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Diagnosis: Collapsing glomerulopathy

Collapsing glomerulopathy has been considered a variant of focal segmental glomerulosclerosis (FSGS). It is characterized clinically by heavy proteinuria, progressive renal insufficiency and rapid evolution to end-stage renal disease (ESRD). While human immunodeficiency virus (HIV) has been considered the most commonly recognized cause, non-HIV-associated collapsing glomerulopathy is well described in native as well as transplanted kidneys (Swaminathan S, et al. Collapsing and non-collapsing focal segmental glomerulosclerosis in kidney transplants. Nephrol Dial Transplant. 2006;21(9):2607-14. [PubMed link] [Free full text]).

Collapsing glomerulopathy is associated with a growing list of intrinsic and extrinsic insults to podocytes, all of which ultimately lead to the collapse of glomerular capillary loops and marked podocyte proliferation (hypertrophy and hyperplasy). This glomerulopathy remains poorly understood, and it is not known how disparate insults induce collapsing glomerulopathy (Barisoni L, Nelson PJ. Collapsing glomerulopathy: an inflammatory podocytopathy? Curr Opin Nephrol Hypertens. 2007;16(3):192-5. [PubMed link]).

Although the term “collapsing FSGS” has been largely used since the mid 1990s, a growing number of authors prefer to use the term “collapsing glomerulopathy.” This preference may have clinical relevance. The mechanism of these glomerulopathies is distinct: podocyte proliferation characterizes collapsing glomerulopathy, whereas other podocyte alterations are implicated in the pathogenesis of FSGS. Collapsing glomerulopathy is resistant to standard therapies used for FSGS. Another term, “cellular lesion,” was introduced in the 1980s to identify this glomerular change (Schwartz MM, Lewis EJ: Focal segmental glomerular sclerosis: the cellular lesion. Kidney Int 28: 968–974, 1985 [PubMed link]). The recently proposed Columbia classification suggests using “cellular lesion” for glomerulopathies characterized by hypercellularity in the intracapillary compartment, in contrast to “collapsing lesions”, where the glomerular tuft appears hypocellular, and increased cellularity is limited to the urinary space (D’Agati VD, et al. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 43: 368–382, 2004 [PubMed link])

Some works suggests that podocytes may become macrophage-like inflammatory mediators of proliferative epithelial injury within the glomerulus. This may manifest as collapsing glomerulopathy or crescentic glomerulonephritis, "lesions that appear to be anatomically and pathogenically linked" (Barisoni L, Nelson PJ. Collapsing glomerulopathy: an inflammatory podocytopathy? Curr Opin Nephrol Hypertens. 2007;16(3):192-5. [PubMed link]).

The cause of this disorder is unknown, but nearly identical pathologic findings are present in idiopathic collapsing glomerulopathy and human immunodeficiency virus (HIV)-associated nephropathy, and collapsing glomerulopathy has been associated with parvovirus B19 infection and treatment with pamidronate. The pathogenesis of collapsing glomerulopathy involves visceral epithelial cell injury leading to cell cycle dysregulation and a proliferative phenotype. Clinically, collapsing glomerulopathy is characterized by black racial predominance, a high incidence of nephrotic syndrome, and rapidly progressive renal failure. Collapsing glomerulopathy also may recur after renal transplantation or present de novo, often leading to loss of the allograft. The optimal treatment for collapsing glomerulopathy is unknown. Treatments may include steroids or cyclosporine in addition to aggressive blood pressure control, angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, and lipid lowering agents. The role of other immunosuppressive agents such as mycophenolate mofetil in the treatment of collapsing FSGS remains to be defined (Schwimmer JA, et al Collapsing glomerulopathy. Semin Nephrol. 2003;23(2):209-18. [PubMed link]).

A recently proposed taxonomy for the podocytopathies classifies colapsing glomerulopathy apart from FSGS and recognizes three major categories: idiopathic, genetic, and secondary or reactive (to viruses, drugs, autoimmune diseases, etcetera) (Barisoni L, et al. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic syndrome. Clin J Am Soc Nephrol 2: 529–542, 2007 [PubMed link][Free full text]).

In our case the glomerulopathy was associated to lymphoproliferative disease and multiple drugs that the patient received. The precise "etiologic" factor is not possible to determine. Unfortunately the patient died three months after renal biopsy due to a severe lung infection and sepsis, she still had nephrotic syndrome.

See the chapters Focal and Segmental Glomerulosclerosis in our Tutorial.

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Bibliography

• Nelson PJ, Bruggeman LA. Collapsing glomerulopathy: beyond serendipity in mouse genetics. Kidney Int. 2009;75(4):353-5. [PubMed link]
• Gulati A, Sharma A, Hari P, Dinda AK, Bagga A. Idiopathic collapsing glomerulopathy in children. Clin Exp Nephrol. 2008;12(5):348-53. [PubMed link]
• Haas M. Collapsing glomerulopathy: many means to a similar end. Kidney Int. 2008;73(6):669-71. [PubMed link]
• Albaqumi M, Barisoni L. Current views on collapsing glomerulopathy. J Am Soc Nephrol. 2008;19(7):1276-81. [PubMed link]
• Barisoni L, Nelson PJ. Collapsing glomerulopathy: an inflammatory podocytopathy? Curr Opin Nephrol Hypertens. 2007;16(3):192-5. [PubMed link]
• Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol. 2007;2(3):529-42. [PubMed link][Free full text]
• El-Refaey AM, Kapur G, Jain A, Hidalgo G, Imam A, Valentini RP, Mattoo TK. Idiopathic collapsing focal segmental glomerulosclerosis in pediatric patients. Pediatr Nephrol. 2007;22(3):396-402. [PubMed link]
• Swaminathan S, Lager DJ, Qian X, Stegall MD, Larson TS, Griffin MD. Collapsing and non-collapsing focal segmental glomerulosclerosis in kidney transplants. Nephrol Dial Transplant. 2006;21(9):2607-14. [PubMed link] [Free full text]
• Albaqumi M, Soos TJ, Barisoni L, Nelson PJ. Collapsing glomerulopathy. J Am Soc Nephrol. 2006;17(10):2854-63 [PubMed link] [Free full text]
• D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43(2):368-82. [PubMed link]
• Schwimmer JA, Markowitz GS, Valeri A, Appel GB. Collapsing glomerulopathy. Semin Nephrol. 2003;23(2):209-18. [PubMed link]
• Laurinavicius A, Rennke HG. Collapsing glomerulopathy--a new pattern of renal injury. Semin Diagn Pathol. 2002;19(3):106-15. [PubMed link]
• Schwartz MM, Lewis EJ. Focal segmental glomerular sclerosis: the cellular lesion. Kidney Int. 1985;28(6):968-74. [PubMed link]

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