Focal segmental glomerulosclerosis pathophysiology: Difference between revisions
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==Associated Conditions== | ==Associated Conditions== | ||
Conditions associated with focal segmental glomerulosclerosis (FSGS):<ref name="pmid23431071">{{cite journal |vauthors=Hogan J, Radhakrishnan J |title=The treatment of minimal change disease in adults |journal=J. Am. Soc. Nephrol. |volume=24 |issue=5 |pages=702–11 |date=April 2013 |pmid=23431071 |doi=10.1681/ASN.2012070734 |url=}}</ref><ref name="pmid21184928">{{cite journal |vauthors=Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A, Kasiske B, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Gustafson S, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L |title=US Renal Data System 2010 Annual Data Report |journal=Am. J. Kidney Dis. |volume=57 |issue=1 Suppl 1 |pages=A8, e1–526 |date=January 2011 |pmid=21184928 |doi=10.1053/j.ajkd.2010.10.007 |url=}}</ref><ref name="pmid3070550">{{cite journal |vauthors=Cohen AH, Nast CC |title=HIV-associated nephropathy. A unique combined glomerular, tubular, and interstitial lesion |journal=Mod. Pathol. |volume=1 |issue=2 |pages=87–97 |date=March 1988 |pmid=3070550 |doi= |url=}}</ref> | Conditions associated with focal segmental glomerulosclerosis (FSGS):<ref name="pmid23431071">{{cite journal |vauthors=Hogan J, Radhakrishnan J |title=The treatment of minimal change disease in adults |journal=J. Am. Soc. Nephrol. |volume=24 |issue=5 |pages=702–11 |date=April 2013 |pmid=23431071 |doi=10.1681/ASN.2012070734 |url=}}</ref><ref name="pmid21184928">{{cite journal |vauthors=Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A, Kasiske B, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Gustafson S, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L |title=US Renal Data System 2010 Annual Data Report |journal=Am. J. Kidney Dis. |volume=57 |issue=1 Suppl 1 |pages=A8, e1–526 |date=January 2011 |pmid=21184928 |doi=10.1053/j.ajkd.2010.10.007 |url=}}</ref><ref name="pmid3070550">{{cite journal |vauthors=Cohen AH, Nast CC |title=HIV-associated nephropathy. A unique combined glomerular, tubular, and interstitial lesion |journal=Mod. Pathol. |volume=1 |issue=2 |pages=87–97 |date=March 1988 |pmid=3070550 |doi= |url=}}</ref><ref name="pmid24840607">{{cite journal |vauthors=Ataga KI, Derebail VK, Archer DR |title=The glomerulopathy of sickle cell disease |journal=Am. J. Hematol. |volume=89 |issue=9 |pages=907–14 |date=September 2014 |pmid=24840607 |pmc=4320776 |doi=10.1002/ajh.23762 |url=}}</ref><ref name="pmid21074826">{{cite journal |vauthors=Gopalakrishnan I, Iskandar SS, Daeihagh P, Divers J, Langefeld CD, Bowden DW, Hicks PJ, Rocco MV, Freedman BI |title=Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variants |journal=Hum. Pathol. |volume=42 |issue=2 |pages=291–4 |date=February 2011 |pmid=21074826 |pmc=3022108 |doi=10.1016/j.humpath.2010.07.016 |url=}}</ref> | ||
*Diabetes | *Diabetes | ||
*Human immunodeficiency virus (HIV) | *Human immunodeficiency virus (HIV) | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [3] Cafer Zorkun, M.D., Ph.D. [4] Olufunmilola Olubukola M.D.[5]
Overview
Pathophysiology
There are two types of FSGS, primary FSGS and secondary FSGS, pathophysiology is discussed below:
Pathogenesis of primary FSGS
- The pathogenesis of primary or Idiopathic FSGS is not so clear.[1]
- Many studies had theorized that FSGS occurs as a consequence of effects of circulating immune activating factors on the glomerular epithelium.[1]
- Indeed, the damaging role of circulating factors like the soluble urokinase plasminogen activating receptor (suPAR) on the glomerular podocytes had been postulated.[1]
- The underlying pathogenesis of FSGS is fusion or effacement of the foot processes (podocytes) of the glomeruli, with sclerosing of some part of the glomeruli (hence its name as focal segmental).
