PDF herunterladen
Dialyse aktuell 2012; 16(9): 523-527
DOI: 10.1055/s-0032-1333551
Nephrologie
© Georg Thieme Verlag Stuttgart · New York

Glomerulonephritiden – Genetische Aspekte

Glomerulonephritis – Genetic Aspects
Christian Krebs
1   III. Medizinische Klinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf (Klinikdirektor: Prof. Dr. Rolf A. K. Stahl)
,
Ulf Panzer
1   III. Medizinische Klinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf (Klinikdirektor: Prof. Dr. Rolf A. K. Stahl)
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
02. Januar 2013 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Glomerulonephritiden zählen zu den häufigsten Ursachen für das Auftreten einer terminalen Niereninsuffizienz in der westlichen Welt. In den letzten Jahren konnten große Fortschritte im Verständnis der Ätiologie und Pathogenese dieser heterogenen, immunvermittelten Gruppe von Erkrankungen erzielt werden. Einem signifikanten Teil dieser Erkenntnisgewinne liegen genetische Untersuchungen zugrunde. Dieser Artikel fasst die wichtigsten genetischen Aspekte der IgA-Nephropathie, der membranösen Nephropathie, der FSGS und der Minimal-Change-Disease, der Anti-GBM-Nephritis, der ANCA-assozierten Glomerulonephritiden und der Lupusnephritis zusammen. Bislang haben diese Errungenschaften jedoch nur eine geringe Relevanz im klinischen Alltag erlangt. Es ist aber zu erwarten, dass ein besseres Verständnis einzelner Formen von Glomerulonephritiden in der Zukunft das therapeutische Repertoire bei deren Behandlung erweitert und gezieltere Therapieoptionen ermöglichen wird.

Glomerulonephritis as a disease category is one of the leading causes of end-stage renal disease in the Western world and is associated with significant morbidity and mortality. Glomerulonephritis represents a heterogeneous collection of disease entities. However, fundamental to most forms of glomerulonephritis is the immune-mediated renal damage. Some important advances, including a better understanding of genetic factors, have been achieved in the last few years and can serve as encouragement for further research in the field of glomerulonephritis. This review summarizes important genetic aspects in IgA nephropathy, membranous nephropathy, FSGS, minimal change disease, anti-GBM nephritis, ANCA-associated glomerulonephritis and lupus nephritis. We believe that this better understanding will lead to the development of new and more specific individual therapeutic strategies.

Key words

glomerulonephritis - genetic aspects - IgA nephropathy - membranous nephropathy - FSGS - minimal change disease - anti-GBM nephritis - ANCA-associated glomerulonephritis - lupus nephritis
 

