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Nephrotisches Syndrom

Minimal-Change-Glomerulopathie und Fokal-Segmentale Glomerulosklerose

Nephrotic Syndrome

Minimal Change Disease and Focal Segmental Glomerulosclerosis

Zusammenfassung

Minimal-Change-Nephropathie („minimal change disease“, MCD) und fokal-segmentale Glomerulosklerose (FSGS) sind histopathologisch definierte Podozytopathien, die sich klinisch als nephrotisches Syndrom manifestieren. Während die MCD vor allem bei Kindern auftritt und meist benigne verläuft, zeigt die FSGS eine höhere Prävalenz bei Erwachsenen und oftmals einen gleichzeitigen Verlust der Nierenfunktion bis hin zur terminalen Niereninsuffizienz. Primäre und sekundäre FSGS sind hinsichtlich Ätiologie, Klinik und Therapieoptionen erheblich differierende Erkrankungen [1, 2]. Bezüglich der Pathogenese von MCD und FSGS haben sich in den letzten Jahren neue Hypothesen etabliert, welche in die klinische Diagnostik noch nicht Einzug gehalten haben, jedoch langfristig zu einem besseren Verständnis der Erkrankungen und möglicherweise zu neuen Therapieansätzen beitragen könnten.

Abstract

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are histopathologically defined podocytopathies which are clinically manifested as nephrotic syndrome. While MCD is most commonly seen in children and usually exhibits a benign clinical course, FSGS has a higher prevalence in adult patients and often leads to a deterioration of renal function possibly resulting in end-stage renal disease. Primary and secondary FSGS differ substantially concerning etiology, clinical presentation and therapy [1, 2]. New hypotheses have been established in recent years regarding the pathogenesis of MCD and FSGS but have not yet been incorporated into clinical diagnostics. However, these insights might translate into a better understanding of these diseases in the long run and possibly contribute to new therapeutic approaches.

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Literatur

  1. 1.

    Hogan J, Radhakrishnan J (2013) The treatment of minimal change disease in adults. J Am Soc Nephrol 24(5):702–711

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    D’Agati V, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365(25):2398–2411

    Article  PubMed  Google Scholar 

  3. 3.

    Orth SR, Ritz E (1998) The Nephrotic Syndrome. N Engl J Med 338(17):1202–1211

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Wiggins RC (2007) The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 71(12):1205–1214

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Kang HG, Cheong H (2015) Il. Nephrotic syndrome: what’s new, what’s hot? Korean J Pediatr 58(8):275–282

    PubMed Central  Article  PubMed  Google Scholar 

  6. 6.

    Meyrier AY (2009) Treatment of focal segmental glomerulosclerosis with immunophilin modulation: when did we stop thinking about pathogenesis? Kidney Int 76(5):487–491

    Article  PubMed  Google Scholar 

  7. 7.

    Glassock RJ (2003) Secondary minimal change disease. Nephrol Dial Transplant 18(Suppl 6):vi52–i58

    PubMed  Google Scholar 

  8. 8.

    Abdel-Hafez M, Shimada M, Lee PY, Johnson RJ, Garin EH (2010) Idiopathic nephrotic syndrome and atopy: is there a common link? Am J Kidney Dis 54(5):945–953

    Article  Google Scholar 

  9. 9.

    Bertelli R, Bonanni A, Di Donato A, Cioni M, Ravani P, Ghiggeri GM (2015) Regulatory T cells and minimal change nephropathy: in the mid of a complex network. Clin Exp Immunol. doi: 10.1111/cei.12675

    PubMed  Google Scholar 

  10. 10.

    Lai K-W, Wei C-L, Tan L-K et al (2007) Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol 18(5):1476–1485

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Reiser J, Von Gersdorff G, Loos M et al (2004) Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 113(10):1390–1397

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  12. 12.

    Garin EH, Mu W, Arthur JM et al (2010) Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int 78(3):296–302

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Shimada M, Ishimoto T, Lee PY et al (2012) Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-kB-dependent pathway. Nephrol Dial Transplant 27(1):81–89

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Gagliardini E, Novelli R, Corna D et al (2015) B7-1 is not induced in podocytes of human and experimental diabetic nephropathy. J Am Soc Nephrol. doi: 10.1681/ASN.2015030266

    Google Scholar 

  15. 15.

    Clement LC, Avila-Casado C, Macé C et al (2011) Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med 17(1):117–122

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  16. 16.

    Clement LC, Macé C, Avila-Casado C, Joles JA, Kersten S, Chugh SS (2014) Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome. Nat Med 20(1):37–46

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  17. 17.

    Cara-Fuentes G, Changli W, Segarra A et al (2014) CD80 and suPaR in patients with minimal change disease and focal segmental gomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol 29(8):1363–1371

    PubMed Central  Article  PubMed  Google Scholar 

  18. 18.

    Sethi S, Glassock RJ, Fervenza FC (2015) Focal segmental glomerulosclerosis: towards a better understanding for the practicing nephrologist. Nephrol Dial Transplant 30(3):375–384

    Article  PubMed  Google Scholar 

  19. 19.

