HIV associated nephropathy overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]
Overview
AIDS was first reported in 1981. The first reported cases of HIV-associated nephropathy (HIVAN) were described in 1984. HIV-associated nephropathy (HIVAN) is mostly seen in male patients and of African decent. It is associated with polymorphysim of Apolipoprotein 1 (APOL1) gene. Renal biopsy is the diagnostic study of choice in HIVAN. The treatment of HIV associated nephropathy (HIVAN) includes: combined antiretroviral therapy (cART), renin–angiotensin–aldosterone system (RAAS) blockade, corticosteroids and renal replacement with dialysis.
Historical Perspective
- AIDS was first reported in 1981.[1][2]
- The first reported cases of HIV-associated nephropathy (HIVAN) were described in 1984.[3]
Pathophysiology
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.[4]
Causes
Currently there are no known established causes of HIV-associated nephropathy. However, the genetic component, a key to the pathogenesis of the disease in blacks but not in other races is a factor that is seen in HIV-associated nephropathy.[5]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).[6]
Differentiating HIV associated nephropathy from other Diseases
HIV-associated nephropathy must be differentiated form other diseases that cause focal segmental glomerulonephritis, high grade proteinuria, and elevated serum creatinine levels.
Epidemiology and Demographics
HIV-associated nephropathy (HIVAN) is mostly seen in male patients and of African decent. The prevalence of HIVAN in the population of patients with African descent has been reported to be 3% to 12%.[7]
Risk Factors
The risk factors that attribute to HIV-associated nephropathy are similar to those seen with HIV. Positive predicators for HIV-associated nephropathy include: polymorphysim of Apolipoproetin-1 (APOL1) gene, high viral load, low CD-4 count, proteinuria (nephrotic range), and higher level of renal echogenicity on ultrasound.[4]
Screening
Screening for kidney disease is recommended in high risk populations in all patients with seropositive HIV-1 (upon detection).[8]
Natural History, Complications and Prognosis
HIV-associated nephropathy (HIVAN) will progress to end-stage renal disease (ESRD) in a few weeks to months without treatment. However, early diagnosis and treatment has shown better outcome.[9]
Diagnosis
History and Symptoms
Obtaining a complete history is an important aspect in making a clinical diagnosis of HIV-associated nephropathy. The initial symptoms that are seen in patients presenting with HIV-associated nephropathy are non specific in nature as other glomerular diseases may express similar clinical presentations. The following are symptoms that are seen in HIV-associated nephropathy: fatigue, malaise, anorexia and pruritus.[10]
Physical Examination
A complete physical examination in a patient with HIV-associated nephropathy is dependent on the stage of the disease. Physical examinations findings seen in patients are typically similar to those who are infected with HIV but do not present with renal involvement.
Diagnostic Study of Choice
Renal biopsy is the diagnostic study of choice for HIV-associated nephropathy (HIVAN). Renal biopsy reveals the following findings: collapsing focal segmental glomerulonephritis, significant tubulointerstitial injury, interstitial fibrosis and inflammation and microcystic tubular dilation.[11]
Laboratory Findings
Laboratory findings in HIV-associated nephropathy include: proteinuria, elevated serum creatinine levels, decreased GFR, dyslipidemia, and CD4 counts below 200 cells/mm3.[12][13]
KUB X-ray
There are no x-ray findings associated with HIV associated nephropathy.
CT
There are no CT findings associated with HIV associated nephropathy.
MRI
There are no MRI findings associated with HIV associated nephropathy.
Ultrasound
Renal ultrasound in patients with HIV-associated nephropathy (HIVAN) reveals higher renal echogenicity.[14]
Other Imaging Findings
There are no other imaging findings associated with HIV associated nephropathy.
Other Diagnostic Studies
There are no other diagnostic studies associated with HIV associated nephropathy.
Treatmennt
Medical Therapy
The treatment of HIV associated nephropathy (HIVAN) includes: combined antiretroviral therapy (cART), renin–angiotensin–aldosterone system (RAAS) blockade, corticosteroids and renal replacement with dialysis.[15]
Surgery
- Kidney transplantation is increasing in HIV-positive patients with end-stage renal disease (ESRD).[8]
- Although the rejection rate is high, the graft survival rates are high.[16][17]
- Recently reports have shown successful kidney transplantation from HIV-positive donors to HIV-positive recipients.[18][19]
Prevention
HIV-positive patients should be screened for chronic kidney disease (CKD). Interventions in HIV-positive patients with renal disease should be done in order to slow the progress and prevent end stage renal disease (ESRD) and they should be referred to a nephrologist.[8][20]
Cost-Effectiveness of Therapy
There is insufficient information about the cost-effectiveness of therapy in HIV associated nephropathy. The World Health Organization (WHO) data on HIV/AIDS for 2018 is 37.9 million people living with HIV/AIDS worldwide and 770 000 deaths due to HIV-related illnesses worldwide.[21]
Future or Investigational Therapies
- Therapies such as molecular targeting require more research.[7]
- Recently, there have been reports of successful kidney transplantation from HIV-positive donors to HIV-positive recipients.[18][19]
References
- ↑ Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA; et al. (1981). "Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency". N Engl J Med. 305 (24): 1425–31. doi:10.1056/NEJM198112103052401. PMID 6272109.
