Abstract
Tubulointerstitial nephritis (TIN) describes a range of pathological processes that are at least partly responsible for the progression of renal disease of nearly all aetiologies. TIN is frequently the most important pathological manifestation of progressive glomerulonephritis, obstructive uropathy, reflux nephropathy and cystic diseases, although it may also present as a primary disease process associated with infection, drug use or other immunologically mediated disease. Recent clinical and laboratory research has increased our knowledge of tubulointerstitial structure, physiological function and tubulointerstitial response to injury. This review presents a classification of TIN in which acute and chronic tubulointerstitial diseases are recognized as forming a continuum. Primary TIN and TIN associated with glomerulonephritis, obstructive nephropathy and chronic progressive renal disease are discussed from both clinical and pathogenic aspects. It is argued that chronic TIN is a disease process in which inflammation is accompanied by a destructive tubulopathy and fibrogenesis. In acute TIN there is a cessation and reversal of this process. It is suggested that most forms of TIN have an immunological basis because of the presence of immune cell infiltrates, the occurrence of TIN in several immune diseases and immunological animal models of TIN. However, to date TIN has not been convincingly modified in patients by immune manipulation. Experimental evidence suggesting an important pathogenic role for proteinuria and antigenuria, and the renal tubule cell acting as an antigen-presenting cell is discussed.
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References
Lemley KV, Kriz W (1991) Anatomy of the renal interstitium. Kidney Int 39: 370–381
Knepper MA, Danielson RA, Saidel GM, Post RS (1977) Quantitative analysis of renal medullary, anatomy in rats and rabbits. Kidney Int 12: 313–323
Bohman S-O (1983) The ultrastructure of the renal interstitium. In: Brenner BM, Stein JH (eds) Contempory issues in nephrology. Churchill Livingston, New York, pp 1–34
Gurner AC, Smith J, Cattel V (1987) The origin of the Ia antigen presenting cells in the rat kidney. Am J Pathol 127: 342–348
Alexopoulos E, Seron D, Hartley RB, Cameron JS (1990) Lupus nephritis: correlation of interstitial cells with glomerular function. Kidney Int 37: 100–109
Brown CA, Susman RM, Haber E (1980) Identification of an angiotensin receptor in rabbit renomedullary cells in tissue culture. Circ Res 46: 802–807
Kuroda M, Ueno H, Sakato S, Funaki N Takeda R (1979) A unique affinity and adaption of renomedullary interstitial cells for hypertonic medium. Prostaglandins 18: 209–220
Pitcock JA, Lyons H, Brown PS, Rightsel WA, Muirhead EE (1988) Glycosaminoglycans of the rat renomedullary interstitium: ultrastructural and biochemical observations. Exp Mol Pathol 49: 373–387
Fursato M (1977) Ultrastructure and histochemistry of the medullary interstitial matrix of the rat kidney. Acta Pathol Jpn 27: 331–344
Ruoslahti E (1991) Integrins.. J Clin Invest 87: 1–5
Bernfield M, Sanderson RD (1990) Syndecan, a developmentally regulated cell surface proteoglycan that binds extracellular matrix and growth factors. Philos Trans R Soc Lond [Biol] 327: 171–186
Ekblom P, Weller A (1991) Ontogeny of tubulointerstitial cells. Kidney Int 39: 394–400
Vainio MS, Jalkanen M, Lehtonen E, Bernfield M, Saxen L (1989) Epithelial-mesenchymal interactions regulating the stage specific expression of a cell surface proteoglycan, syndecan., in the developing kidney. Dev Biol 134: 382–391
