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__NOTOC__
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{{HIV associated nephropathy}}
{{HIV associated nephropathy}}
{{CMG}}{{APM}};{{AE}}{{KW}}
{{CMG}}{{APM}};{{AE}}{{SHA}}{{KW}}
==Overview==
==Overview==
HIV associated nephropathy (HIVAN) is mostly seen in patients of African decent. Some factors involving HIV associated nephropathy (HIVAN) pathology includes: HIV-1 replication in the kidney, [[Human Immunodeficiency Virus (HIV)|HIV-1]] gene products, increased proliferation, [[apoptosis]] and dedifferentiation of [[Podocyte|podocytes]] and polymorphysim of [[APOL1|Apolipoprotein 1 (APOL1)]] polymorphysim gene.<ref name="pmid24655211" />
==Pathogenesis==
==Pathogenesis==
The pathogenesis of HIV-associated nephropathy is heavily dependent upon viral, genetic, and enviornmental co factors.<ref name="pmid9692355">{{cite journal| author=Schwartz EJ, Klotman PE| title=Pathogenesis of human immunodeficiency virus (HIV)-associated nephropathy. | journal=Semin Nephrol | year= 1998 | volume= 18 | issue= 4 | pages= 436-45 | pmid=9692355 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9692355  }}</ref>
HIV associated nephropathy (HIVAN) is mostly seen in patients of African decent.<ref name="pmid24655211" />


'''Viral:'''
Some factors involving HIV associated nephropathy (HIVAN) pathology includes:<ref name="pmid24655211">{{cite journal| author=Waheed S, Atta MG| title=Predictors of HIV-associated nephropathy. | journal=Expert Rev Anti Infect Ther | year= 2014 | volume= 12 | issue= 5 | pages= 555-63 | pmid=24655211 | doi=10.1586/14787210.2014.901170 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24655211  }} </ref>


HIV-1 is the strongest risk factor that is associated with the development of HIV-associated nephropathy. It has been found through murine studies, that showed HIV-1 infected mice expressed similar renal disease clinical and pathological characteristics of patients who had HIV-associated nephropathy.
=== Pathogenesis ===


'''Genetic and Enviornmental Co factors''':
===== Viral Factors =====


Genetic factors most certainly play an intricate role in disease progression. Approximately 90% of patient infected with HIV-associated nephropathy are black. This suggests a strong racial predilection for HIV-associated nephropathy. It is also important to note that through genetic tests APOL1 gene that is found on chromosome 22 is found more commonly in blacks than in any other races.
* Proviral [[DNA]] has been reported in the renal tissue of all patients with HIV associated nephropathy (HIVAN) even in those with negative HIV-1 RNA levels in plasma.<ref name="pmid20624771">{{cite journal| author=Izzedine H, Acharya V, Wirden M, Cluzel P, Sene D, Lucas GM | display-authors=etal| title=Role of HIV-1 DNA levels as clinical marker of HIV-1-associated nephropathies. | journal=Nephrol Dial Transplant | year= 2011 | volume= 26 | issue= 2 | pages= 580-3 | pmid=20624771 | doi=10.1093/ndt/gfq414 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20624771  }} </ref>
*[[Human Immunodeficiency Virus (HIV)|HIV-1]] can replicate in the kidney even in those patients who are on treatment.<ref name="pmid21358326">{{cite journal| author=Medapalli RK, He JC, Klotman PE| title=HIV-associated nephropathy: pathogenesis. | journal=Curr Opin Nephrol Hypertens | year= 2011 | volume= 20 | issue= 3 | pages= 306-11 | pmid=21358326 | doi=10.1097/MNH.0b013e328345359a | pmc=3153858 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21358326  }} </ref> 
*[[Human Immunodeficiency Virus (HIV)|HIV-1]] gene products such as nef (negative effector) and vpr (viral protein r) are reported to be involved in the [[pathogenesis]].<ref name="pmid20005489">{{cite journal| author=Atta MG| title=Diagnosis and natural history of HIV-associated nephropathy. | journal=Adv Chronic Kidney Dis | year= 2010 | volume= 17 | issue= 1 | pages= 52-8 | pmid=20005489 | doi=10.1053/j.ackd.2009.08.005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20005489  }} </ref>
* Increased proliferation, [[apoptosis]] and dedifferentiation of [[Podocyte|podocytes]] have been reported in HIVAN.<ref name="pmid21358326">{{cite journal| author=Medapalli RK, He JC, Klotman PE| title=HIV-associated nephropathy: pathogenesis. | journal=Curr Opin Nephrol Hypertens | year= 2011 | volume= 20 | issue= 3 | pages= 306-11 | pmid=21358326 | doi=10.1097/MNH.0b013e328345359a | pmc=3153858 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21358326  }} </ref>


