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Epidemiology, pathogenesis, treatment and outcomes of infection-associated glomerulonephritis

Nature Reviews Nephrology volume 16, pages 32–50 (2020)Cite this article

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Abstract

For over a century, acute ‘post-streptococcal glomerulonephritis’ (APSGN) was the prototypical form of bacterial infection-associated glomerulonephritis, typically occurring after resolution of infection and a distinct infection-free latent period. Other less common forms of infection-associated glomerulonephritides resulted from persistent bacteraemia in association with subacute bacterial endocarditis and shunt nephritis. However, a major paradigm shift in the epidemiology and bacteriology of infection-associated glomerulonephritides has occurred over the past few decades. The incidence of APSGN has sharply declined in the Western world, whereas the number of Staphylococcus infection-associated glomerulonephritis (SAGN) cases increased owing to a surge in drug-resistant Staphylococcus aureus infections, both in the hospital and community settings. These Staphylococcus infections range from superficial skin infections to deep-seated invasive infections such as endocarditis, which is on the rise among young adults owing to the ongoing intravenous drug use epidemic. SAGN is markedly different from APSGN in terms of its demographic profile, temporal association with active infection and disease outcomes. The diagnosis and management of SAGN is challenging because of the lack of unique histological features, the frequently occult nature of the underlying infection and the older age and co-morbidities in the affected patients. The emergence of multi-drug-resistant bacterial strains further complicates patient treatment.

Key points

  • In the last century, acute post-streptococcal glomerulonephritis (APSGN) was the prototypical infection-associated GN.

  • Over the past few decades, the incidence of APSGN declined sharply in the Western world, whereas the number of Staphylococcus infection-associated glomerulonephritis (SAGN) cases increased. The surge in staphylococcal infections, mainly methicillin-resistant Staphylococcus aureus (MRSA), is a probable contributing factor.

  • APSGN still occurs with high frequency among highly populated and economically disadvantaged communities around the world, where group A β-haemolytic streptococcal infections are common.

  • APSGN remains the most common cause of acute GN among children, whereas SAGN has very different demographic features and mainly affects the elderly population.

  • SAGN is associated with ongoing infection when the patient presents with acute GN and antibiotic treatment is the mainstay of management; aggressive immunosuppressive treatment is clearly contraindicated and detrimental to the patient when the infection is still active.

  • Infective endocarditis is one of the most frequent infections implicated in SAGN; epidemic intravenous drug use is a major contributing factor, as well as the increased use of cardiac devices in elderly patients.

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Fig. 1: Schema for classification of bacterial infection-associated glomerulonephritis.
Fig. 2: Global APSGN incidence.
Fig. 3: Glomerular pathology and histological features in APSGN.
Fig. 4: Histological features in SAGN.
Fig. 5: Algorithmic approach to the management of SAGN.

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References

  1. Jennette, J. C., Silva, F. G., Olson, J. L., D’Agati, V. D. (eds) Heptinstall’s Pathology of the Kidney 7th edn Vol. 1 Ch. 3 91–118 (Wolters Kluwer, 2014).

  2. Cook, H. T. & Pickering, M. C. in Heptinstall’s Pathology of the Kidney 7th edn Vol. 1 Ch. 9 (eds Jennette, J. C. et al.) 341–366 (Wolters Kluwer, 2014).

  3. Satoskar, A. A. & Nadasdy, T. in Silva’s Diagnostic Renal Pathology 2nd edn Ch. 7 (eds Zhou, X. J. et al.) 243–264 (Cambridge Univ. Press, 2017).

  4. Satoskar, A. A., Nadasdy, T. & Silva, F. in Heptinstall’s Pathology of the Kidney 7th edn Vol. 1 Ch. 10 (eds Jennette, J. C. et al.) (Wolters Kluwer, 2014).

  5. Boils, C. L. in Bacterial Infections and the Kidney Ch. 4 (eds Satoskar, A. A. & Nadasdy, T.) 87–116 (Springer, 2017).

  6. Longcope, W. T. et al. Relationship of acute infections to glomerular nephritis. J. Clin. Invest. 5, 7 (1928).

    Google Scholar 

  7. Dillon, H. C., Reeves, M. S. & Maxted, W. R. Acute glomerulonephritis following skin infection due to streptococci of M-type 2. Lancet 291, 543–545 (1968).

    Google Scholar 

  8. Wilmers, M. J., Cunliffe, A. C. & Williams, R. E. Type-12 streptococci associated with acute haemorrhagic nephritis. Lancet 267, 17–18 (1954).

    CAS  PubMed  Google Scholar 

  9. World Health Organization. The current evidence for the burden of group A streptococcal diseases (WHO, 2005).

  10. Carapetis, J. R., Steer, A. C., Mulholland, E. K. & Weber, M. The global burden of group A streptococcal diseases. Lancet Infect. Dis. 5, 685–694 (2005).

    PubMed  Google Scholar 

  11. Rodriguez-Iturbe, B. & Musser, J. M. The current state of post-streptococcal glomerulonephritis. J. Am. Soc. Nephrol. 19, 1855–1864 (2008).

