Abstract
Recurrent bacterial infection of the kidney was previously thought to be responsible for the renal scarring typical of chronic pyelonephritis until recent studies suggested that recurrent bacteriuria rarely produces chronic pyelonephritis in the absence of obstructive uropathy. In contrast, the association between vesicoureteral reflux (VUR) and chronic pyelonephritis has been observed frequently in the absence of urinary infection. Although the mechanism by which VUR injures the kidney has not been defined, recent observations have suggested that some component of urine might serve as an antigenic determinant involved in the immunopathogenesis of renal scarring in VUR. Therefore, the present studies investigated the immunopathogenic role of Tamm-Horsfall protein (THP) in (1) a rabbit model of tubulointerstitial nephritis; (2) a swine model of reflux nephropathy; and (3) patients with recurrent nephrolithiasis. The antigenic similarities between THP and uropathic bacteria were also studied. Our observations indicate that autoimmune responses to THP may occur after exposure to THP by intravenous challenge in rabbits, by urinary reflux in pigs, and in recurrent nephrolithiasis in man. Also, extracts of uropathic coliforms competitively inhibit the binding of human THP to its antibody. These studies suggest that autoimmune responses to THP may be the pathogenetic mechanism by which these factors, including bacteriuria, contribute to "chronic pyelonephritis."
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amar A. D. Calicotubular backflow with vesicoureteral reflux. Relation to pyelonephritis. JAMA. 1970 Jul 13;213(2):293–294. [PubMed] [Google Scholar]
- Angell M. E., Relman A. S., Robbins S. L. "Active" chronic pyelonephritis without evidence of bacterial infection. N Engl J Med. 1968 Jun 13;278(24):1303–1308. doi: 10.1056/NEJM196806132782401. [DOI] [PubMed] [Google Scholar]
- Arant B. S., Jr, Sotelo-Avila C., Bernstein J. Segmental "hypoplasia" of the kidney (Ask-Upmark). J Pediatr. 1979 Dec;95(6):931–939. doi: 10.1016/s0022-3476(79)80279-6. [DOI] [PubMed] [Google Scholar]
- Asscher A. W., McLachlan M. S., Jones R. V., Meller S., Sussman M., Harrison S., Johnston H. H., Sleight G., Fletcher E. W. Screening for asymptomatic urinary-tract infection in schoolgirls. A two-centre feasibility study. Lancet. 1973 Jul 7;2(7819):1–4. doi: 10.1016/s0140-6736(73)91943-0. [DOI] [PubMed] [Google Scholar]
- Bailey R. R. End-stage reflux nephropathy. Nephron. 1981;27(6):302–306. doi: 10.1159/000182075. [DOI] [PubMed] [Google Scholar]
- Bailey R. R. The relationship of vesico-ureteric reflux to urinary tract infection and chronic pyelonephritis-reflux nephropathy. Clin Nephrol. 1973 May-Jun;1(3):132–141. [PubMed] [Google Scholar]
- Berke E. S., Mayrer A. R., Miniter P., Andriole V. T. Tubulointerstitial nephritis in rabbits challenged with homologous Tamm-Horsfall protein: the role of endotoxin. Clin Exp Immunol. 1983 Sep;53(3):562–572. [PMC free article] [PubMed] [Google Scholar]
- Bhagavan B. S., Wenk R. E., Dutta D. Pathways of urinary backflow in obstructive uropathy. Demonstration by pigmented gelatin injection and Tamm-Horsfall uromucoprotein markers. Hum Pathol. 1979 Nov;10(6):669–683. doi: 10.1016/s0046-8177(79)80111-2. [DOI] [PubMed] [Google Scholar]
- Brodeur A. E., Goyer R. A., Melick W. A potential hazard of barium cystography. Radiology. 1965 Dec;85(6):1080–1084. doi: 10.1148/85.6.1080. [DOI] [PubMed] [Google Scholar]
- Chrispin A. R. Medullary necrosis in infancy. Br Med Bull. 1972 Sep;28(3):233–236. doi: 10.1093/oxfordjournals.bmb.a070935. [DOI] [PubMed] [Google Scholar]
- Cotran R. S., Galvanek E. Immunopathology of human tubulo-interstitial diseases: localization of immunoglobulins complement and Tamm-Horsfall protein. Contrib Nephrol. 1979;16:126–131. doi: 10.1159/000402886. [DOI] [PubMed] [Google Scholar]
