Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2008, vol. 17, nr 2, March-April, p. 221–226

Publication type: review article

Language: English

Focal Segmental Glomerulosclerosis – Pathogenesis, Clinical Manifestation and Treatment

Ogniskowe segmentalne stwardnienie kłębuszków nerkowych – patogeneza, obraz kliniczny i leczenie

Oktawia Mazanowska1,, Dorota Kamińska1,, Magdalena Krajewska1,, Irenawikiera−magot Irenawikiera−Magott2,

1 Department of Nephrology and Transplantation Medicine, Silesian Piasts University of Medicine, Poland

2 Department of Pediatric Nephrology, Silesian Piasts University of Medicine, Poland

Abstract

Focal segmental glomerulosclerosis (FSGS) is a clinicopathological entity of not fully explained etiology characterized by focal and segmental occurrence of lesions. It is currently believed that primary FSGS is caused by alterations in glomerular epithelial cells (podocytes). FSGS is one of the most frequent causes of nephrotic syndrome in adults. The course of the disease is strongly influenced by proteinuria or nephrotic syndrome and renal insufficiency at presentation. The prognosis of FSGS is poor because there are no spontaneous remissions and because of resistance to treatment. FSGS has a high recurrence rate after kidney transplantation with loss of graft function in half of affected individuals. The efficacy of treatment of FSGS depends on histopathological findings in renal biopsy and clinical presentation, especially on the intensity of proteinuria. There is no uniform standard of therapy for FSGS. A six−month course of steroids and/or cyclosporine A (CsA) as well as ACE inhibitors and/or angiotensin receptor blockers (ARBs) and lipid−lowering agents are recommended. In steroid−dependent patients or those with frequent relapse of proteinuria, cyclophosphamide with prednisone should be administered. In steroid−resistant nephrotic syndrome the podocine gene mutation (NPHS2 gene) should be assessed to avoid prolonged and ineffective treatment with adverse effects and evaluation before further kidney allograft transplantation, with a low risk of recurrence in homozygous mutation patients.

Streszczenie

Pierwotne ogniskowe segmentalne stwardnienie kłębuszków nerkowych (FSGS – focal segmental glomerulosclerosis) jest postacią uszkodzenia kłębuszków nerkowych o niecałkowicie wyjaśnionej etiologii, charakteryzującą się ogniskowym (w niektórych kłębuszkach) i segmentalnym (w niektórych pętlach naczyniowych) występowaniem zmian. Uważa się obecnie, że pierwotną przyczyną jest uszkodzenie komórek nabłonka trzewnego kłębuszków nerkowych (podocytów). FSGS jest jedną z najczęstszych przyczyn zespołu nerczycowego u osób dorosłych. Znaczący wpływ na przebieg choroby ma nasilenie białkomoczu i ubytek filtracji kłębuszkowej w momencie rozpoznania. Rokowanie w FSGS jest złe ze względu na brak samoistnych remisji i częstą oporność na leczenie. FSGS często nawraca w nerce przeszczepionej, powodując utratę czynności nerki przeszczepionej u około połowy chorych. Skuteczność leczenia FSGS zależy od postaci histopatologicznej i obrazu klinicznego, szczególnie od nasilenia białkomoczu. Nie ma jednej ustalonej standardowej terapii FSGS. Rekomendowane jest 6−miesięczne leczenie steroidami i/lub cyklosporyną A (CsA), jak również inhibitorami enzymu konwertującego (IEK) i/lub lekami blokującymi receptor angiotensyny (ARB) oraz statynami. U pacjentów steroidozależnych lub przy częstym nawrocie białkomoczu jest wskazane leczenie cyklofosfamidem wraz ze steroidami. W steroidoopornym zespole nerczycowym należy poszukiwać mutacji genu dla podocyny (NPHS2), aby uniknąć długotrwałego a nieskutecznego leczenia z jego możliwymi objawami ubocznymi i ocenić ryzyko nawrotu po przeszczepie nerki, które w postaci homozygotycznej jest niskie.

Key words

FSGS, pathogenesis, treatment, recurrence after kidney transplantation

Słowa kluczowe

FSGS, patogeneza, leczenie, nawrót po przeszczepie nerki

References (28)