    PubMed  Google Scholar 

  12. Kanjanabuch, T., Kittikowit, W. & Eiam-Ong, S. An update on acute postinfectious glomerulonephritis worldwide. Nat. Rev. Nephrol. 5, 259–269 (2009).

    PubMed  Google Scholar 

  13. World Health Organization. A review of the technical basis for the control of conditions associated with GAS infections (WHO, 2005).

  14. DeLeo, F. R., Otto, M., Kreiswirth, B. N. & Chambers, H. F. Community-associated methicillin-resistant Staphylococcus aureus. Lancet 375, 1557–1568 (2010).

    PubMed  PubMed Central  Google Scholar 

  15. Tattevin, P., Diep, B. A., Jula, M. & Perdreau-Remington, F. Long-term follow-up of methicillin-resistant Staphylococcus aureus molecular epidemiology after emergence of clone USA300 in San Francisco jail populations. J. Clin. Microbiol. 46, 4056–4057 (2008).

    PubMed  PubMed Central  Google Scholar 

  16. Tattevin, P., Diep, B. A., Jula, M. & Perdreau-Remington, F. Methicillin-resistant Staphylococcus aureus USA300 clone in long-term care facility. Emerg. Infect. Dis. 15, 953–955 (2009).

    PubMed  PubMed Central  Google Scholar 

  17. Nimmo, G. R. USA300 abroad: global spread of a virulent strain of community-associated methicillin-resistant Staphylococcus aureus. Clin. Microbiol. Infect. 18, 725–734 (2012).

    CAS  PubMed  Google Scholar 

  18. Pan, E. S. et al. Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails. Clin. Infect. Dis. 37, 1384–1388 (2003).

    PubMed  Google Scholar 

  19. King, M. D. et al. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann. Intern. Med. 144, 309–317 (2006).

    PubMed  Google Scholar 

  20. Chatterjee, S. S. & Otto, M. Improved understanding of factors driving methicillin-resistant Staphylococcus aureus epidemic waves. Clin. Epidemiol. 5, 205–217 (2013).

    PubMed  PubMed Central  Google Scholar 

  21. Nasr, S. et al. IgA dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy. Hum. Pathol. 34, 1235 (2003).

    CAS  PubMed  Google Scholar 

  22. Pola, E. et al. Onset of Berger disease after Staphylococcus aureus infection: septic arthritis after anterior cruciate ligament reconstruction. Arthroscopy 19, E29 (2003).

    PubMed  Google Scholar 

  23. Satoskar, A. A. et al. Staphylococcus infection-associated glomerulonephritis mimicking IgA nephropathy. Clin. J. Am. Soc. Nephrol. 1, 1179–1186 (2006).

    PubMed  Google Scholar 

  24. Haas, M., Racusen, L. C. & Bagnasco, S. M. IgA-dominant postinfectious glomerulonephritis: a report of 13 cases with common ultrastructural features. Hum. Pathol. 39, 1309–1316 (2008).

    CAS  PubMed  Google Scholar 

  25. Worawichawong, S. et al. Immunoglobulin A-dominant postinfectious glomerulonephritis: frequent occurrence in nondiabetic patients with Staphylococcus aureus infection. Hum. Pathol. 42, 279–284 (2011).

    CAS  PubMed  Google Scholar 

  26. Satoskar, A. A. et al. Staphylococcus infection-associated GN — spectrum of IgA staining and prevalence of ANCA in a single-center cohort. Clin. J. Am. Soc. Nephrol. 12, 39–49 (2017).

    CAS  PubMed  Google Scholar 

  27. Jackson, K. A. et al. Invasive methicillin-resistant staphylococcus aureus infections among persons who inject drugs — six sites, 2005–2016. MMWR Morb. Mortal. Wkly Rep. 67, 625–628 (2018).

    PubMed  PubMed Central  Google Scholar 

  28. Vosti, K. L., Johnson, R. H. & Dillon, M. F. Further characterization of purified fractions of M protein from a strain of group A, type 12 streptococcus. J. Immunol. 107, 104–114 (1971).

    CAS  PubMed  Google Scholar 

  29. Nordstrand, A., McShan, W. M., Ferretti, J. J., Holm, S. E. & Norgren, M. Allele substitution of the streptokinase gene reduces the nephritogenic capacity of group A streptococcal strain NZ131. Infect. Immun. 68, 1019–1025 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ohkuni, H. et al. Immunological studies of post-streptococcal sequelae: serological studies with an extracellular protein associated with nephritogenic streptococci. Clin. Exp. Immunol. 54, 185–193 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Anthony, B. F., Kaplan, E. L., Wannamaker, L. W., Briese, F. W. & Chapman, S. S. Attack rates of acute nephritis after type 49 streptococcal infection of the skin and of the respiratory tract. J. Clin. Invest. 48, 1697–1704 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Rodriguez-Iturbe, B., Castillo, L., Valbuena, R. & Cuenca, L. Attack rate of poststreptococcal nephritis in families: a prospective study. Lancet 317, 401–403 (1981).

