Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Collapsing focal segmental glomerulosclerosis not associated with HIV infection

Gerald B Appel, MD
Peter J Nelson, MD
Section Editor
Richard J Glassock, MD, MACP
Deputy Editor
Albert Q Lam, MD


Collapsing focal segmental glomerulosclerosis (collapsing FSGS, also known as collapsing glomerulopathy) is most often seen in association with HIV infection [1]. In this setting, the renal disease is also called "HIV-associated nephropathy." Collapsing FSGS has also been increasingly recognized in non-HIV-infected patients.

Whether associated with HIV infection or other disorders, patients typically present with the nephrotic syndrome and, on renal biopsy, show segmentally or globally collapsed and sclerotic glomerular capillaries, pseudocrescents composed of hyperplastic glomerular epithelial cells, and severe tubulointerstitial disease.

Collapsing FSGS not associated with HIV infection will be reviewed here. Collapsing FSGS and other renal diseases that occur in association with HIV infection are discussed separately. (See "HIV-associated nephropathy (HIVAN)" and "Overview of kidney disease in HIV-positive patients".)


The pathogenesis of collapsing focal segmental glomerulosclerosis (FSGS) in patients not infected with HIV is not clear [1]. As with HIV-associated nephropathy, the underlying pathogenic event appears to be a severe insult to the integrity and biology of the glomerular visceral (podocytes) and parietal epithelial cells [1,2]. This damage ultimately results in cellular dedifferentiation and proliferation of these glomerular epithelial cells accompanied by a profound loss of the glomerular filtration barrier function [1].

