Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of primary focal segmental glomerulosclerosis

Daniel C Cattran, MD
Gerald B Appel, MD
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD


Focal and segmental glomerulosclerosis (FSGS; often incorrectly abbreviated as focal sclerosis) is a morphologic pattern of glomerular injury primarily directed at the glomerular visceral epithelial cell (the podocyte) and defined by the presence of sclerosis in parts (segmental) of some (focal) glomeruli by light microscopy of a renal biopsy specimen. The lesion may be found either without an identifiable cause (in which case it is called "idiopathic" or "primary") or in response to previous glomerular injury, glomerular hypertension, or hypertrophy ("secondary") [1]. FSGS is distinct from focal and global glomerulosclerosis, which has a different prognosis and treatment. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis".)

Primary FSGS can present acutely with overt nephrotic syndrome characterized by hypoalbuminemia and edema. However, primary FSGS can also present insidiously with less dramatic manifestations, possibly related to the underlying histologic variant. The diagnosis of primary FSGS is confirmed by a renal biopsy that reveals the morphologic features mentioned above plus diffuse (greater than 80 percent) effacement of the foot processes by electron microscopy. In contrast, secondary FSGS most often presents as asymptomatic proteinuria without hypoalbuminemia or edema [2]. In addition, the kidney biopsy usually reveals glomerulomegaly, focal (rather than diffuse) foot process effacement, and, sometimes, evidence of a separate kidney disease that is responsible for the development of secondary FSGS. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis".)

Distinguishing between primary and secondary disease is particularly important because of the markedly different approach to therapy in the two disorders. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis", section on 'Distinguishing between primary and secondary FSGS'.) Primary FSGS is often responsive to immunosuppressive therapy, including glucocorticoids, cyclosporine, and other immunosuppressive agents. In contrast, immunosuppression is not indicated in secondary FSGS.

Renin-angiotensin-aldosterone system blockade (with angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) reduces proteinuria and slows progression in proteinuric kidney diseases. However, whether or not this is effective in primary FSGS is unknown.