    Google Scholar 

  33. Poon-King, T. et al. Recurrent epidemic nephritis in South Trinidad. N. Engl. J. Med. 277, 728 (1967).

    CAS  PubMed  Google Scholar 

  34. Fish, A. J., Herdman, R. C., Michael, A. F., Pickering, R. J. & Good, R. A. Epidemic acute glomerulonephritis associated with type 49 streptococcal pyoderma. II. Correlative study of light, immunofluorescent and electron microscopic findings. Am. J. Med. 48, 28–39 (1970).

    CAS  PubMed  Google Scholar 

  35. Rodriguez-Iturbe, B. Epidemic post-streptococcal glomerulonephritis. Kidney Int. 25, 129–136 (1984).

    CAS  PubMed  Google Scholar 

  36. Rodriguez-Iturbe, B. et al. Epidemic glomerulonephritis in Maracaibo: evidence for progression to chronicity. Clin. Nephrol. 5, 197 (1976).

    CAS  PubMed  Google Scholar 

  37. Drachman, R., Aladjem, M. & Vardy, P. A. Natural-history of an acute glomerulonephritis epidemic in children — an 11-year to 12-year follow-up. Isr. J. Med. Sci. 18, 603–607 (1982).

    CAS  PubMed  Google Scholar 

  38. Mori, K., Ito, Y., Kamikawaji, N. & Sasazuki, T. Elevated IgG titer against the C region of streptococcal M protein and its immunodeterminants in patients with poststreptococcal acute glomerulonephritis. J. Pediatr. 131, 293–299 (1997).

    CAS  PubMed  Google Scholar 

  39. Perlman, L. V., Herdman, R. C., Kleinman, H. & Vernier, R. L. Poststreptococcal glomerulonephritis. A ten-year follow-up of an epidemic. JAMA 194, 63–70 (1965).

    CAS  PubMed  Google Scholar 

  40. VanDeVoorde, R. G. 3rd Acute poststreptococcal glomerulonephritis: the most common acute glomerulonephritis. Pediatr. Rev. 36, 3–12 (2015).

    PubMed  Google Scholar 

  41. Vogel, A. M. et al. Post-streptococcal glomerulonephritis: some reduction in a disease of disparities. J. Paediatr. Child Health 55, 652–658 (2019).

    PubMed  Google Scholar 

  42. Ramanathan, G. et al. Analysis of clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in adult indigenous people of the Northern Territory of Australia. Nephrology 22, 403–411 (2017).

    CAS  PubMed  Google Scholar 

  43. Coppo, R., Gianoglio, B., Porcellini, M. G. & Maringhini, S. Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal Immunopathology of the Italian Society of Nephrology. Nephrol. Dial. Transplant. 13, 293–297 (1998).

    CAS  PubMed  Google Scholar 

  44. Shulman, S. T. et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 55, 1279–1282 (2012).

    CAS  PubMed  Google Scholar 

  45. Bisno, A. L. et al. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Clin. Infect. Dis. 35, 113–125 (2002).

    PubMed  Google Scholar 

  46. Parks, T., Smeesters, P. R., Curtis, N. & Steer, A. C. ASO titer or not? When to use streptococcal serology: a guide for clinicians. Eur. J. Clin. Microbiol. Infect. Dis. 34, 845–849 (2015).

    CAS  PubMed  Google Scholar 

  47. Nasr, S. H. et al. Postinfectious glomerulonephritis in the elderly. J. Am. Soc. Nephrol. 22, 187–195 (2011).

    PubMed  Google Scholar 

  48. Mazzucco, G. et al. Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. Am. J. Kidney Dis. 39, 713–720 (2002).

    PubMed  Google Scholar 

  49. Lien, J. W., Mathew, T. H. & Meadows, R. Acute post-streptococcal glomerulonephritis in adults: a long-term study. Q. J. Med. 48, 99–111 (1979).

    CAS  PubMed  Google Scholar 

  50. Gunasekaran, K., Krishnamurthy, S., Mahadevan, S., Harish, B. N. & Kumar, A. P. Clinical characteristics and outcome of post-infectious glomerulonephritis in children in Southern India: a prospective study. Indian J. Pediatr. 82, 896–903 (2015).

    PubMed  Google Scholar 

  51. Rodriguez-Iturbe, B. et al. Characterization of the glomerular antibody in acute poststreptococcal glomerulonephritis. Ann. Intern. Med. 92, 478 (1980).

    CAS  PubMed  Google Scholar 

  52. Parikh, S. V., Haddad, N. & Hebert, L. A. in Comprehensive Clinical Nephrology 5th edn Ch. 80 (eds Johnson, R., Feehally, J. & Floege, J.) (Saunders, 2014).

  53. Pavelsky, P. M. Renal replacement therapy in AKI. Adv. Chronic Kidney Dis. 20, 76–84 (2013).

    Google Scholar 

  54. Roy, S. 3rd, Murphy, W. M. & Arant, B. S. Jr Poststreptococcal crescenteric glomerulonephritis in children: comparison of quintuple therapy versus supportive care. J. Pediatr. 98, 403–410 (1981).

