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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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
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
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
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
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
Boucher A, Droz D, Adafer E, Noel L-H (1986) Characterization of mononuclear cell subsets in renal cellular infiltrates. Kidney Int 29:1043–1049
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
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
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
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
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
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
Faull RJ, Russ GR (1989) Tubular expression of intercellular adhesion molecule-1 during renal allograft rejection. Transplantation 48:226–230
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
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
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
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
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
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
Hagerty DT, Allen PM (1992) Processing and presentation of self and foreign antigens by the renal proximal tubule. J Immunol 148:2324–2330
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
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
Husby G, Tung KSK, Williams RC (1981) Characterization of renal tissue lymphocytes in patients with interstitial nephritis. Am J Med 70:31–38
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
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
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
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
Iványi B, Marcussen N, Olsen S (1995) Tubulitis in primary vascular and glomerular renal disease. Pathol Res Pract 191:1245–1251
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
Kopolovic J, Pinkus G, Rosen S (1988) Interstitial nephritis in infectious mononucleosis. Am J Kidney Dis 12:76–77
Laberke HG, Bohle A (1980) Acute interstitial nephritis: correlations between clinical and morphological findings. Clin Nephrol 14:263–273
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
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
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
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
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
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
Olsen TS, Hansen HE (1990) Ultrastructure of medullary tubules in ischemic acute tubular necrosis and acute interstitial nephritis in man. APMIS 98:1139–1148
Olsen TS, Wassef NF, Olsen HT, Hansen HE (1986) Ultrastructure of the kidney in acute interstitial nephritis. Ultrastruct Pathol 10:1–16
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
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
Racusen LC (1995) Problematic lesions for the Banff schema for renal allograft pathology. Transplant Proc 27:1009–1011
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
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
Schuster V, Kreth HW (1992) Epstein-Barr virus infection and associated diseases in children. Eur J Pediatr 151:794–798
Seron D, Cameron JS, Haskard DO (1991) Expression of VCAM-1 in the normal and diseased kidney. Nephrol Dial Transplant 6:917–922
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
Stachura I, Jayakumar S, Bourke E (1983) T and B lymphocyte subsets in fenoprofen nephropathy. Am J Med 75:9–16
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
Truong LD, Farhood A, Tasby J, Gillum D (1992) Experimental chronic renal ischemia: morphologic and immunologic studies. Kidney Int 41:1676–1689
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
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
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
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
Zollinger HU, Mihatsch MJ (1979) Morphology of acute interstitial nephropathies. Contrib Nephrol 16:118–125
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00192921