  1. Cattran DC: Outcomes of research in glomerulonephritis. Semin Nephrol 2003, 23, 340–354.
  2. Brenchley PEC: Vascular permeability factors in steroid−sensitive nephrotic syndrome and focal segmental glomerulosclerosis. Nephrol Dial Transplant 2003, 18, Suppl 6, 21–25.
  3. Shalhoub RJ: Pathogenesis of lipoid nephrosis: a disorder of T cell function. Lancet 1974, 2, 556–560.
  4. Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf E−M, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F, and the Arbeitsgemeinschaft für Pädiatrische Nephrologie Study Group. J Am Nephrol 2004, 15, 722–732.
  5. Kritz W: Progressive renal failure – Inability of podocytes to replicate and the consequence for development of glomerulosclerosis. Nephrol Dial Transplant 1996, 11, 1738–1742.
  6. Schwimmer JA, Markowitz GS, Valeri A, Appel GB: Collapsing glomerulopathy. Semin Nephrol 2003, 23, 209–218.
  7. Ohtaka A, Ootaka T, Sato H, Ito S: Phenotypic change of glomerular podocytes in primary focal segmental glomerulosclerosis: Developmental paradigm? Nephrol Dial Transplant 2002, 17, Suppl 9, 11–15.
  8. Shankland SJ: The podocyte’s response to injury: role of proteinuria and glomerulsclerosis. Kidney Int 2006, 69, 2131–2147.
  9. Bariety J, Bruneval P: Activated parietal epithelial cells or dedifferentiated podocytes in FSGS: Can we make the difference? Kidney Int 2006, 69, 194.
  10. Schwartz MM: The blind men and the elephant. Kidney Int 2005, 68, 1894–1895.
  11. Dijkman H, Smeets B, van der Laak J, Steenbergen E, Wetzels J: The parietal epithelial cell is crucially involved in human idiopathic focal segmental glomerulosclerosis. Kidney Int 2005, 68, 1562–1572.
  12. D’Agati VD, Fogo AB, Bruijn JA, Jennette JC: Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 2004, 43, 368–382.
  13. Howie AJ, Brewer DB: The glomerular tip lesion: a previously undescribed type of segmental glomerular abnormality. J Pathol 1984, 142, 205–220.
  14. Hara M, Yanagihara T, Kihara I: Urinary podocytes in primary focal segmental glomerulosclerosis. Nephron 2001, 89, 342–347.
  15. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Ebihara I, Koide H: The urinary podocyte as a marker for the differential diagnosis of idiopathic focal glomerulosclerosis and minimal−change nephrotic syndrome. Am J Nephrol 2000, 20, 175–179.
  16. Weber S, Tönshoff B: Recurrence of focal segmental glomerulosclerosis in children after renal transplantation: clinical and genetic aspects. Transplantation 2005, 80, S128–S134.
  17. Senggutuvan P, Cameron JS, Hartley RB, Rigden S, Chantler C, Haycock G, Williams DG, Ogg C, Koffman G: Recurrence of focal segmental glomerulosclerosis in transplanted kidneys: analysis of incidence and risk factors in 59 allografts. Pediatr Nephrol 1990, 4, 21–28.
  18. Weber S, Gribouval O, Esquivel EL, Morinière V, Tete MJ, Legendre C, Niaudet P, Antignac C: NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int 2004, 66, 571–579.
  19. Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, Maxwell DR, Kunis CL, for the North America Nephrotic Syndrome Study Group. Kidney Int 1999, 56, 2220–2226.
  20. Deegens JK, Wetzels JFM: Diagnosis and treatment of primary glomerular diseases. Minerva Urol Nefrol 2005, 57, 211–236.
  21. Meyrier A: Nephrotic focal segmental glomerulosclerosis in 2004: an update. Nephrol Dial Transplant 2004, 19, 2437–2444.
  22. Choi MJ: Role of mycophenolate mofetil in glomerular disease, FSGS and membranous nephropathy. American Society of Nephrology Meeting, Syllabus 2004, 838–839.
  23. Karim MY, Abbs IC: Mycophenolate mofetil in nonlupus glomerulonephropathy. Lupus 2005, 14, s39–s41.
  24. Tumlin JA, Miller D, Near M, Selvaraj S, Henniger R, Guasch A: A prospective, open−label trial of sirolimus in the treatment of focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2006, 1, 109–116.
  25. Dantal J, Bigot E, Bogers W, Testa A, Kriaa F, Jacques Y, Hurault de Ligny B, Niaudet P, Charpentier B, Soulillou JP: Effect of plasma protein adsorption on protein excretion in kidney−transplant recipients with recurrent nephrotic syndrome. N Engl J Med 1994, 330, 7–14.
  26. Okamoto T: Requirement of drug development for chronic renal disease: Other strategies than blockade of the renin−angiotensin system (Review). Intern J Molecular Med 2003, 11, 651–654.
  27. Ponticelli C, Villa M, Banfi G, Cesane B, Pozzi C, Pani A, Passerini P, Farina M, Grassi C, Baroli A: Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis. Am J Kidney Dis 1999, 34, 618–625.
  28. Chun MJ, Korbet SM, Schwartz MM, Lewis EJ: Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic varians. J Am Soc Nephrol 2004, 15, 2169–2117.
© Wroclaw Medical University