Focal segmental glomerulosclerosis pathophysiology: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 10: | Line 10: | ||
==Overview== | ==Overview== | ||
The pathophysiology of focal segmental glomerulosclerosis (FSGS) is based on two types of FSGS. Primary FSGS is also known as idiopathic FSGS, there is a hypothesis that suggests it occurs as a result of circulating immune activating factors interacting with the glomerular epithelium. The underlying pathogenesis of FSGS is fusion or effacement of the foot processes (podocytes) of the glomeruli and sclerosing of some parts of the glomeruli. These changes result in apoptosis and detachment of the glomerular basement membrane (GBM) resulting in subsequent loss of negative charge on podocytes and podocytopenia. Secondary FSGS is based on glomerular hypertrophy and hyperfiltration and over expression of inflammatory | The [[pathophysiology]] of focal segmental glomerulosclerosis (FSGS) is based on two types of FSGS. Primary FSGS is also known as [[idiopathic]] FSGS, there is a [[hypothesis]] that suggests it occurs as a result of circulating [[immune]] activating factors interacting with the [[glomerular]] [[epithelium]]. The underlying [[pathogenesis]] of FSGS is fusion or [[effacement]] of the foot processes ([[podocytes]]) of the [[glomeruli]] and sclerosing of some parts of the [[glomeruli]]. These changes result in [[apoptosis]] and detachment of the [[Glomerular basement membrane|glomerular basement membrane (GBM)]] resulting in subsequent loss of negative charge on [[podocytes]] and podocytopenia. Secondary FSGS is based on [[glomerular]] [[hypertrophy]] and hyperfiltration and over expression of [[inflammatory]] mediators such as, [[TGF-beta]], [[PDGF]] and [[VEGF]]. The underlying [[pathogenesis]] can be based on multiple [[genetic]] [[mutations]] in NPHS1, NEPH1, [[NPHS2]], [[WT1]] and [[INF2]] [[genes]]. Conditions associated with [[FSGS]] include, [[diabetes]], [[HIV]], [[sickle cell disease]], [[nephrotic syndrome]] and [[minimal change disease]]. On [[microscopic]] [[histopathological]] analysis progressive changes seen are, foot process [[effacement]], [[podocyte]] [[apoptosis]], exposed [[GBM]], [[capillary]] expansion and mesangial [[matrix]] [[proliferation]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
Revision as of 21:17, 14 August 2018
| https://https://www.youtube.com/watch?v=l7ZyAmGA98w%7C350}} |
|
Focal segmental glomerulosclerosis Microchapters |
|
Differentiating Focal segmental glomerulosclerosis from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Focal segmental glomerulosclerosis pathophysiology On the Web |
|
American Roentgen Ray Society Images of Focal segmental glomerulosclerosis pathophysiology |
|
Focal segmental glomerulosclerosis pathophysiology in the news |
|
Directions to Hospitals Treating Focal segmental glomerulosclerosis |
|
Risk calculators and risk factors for Focal segmental glomerulosclerosis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [3], Manpreet Kaur, MD [4], Cafer Zorkun, M.D., Ph.D. [5], Olufunmilola Olubukola M.D.[6]
Overview
The pathophysiology of focal segmental glomerulosclerosis (FSGS) is based on two types of FSGS. Primary FSGS is also known as idiopathic FSGS, there is a hypothesis that suggests it occurs as a result of circulating immune activating factors interacting with the glomerular epithelium. The underlying pathogenesis of FSGS is fusion or effacement of the foot processes (podocytes) of the glomeruli and sclerosing of some parts of the glomeruli. These changes result in apoptosis and detachment of the glomerular basement membrane (GBM) resulting in subsequent loss of negative charge on podocytes and podocytopenia. Secondary FSGS is based on glomerular hypertrophy and hyperfiltration and over expression of inflammatory mediators such as, TGF-beta, PDGF and VEGF. The underlying pathogenesis can be based on multiple genetic mutations in NPHS1, NEPH1, NPHS2, WT1 and INF2 genes. Conditions associated with FSGS include, diabetes, HIV, sickle cell disease, nephrotic syndrome and minimal change disease. On microscopic histopathological analysis progressive changes seen are, foot process effacement, podocyte apoptosis, exposed GBM, capillary expansion and mesangial matrix proliferation.
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]
- The damaging role of circulating factors like the soluble urokinase plasminogen activating receptor (suPAR) on the glomerular podocytes had been suggested.[1]
- The underlying pathogenesis of FSGS is fusion or effacement of the foot processes (podocytes) of the glomeruli, with sclerosing of some parts of the glomeruli (hence the name focal segmental).
- The involvement of the permselective filtration barrier and effacement of podocyte foot processes are inevitable.
- 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:
- Soluble urokinase plasminogen activating receptor (suPAR) and MicroRNAs.[1]
- suPAR is a heavily glycosylated protein that can be found in several places.[4][5][6][7]
- Cardiotrophin-like cytokine factor-1 (CLCF1)
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]
- Various inflammatory mediators include over-expression of:[3][10][11]
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
- Mitochondrial cytopathies
Associated Conditions
Conditions associated with focal segmental glomerulosclerosis (FSGS):[19][20][21][22][23][24][25]
- Diabetes
- Human immunodeficiency virus (HIV)
- Sickle cell disease
- Systemic lupus erythematosus (SLE)
- Nephrotic syndrome
- End stage renal disease (ESRD)
- Minimal change disease
Microscopic Pathology
On microscopic histopathological analysis progressive changes seen are:[10][26]
- Foot process effacement
- Podocyte apoptosis
- Exposed glomerular basement membrane
- Capillary expansion
- Formation of synechiae
- Mesangial matrix proliferation
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 10.2 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.
- ↑ Hanaoka H, Hashiguchi A, Konishi K, Kuwana M, Takeuchi T (May 2015). "An unusual association between focal segmental sclerosis and lupus nephritis: a distinct concept from lupus podocytopathy?". CEN Case Rep. 4 (1): 70–75. doi:10.1007/s13730-014-0142-1. PMC 5411626. PMID 28509272.
- ↑ Brown EJ, Pollak MR, Barua M (May 2014). "Genetic testing for nephrotic syndrome and FSGS in the era of next-generation sequencing". Kidney Int. 85 (5): 1030–8. doi:10.1038/ki.2014.48. PMC 4118212. PMID 24599252.
- ↑ Reidy K, Kaskel FJ (March 2007). "Pathophysiology of focal segmental glomerulosclerosis". Pediatr. Nephrol. 22 (3): 350–4. doi:10.1007/s00467-006-0357-2. PMC 1794138. PMID 17216262.