    PubMed  Google Scholar 

  55. Melby, P. C. et al. Poststreptococcal glomerulonephritis in the elderly. Report of a case and review of the literature. Am. J. Nephrol. 7, 235–240 (1987).

    CAS  PubMed  Google Scholar 

  56. Wong, W., Morris, M. C. & Zwi, J. Outcome of severe acute post-streptococcal glomerulonephritis in New Zealand children. Pediatr. Nephrol. 24, 1021–1026 (2009).

    PubMed  Google Scholar 

  57. Zent, R. et al. Crescentic nephritis at Groote Schuur Hospital, South Africa—not a benign disease. Clin. Nephrol. 42, 22–29 (1994).

    CAS  PubMed  Google Scholar 

  58. Clark, G. et al. Poststreptococcal glomerulonephritis in children: clinicopathological correlations and long-term prognosis. Pediatr. Nephrol. 2, 381–388 (1998).

    Google Scholar 

  59. Potter, E. V. et al. Twelve to seventeen-year follow-up of patients with poststreptococcal acute glomerulonephritis in Trinidad. N. Engl. J. Med. 307, 725–729 (1982).

    CAS  PubMed  Google Scholar 

  60. Baldwin, D. S. Poststreptococcal glomerulonephritis. A progressive disease? Am. J. Med. 62, 1–11 (1977).

    CAS  PubMed  Google Scholar 

  61. Buzio, C. et al. Significance of albuminuria in the follow-up of acute poststreptococcal glomerulonephritis. Clin. Nephrol. 41, 259–264 (1994).

    CAS  PubMed  Google Scholar 

  62. Vogl, W. et al. Long-term prognosis for endocapillary glomerulonephritis of poststreptococcal type in children and adults. Nephron 44, 58–65 (1986).

    CAS  PubMed  Google Scholar 

  63. Spector, D. A., Millan, J., Zauber, N. & Burton, J. Glomerulonephritis and Staphylococcus aureus infections. Clin. Nephrol. 14, 256 (1980).

    CAS  PubMed  Google Scholar 

  64. Danovitch, G. M., Nord, E. P., Barki, Y. & Krugliak, L. Staphylococcal lung abscess and acute glomerulonephritis. Isr. J. Med. Sci. 15, 840–843 (1979).

    CAS  PubMed  Google Scholar 

  65. Sato, M., Nakazoro, H. & Ofuji, T. The pathogenetic role of Staphylococcus aureus in primary human glomerulonephritis. Clin. Nephrol. 11, 190–195 (1979).

    CAS  PubMed  Google Scholar 

  66. Maher, E. R., Hamilton, D. V., Thiru, S. & Wheatley, T. Acute renal failure due to glomerulonephritis associated with staphylococcal infection. Postgrad. Med. J. 60, 433–434 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Salyer, W. R. & Salyer, D. C. Unilateral glomerulonephritis. J. Pathol. 113, 247–251 (1974).

    CAS  PubMed  Google Scholar 

  68. Koyama, A. et al. Glomerulonephritis associated with MRSA infection: a possible role of bacterial superantigen. Kidney Int. 47, 207–216 (1995).

    CAS  PubMed  Google Scholar 

  69. Yoh, K. et al. A case of superantigen-related glomerulonephritis after methicillin-resistant Staphylococcus aureus (MRSA) infection. Clin. Nephrol. 48, 311–316 (1997).

    CAS  PubMed  Google Scholar 

  70. Kobayashi, M. & Koyama, A. Methicillin-resistant Staphylococcus aureus (MRSA) infection in glomerulonephritis—a novel hazard emerging on the horizon. Nephrol. Dial Transplant. 13, 2999–3001 (1998).

    CAS  PubMed  Google Scholar 

  71. Hirayama, K. et al. Henoch-Schonlein purpura nephritis associated with methicillin-resistant Staphylococcus aureus infection. Nephrol. Dial Transplant. 13, 2703–2704 (1998).

    CAS  PubMed  Google Scholar 

  72. Yoh, K. et al. Cytokines and T cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection. Nephrol. Dial Transplant. 15, 1170–1174 (2000).

    CAS  PubMed  Google Scholar 

  73. Yamashita, Y. et al. Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure. Intern. Med. 40, 424–427 (2001).

    CAS  PubMed  Google Scholar 

  74. Satoskar, A. A. et al. Henoch-Schönlein purpura-like presentation in IgA-dominant Staphylococcus infection-associated glomerulonephritis-a diagnostic pitfall. Clin. Nephrol. 79, 302–312 (2013).

    CAS  PubMed  Google Scholar 

  75. Montoliu, J. et al. Henoch-Schonlein purpura complicating staphylococcal endocarditis in a heroin addict. Am. J. Nephrol. 7, 137–139 (1987).

    CAS  PubMed  Google Scholar 

  76. Kitamura, T., Nakase, H. & Iizuka, H. Henoch-Schonlein purpura after postoperative Staphylococcus aureus infection with hepatic IgA nephropathy. J. Nephrol. 19, 687–690 (2006).

    PubMed  Google Scholar 

  77. Hemminger, J. A. & Satoskar, A. A. in Bacterial Infections and the Kidney Ch. 2 (eds Satoskar, A. A. & Nadasdy, T.) 37–61 (Springer, 2017).