  • Literatur

  • 1 Couser WG. Glomerulonephritis. Lancet 1999; 353: 1509-1515
    CrossrefGoogle Scholar
  • 2 Barratt J, Eitner F, Feehally J, Floege J. Immune complex formation in IgA nephropathy: a case of the 'right' antibodies in the 'wrong' place at the 'wrong' time?. Nephrol Dial Transplant 2009; 24: 3620-3623
    CrossrefGoogle Scholar
  • 3 Floege J. The pathogenesis of IgA nephropathy: what is new and how does it change therapeutic approaches?. Am J Kidney Dis 2011; 58: 992-1004
    CrossrefGoogle Scholar
  • 4 Glassock RJ. The pathogenesis of IgA nephropathy. Curr Opin Nephrol Hypertens 2011; 20: 153-160
    CrossrefGoogle Scholar
  • 5 Gharavi AG, Kiryluk K, Choi M et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 2011; 43: 321-327
    CrossrefGoogle Scholar
  • 6 Yamamoto R, Nagasawa Y, Shoji T et al. A candidate gene approach to genetic prognostic factors of IgA nephropathy--a result of Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgA Nephropathy (PREDICT-IgAN). Nephrol Dial Transplant 2009; 24: 3686-3694
    CrossrefGoogle Scholar
  • 7 Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet 2012;
    Google Scholar
  • 8 Beck Jr LH, Bonegio RG, Lambeau G et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361: 11-21
    CrossrefPubMedGoogle Scholar
  • 9 Hofstra JM, Beck Jr L, Beck DM et al. Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011; 6: 1286-1291
    CrossrefGoogle Scholar
  • 10 Qin W et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 2011; 22: 1137-1143
    CrossrefGoogle Scholar
  • 11 Stahl R, Hoxha E, Fechner K. PLA2R autoantibodies and recurrent membranous nephropathy after transplantation. N Engl J Med 2010; 363: 496-498
    CrossrefPubMedGoogle Scholar
  • 12 Stanescu HC, Arcos-Burgos M, Medlar A et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 2011; 364: 616-626
    CrossrefGoogle Scholar
  • 13 Cattran DC, Reich HN, Beanlands HJ et al. Genes, Gender and Glomerulonephritis Group. The impact of sex in primary glomerulonephritis. Nephrol Dial Transplant 2008; 23: 2247-2253
    CrossrefGoogle Scholar
  • 14 Piscione TD, Licht C. Genetics of proteinuria: an overview of gene mutations associated with nonsyndromic proteinuric glomerulopathies. Adv Chron Kidney Dis 2011; 18: 273-289
    CrossrefGoogle Scholar
  • 15 Jungraithmayr TC, Hofer K, Cochat P et al. Screening for NPHS2 mutations may help predict FSGS recurrence after transplantation. J Am Soc Nephrol 2011; 22: 579-585
    CrossrefGoogle Scholar
  • 16 Santín S, García-Maset R, Ruíz P et al. FSGS Spanish Study Group. Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis. Kidney Int 2009; 76: 1268-1276
    CrossrefGoogle Scholar
  • 17 Santín S, Tazón-Vega B, Silva I et al. FSGS Spanish Study Group. Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2011; 6: 344-354
    CrossrefGoogle Scholar
  • 18 Nachman PH, Glassock RJ. Glomerular, vascular, and tululointerstitial diseases. NephSAP 2012; 11: 140-217
    Google Scholar
  • 19 Genovese G, Friedman DJ, Ross MD et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329: 841-845
    CrossrefPubMedGoogle Scholar
  • 20 Shimada M, Araya C, Rivard C et al. Minimal change disease: a “two-hit” podocyte immune disorder?. Pediatr Nephrol 2011; 26: 645-649
    CrossrefGoogle Scholar
  • 21 Wei C, Reiser J. Minimal change disease as a modifiable podocyte paracrine disorder. Nephrol Dial Transplant 2011; 26: 1776-1777
    CrossrefGoogle Scholar
  • 22 Zhu L, Yu L, Wang CD et al. Genetic effect of the NPHS2 gene variants on proteinuria in minimal change disease and immunoglobulin A nephropathy. Nephrology (Carlton) 2009; 14: 728-734
    CrossrefGoogle Scholar
  • 23 Liu Z, Blattner SM, Tu Y et al. Alpha-actinin-4 and CLP36 protein deficiencies contribute to podocyte defects in multiple human glomerulopathies. J Biol Chem 2011; 286: 30795-30805
    CrossrefGoogle Scholar
  • 24 Borza DB. Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis. Nephron Exp Nephrol 2007; 106
    Google Scholar