Ekblom P (1989) Developmentally, regulated conversion of mesenchyme into epithelium. FASEB J 3: 2142–2150
Klein G, Langegger M, Timpl R, Ekblom P (1988) Role of laminin A chain in the development of epithelial cell polarity. Cell 55: 331–341
Segal R, Fine LG (1989) Polypeptide growth factors and the kidney. Kidney Int 36: S2-S10
Kujuba DA, Fine LG (1989) Physiology and cell biology update: polypeptide growth factors and their relation to renal disease. Am J Kidney Dis 14: 61–73
Cameron, JS (1988) Allergic interstitial nephritis: clinical features and pathogenesis. Q J Med 250: 97–115
Toto RD (1990) Review: acute tubulointerstitial nephritis. Am J Med Sci 299: 392–410
Cotran RS, Rubin RH, Tolkoff-Rubin NE (1986) Tubulointerstitial diseases. In: Brenner BM, Rector F (eds) The kidney, 3rd edn, vol 2. Saunders, Philadelphia, pp 1143–1173
Ellis D, Fried WA, Yunis EJ, Blau BB (1981) Acute interstitial nephritis in children: a report of 13 cases and review of the literature. Pediatrics 67: 862–870
Frosch M, Ganser G, Schmidt H, Bulla M (1987) Acute focal bacterial nephritis in childhood. Monatsschr Kinderheilkd 135: 842–846
Cogan MG (1980) Tubulo-interstitial nephropathies: a pathophysiological approach. West J Med 132: 134–140
Neilson EG (1989) Pathogenesis and therapy of interstitial nephritis. Kidney Int 35: 1257–1270
Ten RM, Torres VE, Milliner DS, Schwab TR, Holley KE, Gleich, GJ (1988) Acute interstitial nephritis: immunologic and clinical aspects. Mayo Clin Proc 63: 921–930
Ooi BS, Wellington J, First MD, Mancilla R Pollak V (1975) Acute interstitial nephritis. A clinical and pathologic study based on renal biopsies. Am J Med 59: 614–628
Olsen TS, Hansen HE (1990) Ultrastructure of medullary tubules in ischaemic acute tubular necrosis and acute interstitia nephritis in man. APMIS 98: 1139–1148
Platt JL, Sibley RK, Michael AF (1985) Interstitial nephritis associated with cytomegalovirus infection. Kidney Int 28:550–552
Husby G, Tung KSK, Williams RC (1981) Characterization of renal tissue lymphocytes in patients with interstitial nephritis. Am J Med 70:31–38
McCluskey RT, Bhan AK (1982) Cell-mediated mechanisms in renal diseases. Kidney Int 21:[Suppl 11] S6-S12
Watson AJS, Dalbow MH, Strachura 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
Strachura I, Si L, Madan E, Whiteside T (1984) Mononuclear cell monoclonal antibodies. Clin Immunol Immunopathol 30:362–373
Pamucku R, Moorthy AV, Singer JR, Hong R, Simpson DP (1984) Idiopathic acute interstitial nephritis: characterization of the infiltrating cells in the renal interstitium as T helper lymphocytes. Am J Kidney Dis 4:24–29
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., Immunologic characterization of the inflammatory infiltrate. Am J Med 76: 1006–1012
Boucher A, Droz D, Adafer E, Noel L-H (1986) Characterization of mononuclear cell subsets in renal cellular infiltrates. Kidney Int 29: 1043–1049
Brunati C, Brando B, Confalonieri R Belli LS Lavagni MG, Minetti L (1986) Immunophenotyping of 125 nuclear cell infiltrates associated with renal disease. Clin Nephrol 26:15–20
Hooke DH, Gee DC, Atkins RC, (1987) Leukocyte analysis using monoclonal antibodies in human glomerulonephritis. Kidney Int 31: 964–972
Eddy AA (1989) Interstitial nephritis induced by protein-overload proteinuria. Am J Pathol 135:719–733
Marcussen N, Olsen TS (1990) Atubular glomeruli in patients with chronic pyelonephritis. Lab Invest 62:467–473
Mackensen S, Grund KE, Sindjic M, Bohle A (1979) Influence of the renal cortical interstitium on the serum creatinine concentration and serum creatinine clearance in different chronic sclerosing interstitial nephritides. Nephron 24:30–34