This topic will review the prognosis and treatment of primary FSGS in adults, focusing on patients with nephrotic-range proteinuria. The causes of FSGS and the treatment of children with FSGS are discussed separately. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of idiopathic nephrotic syndrome in children".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Feb 25, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. D'Agati V. The many masks of focal segmental glomerulosclerosis. Kidney Int 1994; 46:1223.
  2. Praga M, Morales E, Herrero JC, et al. Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis 1999; 33:52.
  3. Deegens JK, Assmann KJ, Steenbergen EJ, et al. Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients? Neth J Med 2005; 63:393.
  4. Rydel JJ, Korbet SM, Borok RZ, Schwartz MM. Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment. Am J Kidney Dis 1995; 25:534.
  5. Korbet SM, Schwartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis: clinical course and response to therapy. Am J Kidney Dis 1994; 23:773.
  6. Wehrmann M, Bohle A, Held H, et al. Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes. Clin Nephrol 1990; 33:115.
  7. Velosa JA, Torres VE. Benefits and risks of nonsteroidal antiinflammatory drugs in steroid-resistant nephrotic syndrome. Am J Kidney Dis 1986; 8:345.
  8. Korbet SM. Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis. Semin Nephrol 2003; 23:219.
  9. Cattran DC, Rao P. Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 1998; 32:72.
  10. Stirling CM, Mathieson P, Boulton-Jones JM, et al. Treatment and outcome of adult patients with primary focal segmental glomerulosclerosis in five UK renal units. QJM 2005; 98:443.
  11. Abrantes MM, Cardoso LS, Lima EM, et al. Clinical course of 110 children and adolescents with primary focal segmental glomerulosclerosis. Pediatr Nephrol 2006; 21:482.
  12. Troyanov S, Wall CA, Miller JA, et al. Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. J Am Soc Nephrol 2005; 16:1061.
  13. Korbet SM. Primary focal segmental glomerulosclerosis. J Am Soc Nephrol 1998; 9:1333.
  14. Chitalia VC, Wells JE, Robson RA, et al. Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. Kidney Int 1999; 56:2236.
  15. Banfi G, Moriggi M, Sabadini E, et al. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. Clin Nephrol 1991; 36:53.
  16. Thomas DB, Franceschini N, Hogan SL, et al. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006; 69:920.
  17. Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. J Am Soc Nephrol 2004; 15:2169.
  18. Stokes MB, Markowitz GS, Lin J, et al. Glomerular tip lesion: a distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum. Kidney Int 2004; 65:1690.
  19. Beaman M, Howie AJ, Hardwicke J, et al. The glomerular tip lesion: a steroid responsive nephrotic syndrome. Clin Nephrol 1987; 27:217.
  20. Nash MA, Greifer I, Olbing H, et al. The significance of focal sclerotic lesions of glomeruli in children. J Pediatr 1976; 88:806.
  21. Cattran DC, Appel GB, Hebert LA, et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999; 56:2220.
  22. Ponticelli C, Villa M, Banfi G, et al. Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis? Am J Kidney Dis 1999; 34:618.
  23. Pei Y, Cattran D, Delmore T, et al. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis. Regional Glomerulonephritis Registry Study. Am J Med 1987; 82:938.
  24. Cattran DC, Reich HN, Beanlands HJ, et al. The impact of sex in primary glomerulonephritis. Nephrol Dial Transplant 2008; 23:2247.
  25. Korbet SM. Treatment of primary focal segmental glomerulosclerosis. Kidney Int 2002; 62:2301.
  26. Meyrier A. Nephrotic focal segmental glomerulosclerosis in 2004: an update. Nephrol Dial Transplant 2004; 19:2437.
  27. Pokhariyal S, Gulati S, Prasad N, et al. Duration of optimal therapy for idiopathic focal segmental glomerulosclerosis. J Nephrol 2003; 16:691.
  28. Crook ED, Habeeb D, Gowdy O, et al. Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population. Am J Med Sci 2005; 330:19.
  29. Sesso R, Santos AP, Nishida SK, et al. Prediction of steroid responsiveness in the idiopathic nephrotic syndrome using urinary retinol-binding protein and beta-2-microglobulin. Ann Intern Med 1992; 116:905.
  30. Velosa JA, Holley KE, Torres VE, Offord KP. Significance of proteinuria on the outcome of renal function in patients with focal segmental glomerulosclerosis. Mayo Clin Proc 1983; 58:568.
  31. Freedman BI. APOL1 and nephropathy progression in populations of African ancestry. Semin Nephrol 2013; 33:425.
  32. Ingulli E, Tejani A. Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr Nephrol 1991; 5:393.
  33. Kao WH, Klag MJ, Meoni LA, et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 2008; 40:1185.
  34. Duncan N, Dhaygude A, Owen J, et al. Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 2004; 19:3062.
  35. Matalon A, Valeri A, Appel GB. Treatment of focal segmental glomerulosclerosis. Semin Nephrol 2000; 20:309.
  36. Meyrier A, Noël LH, Auriche P, Callard P. Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Société de Néphrologie. Kidney Int 1994; 45:1446.
  37. Niaudet P. Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone. French Society of Pediatric Nephrology. J Pediatr 1994; 125:981.
  38. Lieberman KV, Tejani A. A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. J Am Soc Nephrol 1996; 7:56.
  39. Ponticelli C, Rizzoni G, Edefonti A, et al. A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int 1993; 43:1377.
  40. Heering P, Braun N, Müllejans R, et al. Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis. Am J Kidney Dis 2004; 43:10.
  41. Burgess E. Management of focal segmental glomerulosclerosis: evidence-based recommendations. Kidney Int Suppl 1999; 70:S26.
  42. KDIGO. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl 2012; 2:209. http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf (Accessed on December 23, 2013).
  43. McCauley J, Shapiro R, Ellis D, et al. Pilot trial of FK 506 in the management of steroid-resistant nephrotic syndrome. Nephrol Dial Transplant 1993; 8:1286.