Most cases of collapsing FSGS not associated with HIV infection are idiopathic [1,2]. However, collapsing FSGS has been reported to occur in association with a growing list of disorders (table 1) [1]. In one series of 42 patients, for example, concurrent illnesses were present in 13 (31 percent); these included a systemic lupus erythematosus (SLE)-like disorder, hepatitis C virus infection, and multiple myeloma [3].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Apr 13, 2017.
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 ©2017 UpToDate, Inc.
  1. Albaqumi M, Soos TJ, Barisoni L, Nelson PJ. Collapsing glomerulopathy. J Am Soc Nephrol 2006; 17:2854.
  2. Schwimmer JA, Markowitz GS, Valeri A, Appel GB. Collapsing glomerulopathy. Semin Nephrol 2003; 23:209.
  3. Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int 1999; 56:2203.
  4. Nichols B, Jog P, Lee JH, et al. Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1. Kidney Int 2015; 87:332.
  5. Ma L, Shelness GS, Snipes JA, et al. Localization of APOL1 protein and mRNA in the human kidney: nondiseased tissue, primary cells, and immortalized cell lines. J Am Soc Nephrol 2015; 26:339.
  6. Moudgil A, Nast CC, Bagga A, et al. Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy. Kidney Int 2001; 59:2126.
  7. Coventry S, Shoemaker LR. Collapsing glomerulopathy in a 16-year-old girl with pulmonary tuberculosis: the role of systemic inflammatory mediators. Pediatr Dev Pathol 2004; 7:166.
  8. Tomlinson L, Boriskin Y, McPhee I, et al. Acute cytomegalovirus infection complicated by collapsing glomerulopathy. Nephrol Dial Transplant 2003; 18:187.
  9. Leblond V, Beaufils H, Ginsburg C, et al. Collapsing focal segmental glomerulosclerosis associated with visceral leishmaniasis. Nephrol Dial Transplant 1994; 9:1353.
  10. Beltrame A, Arzese A, Camporese A, et al. Acute renal failure due to visceral leishmaniasis by Leishmania infantum successfully treated with a single high dose of liposomal amphotericin B. J Travel Med 2008; 15:358.
  11. Thaunat O, Delahousse M, Fakhouri F, et al. Nephrotic syndrome associated with hemophagocytic syndrome. Kidney Int 2006; 69:1892.
  12. Niang A, Niang SE, Ka el HF, et al. Collapsing glomerulopathy and haemophagocytic syndrome related to malaria: a case report. Nephrol Dial Transplant 2008; 23:3359.
  13. Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int 2008; 74:1385.
  14. Markowitz GS, Appel GB, Fine PL, et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 2001; 12:1164.
  15. Markowitz GS, Fine PL, D'agati VD. Nephrotic syndrome after treatment with pamidronate. Am J Kidney Dis 2002; 39:1118.
  16. Barri YM, Munshi NC, Sukumalchantra S, et al. Podocyte injury associated glomerulopathies induced by pamidronate. Kidney Int 2004; 65:634.
  17. Lockridge L, Papac RJ, Perazella MA. Pamidronate-associated nephrotoxicity in a patient with Langerhans's histiocytosis. Am J Kidney Dis 2002; 40:E2.
  18. Pascual J, Torrealba J, Myers J, et al. Collapsing focal segmental glomerulosclerosis in a liver transplant recipient on alendronate. Osteoporos Int 2007; 18:1435.
  19. Herlitz LC, Markowitz GS, Farris AB, et al. Development of focal segmental glomerulosclerosis after anabolic steroid abuse. J Am Soc Nephrol 2010; 21:163.
  20. Markowitz GS, Nasr SH, Stokes MB, D'Agati VD. Treatment with IFN-{alpha}, -{beta}, or -{gamma} is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2010; 5:607.
  21. Meehan SM, Pascual M, Williams WW, et al. De novo collapsing glomerulopathy in renal allografts. Transplantation 1998; 65:1192.
  22. Stokes MB, Davis CL, Alpers CE. Collapsing glomerulopathy in renal allografts: a morphological pattern with diverse clinicopathologic associations. Am J Kidney Dis 1999; 33:658.
  23. Swaminathan S, Lager DJ, Qian X, et al. Collapsing and non-collapsing focal segmental glomerulosclerosis in kidney transplants. Nephrol Dial Transplant 2006; 21:2607.
  24. Salvatore SP, Barisoni LM, Herzenberg AM, et al. Collapsing glomerulopathy in 19 patients with systemic lupus erythematosus or lupus-like disease. Clin J Am Soc Nephrol 2012; 7:914.
  25. Amoura Z, Georgin-Lavialle S, Haroche J, et al. Collapsing glomerulopathy in systemic autoimmune disorders: a case occurring in the course of full blown systemic lupus erythematosus. Ann Rheum Dis 2006; 65:277.
  26. Marques LP, Pacheco GG, Rioja LS, et al. Can systemic lupus erythematosus be the cause of collapsing glomerulopathy? Lupus 2005; 14:853.
  27. Melo NC, Malheiros DM, Barros RT, Woronik V. Collapsing glomerulopathy associated with proliferative lupus nephritis: reversible acute kidney injury. Lupus 2011; 20:98.
  28. Gupta R, Sharma A, Bhowmik D, et al. Collapsing glomerulopathy occurring in HIV-negative patients with systemic lupus erythematosus: report of three cases and brief review of the literature. Lupus 2011; 20:866.
  29. Larsen CP, Beggs ML, Saeed M, Walker PD. Apolipoprotein L1 risk variants associate with systemic lupus erythematosus-associated collapsing glomerulopathy. J Am Soc Nephrol 2013; 24:722.
  30. El Karoui K, Hill GS, Karras A, et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int 2011; 79:643.
  31. Cook HT. Focal segmental glomerulosclerosis in IgA nephropathy: a result of primary podocyte injury? Kidney Int 2011; 79:581.
  32. Salvatore SP, Reddi AS, Chandran CB, et al. Collapsing glomerulopathy superimposed on diabetic nephropathy: insights into etiology of an under-recognized, severe pattern of glomerular injury. Nephrol Dial Transplant 2014; 29:392.
  33. Diomedi-Camassei F, Di Giandomenico S, Santorelli FM, et al. COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol 2007; 18:2773.
  34. Gasser DL, Winkler CA, Peng M, et al. Focal segmental glomerulosclerosis is associated with a PDSS2 haplotype and, independently, with a decreased content of coenzyme Q10. Am J Physiol Renal Physiol 2013; 305:F1228.
  35. Avila-Casado MC, Vargas-Alarcon G, Soto ME, et al. Familial collapsing glomerulopathy: clinical, pathological and immunogenetic features. Kidney Int 2003; 63:233.
  36. Liakopoulos V, Huerta A, Cohen S, et al. Familial collapsing focal segmental glomerulosclerosis. Clin Nephrol 2011; 75:362.
  37. Divers J, Freedman BI. Susceptibility genes in common complex kidney disease. Curr Opin Nephrol Hypertens 2010; 19:79.
  38. Kopp JB, Smith MW, Nelson GW, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 2008; 40:1175.
  39. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329:841.
  40. Avila-Casado Mdel C, Perez-Torres I, Auron A, et al. Proteinuria in rats induced by serum from patients with collapsing glomerulopathy. Kidney Int 2004; 66:133.
  41. Nasr SH, Markowitz GS, Sentman RL, D'Agati VD. Sickle cell disease, nephrotic syndrome, and renal failure. Kidney Int 2006; 69:1276.
  42. Kumar S, Sheaff M, Yaqoob M. Collapsing glomerulopathy in adult still's disease. Am J Kidney Dis 2004; 43:e4.
  43. Weiss MA, Daquioag E, Margolin EG, Pollak VE. Nephrotic syndrome, progressive irreversible renal failure, and glomerular "collapse": a new clinicopathologic entity? Am J Kidney Dis 1986; 7:20.
  44. Detwiler RK, Falk RJ, Hogan SL, Jennette JC. Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 1994; 45:1416.
  45. Valeri A, Barisoni L, Appel GB, et al. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney Int 1996; 50:1734.
  46. Grcevska L, Polenakovik M. Collapsing glomerulopathy: clinical characteristics and follow-up. Am J Kidney Dis 1999; 33:652.
  47. D'Agati V. Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 2003; 23:117.
  48. Thorner PS, Ho M, Eremina V, et al. Podocytes contribute to the formation of glomerular crescents. J Am Soc Nephrol 2008; 19:495.
  49. Laurin LP, Gasim AM, Derebail VK, et al. Renal Survival in Patients with Collapsing Compared with Not Otherwise Specified FSGS. Clin J Am Soc Nephrol 2016; 11:1752.
  50. D'Agati VD, Alster JM, Jennette JC, et al. Association of histologic variants in FSGS clinical trial with presenting features and outcomes. Clin J Am Soc Nephrol 2013; 8:399.
  51. 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.
  52. Laurin LP, Gasim AM, Poulton CJ, et al. Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGS. Clin J Am Soc Nephrol 2016; 11:386.
  53. Burns GC, Paul SK, Toth IR, Sivak SL. Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy. J Am Soc Nephrol 1997; 8:1140.
  54. Kimmel PL, Mishkin GJ, Umana WO. Captopril and renal survival in patients with human immunodeficiency virus nephropathy. Am J Kidney Dis 1996; 28:202.
  55. Toth CM, Pascual M, Williams WW Jr, et al. Recurrent collapsing glomerulopathy. Transplantation 1998; 65:1009.