  78. Nasr, S. H., Radhakrishnan, J. & D’Agati, V. D. Bacterial infection-related glomerulonephritis in adults. Kidney Int. 83, 792–803 (2013).

    CAS  PubMed  Google Scholar 

  79. Bu, R. et al. Clinicopathologic features of IgA-dominant infection-associated glomerulonephritis: a pooled analysis of 78 cases. Am. J. Nephrol. 41, 98–106 (2015).

    CAS  PubMed  Google Scholar 

  80. Kimata, T., Tsuji, S., Yoshimura, K., Tsukaguchi, H. & Kaneko, K. Methicillin-resistant Staphylococcus aureus-related glomerulonephritis in a child. Pediatr. Nephrol. 27, 2149–2152 (2012).

    PubMed  Google Scholar 

  81. Peacock, S. J., de Silva, I. & Lowy, F. D. What determines nasal carriage of Staphylococcus aureus? Trends Microbiol. 9, 605–610 (2001).

    CAS  PubMed  Google Scholar 

  82. Von Eiff, C., Becker, K., Machka, K., Stammer, H. & Peters, G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study group. N. Engl. J. Med. 344, 11–16 (2001).

    Google Scholar 

  83. Wertheim, H. F. et al. Risk and outcome of nosocomial Staphylococcus aureus bacteremia in nasal carriers versus non-carriers. Lancet 364, 703–705 (2004).

    PubMed  Google Scholar 

  84. Foster, T. J. Colonization and infection of the human host by staphylococci: adhesion, survival and immune evasion. Vet. Dermatol. 20, 456–470 (2009).

    PubMed  Google Scholar 

  85. Boils, C. L., Nasr, S. H., Walker, P. D., Couser, W. G. & Larsen, C. P. Update on endocarditis-associated glomerulonephritis. Kidney Int. 87, 1241–1249 (2015).

    PubMed  PubMed Central  Google Scholar 

  86. Hemminger, J. et al. Acute glomerulonephritis with large confluent IgA-dominant deposits associated with liver cirrhosis. PLOS ONE 13, e0193274 (2018).

    PubMed  PubMed Central  Google Scholar 

  87. Takada, D. et al. IgA nephropathy featuring massive wire loop-like deposits in two patients with alcoholic cirrhosis. BMC Nephrol. 18, 362 (2017).

    PubMed  PubMed Central  Google Scholar 

  88. Nagaba, Y. et al. Effective antibiotic treatment of methicillin-resistant Staphylococcus aureus-associated glomerulonephritis. Nephron 92, 297–303 (2002).

    CAS  PubMed  Google Scholar 

  89. Riley, A. M., Wall, B. M. & Cooke, C. R. Favorable outcome after aggressive treatment of infection in a diabetic patient with MRSA-related IgA nephropathy. Am. J. Med. Sci. 337, 221–223 (2009).

    PubMed  Google Scholar 

  90. Kapadia, A. S., Panda, M. & Fogo, A. B. Postinfectious glomerulonephritis: is there a role for steroids? Indian J. Nephrol. 21, 116–119 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Zeledon, J. I. et al. Glomerulonephritis causing acute renal failure during the course of bacterial infections. Histological varieties, potential pathogenetic pathways and treatment. Int. Urol. Nephrol. 40, 461–470 (2008).

    CAS  PubMed  Google Scholar 

  92. Montseny, J. J. et al. The current spectrum of infectious glomerulonephritis. Experience with 76 patients and review of the literature. Medicine 74, 63–73 (1995).

    CAS  PubMed  Google Scholar 

  93. Wang, S. et al. Clinical, pathological, and prognostic characteristics of glomerulonephritis related to staphylococcal infection. Medicine 95, e3386 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Ebright, J. R. & Komorowski, R. Gonococcal endocarditis associated with immune complex glomerulonephritis. Am. J. Med. 68, 793–796 (1980).

    CAS  PubMed  Google Scholar 

  95. Bookman, I., Scholey, J. W., Jassal, S. V., Lajoie, G. & Herzenberg, A. M. Necrotizing glomerulonephritis caused by Bartonella henselae endocarditis. Am. J. Kidney Dis. 43, e25–e30 (2004).

    PubMed  Google Scholar 

  96. Elzouki, A. Y., Akthar, M. & Mirza, K. Brucella endocarditis associated with glomerulonephritis and renal vasculitis. Pediatr. Nephrol. 10, 748–751 (1996).

    CAS  PubMed  Google Scholar 

  97. Bell, E. T. Glomerular lesions associated with endocarditis. Am. J. Pathol. 8, 639–664 (1932).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Cordeiro, A., Costa, H. & Laginha, F. Immunologic phase of subacute bacterial endocarditis. A new concept and general considerations. Am. J. Cardiol. 16, 477–481 (1965).

    CAS  PubMed  Google Scholar 

  99. Bayer, A. S. & Theofilopoulos, A. N. Immunopathogenetic aspects of infective endocarditis. Chest 97, 204–212 (1990).

    CAS  PubMed  Google Scholar 

  100. Gutman, R. A., Striker, G. E., Gilliland, B. C. & Cutler, R. E. The immune complex glomerulonephritis of bacterial endocarditis. Medicine 51, 1–25 (1972).

