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Acute tubulointerstitial nephritis: phenotype of infiltrating cells and prognostic impact of tubulitis

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Abstract

The prognostic impact of tubulitis and the phenotype of the infiltrating cells in the tubules were studied in ten percutaneous renal biopsies from six patients with acute tubulointerstitial nephritis (ATIN). The inflammatory cell subsets in the tubules and interstitium (CD3+, CD4+, CD8+, CD20+, CD45RO+, CD56+, CD57+, CD68+ and TIA-1+ cells), the expression of vimentin and the proliferation-associated antigen Ki-67 by cortical tubular cells, and the grade of tubulitis, interstitial infiltration and fibrosis were analysed. Cytotoxic injury to tubular cells in the vicinity of tubular-wall-localized lymphocytes was studied ultrastructurally. ATIN was drug-induced in three patients, related to Legionella infection in two and idiopathic in one patient. Four patients recovered, one with reduced renal function. Two patients developed end-stage renal disease. CD8+ and CD4+ lymphocytes, and a smaller number of macrophages, infiltrated the tubules. The predominant lymphocyte subset in the tubules was the same as in the interstitium. Cytotoxic injury to tubular cells was not seen electron microscopically. The tubular cells exhibited increased proliferative activity and expressed vimentin, indicating non-specific tubular damage. The cell subset, the severity of tubulitis, and the tubular expression of vimentin were not related to outcome. the main prognostic factor was the severity of the interstitial fibrosis. Tubulitis in ATIN may be a harmless non-immune reaction, mediated by tubular expression of cytokines, together with adhesion and other molecules.

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References

  1. Akbar AN, Terry L, Timms A, Beverley PCL, Janossy G (1988) Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol 140:2171–2178

    Google Scholar 

  2. Akbar AN, Timms A, Janossy G (1989) Cellular events during memory T-cell activation in vitro: the UCHL1 (180000 MW) determinant is newly synthesized after mitosis. Immunology 66:213–218

    Google Scholar 

  3. Andersen CB, Blaehr H, Ladefoged S, Larsen S (1992) Expression of the intercellular adhesion molecule-1 (ICAM-1) in human renal allografts and cultured human tubular cells. Nephrol Dial Transplant 7:147–154

    Google Scholar 

  4. Anderson P, Nagler-Anderson C, O'Brien C, Levine H, Watkins S, Slayter HS, Blue M-L, Schlossman SF (1990) A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes. J Immunol 144:574–582

    Google Scholar 

  5. Bender WL, Whelton A, Beschorner WE, Darwish MO, Hall-Craggs M, Solez K (1984) Interstitial nephritis, proteinuria, and renal failure caused by nonsteroidal anti-inflammatory drugs. Am J Med 76:1006–1019

    Google Scholar 

  6. Boucher A, Droz D, Adafer E, Noel L-H (1986) Characterization of mononuclear cell subsets in renal cellular infiltrates. Kidney Int 29:1043–1049

    Google Scholar 

  7. Briscoe DM, Pober JS, Cotran RS (1992) Expression of vascular cell adhesion molecule-1 in human renal allografts. J Am Soc Nephrol 3:1180–1185

    Google Scholar 

  8. Brockmeyer C, Ulbrecht M, Schendel DJ, Weiss EH, Hillebrand G, Burkhardt K, Land W, Gokel MJ, Riethmüller G, Feucht HE (1993) Distribution of cell adhesion molecules (ICAM-1, VCAM-1, ELAM-1) in renal tissue during allograft rejection. Transplantation 55:610–615

    Google Scholar 

  9. Buysen JGM, Houthoff HJ, Krediet RT, Arisz L (1990) Acute interstitial nephritis: a clinical and morphological study in 27 patients. Nephrol Dial Transplant 5:94–99

    Google Scholar 

  10. Cheng H-F, Nolasco F, Cameron JS, Hildreth G, Neild G, Hartley B (1989) HLA-DR display by renal tubular epithelium and phenotype of infiltrate in interstitial nephritis. Nephrol Dial Transplant 4:205–215

    Google Scholar 

  11. Colvin RB, Fang LST (1994) Interstitial nephritis. In: Tisher CC, Brenner BM (eds) Renal pathology: with clinical and functional correlations. Lippincott, Philadelphia, pp 723–767

    Google Scholar 

  12. D'Agati VD, Theise ND, Pirani CL, Knowles DM, Appel GB (1989) Interstitial nephritis related to nonsteroidal anti-inflammatory agents and beta-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies. Mod Pathol 2:390–396

    Google Scholar 

  13. Faull RJ, Russ GR (1989) Tubular expression of intercellular adhesion molecule-1 during renal allograft rejection. Transplantation 48:226–230

    Google Scholar 

  14. Feinfeld DA, D'Agati V, Dutcher JP, Werfel SB, Lynn RI, Wiernik PH (1991) Interstitial nephritis in a patient receiving adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells. Am J Nephrol 11:489–492