    D’Agati VD, Alster JM, Jennette JC et al (2013) Association of histologic variants in FSGS clinical trial with presenting features and outcomes. Clin J Am Soc Nephrol 8(3):399–406

    PubMed Central  Article  PubMed  Google Scholar 

  20. 20.

    Kestilä M, Lenkkeri U, Männikkö M et al (1998) Positionally cloned gene for a novel glomerular protein-nephrin – is mutated in congenital nephrotic syndrome. Mol Cell 1(4):575–582

    Article  PubMed  Google Scholar 

  21. 21.

    Barua M, Brown EJ, Charoonratana VT, Genovese G, Sun H, Pollak MR (2012) Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis. Kidney Int 83(2):316–322

    PubMed Central  Article  PubMed  Google Scholar 

  22. 22.

    Parsa A, Kao WHL, Xie D et al (2013) APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med 369(23):2183–2196

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  23. 23.

    Santin S, Bullich G, Tazon-Vega B et al (2011) Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 6(5):1139–1148

    PubMed Central  Article  PubMed  Google Scholar 

  24. 24.

    Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis (2012) Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2(Suppl):139–274

    Google Scholar 

  25. 25.

    Gallon L, Leventhal J, Skaro A, Kanwar Y, Alvarado A (2012) Resolution of recurrent focal segmental glomerulosclerosis after retransplantation. N Engl J Med 366(17):1648–1649

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Wei C, El Hindi S, Li J et al (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17(8):952–960

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  27. 27.

    Jefferson AJ, Shankland SJ (2013) Has the circulating permeability factor in primary FSGS been found? Kidney Int 84(2):235–238

    PubMed Central  Article  PubMed  Google Scholar 

  28. 28.

    Meijers B, Maas RJH, Sprangers B et al (2014) The soluble urokinase receptor is not a clinical marker for focal segmental glomerulosclerosis. Kidney Int 85(3):636–640

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Maas RJ, Deegens JK, Wetzels JF (2014) Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future. Nephrol Dial Transplant 29(12):2207–2216

    Article  PubMed  Google Scholar 

  30. 30.

    Gebeshuber CA, Kornauth C, Dong L et al (2013) Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1. Nat Med 19(4):481–487

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Wu J, Zheng C, Fan Y et al (2014) Downregulation of microRNa-30 facilitates podocyte injury and is prevented by glucocorticoids. J Am Soc Nephrol 25(1):92–104

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  32. 32.

    Floege A, Floege J (2013) KDIGO-Leitlinien zur Behandlung von Glomerulonephritiden. Nephrologe 8(4):327–335

    Article  Google Scholar 

  33. 33.

    Zhao L, Cheng J, Zhou J, Wu C, Chen J (2015) Enhanced steroid therapy in adult minimal change nephrotic syndrome: a systematic review and meta-analysis. Intern Med 54:2101–2108

    Article  PubMed  Google Scholar 

  34. 34.

    Kronbichler A, Bruchfeld A (2014) Rituximab in adult minimal change disease and focal segmental glomerulosclerosis. Nephron Clin Pract 128:277–282

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Garin EH, Reiser J, Cara-Fuentes G et al (2015) Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. Pediatr Nephrol 30(3):469–477

    Article  PubMed  Google Scholar 

  36. 36.

    Straatmann C, Kallash M, Killackey M et al (2014) Success with plasmapheresis treatment for recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients. Pediatr Transplant 18(1):29–34

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Park HS, Hong Y, Sun IO et al (2014) Effects of pretransplant plasmapheresis and rituximab on recurrence of focal segmental glomerulosclerosis in adult renal transplant recipients. Korean J Intern Med 29(4):482–488

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  38. 38.

    Malaga-Dieguez L, Bouhassira D, Gipson D, Trachtman H (2015) Novel therapies for FSGS: preclinical and clinical studies. Adv Chronic Kidney Dis 22(2):e1–e6

    Article  PubMed  Google Scholar 

  39. 39.

    Basu B (2014) Ofatumumab for rituximab-resistant nephrotic syndrome. N Engl J Med 370(13):1268–1270

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Yu C-C, Fornoni A, Weins A et al (2013) Abatacept in B7-1–Positive Proteinuric Kidney Disease. N Engl J Med 369(25):2416–2423

    PubMed Central  Article  CAS  PubMed  Google Scholar 

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Correspondence to T. B. Huber or J. F. Grünewald.

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J. F. Grünewald und T. B. Huber geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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J. Floege, Aachen

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Huber, T.B., Grünewald, J.F. Nephrotisches Syndrom. Nephrologe 11, 106–115 (2016). https://doi.org/10.1007/s11560-015-0018-1

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Schlüsselwörter

  • „Minimal-Change“-Glomerulopathie
  • Fokal-Segmentale Glomerulosklerose
  • Niereninsuffizienz
  • Podozyt
  • Nephrotisches Syndrom

Keywords

  • Minimal change disease
  • Focal segmental glomerulosclerosis
  • Renal insuffciency
  • Podocyte
  • Nephrotic syndrome