HIV associated nephropathy pathophysiology: Difference between revisions

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==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, HIV-1 gene products, increased proliferation, apoptosis and dedifferentiation of podocytes and polymorphysim of Apolipoprotein 1 (APOL1) polymorphysim gene.
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.


==Pathogenesis==
==Pathogenesis==
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===== Viral Factors =====
===== 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 plama.<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>
* 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>
* 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]] 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> 
* 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>
*[[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 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>
* 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>


===== Genetic Factor =====
===== 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).<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>
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>


==Gross Pathology==
==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>
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>


* Pale
* Pale
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|}
|}


On microscopic pathology, kidneys in HIV-associated nephropathy have the following features:<ref name="pmid2770114" />
On [[microscopic]] [[pathology]], kidneys in HIV-associated nephropathy have the following features:<ref name="pmid2770114" />
{| class="wikitable"
{| class="wikitable"
|+
|+
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|-
|-
|
|
* Collapsing  focal segmental glomerulosclerosis (FSGS)  
* Collapsing  [[Focal segmental glomerulosclerosis|focal segmental glomerulosclerosis (FSGS)]]
* Hypertrophied visceral epithelial cells  
* Hypertrophied visceral epithelial cells  
* Tubulointerstitial Injury:
* Tubulointerstitial Injury:
** Microcysts tubular dilation  
** Microcysts tubular dilation
** Interstitial fibrosis and inflammation  
** Interstitial [[fibrosis]] and [[inflammation]]  
|
|
** Wrinkling and folding of the glomerular basement membrane (GBM)  
** Wrinkling and folding of the [[Glomerular basement membrane|glomerular basement membrane (GBM)]]
** Hypertrophied visceral epithelial cells   
** Hypertrophied visceral epithelial cells   
** Visceral epithelial cells foot process effacement.  
** Visceral epithelial cells foot process effacement.  
Line 86: Line 86:
|
|
* No specific findings   
* No specific findings   
* Variable amounts of immunoglobulins and/or complement  
* Variable amounts of [[Antibody|immunoglobulins]] and/or [[complement]]
|}
|}
 
 

Revision as of 16:14, 29 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.

Pathogenesis

The pathogenesis of HIV-associated nephropathy is heavily dependent upon viral, genetic, and enviornmental co factors.[1]

Viral:

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 HIV-1 infected mice expressed similar clinical and pathological characteristics to those affected by HIV-associated nephropathy.

Genetic and Enviornmental Co 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 found on chromosome 22 is more commonly found in blacks than in any other race.

Environmental factors associated with HIV-associated nephropathy:


Increased risk of developing HIV
Intravenous drug use
Men having sex with men
Having more than one sexual partner


It is hypothesized that HIV-associated nephropathy is attributed to the HIV-1 virus attacking the renal epithelium, suggesting that a localized replication of the virus of the renal epithelium is needed. However, the mechanism of how the virus induces renal injure is still inconclusive. However, what is known is that in order for the virus to proliferate, the virus induces apoptosis. In various conducted studies, HIV protease (encoded in the pol gene) is found to cleave Bcl-2 and inducing apoptosis of the renal cells monkeys. However, this still not well established.[2] 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.[1]

HIV associated nephropathy (HIVAN) is mostly seen in patients of African decent.[3]

Some factors involving HIV associated nephropathy (HIVAN) pathology includes:[3]

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.[4]
  • HIV-1 can replicate in the kidney even in those patients who are on treatment.[5] 
  • HIV-1 gene products such as nef (negative effector) and vpr (viral protein r) are reported to be involved in the pathogenesis.[6]
  • Increased proliferation, apoptosis and dedifferentiation of podocytes have been reported in HIVAN.[5]
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).[7]

Gross Pathology

On gross pathology, kidneys in HIV-associated nephropathy have the following features:[8]

  • Pale
  • Unevenly enlarged
  • Smooth cortical surface.

Microscopic Pathology

Light Microscopy[9] Electron Microscopy[10] Immunofluorescence[11]
characteristically seen as a visceral epithelium that displays hyperplasia and hypertrophy; due a segmental or global glomerular tuft collapse. When examining the hypertrophic portions of the visceral epithelium protein droplets are seen. a glomerular basement membrane that is wrinkled and collapsed; displaying vacuoles and protein droplets hypertrophic and hyperplastic portions of the visceral epithelium, foot process effacements that are quite extensive and tubuloreticular aggregates that are present in endothelial cells. However, not all patients display tubuloreticular aggregates as the pattern is no seen in patients who express low viral loads (due to combined antiretroviral therapy). Immune deposits that show a limited nonspecific deposition (IgM and C3 in collapsed segments) or no deposits. Visceral

On microscopic pathology, kidneys in HIV-associated nephropathy have the following features:[8]

Histopathology of HIV-associated nephropathy
Light Microscopy[8] Electron Microscopy[8] Immunofluorescence[8]
    • 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 Schwartz EJ, Klotman PE (1998). "Pathogenesis of human immunodeficiency virus (HIV)-associated nephropathy". Semin Nephrol. 18 (4): 436–45. PMID 9692355.
  2. ↑ Strack PR, Frey MW, Rizzo CJ, Cordova B, George HJ, Meade R; et al. (1996). "Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2". Proc Natl Acad Sci U S A. 93 (18): 9571–6. PMC 38469. PMID 8790371.
  3. ↑ 3.0 3.1 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.
  4. ↑ 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.
  5. ↑ 5.0 5.1 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 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.
  9. ↑ Fogo AB, Lusco MA, Najafian B, Alpers CE (2016). "AJKD Atlas of Renal Pathology: HIV-Associated Immune Complex Kidney Disease (HIVICK)". Am J Kidney Dis. 68 (2): e9–e10. doi:10.1053/j.ajkd.2016.06.003. PMID 27477364.
  10. ↑ Fogo AB, Lusco MA, Najafian B, Alpers CE (2016). "AJKD Atlas of Renal Pathology: HIV-Associated Immune Complex Kidney Disease (HIVICK)". Am J Kidney Dis. 68 (2): e9–e10. doi:10.1053/j.ajkd.2016.06.003. PMID 27477364.
  11. ↑ Fogo AB, Lusco MA, Najafian B, Alpers CE (2016). "AJKD Atlas of Renal Pathology: HIV-Associated Immune Complex Kidney Disease (HIVICK)". Am J Kidney Dis. 68 (2): e9–e10. doi:10.1053/j.ajkd.2016.06.003. PMID 27477364.

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