    Google Scholar 

  15. Frank J, Engler-Blum G, Rodemann HP, Müller GA (1993) Human renal tubular cells as a cytokine source: PDGF-B, GM-CSF and IL-6 mRNA expression in vitro. Exp Nephrol 1:26–35

    Google Scholar 

  16. Fuggle SV, Sanderson JB, Gray DWR, Richardson A, Morris PJ (1993) Variation in expression of endothelial adhesion molecules in pretransplant and transplanted kidneys — correlation with intragraft events. Transplantation 55:117–123

    Google Scholar 

  17. Fukatsu A, Matsuo S, Yuzawa Y, Miyai H, Futenma A, Kato K (1993) Epression of interleukin-6 and major histocompatibility complex molecules in tubular epithelial cells of diseased human kidneys. Lab Invest 69:58–67

    Google Scholar 

  18. Gallego N, Teruel JL, Mampaso F, Gonzalo A, Ortuno J (1991) Acute interstitial nephritis superimposed on glomerulonephritis: report of a case. Pediatr Nephrol 5:229–231

    Google Scholar 

  19. Gröne H-J, Weber K, Gröne E, Helmchen U, Osborn M (1987) Coexpression of keratin and vimentin in damaged and regenerating tubular epithelia of the kidney. Am J Pathol 129:1–8

    Google Scholar 

  20. Hagerty DT, Allen PM (1992) Processing and presentation of self and foreign antigens by the renal proximal tubule. J Immunol 148:2324–2330

    Google Scholar 

  21. Hamilton-Dutoit SJ, Pallesen G (1994) Detection of Epstein-Barr virus small RNAs in routine paraffin sections using non-isotropic RNA/RNA in situ hybridization. Histopathology 25:101–111

    Google Scholar 

  22. Holthöfer H, Miettinen A, Lehto V-P, Lehtonen E, Virtanen I (1984) Expression of vimentin and cytokeratin types of intermediate filament proteins in developing and adult human kidneys. Lab Invest 50:552–559

    CAS  PubMed  Google Scholar 

  23. Husby G, Tung KSK, Williams RC (1981) Characterization of renal tissue lymphocytes in patients with interstitial nephritis. Am J Med 70:31–38

    Google Scholar 

  24. Ibrahim S, Dawson DV, Van Trigt P, Sanfilippo F (1993) Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft reaction. Am J Pathol 142:1794–1803

    Google Scholar 

  25. Iványi B, Olsen S (1995) Tubulitis in renal disease. In: Dodd S (ed) Tubulointerstitial and cystic kidney disease. (Current topics in pathology, vol 88) Springer, Berlin Heidelberg New York, pp 117–143

    Google Scholar 

  26. Iványi B, Marcussen N, Kemp E, Olsen TS (1992) The distal nephron is preferentially infiltrated by inflammatory cells in acute interstitial nephritis. Virchows Arch [A] 420:37–42

    Google Scholar 

  27. Iványi B, Hansen HE, Olsen S (1993) Segmental localization and quantitative characteristics of tubulitis in kidney biopsies from patients undergoing acute rejection. Transplantation 56:581–585

    Google Scholar 

  28. Iványi B, Marcussen N, Olsen S (1995) Tubulitis in primary vascular and glomerular renal disease. Pathol Res Pract 191:1245–1251

    Google Scholar 

  29. Jevnikar AM, Wuthrich RP, Takei F, Xu H-W, Brennan DC, Glimcher LH, Rubin-Kelley VE (1990) Differing regulation and function of ICAM-1 and class II antigens on renal tubular cells. Kidney Int 38:417–425

    Google Scholar 

  30. Kopolovic J, Pinkus G, Rosen S (1988) Interstitial nephritis in infectious mononucleosis. Am J Kidney Dis 12:76–77

    Google Scholar 

  31. Laberke HG, Bohle A (1980) Acute interstitial nephritis: correlations between clinical and morphological findings. Clin Nephrol 14:263–273

    Google Scholar 

  32. Lipman ML, Stevens AC, Bleackley RC, Helderman JH, McCune TR, Harmon WE, Shapiro ME, Rosen S, Strom TB (1992) The strong correlation of cytotoxic T lymphocyte-specific serine protease gene transcripts with renal allograft rejection. Transplantation 53:73–79

    Google Scholar 

  33. Moll R, Hage C, Thoenes W (1991) Expression of intermediate filament proteins in fetal and adult human kidney: modulations of intermediate filament patterns during development and in damaged tissue. Lab Invest 65:74–86

    Google Scholar 

  34. Muso E, Fujiwara Y, Yoshida H, Hosokawa R, Yashiro M, Hongo Y, Matumiya T, Yamabe H, Kikuta H, Hironaka H, Hirai K, Kawai C (1993) Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with Kawasaki disease-like coronary aneurysms. Clin Nephrol 40:7–15

