HIV associated nephropathy pathophysiology
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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
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:
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]
Some factors involving HIV associated nephropathy (HIVAN) pathology includes:[3]
Pathogenesis
- 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.[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
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).
Gross Pathology
On gross pathology, kidneys in HIV-associated nephropathy have the following features:[7]
- Pale
- Unevenly enlarged
- Smooth cortical surface.
Microscopic Pathology
| Light Microscopy[8] | Electron Microscopy[9] | Immunofluorescence[10] |
On microscopic pathology, kidneys in HIV-associated nephropathy have the following features:[7]
| Histopathology of HIV-associated nephropathy | ||
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| Light Microscopy[7] | Electron Microscopy[7] | Immunofluorescence[7] |
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References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 5.0 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.
- ↑ 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.
- ↑ 7.0 7.1 7.2 7.3 7.4 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.