Helezynski L, Landing BH (1984) Tubulointerstitial diseases of children: pathologic features and pathogenic mechanisms in Fanconi's familial nephronophthisis, anti-tubular basement membrane antibody disease, and medullary cyst disease. Pediatr Pathol 2:1–24
Scully RE (1982) Renal, cystic disease, acquired, associated with long term hemodialysis. Case records of the Massachusetts General Hospital. N Engl J Med 306:975–984
Steele BT, Lirenman DS, Beattie LW (1980) Nephronophthisis. Am J Med 68:531–538
Landing BH, Wells TR, Helczynski L (1988) Some problems in the meaning of terms, as exemplified by tubulointerstitial and medullary cystic diseases of the kidneys. Perspect Pediatr Pathol 12:20–43
Ellis D (1986) Tubulointerstitial disorders. In: Holliday MA, Barratt TM, Vernier RV (eds) Pediatric nephrology. Williams and Wilkins, Baltimore pp 476–481
Greising J, Trachtman H, Gauthier B, Valderrama E (1990) Acute interstitial nephritis in adolescents and young adults. Child Nephrol Urol 10:189–195
Chugh KS, Narang A, Kumar L, Sakhuja V, Unni VN, Pirzada R, Singh N, Pereira BJ, Singhal PC (1987) Acute renal failure amongst children in a tropical environment. Int J Artif Organs 10:97–101
Councilman WT (1898) Acute interstitial nephritis. J Exp Med 3: 393–420
Kimmelsteil P (1939) Acute hematogenous interstitial nephritis. Am J Pathol 14:737–761
Knepshield JH, Carstens PHB, Gentile DE (1969) Recovery from renal failure due to diffuse interstitial nephritis. Pediatrics 43: 533–539
Haddow JE, Sher N, Gall DG, Green D (1971) Streptococcal wound infection with evidence of widespread tissue involvement. Pediatrics 48:458–462
Woodroffe AJ, Row PG, Meadows R, Lawrence JR (1974) Nephritis in infectious mononucleosis. Q J Med 43:451–460
Silbert PL, Matz LR, Christiansen K, Saker BM, Richardson M (1990) Herpes simplex virus interstitial nephritis in a renal allograft. Clin Nephrol 33:264–268
Guinard JP, Torrado A (1974) Interstitial nephritis and toxoplasmosis in a 10-year old child. J Pediatr 85:381–382
Zibley B (1958) Anuria following penicillin administration. S Afr Med J 32:350–354
Grattan, WA (1964) Hematuria and azotemia associated with methicillin therapy. J Pediatr 64:285–288
Feigin RD, Fiascone A (1965) Hematuria and proteinuria associated with methicillin administration. N Engl J Med 272:903–906
London RD (1965) Hematuria associated with methicillin therapy. J Pediatr 70:285–288
Brauninger GE, Remington JS (1968) Nephropathy associated with methicillin therapy. JAMA 203:103–107
Sanjad SA, Haddad GG, Nasser VH (1974) Nephropathy, an underestimated complication of methicillin therapy. J Pediatr 84:873–877
Carre IJ, Squire JH (1956) Anuria ascribed to acute tubular necrosis in infancy and early childhood. Arch Dis Child 31:512–516
Tannenberg AM, Wicher KJ, Rose NR (1971) Ampicillin nephropathy. JAMA 218:419–423
Ruley EJ, Lisi LM (1974) Interstitial nephritis and renal failure due to ampicillin. J Pediatr 84:878–881
Parry MF, Ball WD, Conte JE Jnr (1973) Nafcillin nephritis. JAMA 225:178–182
Nguyen VD, Nagelberg H, Agarwal BN (1990) Acute tubulointerstitial nephritis associated with cefotetan therapy. Am J Kidney Dis 16: 259–261
Murray KM, Wilson MG (1990) Suspected ciprofloxacin-induced interstitial nephritis. DICP 24:379–380
Rashed A, Azadeh B, Abu Romeh SH (1990) Acyclovir-induced acute tubulointerstitial nephritis. Nephron 56:436–438
Ray PE, Rigolizzo D, Ware DR, Piel CF (1988) Naproxen nephrotoxicity in a two year old child. Am J Dis Child 142:524–525