    CAS  PubMed  Google Scholar 

  101. Morel-Maroger, L., Sraer, J. D., Herreman, G. & Godeau, P. Kidney in subacute endocarditis. Pathological and immunofluorescence findings. Arch. Pathol. 94, 205–213 (1972).

    CAS  PubMed  Google Scholar 

  102. Agarwal, A. et al. Subacute bacterial endocarditis masquerading as type III essential mixed cryoglobulinemia. J. Am. Soc. Nephrol. 8, 1971–1976 (1997).

    CAS  PubMed  Google Scholar 

  103. Majumdar, A. et al. Renal pathological findings in infective endocarditis. Nephrol. Dial. Transplant. 15, 1782–1787 (2000).

    CAS  PubMed  Google Scholar 

  104. Eknoyan, G., Lister, B. J., Kim, H. S. & Greenberg, S. D. Renal complications of bacterial endocarditis. Am. J. Nephrol. 5, 457–469 (1985).

    CAS  PubMed  Google Scholar 

  105. Fatima, S. et al. Epidemiology of infective endocarditis in rural upstate New York, 2011–2016. J. Clin. Med. Res. 9, 754–758 (2017).

    PubMed  PubMed Central  Google Scholar 

  106. Fleischauer, A. T., Ruhl, L., Rhea, S. & Barnes, E. Hospitalizations for endocarditis and associated health care costs among persons with diagnosed drug dependence — North Carolina, 2010–2015. MMWR Morb. Mortal. Wkly Rep. 66, 569–573 (2017).

    PubMed  PubMed Central  Google Scholar 

  107. Shiffman, M. L. The next wave of hepatitis C virus: the epidemic of intravenous drug use. Liver. Int. 38, (Suppl. 1), 34–39 (2018).

    PubMed  Google Scholar 

  108. Bassetti, S. & Battegay, M. Staphylococcus aureus infections in injection drug users: risk factors and prevention strategies. Infection 3, 163–169 (2003).

    Google Scholar 

  109. Chirinos, J. A. et al. Endocarditis associated with antineutrophil cytoplasmic antibodies: a case report and review of the literature. Clin. Rheumatol. 26, 590–595 (2007).

    PubMed  Google Scholar 

  110. Tiliakos, A. M. & Tiliakos, N. A. Dual ANCA positivity in subacute bacterial endocarditis. J. Clin. Rheumatol. 14, 38–40 (2008).

    PubMed  Google Scholar 

  111. Uh, M., McCormick, I. A. & Kelsall, J. T. Positive cytoplasmic antineutrophil cytoplasmic antigen with PR3 specificity glomerulonephritis in a patient with subacute bacterial endocarditis. J. Rheumatol. 38, 1527–1528 (2011).

    PubMed  Google Scholar 

  112. Langlois, V. et al. Antineutrophil cytoplasmic antibodies associated with infective endocarditis. Medicine 95, e2564 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Bor, D. H., Woolhandler, S., Nardin, R., Brusch, J. & Himmelstein, D. U. Infective endocarditis in the U.S., 1998–2009: a nationwide study. PLOS ONE 8, e60033 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Johnson, J. A., Boyce, T. G., Cetta, F., Steckelberg, J. M. & Johnson, J. N. Infective endocarditis in the pediatric patient: a 60-year single-institution review. Mayo Clinic Proc. 87, 629–635 (2012).

    Google Scholar 

  115. Fournier, P. E. et al. Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases. Clin. Infect. Dis. 51, 131–140 (2010).

    CAS  PubMed  Google Scholar 

  116. Hoen, B. et al. Infective endocarditis in patients with negative blood cultures: analysis of 88 cases from a one-year nationwide survey in France. Clin. Infect. Dis. 20, 501–506 (1995).

    CAS  PubMed  Google Scholar 

  117. Yates, M. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann. Rheum. Dis. 75, 1583–1594 (2016).

    CAS  PubMed  Google Scholar 

  118. Baddour, L. et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications. Circulation 132, 1435–1486 (2015).

    CAS  PubMed  Google Scholar 

  119. Haas, M. in Heptinstall’s Pathology of the Kidney 7th edn Vol. 1 Ch. 12 (eds Jennette, J. C. et al.) 463–524 (Wolters Kluwer, 2014).

  120. Glassock, R. J. et al. Staphylococcus-related glomerulonephritis and poststreptococcal glomerulonephritis: why defining “post” is important in understanding and treating infection-related glomerulonephritis. Am. J. Kidney Dis. 65, 826–832 (2015).

    PubMed  Google Scholar 

  121. Nadasdy, T. & Hebert, L. A. Infection-related glomerulonephritis: understanding mechanisms. Semin. Nephrol. 31, 369–375 (2011).

    CAS  PubMed  Google Scholar 

  122. Nasr, S. H. & D’Agati, V. D. IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease. Nephron Clin. Pract. 119, c18–c26 (2011).