- As such, the involvement of the permselective filtration barrier and effacement of podocyte foot processes are inevitable.
- The four major causes that lead to the reaction of podocyte foot processes.
- These changes result in:[2][3][4]
- Apoptosis
- Detachment from the glomerular basement membrane (GBM)
- Subsequent podocytopenia
- Interference with slit diaphragm and its corresponding lipid raft
- Interference with actin cytoskeleton
- Interference with the GBM or with the interaction of the GBM and the podocytes
- Interference with the negative charge of podocytes
- Circulating factors implicated in the pathogenesis of Primary FSGS include:
Pathogenesis of secondary FSGS
The pathogenesis of secondary focal segmental glomerulosclerosis (FSGS) occurs due to the following factors:
- Glomerular hypertrophy and hyperfiltration, which is due to the following:[8][9]
- Scarring due to the previous injury
- Glomerular abnormality
- Direct toxic injury to podocytes
- Various inflammatory mediators include over-expression of:[3][10][11]
- Tumor growth factor-beta (TGF-beta)
- Platelet-derived growth factor (PDGF)
- Vascular endothelial growth factor (VEGF)
Genetics
The development of focal segmental glomerulosclerosis is the result of multiple genetic mutations such as:[12][10][13][14][15][16][17][18]
- Nephrin gene in congenital Finnish-type nephrotic syndrome - NPHS1
- Nephrin-like transmembrane gene - NEPH1
- Podocin gene - NPHS2
- CD2-associated protein (CD2AP)
- Alpha-actinin-4 gene
- Transient receptor potential cation channel - TRPC6
- Mutation in wilms tumor gene - WT1
- Mutation in SCARB2 (LIMP2) gene
- Mutation in formin gene - INF2
- Mitochondrial cytopathies
Associated Conditions
Conditions associated with focal segmental glomerulosclerosis (FSGS):[19][20][21][22][23]
- Diabetes
- Human immunodeficiency virus (HIV)
- Sickle cell disease
- Systemic lupus erythematosus (SLE)
- Nephrotic syndrome
- End stage renal disease (ESRD)
- Minimal change disease
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis:
- There is a focal and segmental hypercellularity inside the capillary
- The lumens of capillary are occluded with foams cells
- The podocytes which undergo hyperplasia resembles the crescent
- There is focal and segmental areas of collapse
References
- ↑ 1.0 1.1 1.2 1.3 Reiser J, Nast CC, Alachkar N (2014). "Permeability factors in focal and segmental glomerulosclerosis". Adv Chronic Kidney Dis. 21 (5): 417–21. doi:10.1053/j.ackd.2014.05.010. PMC 4149759. PMID 25168830 PMID 25168830 Check
|pmid=value (help). - ↑ Asanuma K, Mundel P (2003). "The role of podocytes in glomerular pathobiology". Clin Exp Nephrol. 7 (4): 255–9. doi:10.1007/s10157-003-0259-6. PMID 14712353.
- ↑ 3.0 3.1 Fogo AB (2003). "Animal models of FSGS: lessons for pathogenesis and treatment". Semin Nephrol. 23 (2): 161–71. doi:10.1053/snep.2003.50015. PMID 12704576.
- ↑ 4.0 4.1 Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ; et al. (2012). "Circulating suPAR in two cohorts of primary FSGS". J Am Soc Nephrol. 23 (12): 2051–9. doi:10.1681/ASN.2012030302. PMC 3507361. PMID 23138488.
- ↑ Rea R, Smith C, Sandhu K, Kwan J, Tomson C (2001). "Successful transplant of a kidney with focal segmental glomerulosclerosis". Nephrol Dial Transplant. 16 (2): 416–7. PMID 11158426.