Gallego N, Teruel JL, Mampasso F, Gonzalo A, Ortuno J (1991) Acute tubulointerstitial nephritis superimposed on glomerulonephritis: report of a case. Pediatr Nephrol 5:229–231
McMenamin RA, Davies LM, Craswell PW (1976) Drug-induced interstitial nephritis, hepatitis, and exfoliative dermatitis. Aust NZ J Med 6:583–587
Hyman LR, Ballow M, Knieser MR (1978) Diphenylhydantoin interstitial nephritis. Roles of cellular and humoral immunologic injury. J Pediatr 92:915–920
Sheth KJ, Casper JT, Good TA (1977) Interstitial nephritis due to phenytoin hypersensitivity. J Pediatr 91:438–441
Islam S, Dubigeon MP, Guenel J (1990) Acute and reversible interstitial granulomatous nephropathy after treatment with captopril. Rev med Interne 11:231–233
Porile JL, Bakris GL, Garella S (1990) Acute interstitial nephritis with glomerulopathy due to nonsteroidal, anti-inflammatory agents: a review of its clinical spectrum and effects of steroid therapy. J Clin Pharmacol 30:468–475
Sanjad SA, Haddad GG, Nasser VH (1974) Nephropathy. An underestimated complication of methicillin therapy. J Pediatr 84:873–877
Linton AL, Clark WF, Driedger AP, Turnbull DI, Lindsay RM (1980) Acute interstitial nephritis due to drugs., Ann Intern Med 93: 735–741
Galpin JE, Shinaberger JH, Stanley TM, Blumenkratz MJ, Bayer AS, Friedman GS, Montgomerie, JZ, Guze LB, Coburn RJ (1978) Acute interstitial nephritis due to methicillin. Am J Med 65:756–765
Bohle A, Glomb D, Grund KE, Mackenson S (1977) Correlations between relative interstitial volume of the renal cortex and serum creatinine concentrations in minimal changes with nephrotic syndrome and in focal sclerosing glomerulonephritis. Virchows Arch [A] 376:221–232
Bohle A, Grund KE, Mackenson S, Tolon M (1977) Correlations between renal interstitium and level of serum creatinine. Morphometric investigations of biopsies in perimembranous glomerulonephritis. Virchows Arch [A] 373:15–22
Wehrmann M, Bohle A, Bogenschutz, O, Eissele, R, Freislederer A, Ohlschlegel C, Schumm G, Batz C, Gartner H-V (1989) Long-term prognosis of chronic idiopathic membranous glomerulonephritis. An analysis of 334 cases with particular regard to tubulo-interstitial changes. Clin Nephrol 31:67–76
Bohle A, Bader R, Grund KE, Mackensen S, Neunhoeffer J (1977) Serum creatinine concentration and renal interstitial volume. Analysis of correlations in endocapillary (acute) glomerulonephritis and in moderately severe mesangioproliferative glomerulonephritis. Virchows Arch [A] 375:87–96
Schwartz MM, Fennel JS, Lewis EJ (1982) Pathologic changes in the renal tubule in systemic lupus erythematosus. Hum Pathol 13: 534–547
Alexopoulos E, Seron D, Hartley RB, Cameron JS (1990) Lupus nephritis: correlation of interstitial cells with glomerular function. Kidney Int 37:100–109
Bohle A, Mackenson-Haen S, Gise HV (1987) Significance of tubulointerstitial changes in the renal cortex for the excretory function and concentration ability of the kidney: a morphometric contribution. Am J Nephrol 7:421–433
Risdon RA, Sloper JC, De Wardner HE (1968) Relationship between renal function and histologic changes found in renal-biopsy specimens from patients with persistent glomerulonephritis. Lancet II: 363–366
Schainuck LI, Striker GE, Cutler RE, Benditt EP (1970) Structuralfunctional correlations in renal disease. II. The correlations. Hum Pathol 1:631–641
Fischbach H, Mackensen S, Grund KE, Keller A, Bohle A (1977) Relationship between glomerular lesions, serum creatinine and interstitial volume in membranoproliferative glomerulonephritis. Klin Wochenschr 55:603–608
