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 mediator 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.   
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

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Focal segmental glomerulosclerosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X-Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Focal segmental glomerulosclerosis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Focal segmental glomerulosclerosis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Focal segmental glomerulosclerosis pathophysiology

CDC on Focal segmental glomerulosclerosis pathophysiology

Focal segmental glomerulosclerosis pathophysiology in the news

Blogs on Focal segmental glomerulosclerosis pathophysiology

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

Pathogenesis of secondary FSGS

The pathogenesis of secondary focal segmental glomerulosclerosis (FSGS) occurs due to the following factors:

Genetics

The development of focal segmental glomerulosclerosis is the result of multiple genetic mutations such as:[12][10][13][14][15][16][17][18]

Associated Conditions

Conditions associated with focal segmental glomerulosclerosis (FSGS):[19][20][21][22][23][24][25]

Microscopic Pathology

On microscopic histopathological analysis progressive changes seen are:[10][26]

References

  1. 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).
  2. 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. 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. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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. 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.
  11. Hostetter TH (2003). "Hyperfiltration and glomerulosclerosis". Semin Nephrol. 23 (2): 194–9. doi:10.1053/anep.2003.50017. PMID 12704579.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.


Template:WH Template:WS