- Dziukas L. J., Sterzel R. B., Hodson C. J., Hoyer J. R. Renal localization of Tamm-horsfall protein in unilateral obstructive uropathy in rats. Lab Invest. 1982 Aug;47(2):185–193. [PubMed] [Google Scholar]
- Edwards B., White R. H., Maxted H., Deverill I., White P. A. Screening methods for covert bacteriuria in schoolgirls. Br Med J. 1975 May 31;2(5969):463–467. doi: 10.1136/bmj.2.5969.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fasth A., Ahlstedt S., Hanson L. A., Jann B., Jann K., Kaijser B. Cross-reactions between the Tamm-Horsfall glycoprotein and Escherichia coli. Int Arch Allergy Appl Immunol. 1980;63(3):303–311. doi: 10.1159/000232640. [DOI] [PubMed] [Google Scholar]
- Fasth A., Bengtsson U., Kaijser B., Wieslander J. Antibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults. Kidney Int. 1981 Oct;20(4):500–504. doi: 10.1038/ki.1981.167. [DOI] [PubMed] [Google Scholar]
- Fasth A., Bjure J., Hellström M., Jacobsson B., Jodal U. Autoantibodies to Tamm-Horsfall glycoprotein in children with renal damage associated with urinary tract infections. Acta Paediatr Scand. 1980 Nov;69(6):709–715. doi: 10.1111/j.1651-2227.1980.tb07138.x. [DOI] [PubMed] [Google Scholar]
- Fasth A., Hanson L. A., Asscher A. W. Autoantibodies to Tamm-Horsfall protein in detection of vesicoureteric reflux and kidney scarring. Arch Dis Child. 1977 Jul;52(7):560–562. doi: 10.1136/adc.52.7.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fasth A., Hanson L. A., Jodal U., Peterson H. Autoantibodies to Tamm-Horsfall protein associated with urinary tract infections in girls. J Pediatr. 1979 Jul;95(1):54–60. doi: 10.1016/s0022-3476(79)80081-5. [DOI] [PubMed] [Google Scholar]
- Fletcher A. P., Neuberger A., Ratcliffe W. A. Tamm-Horsfall urinary glycoprotein. The subunit structure. Biochem J. 1970 Nov;120(2):425–432. doi: 10.1042/bj1200425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODSON C. J., EDWARDS D. Chronic pyelonephritis and vesico-ureteric reflex. Clin Radiol. 1960 Oct;11:219–231. doi: 10.1016/s0009-9260(60)80047-5. [DOI] [PubMed] [Google Scholar]
- Hanson L. A., Fasth A., Jodal U. Autoantibodies to Tamm-Horsfall protein, a tool for diagnosing the level of urinary-tract infection. Lancet. 1976 Jan 31;1(7953):226–228. doi: 10.1016/s0140-6736(76)91342-8. [DOI] [PubMed] [Google Scholar]
- Hodson C. J., Cotran R. S. Reflux nephropathy. Hosp Pract (Hosp Ed) 1982 Apr;17(4):133-5, 138-41, 148-56. doi: 10.1080/21548331.1982.11698062. [DOI] [PubMed] [Google Scholar]
- Hodson C. J., Maling T. M., McManamon P. J., Lewis M. G. The pathogenesis of reflux nephropathy (chronic atrophic pyelonephritis). Br J Radiol. 1975;Suppl 13:1–26. [PubMed] [Google Scholar]
- Hodson J. Reflux nephropathy. Med Clin North Am. 1978 Nov;62(6):1201–1201. doi: 10.1016/s0025-7125(16)31734-5. [DOI] [PubMed] [Google Scholar]
- Hoyer J. R., Seiler M. W. Pathophysiology of Tamm-Horsfall protein. Kidney Int. 1979 Sep;16(3):279–289. doi: 10.1038/ki.1979.130. [DOI] [PubMed] [Google Scholar]
- Hoyer J. R., Sisson S. P., Vernier R. L. Tamm-Horsfall glycoprotein: ultrastructural immunoperoxidase localization in rat kidney. Lab Invest. 1979 Aug;41(2):168–173. [PubMed] [Google Scholar]
- Hutch J. A., Smith D. R. Sterile reflux: report of 24 cases. Urol Int. 1969;24(5):460–465. doi: 10.1159/000279643. [DOI] [PubMed] [Google Scholar]
- KUNIN C. M., DEUTSCHER R., PAQUIN A., Jr URINARY TRACT INFECTION IN SCHOOL CHILDREN: AN EPIDEMIOLOGIC, CLINICAL AND LABORATORY STUDY. Medicine (Baltimore) 1964 Mar;43:91–130. [PubMed] [Google Scholar]