Bohle A, Giese H von, Mackensen-Haen S, Stark-Jacob B (1981) The obliteration of the post glomerular capillaries and its influence upon the function of both glomeruli and tubuli. Functional interpretation of morphological findings. Klin Wochenschr 59:1043–1051
Moller JC, Skriver E (1985) Quantitative ultrastructure of human proximal tubules and cortical interstitium in chronic renal disease (hydronephrosis). Virchows Arch [A] 406:389–406
Moller JC, Skriver E, Olsen S, Maunsbach AB (1984) Ultrastructural analysis of human proximal tubules and cortical interstitium in chronic renal disease (hydronephrosis). Virchows Arch [A] 402: 209–237
Schreiner GF, Harris KPG, Purkerson ML, Klahr S (1988) Immunological aspects of acute ureteral obstruction: immune cell infiltrate in the kidney. Kidney Int 34:487–493
Lefkowith JB, Okegawa T, De Schryver-Kekskemeti K, Needleman P (1984) Macrophage-dependent arachidonate metabolism in hydronephrosis. Kidney Int 26:10–17
Harris KPG, Schriener GF, Klahr S (1989) Effect of leukocyte depletion on the function of the postobstructed kidney in the rat. Kidney Int 36:210–215
Spacthe SM, Freed MS, De Schryver-Kecskemeti K, Lefkowith JB, Needleman P (1988) Essential fatty acid deficiency reduces the inflammatory cell invasion in rabbit hydronephrosis resulting in suppression of the exaggerated eicosanoid production. J Pharmacol Exp Ther 245:1088–1094
Thomasson DL, Zenser TV, Davis BB (1988) Cortical interstitial cell interactions induce sensitivity of hydronephrotic kidney to bradykinin Kidney Int 33:71–76
Rovin BH, Harris KPG, Morrison A, Klahr S, Schriener GF (1990) Renal cortical release of a specific macrophage chemoattractant in response to ureteral obstruction. Lab Invest 63:213–220
Schriener GF Lange L (1991) Ethanol modulation of macrophage influx in glomerulonephritis (abstract). J Am Soc Nephrol 2:562
Kees-Folts D, Schriener GF (1991) A lipid chemotactic factor associated with proteinuria and interstitial nephritis induced by protein overload (abstract). J Am Soc Nephrol 2:548
Kuncio GS, Neilson EG, Haverty T (1991) Mechanisms of tubulointerstitial fibrosis. Kidney Int 39:550–556
Jones CL, Buch S, Post M, McCulloch L. Liu E, Eddy AA (1992) Renal extra cellular matrix accumulation in acute purine aminonucleoside nephrosis in rats. Am J Pathol (in press)
Jones CL, Buch S, Post M, McCulloch L, Liu E, Eddy AA (1991) Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int 40:1020–1031
Gonzalez-Avila G, Vadillo-Ortega F, Perez.-Tamayo R (1988) Experimental diffuse interstitial renal fibrosis. A biochemical approach. Lab Invest 59:245–252
Eddy AA, Michael AF (1988) Acute tubulointerstitial nephritis associated with aminonucleoside nephrosis. Kidney Int 33:14–23
Eddy AA, McCulloch L, Liu E, Adams J (1991) A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. Am J Pathol 138:1111–1123
Clark EC, Nath KA, Hostetter MR, Hostetter TH (1991) Role of ammonia in progressive interstitial nephritis. Am J Kidney Dis 17: 15–19
Falk RJ, Dalmasso AP, Kim Y, Tsai CK, Scheinnan JI, Gewurz H, Michael AF (1983) Neoantigen of the polymerized ninth component of complement. J Clin Invest 72:560–573
Wilson CB (1991) Nephritogenic tubulointerstitial, antigens. Kidney Int 39:501–517
Wilson CB (1989) Study of the immunopathogenesis of tubulointerstitial nephritis using model systems. Kidney Int 35:938–953
Clayman MD, Martinez-Hernandez A, Michaud L, Alper R, Mann R, Kefalides NA, Neilson EG (1985) Isolation and characterization of the nephritogenic antigen producing anti-tubular basement membrane disease. J Exp Med 161:290–305
Steblay RW, Rudofsky U (1973) Transfer of experimental autoimmune renal cortical, tubular and interstitial disease in guinea pigs by serum. Science 180:966–968