    CAS  PubMed  Google Scholar 

  123. Nast, C. C. Infection-related glomerulonephritis: changing demographics and outcomes. Adv. Chronic Kidney Dis. 19, 68–75 (2012).

    PubMed  Google Scholar 

  124. Tadema, H., Heeringa, P. & Kallenberg, C. G. Bacterial infections in Wegener’s granulomatosis: mechanisms potentially involved in autoimmune pathogenesis. Curr. Opin. Rheumatol. 23, 366–371 (2011).

    CAS  PubMed  Google Scholar 

  125. Salmela, A. et al. Chronic nasal Staphylococcus aureus carriage identifies a subset of newly diagnosed granulomatosis with polyangiitis with high relapse rate. Rheumatology 56, 965–972 (2017).

    CAS  PubMed  Google Scholar 

  126. Oliveira, D. B. G. Linked help from bacterial proteins drives autoantibody production in small vessel vasculitis. Med. Hypotheses 112, 24–26 (2018).

    CAS  PubMed  Google Scholar 

  127. Sethi, S. et al. Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int. 83, 293–299 (2012).

    PubMed  PubMed Central  Google Scholar 

  128. Smith, R. J. H. et al. C3 glomerulopathy — understanding a rare complement-driven renal disease. Nat. Rev. Nephrol. 15, 129–143 (2019).

    PubMed  PubMed Central  Google Scholar 

  129. Ozlok, A. & Yildiz, A. Hepatitis C virus associated glomerulopathies. World J. Gastroenterol. 20, 7544–7554 (2014).

    Google Scholar 

  130. Sinniah, R. Occurrence of mesangial IgA and IgM deposits in a control necropsy population. J. Clin. Pathol. 36, 276–279 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Ji, S. et al. The fate of glomerular mesangial igA deposition in the donated kidney after allograft transplantation. Clin. Transplant. 18, 536–540 (2004).

    PubMed  Google Scholar 

  132. Suzuki, K. et al. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 63, 2286–2294 (2003).

    PubMed  Google Scholar 

  133. Lange, K., Seligson, G. & Cronin, W. Evidence for the in situ origin of poststreptococcal glomerulonephritis: glomerular localization of endostreptosin and the clinical significance of the subsequent antibody response. Clin. Nephrol. 19, 3–10 (1983).

    CAS  PubMed  Google Scholar 

  134. Vogt, A., Batsford, S., Rodriguez-Iturbe, B. & Garcia, R. Cationic antigens in poststreptococcal glomerulonephritis. Clin. Nephrol. 20, 271–279 (1983).

    CAS  PubMed  Google Scholar 

  135. Yoshizawa, N. et al. Role of streptococcal antigen in the pathogenesis of acute post-streptococcal glomerulonephritis, characterization of the antigen and a proposed mechanism for the disease. J. Immunol. 148, 3110 (1992).

    CAS  PubMed  Google Scholar 

  136. Froude, J., Zabriskie, J. B., Buchen, D., Rzucidlo, E. & Kakani, R. Immunochemical studies of nephritis strain associated protein (Nsap) and streptokinase (Ska). Zentralbl. Bakteriol. 22, S203–S205 (1992).

    Google Scholar 

  137. Kefalides, N. A. et al. Antibodies to basement membrane collagen and to laminin are present in sera from patients with poststreptococcal glomerulonephritis. J. Exp. Med. 163, 588–602 (1986).

    CAS  PubMed  Google Scholar 

  138. Komaru, Y., Ishioka, K., Oda, T., Ohtake, T. & Kobayashi, S. Nephritis-associated plasmin receptor (NAPlr) positive glomerulonephritis caused by Aggregatibacter actinomycetemcomitans bacteremia: a case report. Clin. Nephrol. 90, 155–160 (2018).

    CAS  PubMed  Google Scholar 

  139. Oda, T. et al. The role of nephritis-associated plasmin receptor (NAPlr) in glomerulonephritis associated with streptococcal infection. J. Biomed. Biotechnol. 2012, 417675 (2012).

    PubMed  PubMed Central  Google Scholar 

  140. Batsford, S. R., Mezzano, S., Mihatsch, M., Schiltz, E. & Rodriguez-Iturbe, B. Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Kidney Int. 68, 1120–1129 (2005).

    CAS  PubMed  Google Scholar 

  141. Schick, B. in Scharlach (eds Escherich, T., Shick, B.) 151 (A. Hölder, 1912).

  142. Okamoto, S. & Nagase, S. Pathogenic mechanisms of invasive group A Streptococcus infections by influenza virus-group A Streptococcus superinfection. Microbiol. Immunol. 62, 141–149 (2018).

    CAS  PubMed  Google Scholar 

  143. Pla, E. et al. Onset of Berger’s disease after Staphylococcus aureus infection: septic arthritis after anterior cruciate ligament reconstruction. Arthroscopy 19, 4 (2003).

    Google Scholar 

  144. Delves, P. J., Martin, S. J., Burton, D. R. & Roitt, I. M. Roitt’s Essential Immunology 11th edn (John Wiley & Sons, 2011).