- ↑ Ghiggeri GM, Artero M, Carraro M, Perfumo F (2001). "Permeability plasma factors in nephrotic syndrome: more than one factor, more than one inhibitor". Nephrol Dial Transplant. 16 (5): 882–5. PMID 11328888.
- ↑ Kemper MJ, Wolf G, Müller-Wiefel DE (2001). "Transmission of glomerular permeability factor from a mother to her child". N Engl J Med. 344 (5): 386–7. doi:10.1056/NEJM200102013440517. PMID 11195803.
- ↑ Harris RC, Neilson EG (2006). "Toward a unified theory of renal progression". Annu Rev Med. 57: 365–80. doi:10.1146/annurev.med.57.121304.131342. PMID 16409155.
- ↑ Kang DH, Joly AH, Oh SW, Hugo C, Kerjaschki D, Gordon KL; et al. (2001). "Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1". J Am Soc Nephrol. 12 (7): 1434–47. PMID 11423572.
- ↑ 10.0 10.1 Kwoh C, Shannon MB, Miner JH, Shaw A (2006). "Pathogenesis of nonimmune glomerulopathies". Annu Rev Pathol. 1: 349–74. doi:10.1146/annurev.pathol.1.110304.100119. PMID 18039119.
- ↑ Hostetter TH (2003). "Hyperfiltration and glomerulosclerosis". Semin Nephrol. 23 (2): 194–9. doi:10.1053/anep.2003.50017. PMID 12704579.
- ↑ Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H; et al. (1998). "Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome". Mol Cell. 1 (4): 575–82. PMID 9660941.
- ↑ Tryggvason K, Patrakka J, Wartiovaara J (2006). "Hereditary proteinuria syndromes and mechanisms of proteinuria". N Engl J Med. 354 (13): 1387–401. doi:10.1056/NEJMra052131. PMID 16571882.
- ↑ Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH; et al. (2003). "CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility". Science. 300 (5623): 1298–300. doi:10.1126/science.1081068. PMID 12764198.
- ↑ Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O; et al. (1999). "Congenital nephrotic syndrome in mice lacking CD2-associated protein". Science. 286 (5438): 312–5. PMID 10514378.
- ↑ Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ; et al. (2000). "Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis". Nat Genet. 24 (3): 251–6. doi:10.1038/73456. PMID 10700177.
- ↑ Winn MP (2003). "Approach to the evaluation of heritable diseases and update on familial focal segmental glomerulosclerosis". Nephrol Dial Transplant. 18 Suppl 6: vi14–20. PMID 12953036.
- ↑ Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH; et al. (2013). "KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis". Am J Kidney Dis. 62 (3): 403–41. doi:10.1053/j.ajkd.2013.06.002. PMID 23871408.
- ↑ Hogan J, Radhakrishnan J (April 2013). "The treatment of minimal change disease in adults". J. Am. Soc. Nephrol. 24 (5): 702–11. doi:10.1681/ASN.2012070734. PMID 23431071.
- ↑ Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A, Kasiske B, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Gustafson S, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L (January 2011). "US Renal Data System 2010 Annual Data Report". Am. J. Kidney Dis. 57 (1 Suppl 1): A8, e1–526. doi:10.1053/j.ajkd.2010.10.007. PMID 21184928.
- ↑ Cohen AH, Nast CC (March 1988). "HIV-associated nephropathy. A unique combined glomerular, tubular, and interstitial lesion". Mod. Pathol. 1 (2): 87–97. PMID 3070550.
- ↑ Ataga KI, Derebail VK, Archer DR (September 2014). "The glomerulopathy of sickle cell disease". Am. J. Hematol. 89 (9): 907–14. doi:10.1002/ajh.23762. PMC 4320776. PMID 24840607.
- ↑ Gopalakrishnan I, Iskandar SS, Daeihagh P, Divers J, Langefeld CD, Bowden DW, Hicks PJ, Rocco MV, Freedman BI (February 2011). "Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variants". Hum. Pathol. 42 (2): 291–4. doi:10.1016/j.humpath.2010.07.016. PMC 3022108. PMID 21074826.