Van Zwieten MJ, Bhan AK, McCluskey RT, Collins AB (1976) Studies on the pathogenesis of experimental anti-tubular basement membrane nephritis in the guinea pig. Am J Pathol 83:531–546
Mann R, Zakheim B, Clayman M, McCafferty, Michaud L, Neilson EG (1985) Murine interstitial nephritis. IV. Long term cultured L3T4+T cell lines transfer delayed expression of disease as I-A-restricted inducers of the effector T cell repetoire. J Immunol 135: 286–293
Mann R, Kelly CJ, Hines WH, Clayman M, Blanchard N, Sun MJ, Neilson EG (1987) Effector T cell differentiation in experimental interstitial nephritis. I. The development and modulation of effector lymphocyte maturation by I-J=regulatory T cells. J Immunol 136: 4200–4208
Sugisaki T, Klassen J, Milgrom F, Andres GA, McCluskey RT (1973) Immunopathologic study of an autoimmune tubular and interstitial renal disease in Brown Norway rats. Lab Invest 28: 658–671
Lehman, DH, Wilson CB, Dixon FJ (1974) Interstitial nephritis in rats immunized with heterologous tubular basement membrane. Kidney Int 5:187–195
Clayman MD, Michaud L, Brentjens JR, Andres GA, Butkowski RJ (1986) Isolation of the target antigen in human anti-tubular basement membrane nephritis. J Clin Invest 77:143–147
Fliger FD, Wieslander J, Brentjens, JR, Andres GA, Butkowski RJ (1987) Identification of a target antigen in human anti-tubular basement membrane nephritis. Kidney Int 31:800–807
Wilson CB, Lehman DH, McCoy RC, Gunnells JC, Stickel DL (1974) Antitubular basement membrane antibodies after renal transplantation. Transplantation 18:447–452
Hoyer JR, Sisson SP, Vernier RL (1979) Tamm-Horsfall glycoprotein. Ultrastructural immunoperoxidase localization in rat kidney. Lab Invest 41:168–173
Mayrer AR, Kashgarian M, Ruddle NH, Marier R, Hodson CJ, Richards FF, Andriole VT (1982) Tubulointerstitial responses to Tamm-Horsfall protein in rabbits challenged with homologous urine or Tamm-Horsfall protein. J Immunol 128:2634–2642
Berke ES, Mayrer AR, Miniter P, Andriole VT (1983) Tubulointerstitial nephritis in rabbits challenged with homologous Tamm-Horsfall protein: the role of endotoxin. Clin Exp Immunol 53: 562–572
Seiler MW, Hoyer JR (1981) Ultrastructural studies of tubulointerstitial immune complex nephritis in rats immunized with Tamm-Horsfall protein. Lab Invest 45:321–327
Fasth A, Hoyer JR, Seiler MW (1986) Renal tubular immune complex formation in mice immunized with Tamm-Horsfall protein. Am J Pathol 125:555–562
Ishdate T, Hoyer JR, Seiler MW (1983) Influence of altered glomerular permeability on renal tubular immune complex formation and clearance. Lab Invest 45:321–327
Vernier RL, Resnick J (1976) Medullary cystic disease, the possible role of Tamm-Horsfall protein. Kidney Int 9:450
Schwartz MM, Cotran RS (1976) Primary renal disease in renal transplant recipients. Hum Pathol 7:455
Zager RA, Cotran RS, Hoyer JR (1978) Pathologic localization of Tamm-Horsfall protein in interstitial deposits in renal disease. Lab Invest 38:52–57
Hanson LA, Fasth A, Jodal U (1976) Autoantibodies to Tamm-Horsfall protein, a tool for diagnosing the level or urinary tract infection. Lancet I:226–228
Hodson J, Maling TMJ, McManamon PJ, Lewis MG (1975) Reflux nephropathy. Kidney Int 8:S50-S58
Kincaid-Smith P (1975) The kidney: a clinicopathologic study, Blackwell, Oxford, p 375
Hession C, Decker JM, Sherblom AP, Kumar S, Yue CC, Mattaliano RJ, Tizard R, Kawashima E, Schmeissner U, Heletky S, Chow EP, Burne CA, Shaw A, Muchmore AV (1987) Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. Science 237: 1479–1484.