  • 25 Cui Z et al. Anti-glomerular basement membrane disease: outcomes of different therapeutic regimens in a large single-center Chinese cohort study. Medicine (Baltimore) 2011; 90: 303-311
    Google Scholar
  • 26 Fisher M, Pusey CD, Vaughan RW, Rees AJ. Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes. Kidney Int 1997; 51: 222-229
    CrossrefGoogle Scholar
  • 27 Kitagawa W et al. The HLA-DRB1*1501 allele is prevalent among Japanese patients with anti-glomerular basement membrane antibody-mediated disease. Nephrol Dial Transplant 2008; 23: 3126-3129
    CrossrefGoogle Scholar
  • 28 Zhou XJ, Lv JC, Bu DF et al. Copy number variation of FCGR3A rather than FCGR3B and FCGR2B is associated with susceptibility to anti-GBM disease. Int Immunol 2010; 22: 45-51
    CrossrefGoogle Scholar
  • 29 Zhou XJ, Lv JC, Yu L et al. FCGR2B gene polymorphism rather than FCGR2A, FCGR3A and FCGR3B is associated with anti-GBM disease in Chinese. Nephrol Dial Transplant 2010; 25: 97-101
    CrossrefGoogle Scholar
  • 30 Willcocks LC, Lyons PA, Rees AJ, Smith KG. The contribution of genetic variation and infection to the pathogenesis of ANCA-associated systemic vasculitis. Arthritis Res Ther 2010; 12: 202-202
    CrossrefGoogle Scholar
  • 31 Carr EJ, Niederer HA, Williams J et al. Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis. BMC Med Genet 2009; 10: 121-121
    CrossrefGoogle Scholar
  • 32 Jagiello P, Aries P, Arning L et al. The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. Arthritis Rheum 2005; 52: 4039-4043
    CrossrefGoogle Scholar
  • 33 Slot MC, Sokolowska MG, Savelkouls KG et al. Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis. Clin Immunol 2008; 128: 39-45
    CrossrefGoogle Scholar
  • 34 Ligers A, Teleshova N, Masterman T et al. CTLA-4 gene expression is influenced by promoter and exon 1 polymorphisms. Genes Immun 2001; 2: 145-152
    CrossrefGoogle Scholar
  • 35 Cao Y, Schmitz JL, Yang J et al. DRB1*15 allele is a risk factor for PR3-ANCA disease in African Americans. J Am Soc Nephrol 2011; 22: 1161-1167
    CrossrefGoogle Scholar
  • 36 Hogan SL, Falk RJ, Chin H et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med 2005; 143: 621-631
    CrossrefGoogle Scholar
  • 37 Liu Z, Davidson A. Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med 2012; 18: 871-882
    CrossrefGoogle Scholar
  • 38 Dooley MA, Hogan S, Jennette C, Falk R. Cyclophosphamide therapy for lupus nephritis: poor renal survival in black Americans. Glomerular Disease Collaborative Network. Kidney Int 1997; 51: 1188-1195
    CrossrefGoogle Scholar
  • 39 Gibson KL, Gipson DS, Massengill SA et al. Predictors of relapse and end stage kidney disease in proliferative lupus nephritis: focus on children, adolescents, and young adults. Clin J Am Soc Nephrol 2009; 4: 1962-1967
    CrossrefGoogle Scholar
  • 40 Hiraki LT, Lu B, Alexander SR et al. End-stage renal disease due to lupus nephritis among children in the US, 1995-2006. Arthritis Rheum 2011; 63: 1988-1997
    CrossrefGoogle Scholar
  • 41 Ramos PS, Brown EE, Kimberly RP, Langefeld CD. Genetic factors predisposing to systemic lupus erythematosus and lupus nephritis. Semin Nephrol 2010; 30: 164-176
    CrossrefGoogle Scholar
  • 42 Sanchez E, Nadig A, Richardson BC et al. BIOLUPUS and GENLES. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis 2011; 70: 1752-1757
    CrossrefGoogle Scholar
  • 43 Córdova EJ, Velázquez-Cruz R, Centeno F et al. The NRF2 gene variant, -653G/A, is associated with nephritis in childhood-onset systemic lupus erythematosus. Lupus 2010; 19: 1237-1742
    CrossrefGoogle Scholar
  • 44 Freedman BI, Edberg JC, Comeau ME et al. PROFILE Study Group. The non-muscle Myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans. Am J Nephrol 2010; 32: 66-72
    CrossrefGoogle Scholar
  • 45 Qin L, Lv J, Zhou X et al. Association of IRF5 gene polymorphisms and lupus nephritis in a Chinese population. Nephrology (Carlton) 2010; 15: 710-713
    CrossrefGoogle Scholar
  • 46 Zhao J, Wu H, Khosravi M et al. Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. PLoS Genet 2011; 7
    Google Scholar