  44. Segarra A, Vila J, Pou L, et al. Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or -dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 2002; 17:655.
  45. Loeffler K, Gowrishankar M, Yiu V. Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. Pediatr Nephrol 2004; 19:281.
  46. Li X, Li H, Ye H, et al. Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR. Am J Kidney Dis 2009; 54:51.
  47. Ramachandran R, Kumar V, Rathi M, et al. Tacrolimus therapy in adult-onset steroid-resistant nephrotic syndrome due to a focal segmental glomerulosclerosis single-center experience. Nephrol Dial Transplant 2014; 29:1918.
  48. Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002; 61:1098.
  49. Day CJ, Cockwell P, Lipkin GW, et al. Mycophenolate mofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant 2002; 17:2011.
  50. Montané B, Abitbol C, Chandar J, et al. Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 2003; 18:772.
  51. Cattran DC, Wang MM, Appel G, et al. Mycophenolate mofetil in the treatment of focal segmental glomerulosclerosis. Clin Nephrol 2004; 62:405.
  52. Gipson DS, Trachtman H, Kaskel FJ, et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 2011; 80:868.
  53. Hogg RJ, Friedman A, Greene T, et al. Renal function and proteinuria after successful immunosuppressive therapies in patients with FSGS. Clin J Am Soc Nephrol 2013; 8:211.
  54. Deegens JK, Wetzels JF. Immunosuppressive treatment of focal segmental glomerulosclerosis: lessons from a randomized controlled trial. Kidney Int 2011; 80:798.
  55. Siegel NJ, Gaudio KM, Krassner LS, et al. Steroid-dependent nephrotic syndrome in children: histopathology and relapses after cyclophosphamide treatment. Kidney Int 1981; 19:454.
  56. Schulman SL, Kaiser BA, Polinsky MS, et al. Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: superiority of response to corticosteroid therapy over histopathologic patterns. J Pediatr 1988; 113:996.
  57. Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für Pädiatrische Nephrologie. Arch Dis Child 1987; 62:1102.
  58. Kronbichler A, König P, Busch M, et al. Rituximab in adult patients with multi-relapsing/steroid-dependent minimal change disease and focal segmental glomerulosclerosis: a report of 5 cases. Wien Klin Wochenschr 2013; 125:328.
  59. Ochi A, Takei T, Nakayama K, et al. Rituximab treatment for adult patients with focal segmental glomerulosclerosis. Intern Med 2012; 51:759.
  60. Fernandez-Fresnedo G, Segarra A, González E, et al. Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2009; 4:1317.
  61. Hogan J, Bomback AS, Mehta K, et al. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol 2013; 8:2072.
  62. Bomback AS, Canetta PA, Beck LH Jr, et al. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol 2012; 36:58.
  63. Ginsburg DS, Dau P. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis. Clin Nephrol 1997; 48:282.
  64. Mitwalli AH. Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit patients with focal segmental glomerulosclerosis? Nephrol Dial Transplant 1998; 13:1524.
  65. Feld SM, Figueroa P, Savin V, et al. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys. Am J Kidney Dis 1998; 32:230.
  66. Godfrin Y, Dantal J, Bouhours JF, et al. A new method of measuring albumin permeability in isolated glomeruli. Kidney Int 1996; 50:1352.
  67. Haas M, Godfrin Y, Oberbauer R, et al. Plasma immunadsorption treatment in patients with primary focal and segmental glomerulosclerosis. Nephrol Dial Transplant 1998; 13:2013.
  68. Cattran D, Neogi T, Sharma R, et al. Serial estimates of serum permeability activity and clinical correlates in patients with native kidney focal segmental glomerulosclerosis. J Am Soc Nephrol 2003; 14:448.
  69. Reiser J, Mundel P. Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephrotic syndrome. J Am Soc Nephrol 2004; 15:2246.
  70. Reiser J, von Gersdorff G, Loos M, et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 2004; 113:1390.
  71. Yu CC, Fornoni A, Weins A, et al. Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med 2013; 369:2416.
  72. Alachkar N, Carter-Monroe N, Reiser J. Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med 2014; 370:1263.
  73. Garin EH, Reiser J, Cara-Fuentes G, et al. Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. Pediatr Nephrol 2015; 30:469.
  74. Muso E, Mune M, Fujii Y, et al. Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy. Nephron 2001; 89:408.
  75. Stenvinkel P, Alvestrand A, Angelin B, Eriksson M. LDL-apheresis in patients with nephrotic syndrome: effects on serum albumin and urinary albumin excretion. Eur J Clin Invest 2000; 30:866.
  76. Hattori M, Chikamoto H, Akioka Y, et al. A combined low-density lipoprotein apheresis and prednisone therapy for steroid-resistant primary focal segmental glomerulosclerosis in children. Am J Kidney Dis 2003; 42:1121.
  77. Nakamura T, Sugaya T, Kawagoe Y, et al. Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis. Clin Nephrol 2006; 65:1.
  78. Muso E, Mune M, Yorioka N, et al. Beneficial effect of low-density lipoprotein apheresis (LDL-A) on refractory nephrotic syndrome (NS) due to focal glomerulosclerosis (FGS). Clin Nephrol 2007; 67:341.
  79. Praga M, Hernández E, Montoyo C, et al. Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria. Am J Kidney Dis 1992; 20:240.
  80. Heeg JE, de Jong PE, van der Hem GK, de Zeeuw D. Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril. Kidney Int 1989; 36:272.
  81. Ferder LF, Inserra F, Daccordi H, Smith RD. Enalapril improved renal function and proteinuria in chronic glomerulopathies. Nephron 1990; 55 Suppl 1:90.
  82. Crenshaw G, Bigler S, Salem M, Crook ED. Focal segmental glomerulosclerosis in African Americans: effects of steroids and angiotensin converting enzyme inhibitors. Am J Med Sci 2000; 319:320.
  83. Stiles KP, Abbott KC, Welch PG, Yuan CM. Effects of angiotensin-converting enzyme inhibitor and steroid therapy on proteinuria in FSGS: a retrospective study in a single clinic. Clin Nephrol 2001; 56:89.