  145. Safi, R. et al. Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behçet’s disease. J. Dermatol. Sci. 92, 143–150 (2018).

    CAS  PubMed  Google Scholar 

  146. Skopelja-Gardner, S., Jones, J. D. & Rigby, W. F. C. “NETtling” the host: breaking of tolerance in chronic inflammation and chronic infection. J. Autoimmun. 88, 1–10 (2018).

    CAS  PubMed  Google Scholar 

  147. DeLorenze, G. N. et al. Polymorphisms in HLA class II genes are associated with susceptibility to Staphylococcus aureus infection in a white population. J. Infect. Dis. 213, 816–823 (2016).

    CAS  PubMed  Google Scholar 

  148. Kambham, N. & Troxell, M. in Bacterial Infections and the Kidney Ch. 3 (eds Satoskar, A. A. & Nadasdy, T.) 63–85 (Springer, 2017).

  149. Okada, M. et al. Central venous catheter infection-related glomerulonephritis under long-term parenteral nutrition: a report of two cases. BMC Res. Notes 9, 196 (2016).

    PubMed  PubMed Central  Google Scholar 

  150. Jeffres, M. N., Isakow, W., Doherty, J. A., Micek, S. T. & Kollef, M. H. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health-care associated methicillin-resistant Staphylococcus aureus pneumonia. Clin. Ther. 29, 1107–1115 (2007).

    CAS  PubMed  Google Scholar 

  151. Hernandez, F. J. et al. Non-invasive imaging of Staphylococcus infections with a nuclease-activated probe. Nat. Med. 20, 301–306 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Olson, M. E., Slater, S. R., Rupp, M. E. & Fey, P. D. Rifampicin enhances activity of daptomycin and vancomycin against both a polysaccharide intercellular adhesin (PIA)-dependent and -independent Staphylococcus epidermidis biofilm. J. Antimicrob. Chemother. 65, 2164–2171 (2010).

    CAS  PubMed  Google Scholar 

  153. Olson, M. E. et al. Staphylococcus epidermidis agr quorum-sensing system: signal identification, cross talk, and importance in colonization. J. Bacteriol. 196, 3482–3493 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA

    Anjali A. Satoskar & Tibor Nadasdy

  2. Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA

    Samir V. Parikh

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A.A.S. researched data for the article, made substantial contributions to discussions of the content and wrote, reviewed and edited the manuscript before submission. S.V.P. researched data for the article and wrote part of the manuscript. T.N. reviewed and edited the manuscript before submission.

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Glossary

Scabetic lesions

Contagious skin condition caused by mites, tiny insect-like parasites that infect the top layer of the skin.

Pyoderma

Bacterial skin infection with formation of skin pustules.

Acute nephritic syndrome

Syndrome characterized by abrupt onset oedema and dark ‘cola-coloured’ or ‘tea-coloured’ urine, with or without renal impairment and sub-nephrotic proteinuria.

Hypertensive urgency

Marked elevation of blood pressure without target organ damage, such as pulmonary oedema, cardiac ischaemia, neurological deficits or acute renal failure.

Anti-streptolysin O

Antibody targeted against the toxic Streptolysin O enzyme produced by Group A Streptococcus bacteria.

Superantigens

Class of antigens that binds directly to HLA molecules without internal processing of the antigenic peptide, resulting in non-specific activation of T lymphocytes and polyclonal T cell activation with massive cytokine release.

Pauci-immune staining pattern

Lack of or very few immune complex deposits.

Hyaline thrombi

Intracapillary proteinaceous globules resembling hyaline material.

Osler nodes

Painful red, raised lesions found on hands and feet, associated with a number of conditions including infective endocarditis, caused by immune complex deposition.

Janeway lesions

Non-tender, small erythematous or haemorrhagic macular or nodular lesions on the palms or soles only a few millimetres in diameter that are indicative of infective endocarditis (in contrast to Osler’s nodes, which are painful).

Splinter haemorrhages

Tiny red blood clots running vertically under the nails. These can be associated with multiple autoimmune conditions including infective endocarditis, scleroderma, systemic lupus erythematosus, rheumatoid arthritis and anti-phospholipid syndrome.

Valvular vegetations

Mass of fibrin, platelets, inflammatory cells and microcolonies of microorganisms collecting on heart valvular surfaces in infective endocarditis. Sterile vegetations may also occur (absence of microorganisms in them) in systemic lupus erythematosus.

Membranoproliferative GN

Glomerular inflammatory disease with hypercellularity in the expanded mesangium as well as in the intracapillary lumina, imparting a nodular–lobular appearance to the glomerulus. This can have many different aetiologies.

Serum cryoglobulins

Immune complexes that precipitate at temperatures below normal body temperature.

Cytokine storm

Secretion of large quantities of activating compounds (cytokines) due to a surge in activated immune cells, usually T lymphocytes.

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Satoskar, A.A., Parikh, S.V. & Nadasdy, T. Epidemiology, pathogenesis, treatment and outcomes of infection-associated glomerulonephritis. Nat Rev Nephrol 16, 32–50 (2020). https://doi.org/10.1038/s41581-019-0178-8

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