- ↑ Centers for Disease Control (CDC) (1982). "A cluster of Kaposi's sarcoma and Pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and Orange Counties, California". MMWR Morb Mortal Wkly Rep. 31 (23): 305–7. PMID 6811844.
- ↑ Rao TK, Filippone EJ, Nicastri AD, Landesman SH, Frank E, Chen CK; et al. (1984). "Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome". N Engl J Med. 310 (11): 669–73. doi:10.1056/NEJM198403153101101. PMID 6700641.
- ↑ 4.0 4.1 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.
- ↑ Klotman PE (1999). "HIV-associated nephropathy". Kidney Int. 56 (3): 1161–76. doi:10.1046/j.1523-1755.1999.00748.x. PMID 10469389.
- ↑ 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.
- ↑ 7.0 7.1 Menez S, Hanouneh M, McMahon BA, Fine DM, Atta MG (2018). "Pharmacotherapy and treatment options for HIV-associated nephropathy". Expert Opin Pharmacother. 19 (1): 39–48. doi:10.1080/14656566.2017.1416099. PMC 6381591. PMID 29224373.
- ↑ 8.0 8.1 8.2 Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA; et al. (2018). "HIV-associated nephropathy: links, risks and management". HIV AIDS (Auckl). 10: 73–81. doi:10.2147/HIV.S141978. PMC 5975615. PMID 29872351.
- ↑ Atta MG, Lucas GM, Fine DM (2008). "HIV-associated nephropathy: epidemiology, pathogenesis, diagnosis and management". Expert Rev Anti Infect Ther. 6 (3): 365–71. doi:10.1586/14787210.6.3.365. PMID 18588500.
- ↑ Brook MG, Miller RF (2001). "HIV associated nephropathy: a treatable condition". Sex Transm Infect. 77 (2): 97–100. PMC 1744263. PMID 11287685.
- ↑ 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.
- ↑ Lescure FX, Flateau C, Pacanowski J, Brocheriou I, Rondeau E, Girard PM; et al. (2012). "HIV-associated kidney glomerular diseases: changes with time and HAART". Nephrol Dial Transplant. 27 (6): 2349–55. doi:10.1093/ndt/gfr676. PMID 22248510.
- ↑ Bigé N, Lanternier F, Viard JP, Kamgang P, Daugas E, Elie C; et al. (2012). "Presentation of HIV-associated nephropathy and outcome in HAART-treated patients". Nephrol Dial Transplant. 27 (3): 1114–21. doi:10.1093/ndt/gfr376. PMID 21745806.
- ↑ Atta MG, Longenecker JC, Fine DM, Nagajothi N, Grover DS, Wu J; et al. (2004). "Sonography as a predictor of human immunodeficiency virus-associated nephropathy". J Ultrasound Med. 23 (5): 603–10, quiz 612-3. doi:10.7863/jum.2004.23.5.603. PMID 15154526.
Other Imaging Findings
There are no other imaging findings associated with HIV associated nephropathy.
Other Diagnostic Studies
There are no other diagnostic studies associated with HIV associated nephropathy.
Treatment
Medical Therapy
The treatment of HIV associated nephropathy (HIVAN) includes: combined antiretroviral therapy (cART), renin–angiotensin–aldosterone system (RAAS) blockade, corticosteroids and renal replacement with dialysis.<ref name="pmidpmid29872351">Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA; et al. (2018). "HIV-associated nephropathy: links, risks and management". HIV AIDS (Auckl). 10: 73–81. doi:10.2147/HIV.S141978. PMC 5975615. PMID pmid29872351 Check
|pmid=value (help). - ↑ Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA; et al. (2018). "HIV-associated nephropathy: links, risks and management". HIV AIDS (Auckl). 10: 73–81. doi:10.2147/HIV.S141978. PMC 5975615. PMID pmid29872351 Check
|pmid=value (help). - ↑ Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J; et al. (2010). "Outcomes of kidney transplantation in HIV-infected recipients". N Engl J Med. 363 (21): 2004–14. doi:10.1056/NEJMoa1001197. PMC 3028983. PMID 21083386.
- ↑
- ↑ 18.0 18.1 Muller E, Barday Z, Mendelson M, Kahn D (2015). "HIV-positive-to-HIV-positive kidney transplantation--results at 3 to 5 years". N Engl J Med. 372 (7): 613–20. doi:10.1056/NEJMoa1408896. PMC 5090019. PMID 25671253.
- ↑ 19.0 19.1 Durand CM, Segev D, Sugarman J (2016). "Realizing HOPE: The Ethics of Organ Transplantation From HIV-Positive Donors". Ann Intern Med. 165 (2): 138–42. doi:10.7326/M16-0560. PMC 4949150. PMID 27043422.
- ↑ Fine DM, Perazella MA, Lucas GM, Atta MG (2008). "Kidney biopsy in HIV: beyond HIV-associated nephropathy". Am J Kidney Dis. 51 (3): 504–14. doi:10.1053/j.ajkd.2007.12.005. PMID 18295067.
- ↑ "WHO | HIV/AIDS".