Rubin-Kelly VE, Jevnikar AM (1991) Antigen presentation by renal tubular epithelial cells. J Am Soc Nephrol 2: 13–26
Brown D, McCluskey RT, Ausiello DA (1987) The cell biology of Heymann nephritis: a model of human membranous glomerulonephritis. Am J Kidney Dis 10: 74–76
Klassen J, Sugisaki T, Milgrom F, McCluskey RT (1971) Studies on multiple renal lesions in Heymann nephritis. Lab Invest 25: 577–585
Gronhagen-Riska C, Willebrand E von, Tikkanen T, Honkanen E, Miettinen A, Holthofer H, Tornroth T (1990) The effect of cyclosporin A on the interstitial mononuclear cell infiltration and the induction of Heymann's nephritis. Clin Exp Immunol 79: 266–272
Edgington TS, Glassock RJ, Dixon FJ (1967) Autologous immune complex pathogenesis of experimental allergic glomerulonephritis. Science 155: 1432–1434
Kerjaschki D, Farquhar MG (1982) The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA 79: 5557–5561
Kerjaschki D, Farquhar MG (1983) Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med 157: 667–686
Eddy AA, Ho GG, Thorner PS (1992) The contribution of antibody-mediated cytotoxicity and immune complex formation to tubulointerstitial disease in passive Heymann nephritis. Clin Immunol Immunopathol 62: 42–45
Raychoudhury R, Niles JL, McCluskey RT, Smith JA (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL recepton. Science 244: 1163–1165
Noble B, Mendrick DL, Brentjens JR, Andres GA (1981) Antibody-mediated injury to proximal tubules in the rat kidney induced by passive transfer of homologous anti-brush border serum. Clin Immunol Immunopathol 19: 289–301
Zamlauski-Tucker MJ, Van Liew JB, Noble B (1987) Pathophysiology of the kidney in rats with Heymann nephritis. Kidney Int 28: 504–512
Paul LC, Stuffers-Heiman M, Van Es LA, De Graeff J (1979) Antibodies directed against brush border antigens of proximal tubules in renal allograft recipients. Clin Immunol Immunopathol 14: 238–243
Shwayder M, Ozawa T, Boedecker E, Guggenheim S, McIntosh RM (1976) Nephrotic syndrome associated with Fanconi syndrome. Immunopathogenic studies of tubulointerstitial nephritis with autologous immune-complex glomerulonephritis. Ann Intern Med 84: 433–437
Morrison EB, Kozlowski EJ, McPhaul JJ Jr (1981) Primary tubulointerstitial nephritis caused by antibodies to proximal tubule antigens. Am J Clin Pathol 75: 602–609
Rook G (1989) Cell mediated immune responses. In: Roitt I, Brostoff J, Male D (eds) Immunology, 2nd edn. Gower, London, p 9.2
Kelly CJ, Roth DA, Meyers CM (1991) Immune recognition and response to the renal interstitium. Kidney Int 31: 518–530
Rytel MW (1975) Counterimmunoelectrophoresis in diagnosis of infectious disease. Hosp Pract 10: 75–82
Cheng H-F, Nolasco F, Cameron JS, Hildreth G, Neild G, Hartlet B (1989) HLA-DR display by renal tubular epithelium and phenotype of infiltrate in interstitial nephritis. Nephrol Dial Transplant 4: 205–215
Boucher A, Droz D, Adafer E, Noel LH (1986) Characterization of mononuclear cell subsets in renal cellular interstitial infiltrates. Kidney Int 29: 1043–1049
Bishop GA, Waugh JA, Hall BM (1988) Experesion of HLA antigens on renal tubular cells in culture. II. Effect of increased HLA antigen on tubular cell stimulation of lymphocyte activation and on their vulnerability to cell mediated lysis. Transplantation 46: 303–310
Jevnikar AM, Wuthrich RP, Takei F, Xu H, Brennan DC, Glimcher LH, Rubin Kelly VE. (1990) Differing regulation and function of ICAM-1 and class II antigens on renal tubular cells. Kidney Int 28: 417–425
Hines WH, Haverty TP, Elias JA, Neilson EG, Kelly CJ (1989) T cell recognition of epithelial self. Autoimmunity 5: 37–47
Haverty TP, Kelly CJ, Hines WH, Amenta PS, Watanabe M, Harper PA, Kefalides NA, Neilson EG (1988) Characterization of a renal tubular epithelial cell line which secretes the autologous target antigen of autoimmune experimental interstitial nephritis. J Cell Biol 107: 1359–1368