- Lindberg U., Claësson I., Hanson L. A., Jodal U. Asymptomatic bacteriuria in schoolgirls. I. Clinical and laboratory findings. Acta Paediatr Scand. 1975 May;64(3):425–431. doi: 10.1111/j.1651-2227.1975.tb03859.x. [DOI] [PubMed] [Google Scholar]
- Marier R., Fong E., Jansen M., Hodson C. J., Richards F., Andriole V. T. Antibody to Tamm-Horsfall protein in patients with urinary tract obstruction and vesicoureteral reflux. J Infect Dis. 1978 Dec;138(6):781–790. doi: 10.1093/infdis/138.6.781. [DOI] [PubMed] [Google Scholar]
- Marier R., Jansen M., Andriole V. T. A new method for measuring antibody using radiolabeled protein A1 in a solid-phase radioimmunoassay. J Immunol Methods. 1979;28(1-2):41–49. doi: 10.1016/0022-1759(79)90326-0. [DOI] [PubMed] [Google Scholar]
- Marier R., Smith W., Jansen M., Andriole V. T. A solid-phase radioimmunoassay for the measurement of antibody to Aspergillus in invasive aspergillosis. J Infect Dis. 1979 Nov;140(5):771–779. doi: 10.1093/infdis/140.5.771. [DOI] [PubMed] [Google Scholar]
- Mayrer A. R., Kashgarian M., Ruddle N. H., Marier R., Hodson C. J., Richards F. F., Andriole V. T. Tubulointerstitial nephritis and immunologic responses to Tamm-Horsfall protein in rabbits challenged with homologous urine or Tamm-Horsfall protein. J Immunol. 1982 Jun;128(6):2634–2642. [PubMed] [Google Scholar]
- Mayrer A. R., Miniter P., Andriole V. T. Immunopathogenesis of chronic pyelonephritis. Am J Med. 1983 Jul 28;75(1B):59–70. doi: 10.1016/0002-9343(83)90074-8. [DOI] [PubMed] [Google Scholar]
- Morgan M., Asscher A. W., Moffat D. B. The role of vesico-ureteric (V-U) reflux in the pathogenesis of kidney scars in the rat. Nephron. 1976;17(1):8–19. doi: 10.1159/000180706. [DOI] [PubMed] [Google Scholar]
- Neilson E. G., Jimenez S. A., Phillips S. M. Cell-mediated immunity in interstitial nephritis. III. T lymphocyte-mediated fibroblast proliferation and collagen synthesis: an immune mechanism for renal fibrogenesis. J Immunol. 1980 Oct;125(4):1708–1714. [PubMed] [Google Scholar]
- Neilson E. G., Phillips S. M. Cell-mediated immunity in interstitial nephritis. I. T lymphocyte systems in nephritic guinea pigs: the natural history and diversity of the immune response. J Immunol. 1979 Nov;123(5):2373–2380. [PubMed] [Google Scholar]
- Neilson E. G., Phillips S. M. Cell-mediated immunity in interstitial nephritis. II. T lymphocyte effector mechanisms in nephritic guinea pigs: analysis of the renotropic migration and cytotoxic response. J Immunol. 1979 Nov;123(5):2381–2385. [PubMed] [Google Scholar]
- Nielson E. G., Phillips S. M. Cell-mediated immunity in interstitial nephritis. IV. Anti-tubular basement membrane antibodies can function in antibody-dependent cellular cytotoxicity reactions: observations on a nephritogenic effector mechanism acting as an informational bridge between the humoral and cellular immune response. J Immunol. 1981 May;126(5):1990–1993. [PubMed] [Google Scholar]
- Orskov I., Orskov F., Birch-Andersen A. Comparison of Escherichia coli fimbrial antigen F7 with type 1 fimbriae. Infect Immun. 1980 Feb;27(2):657–666. doi: 10.1128/iai.27.2.657-666.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ransley P. G. Intrarenal reflux: anatomical, dynamic and radiological studies-part I. Urol Res. 1977;5(2):61–69. doi: 10.1007/BF00256843. [DOI] [PubMed] [Google Scholar]
- Ransley P. G., Risdon R. A. Renal papillary morphology and intrarenal reflux in the young pig. Urol Res. 1975 Oct 29;3(3):105–109. doi: 10.1007/BF00256030. [DOI] [PubMed] [Google Scholar]
- Ransley P. G., Risdon R. A. Renal papillary morphology in infants and young children. Urol Res. 1975 Oct 29;3(3):111–113. doi: 10.1007/BF00256031. [DOI] [PubMed] [Google Scholar]
- Resnick J. S., Sisson S., Vernier R. L. Tamm-Horsfall protein. Abnormal localization in renal disease. Lab Invest. 1978 May;38(5):550–555. [PubMed] [Google Scholar]