Environmental factors that are associated with HIV-associated nephropathy, include intravenous drug abuse, men having sex with other men, and those who have more than one sexual partner are at increased risk in the development of HIV.    
===== Genetic Factor =====
High risk [[Allele|alleles]] G1 (a missense mutation) and G2 (a frameshift deletion) for [[APOL1|Apolipoprotein 1 (APOL1)]] are associated with HIVAN ([[APOL1]] gene is on chromosome 22).<ref name="pmid21997394">{{cite journal| author=Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P | display-authors=etal| title=APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. | journal=J Am Soc Nephrol | year= 2011 | volume= 22 | issue= 11 | pages= 2129-37 | pmid=21997394 | doi=10.1681/ASN.2011040388 | pmc=3231787 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21997394  }} </ref>


The development of HIV-associated nephropathy, is suggestive upon HIV-1 affecting the renal epithelium. This reasoning provides that localized replication of the virus in the renal epithelium is needed for the development of HIV-associated nephropathy. However, the mechanism of how the virus induces renal injure is still not conclusive. However, what is known is that in order for the virus to proliferate, the virus's gene products trigger the process of apoptosis. In some studies conducted, HIV protease that is encoded in the pol gene, is found to cleave Bcl-2, which lead to apoptosis of the renal cells in a monkey. However, this still not well established.<ref name="pmid8790371">{{cite journal| author=Strack PR, Frey MW, Rizzo CJ, Cordova B, George HJ, Meade R et al.| title=Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. | journal=Proc Natl Acad Sci U S A | year= 1996 | volume= 93 | issue= 18 | pages= 9571-6 | pmid=8790371 | doi= | pmc=38469 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8790371 }}</ref> The role cytokines play in the mechanism of HIV-associated nephropathy is still not clearly known, and is seen as non essential in HIV-associated nephropathy.<ref name="pmid9692355" />
==Gross Pathology==
 
On gross [[pathology]], kidneys in HIV-associated nephropathy have the following features:<ref name="pmid2770114">{{cite journal| author=D'Agati V, Suh JI, Carbone L, Cheng JT, Appel G| title=Pathology of HIV-associated nephropathy: a detailed morphologic and comparative study. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 6 | pages= 1358-70 | pmid=2770114 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2770114 }}</ref>
==Associated Conditions==
The following are conditions that are associated with HIV-associated nephropathy:


==Gross Pathology==
* Pale
On gross pathology, HIV-associated nephropathy is characterized as the renal being pale, unevenly enlarged, having a smooth cortical surface and tubulars that are dilated.<ref name="pmid2770114">{{cite journal| author=D'Agati V, Suh JI, Carbone L, Cheng JT, Appel G| title=Pathology of HIV-associated nephropathy: a detailed morphologic and comparative study. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 6 | pages= 1358-70 | pmid=2770114 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2770114  }}</ref>
* Unevenly enlarged
* Smooth cortical surface.  
==Microscopic Pathology==
==Microscopic Pathology==
On microscopic histological analysis, focal segmental glomerulosclerosis, tubuointerstital injury, and microcystic tubular dilation are characteristics findings of HIV-associated nephropathy.<ref name="pmid2770114">{{cite journal| author=D'Agati V, Suh JI, Carbone L, Cheng JT, Appel G| title=Pathology of HIV-associated nephropathy: a detailed morphologic and comparative study. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 6 | pages= 1358-70 | pmid=2770114 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2770114  }}</ref>
On [[microscopic]] [[pathology]], kidneys in HIV-associated nephropathy have the following features:<ref name="pmid2770114" />
 
{| class="wikitable"
|+
! colspan="3" |Histopathology of HIV-associated nephropathy
|-
!Light Microscopy<ref name="pmid2770114" />
!Electron Microscopy<ref name="pmid2770114" />
!'''Immunofluorescence<ref name="pmid2770114" />'''
|-
|
* Collapsing  [[Focal segmental glomerulosclerosis|focal segmental glomerulosclerosis (FSGS)]]
* Hypertrophied visceral epithelial cells  
* Tubulointerstitial Injury:
** Microcysts tubular dilation
** Interstitial [[fibrosis]] and [[inflammation]]  
|
** Wrinkling and folding of the [[Glomerular basement membrane|glomerular basement membrane (GBM)]]
** Hypertrophied visceral epithelial cells   
** Visceral epithelial cells foot process effacement.  
** Numerous tubuloreticular inclusions (TRI)
** Nuclear bodies
|
* No specific findings 
* Variable amounts of [[Antibody|immunoglobulins]] and/or [[complement]]
|}
 