    Google Scholar 

  35. Nádasdy T, Lászik Z, Blick KE, Johnson LD, Silva FG (1994) Proliferative activity of intrinsic cell populations in the normal human kidney. J Am Soc Nephrol 4:2032–2039

    Google Scholar 

  36. Noronha IL, Eberlein-Gonska M, Hartley B, Stephens S, Cameron JS, Waldherr R (1992) In situ expression of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 receptors in renal allograft biopsies. Transplantation 54:1017–1024

    Google Scholar 

  37. Nouwen EJ, Verstrepen WA, Buyssens N, Zhu M-Q, De Broe ME (1994) Hyperplasia, hypertrophy, and phenotypic alterations in the distal nephron after acute proximal tubular injury in the rat, Lab Invest 70:479–493

    Google Scholar 

  38. Olsen TS, Hansen HE (1990) Ultrastructure of medullary tubules in ischemic acute tubular necrosis and acute interstitial nephritis in man. APMIS 98:1139–1148

    Google Scholar 

  39. Olsen TS, Wassef NF, Olsen HT, Hansen HE (1986) Ultrastructure of the kidney in acute interstitial nephritis. Ultrastruct Pathol 10:1–16

    Google Scholar 

  40. Ooi BS, Jao W, First MR, Mancilla R, Pollak VE (1975) Acute interstitial nephritis. A clinical and pathologic study based on renal biopsies. Am J Med 59:614–629

    Google Scholar 

  41. Pallesen G, Hamilton-Dutoit SJ, Zhou X (1993) The association of Epstein-Barr virus (EBV) with T cell lymphoproliferations and Hodgkin's disease: two new developments in the EBV field. Adv Cancer Res 62:179–239

    Google Scholar 

  42. Racusen LC (1995) Problematic lesions for the Banff schema for renal allograft pathology. Transplant Proc 27:1009–1011

    Google Scholar 

  43. Sale GE, Anderson P, Browne M, Myerson D (1992) Evidence of cytotoxic T-cell destruction of epidermal cells in human graft-vs-host disease. Arch Pathol Lab Med 116:622–625

    Google Scholar 

  44. Schmouder RL, Strieter RM, Wiggins RC, Chensue SW, Kunkel SL (1992) In vitro and in vivo interleukin-8 production in human renal cortical epithelia. Kidney Int 41:191–198

    Google Scholar 

  45. Schuster V, Kreth HW (1992) Epstein-Barr virus infection and associated diseases in children. Eur J Pediatr 151:794–798

    Google Scholar 

  46. Seron D, Cameron JS, Haskard DO (1991) Expression of VCAM-1 in the normal and diseased kidney. Nephrol Dial Transplant 6:917–922

    Google Scholar 

  47. Solez K, Marcussen N, Flynn GJ, Beschorner WE, Racusen LC, Burdick JF (1992) Pathology of acute tubular necrosis and acute rejection. In: Burdick JF, Racusen LC, Solez K, Williams GM (eds) Kidney transplant rejection. Dekker, New York, pp 373–392

    Google Scholar 

  48. Stachura I, Jayakumar S, Bourke E (1983) T and B lymphocyte subsets in fenoprofen nephropathy. Am J Med 75:9–16

    Google Scholar 

  49. Stachura I, Si L, Madan E, Whiteside T (1984) Mononuclear cell subsets in human renal disease enumeration in tissue sections with monoclonal antibodies. Clin Immunol Immunopathol 30:362–373

    Google Scholar 

  50. Truong LD, Farhood A, Tasby J, Gillum D (1992) Experimental chronic renal ischemia: morphologic and immunologic studies. Kidney Int 41:1676–1689

    Google Scholar 

  51. Ward JM, Stevens JL, Konishi N, Kurata Y, Uno H, Diwan BA, Ohmori T (1992) Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans. Am J Pathol 141:955–964

    Google Scholar 

  52. Watson AJS, Dalbow MH, Stachura I, Fragola JA, Rubin MF, Watson RM, Bourke E (1983) Immunologic studies in cimetidine-induced nephropathy and polymyositis. N Engl J Med 308:142–145

    Google Scholar 

  53. Witzgall R, Brown D, Schwarz C, Bonventre JV (1994) Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. J Clin Invest 93:2175–2188

    Google Scholar 

  54. Wuthrich RP, Glimcher LH, Yui MA, Jevnikar AM, Dumas SE, Kelley VE (1990) MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells. Kidney Int 37:783–792

    Google Scholar 

  55. Zollinger HU, Mihatsch MJ (1979) Morphology of acute interstitial nephropathies. Contrib Nephrol 16:118–125

    Google Scholar 

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Iványi, B., Hamilton-Dutoit, S.J., Olsen, S. et al. Acute tubulointerstitial nephritis: phenotype of infiltrating cells and prognostic impact of tubulitis. Vichows Archiv A Pathol Anat 428, 5–12 (1996). https://doi.org/10.1007/BF00192921

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  • DOI: https://doi.org/10.1007/BF00192921

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