Jacobs JW, Jong MC de, Lommen EJ (1989) The TINU syndrome in children (tubulointerstitial nephritis with uveitis). Tijdschr Dergeneeskd 57: 225–229
Querfeld U, Baisch C, Soergel M, Wingen AM, Waldherr R, Scharer R (1991) Acute tubulointerstitial nephritis and uveitis (TINU syndrome) in childhood. Monatsschr Kinderheilkd 139: 336–341
Yosioka K, Takemura T, Kanasaki M, Akano N, Maki S (1991) Acute interstitial nephritis and uveitis syndrome: activated immune cell infiltration in the kidney. Pediatr Nephrol 5: 232–234
Khaldi F, Karboul, Bennaceur B (1991) Interstitial nephropathy, tapeto-retinal degeneration and cataract. Apropos of a new case. Ann Pediatr (Paris) 38: 107–109
Janda J, Rambousek V, Kolsky A, Stejskal J, Klimesova D, Feber J (1990) Acute interstitial nephritis with uveitis in children and adolescents. Cesk Pediatr 45: 7–11
Bannister KM, Ulich TR, Wilson CB (1987) Induction, characterization, and cell transfer of autoimmune tubulointerstitial nephritis in the Lewis rat. Kidney Int 32: 642–651
Meyers CM, Kelly CJ (1990) An antigen-specific CTL line transfers interstitial nephritis and is cytotoxic to antigen-expressing tubular epithelial cells (abstract). Kidney Int 37: 430
Border WA, Lehman DH, Egan JD, Sass HJ, Glode JE, Wilson CB (1974) Antitubular basement membrane antibodies in methicillin-associated interstitial nephritis. N Engl J Med 291: 381–384
Hyman LR, Ballow M, Kniesser MR (1978) Diphenylhydantoin interstitial nephritis. Roles of cellular and humoral immunologic injury. J Pediatr 92: 915–920
Bergstein J, Litman N (1975) Interstitial nephritis with anti-tubular-basement membrane antibody. N Engl J Med 292: 875–878
Lehman DH, Wilson CB, Dixon FJ (1975) Extraglomerular immunoglobulin deposits in human nephritis. Am J Med 58: 765–786
Andres G, Brentjens J, Kohli R, Anthone R, Anthone S, Baliah T, Montes M, Mookerjee BK, Prezyna A, Sepulveda M, Venuto R, Elwood C (1978) Histology of human tubulo-interstitial nephritis associated with antibodies to renal basement membranes. Kidney Int 13: 480–491
Douglas MFS, Rabideau DP, Schwartz MM, Lewis EJ (1981) Evidence of autologous immune complex nephritis. N Engl J Med 305: 1326–1329
Cotran RS, Galvanek E (1979) Immunopathology of human tubulointerstitial diseases: localization of immunoglobulins, complement and Tamm-Horsfall protein. Contrib Nephrol 16: 126–131
Gur H, Kopolovic Y, Gross DJ (1987) Chronic predominant interstitial nephritis in a patient with systemic lupus erythematosus: a follow-up of three years and review of the literature. Ann Rheum Dis 46: 617–623
Brentjens JR, Sepulveda M, Baliah T, Bentzel C, Erlanger BF, Elwood C, Montes M, Hsu KC, Andres GA (1975) Interstitial immune complex nephritis in patients with systemic lupus erythematosus. Kidney Int 7: 342–350
Makker SP (1980) Tubular basement membrane antibody-induced interstitial nephritis in systemic lupus erythematosus. Am J Med 69: 949–952
Lyon MF, Hulse EV (1971) An inherited kidney disease of mice resembling human nephronophthisis. J Med Genet 8: 41–48
Neilson EG, McCafferty E, Feldman A, Clayton MD, Zakheim B, Korngold R (1984) Spontaneous interstitial nephritis in kd/kd mice. I. An experimental model of autoimmune renal disease. J Immunol 133: 2560–2565
Kelly CJ, Korngold R, Mann R, Clatman MD, Haverty TP, Neilson EG (1986) Spontaneous nephritis in kd/kd mice. II. Characterization of a tubule antigen specific, H-2K restricted Lyt-2+ effector T cell that mediates destructive tubulointerstitial injury. J Immunol 136: 526–531
Kelly CJ, Neilson EG (1987) Contrasuppression in autoimmunity. Abnormal contrasuppression facilititates expression of nephritogenic effector T-cells and interstitial nephritis in kd/kd mice. J Exp Med 165: 107–123
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Jones, C.L., Eddy, A.A. Tubulointerstitial nephritis. Pediatr Nephrol 6, 572–586 (1992). https://doi.org/10.1007/BF00866512
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DOI: https://doi.org/10.1007/BF00866512