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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[[Category:HIV/AIDS]]
[[Category:HIV/AIDS]]
[[Category:Immune system disorders]]
[[Category:Immune system disorders]]
[[Category:Infectious disease]]
 
[[Category:Viral diseases]]
[[Category:Viral diseases]]

Latest revision as of 19:17, 30 June 2020

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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: Shakiba Hassanzadeh, MD[3]Krzysztof Wierzbicki M.D. [4]

Overview

HIV associated nephropathy (HIVAN) is mostly seen in patients of African decent. Some factors involving HIV associated nephropathy (HIVAN) pathology includes: HIV-1 replication in the kidney, HIV-1 gene products, increased proliferation, apoptosis and dedifferentiation of podocytes and polymorphysim of Apolipoprotein 1 (APOL1) polymorphysim gene.[1]

Pathogenesis

HIV associated nephropathy (HIVAN) is mostly seen in patients of African decent.[1]

Some factors involving HIV associated nephropathy (HIVAN) pathology includes:[1]

Pathogenesis

Viral Factors
  • Proviral DNA has been reported in the renal tissue of all patients with HIV associated nephropathy (HIVAN) even in those with negative HIV-1 RNA levels in plasma.[2]
  • HIV-1 can replicate in the kidney even in those patients who are on treatment.[3] 
  • HIV-1 gene products such as nef (negative effector) and vpr (viral protein r) are reported to be involved in the pathogenesis.[4]
  • Increased proliferation, apoptosis and dedifferentiation of podocytes have been reported in HIVAN.[3]
Genetic Factor

High risk alleles G1 (a missense mutation) and G2 (a frameshift deletion) for Apolipoprotein 1 (APOL1) are associated with HIVAN (APOL1 gene is on chromosome 22).[5]

Gross Pathology

On gross pathology, kidneys in HIV-associated nephropathy have the following features:[6]

  • Pale
  • Unevenly enlarged
  • Smooth cortical surface.

Microscopic Pathology

On microscopic pathology, kidneys in HIV-associated nephropathy have the following features:[6]

Histopathology of HIV-associated nephropathy
Light Microscopy[6] Electron Microscopy[6] Immunofluorescence[6]
    • Wrinkling and folding of the glomerular basement membrane (GBM)
    • Hypertrophied visceral epithelial cells  
    • Visceral epithelial cells foot process effacement.  
    • Numerous tubuloreticular inclusions (TRI)
    • Nuclear bodies

 

References

  1. ↑ 1.0 1.1 1.2 Waheed S, Atta MG (2014). "Predictors of HIV-associated nephropathy". Expert Rev Anti Infect Ther. 12 (5): 555–63. doi:10.1586/14787210.2014.901170. PMID 24655211.
  2. ↑ Izzedine H, Acharya V, Wirden M, Cluzel P, Sene D, Lucas GM; et al. (2011). "Role of HIV-1 DNA levels as clinical marker of HIV-1-associated nephropathies". Nephrol Dial Transplant. 26 (2): 580–3. doi:10.1093/ndt/gfq414. PMID 20624771.
  3. ↑ 3.0 3.1 Medapalli RK, He JC, Klotman PE (2011). "HIV-associated nephropathy: pathogenesis". Curr Opin Nephrol Hypertens. 20 (3): 306–11. doi:10.1097/MNH.0b013e328345359a. PMC 3153858. PMID 21358326.
  4. ↑ Atta MG (2010). "Diagnosis and natural history of HIV-associated nephropathy". Adv Chronic Kidney Dis. 17 (1): 52–8. doi:10.1053/j.ackd.2009.08.005. PMID 20005489.
  5. ↑ Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P; et al. (2011). "APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy". J Am Soc Nephrol. 22 (11): 2129–37. doi:10.1681/ASN.2011040388. PMC 3231787. PMID 21997394.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 D'Agati V, Suh JI, Carbone L, Cheng JT, Appel G (1989). "Pathology of HIV-associated nephropathy: a detailed morphologic and comparative study". Kidney Int. 35 (6): 1358–70. PMID 2770114.

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