- Rolleston G. L., Maling T. M., Hodson C. J. Intrarenal reflux and the scarred kidney. Arch Dis Child. 1974 Jul;49(7):531–539. doi: 10.1136/adc.49.7.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rolleston G. L., Shannon F. T., Utley W. L. Relationship of infantile vesicoureteric reflux to renal damage. Br Med J. 1970 Feb 21;1(5694):460–463. doi: 10.1136/bmj.1.5694.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rose J. S., Glassberg K. I., Waterhouse K. Intrarenal reflux and its relationship to renal scarring. J Urol. 1975 Mar;113(3):400–403. doi: 10.1016/s0022-5347(17)59492-6. [DOI] [PubMed] [Google Scholar]
- SMELLIE J. M., HODSON C. J., EDWARDS D., NORMAND I. C. CLINICAL AND RADIOLOGICAL FEATURES OF URINARY INFECTION IN CHILDHOOD. Br Med J. 1964 Nov 14;2(5419):1222–1226. doi: 10.1136/bmj.2.5419.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salvatierra O., Jr, Kountz S. L., Belzer F. O. Primary vesicoureteral reflux and end-stage renal disease. JAMA. 1973 Dec 17;226(12):1454–1456. [PubMed] [Google Scholar]
- Salvatierra O., Jr, Tanagho E. A. Reflux as a cause of end stage kidney disease: report of 32 cases. J Urol. 1977 Apr;117(4):441–443. doi: 10.1016/s0022-5347(17)58492-x. [DOI] [PubMed] [Google Scholar]
- Sanford J. P. Urinary tract symptoms and infections. Annu Rev Med. 1975;26:485–498. doi: 10.1146/annurev.me.26.020175.002413. [DOI] [PubMed] [Google Scholar]
- Savage D. C., Wilson M. I., McHardy M., Dewar D. A., Fee W. M. Covert bacteriuria of childhood. A clinical and epidemiological study. Arch Dis Child. 1973 Jan;48(1):8–20. doi: 10.1136/adc.48.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott J. E., Stansfeld J. M. Ureteric reflux and kidney scarring in children. Arch Dis Child. 1968 Aug;43(230):468–470. doi: 10.1136/adc.43.230.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shannon F. T. Urinary tract infection in infancy. N Z Med J. 1972 May;75(480):282–284. [PubMed] [Google Scholar]
- Sikri K. L., Foster C. L., Bloomfield F. J., Marshall R. D. Localization by immunofluorescence and by light- and electron-microscopic immunoperoxidase techniques of Tamm-Horsfall glycoprotein in adult hamster kidney. Biochem J. 1979 Sep 1;181(3):525–532. doi: 10.1042/bj1810525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smellie J., Edwards D., Hunter N., Normand I. C., Prescod N. Vesico-ureteric reflux and renal scarring. Kidney Int Suppl. 1975 Aug;4:S65–S72. [PubMed] [Google Scholar]
- Solez K., Heptinstall R. H. Intrarenal urinary extravasation with formation of venous polyps containing Tamm-Horsfall protein. J Urol. 1978 Feb;119(2):180–183. doi: 10.1016/s0022-5347(17)57428-5. [DOI] [PubMed] [Google Scholar]
- TAMM I., HORSFALL F. L., Jr A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. J Exp Med. 1952 Jan;95(1):71–97. doi: 10.1084/jem.95.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TAMM I., HORSFALL F. L., Jr Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med. 1950 May;74(1):106–108. [PubMed] [Google Scholar]
- Wein A. J., Schoenberg H. W. A review of 402 girls with recurrent urinary tract infection. J Urol. 1972 Feb;107(2):329–331. doi: 10.1016/s0022-5347(17)61019-x. [DOI] [PubMed] [Google Scholar]
- Work J., Andriole V. T. Tamm-Horsfall protein antibody in patients with end-stage kidney disease. Yale J Biol Med. 1980 Mar-Apr;53(2):133–148. [PMC free article] [PubMed] [Google Scholar]
- Yunis E. J., Jaffe R. Tamm-Horsfall protein in lymph nodes. Hum Pathol. 1981 Feb;12(2):179–183. doi: 10.1016/s0046-8177(81)80105-0. [DOI] [PubMed] [Google Scholar]
- Zager R. A., Cotran R. S., Hoyer J. R. Pathologic localization of Tamm-Horsfall protein in interstitial deposits in renal disease. Lab Invest. 1978 Jan;38(1):52–57. [PubMed] [Google Scholar]