Predictors of Renal Outcome in HIV‐Associated Nephropathy

Post, Frank A.; Campbell, Lucy; Hamzah, Lisa; Collins, Lisa; Jones, Rachael; Siwani, Rizwan; Johnson, Leann; Fisher, Martin; Holt, Stephen G; Bhagani, Sanjay; Frankel, Andrew; Wilkins, E.G.L.; Ainsworth, Jonathan; Larbalestier, N; Macallan, Derek C.; Banerjee, Debasish; Baily, Guy; Thuraisingham, Raj; Donohoe, Paul; Hendry, Bruce M.; Hilton, Rachel; Edwards, Simon; Hangartner, Robert; Howie, Alexander J.; Connolly, John; Easterbrook, Philippa

doi:10.1086/529385

Cited by 81 publications

(63 citation statements)

References 27 publications

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“…In the United States there has been a steady decline in the incidence of HIVAN with the introduction of HAART, in spite of stable frequencies of the risk variants [68] . Risk factors for progression to ESRD in HIVAN are severity of renal dysfunction, percentage of sclerotic glomeruli [25,69] , lack of viral suppression [26,70] , 2 APOL1 risk alleles [63,71] , while use of renin angiotensin system blockers were reported to be protective [25] . HIV-infected individuals with non-HIVAN pathology and two APOL1 risk alleles had an almost 3-fold risk of ESRD, in spite of effective ARTsuppression of viral load and use of renin-angiotensin aldosterone blockers; baseline kidney function was the strongest predictor of progression to ESRD in this study [71] .…”

Section: Apol1 Susceptibilitymentioning

confidence: 99%

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

Kasembeli

Duarte

Ramsay

et al. 2015

WJN

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Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. are more strongly associated with the risk for HIVAN than the previously reported MYH9 E1 risk haplotype in individuals of African ancestry. The high prevalence of HIVAN among individuals of African ancestry could be a result of high frequencies of APOL1 risk variants as well as the prevalence of HIV-1 subtypes and modifying factors or second hits underlying the pathogenesis of kidney disease.Kasembeli AN, Duarte R, Ramsay M, Naicker S. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era. World

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Section: Apol1 Susceptibilitymentioning

confidence: 99%

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

Kasembeli

Duarte

Ramsay

et al. 2015

WJN

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“…6,7 The pathogenesis is believed to be due to dysregulation of podocytes and tubular epithelia by HIV-1 itself. 8,9 Early identification of HIVAN is important because highly active antiretroviral therapy (HAART), corticosteroids, and inhibition of renin-angiotensin may delay disease progression 6,10,11 . Nonetheless, because HIV infection may be associated with other glomerular diseases, definitive diagnosis of HIVAN requires a kidney biopsy.…”

mentioning

confidence: 99%

Urinary NGAL Marks Cystic Disease in HIV-Associated Nephropathy

Paragas¹,

Nickolas²,

Wyatt³

et al. 2009

Journal of the American Society of Nephrology

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“…Interestingly, the benefit of HAART on HIVAN was contradicted by one retrospective study (total 61 HIVAN with 45 biopsy-confirmed). The study demonstrated that once severe HIVAN was diagnosed, HAART and HIV viral suppression could not prevent progression towards ESRD (Post et al, 2008).…”

Section: Antiretroviral Therapymentioning

confidence: 95%