralGoogle Scholar
  131. Swindle MM, Larkin A, Herron A, Clubb F, Frazier KS (2012) Swine as models in biomedical research and toxicologic testing. Vet Pathol 49:344–356PubMedCrossRefPubMedCentralGoogle Scholar
  132. Tomonari Y, Kurotaki T, Sato J, Doi T, Kokoshima H, Kanno T, Tsuchitani M, Seely JC (2016) Spontaneous age-related lesions of the kidney fornices in Sprague-Dawley rats. Toxicol Pathol 44:226–232PubMedCrossRefPubMedCentralGoogle Scholar
  133. Tanner GA, Tielker MA, Connors BA, Phillips CL, Tanner JA, Evan AP (2002) Atubular glomeruli in a rat model of polycystic kidney disease. Kidney Int 62:1947–1957PubMedCrossRefPubMedCentralGoogle Scholar
  134. Tonomura Y, Tsuchiya N, Torii M, Uehara T (2010) Evaluation of the usefulness of urinary biomarkers for nephrotoxicity in rats. Toxicology 273:53–59PubMedCrossRefPubMedCentralGoogle Scholar
  135. Travlos GS, Hard GC, Betz LJ, Kissling GE (2011) Chronic progressive nephropathy in male F344 rats in 90-day toxicity studies: its occurrence and association with renal tubule tumors in subsequent 2-year bioassays. Toxicol Pathol 39:381–389PubMedCrossRefPubMedCentralGoogle Scholar
  136. Van de Water B, Imamdi R, de Graauw M (2005) Signal transduction in renal cell repair and regeneration. In: Tarloff JB, Lash JH (eds) Toxicology of the kidney, 3rd edn. CRC Press, Boca Raton, pp 299–341Google Scholar
  137. Van Meer PJ, Kooijman M, Brinks V, Gispen-de Wied CC, Silva-Lima B, Moors EH, Schellekens H (2013) Immunogenicity of mAbs in nonhuman primates during nonclinical safety assessment. MAbs 5:810–816PubMedPubMedCentralCrossRefGoogle Scholar
  138. Whalen H, Shiels P, Littlejohn M, Clancy M (2016) A novel rodent model of severe renal ischemia reperfusion injury. Ren Fail 38:1694–1701PubMedCrossRefPubMedCentralGoogle Scholar
  139. Wolf DC, Hard GC (1996) Pathology of the kidneys. In: Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM (eds) Pathobiology of the aging mouse. ILSI Press, Washington, DC, pp 331–344Google Scholar
  140. Xie H-G, Wang S-K, Cao C-C, Harpur E (2013) Qualified kidney biomarkers and their potential significance in drug safety evaluation and prediction. Pharmacol Ther 137:100–107PubMedCrossRefPubMedCentralGoogle Scholar
  141. Yamada N, Sato J, Kanno T, Wako Y, Tsuchitani M (2013) Morphological study of progressive glomerulonephropathy in common marmosets (Callithrix jacchus). Toxicol Pathol 41:1106–1115PubMedCrossRefPubMedCentralGoogle Scholar
  142. Yamate J, Iwaki M, Nakatsuji S, Kuwamura M, Kotani T, Sakuma S (1998) Lysozyme-containing renal tubular hyaline droplets in F344 rats bearing a rat fibrosarcoma-derived transplantable tumor. Toxicol Pathol 26:699–703PubMedCrossRefPubMedCentralGoogle Scholar
  143. Zemer D, Pras M, Sohar E, Modan M, Capbill S, Gafni J (1986) Colchicine in the prevention and treatment of amyloidosis of familial Mediterranean fever. N Engl J Med 314:1001–1005PubMedCrossRefPubMedCentralGoogle Scholar
  144. Zhou X, Frohlich ED (2010) Analogy of cardiac and renal complications in essential hypertension and aged SHR or L-NAME/SHR. Med Chem 3:61–65CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Pathology, GlaxoSmithKlineCollegevilleUSA

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