Apolipoprotein L1 gene variants and kidney disease in patients with HIV: a systematic review and meta-analysis

Waziri, Bala; Raji, Yakubu Egigogo; Ekrikpo, Udeme; Naicker, Saraladevi

doi:10.1007/s40620-022-01512-9

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…HIVAN was the primary disease process for only one patient in our cohort, consistent with a recently published Australian series of kidney biopsies in PLWHIV, 15 though this rate is lower than many comparable international cohorts 10,14,15 . We did not collect ethnicity data, though this difference could be explained by higher proportions of patients with black African ancestry with particular alleles of APOL1 gene predisposing to HIVAN in other cohorts 10,14,16 …”

Section: Discussionsupporting

confidence: 85%

“…10,14,15 We did not collect ethnicity data, though this difference could be explained by higher proportions of patients with black African ancestry with particular alleles of APOL1 gene predisposing to HIVAN in other cohorts. 10,14,16 Most patients underwent induction with an anti-IL-2R agent and none received ATG. Our data suggests that a proportion of our recipients received no induction immunosuppression other than steroid which may be a recording error.…”

Section: Discussionmentioning

confidence: 99%

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Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience

McMullen,

Drak,

Basu

et al. 2023

Nephrology

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Kidney transplantation in people living with HIV (PLWHIV) is occurring with increasing frequency. Limited international data suggest comparable patient and graft survival in kidney transplant recipients with and without HIV. All PLWHIV aged ≥18 years who received a kidney transplant between 2000 and 2020 were identified by retrospective data initially extracted from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), with additional HIV‐specific clinical data extracted from linked local health‐care records. Twenty‐five PLWHIV and kidney failure received their first kidney transplant in Australia between January 2000 and December 2020. Majority were male (85%), with median age 54 years (interquartile range, IQR 43–57). Focal segmental glomerulosclerosis was the most common primary kidney disease (20%), followed by polycystic kidney disease (16%). 80% of patients underwent induction with basiliximab and none with anti‐thymocyte globulin (ATG). Participants were followed for median time of 3.5 years (IQR 2.0–6.5). Acute rejection occurred in 24% of patients. Two patients lost their allografts and three died. Virological escape occurred in 28% of patients, with a maximum viral load of 190 copies/mL. In conclusion, kidney transplantation in PLWHIV in Australia is occurring with increasing frequency. Acute rejection is more common than in Australia's general transplant population, but this does not appear to be associated with higher rates of graft failure or mortality out to four years.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience

McMullen,

Drak,

Basu

et al. 2023

Nephrology

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“…Genetics modifiers affecting the penetrance of APOL1 HR alleles: Earlier studies did not identify major genetic modifier loci that altered the penetrance of APOL1 risk alleles [82] Nongenetic modifiers and triggers: Viral induction and other states of elevated Interferon including autoinflammatory type I Interferonopathies, have been elaborated above, with untreated HIV and COVID-19 being the most common [52,88]. Hypoxia and prolyl hydroxylase inhibitors that stabilize hypoxia inducible transcription factors (HIF) were recently shown to induce APOL1 expression in podocytes via active regulatory DNA-element upstream of APOL1 that interacted with HIF [89 & ].…”

Section: Searching For the Second Hitmentioning

confidence: 99%

“…Patients with two APOL1 risk alleles, suffering from autoinflammatory diseases that share a common final pathway of elevated interferon levels, such as systemic lupus erythematosus (SLE), hemophagocytic lymphohistiocytosis (HLH), and STING-associated vasculopathy with onset in infancy (SAVI), can develop collapsing FSGS [49–51]. Similarly, active viral infection such as in under-treated HIV, COVID-19, parvovirus in native kidneys, CMV and BK infection in kidney transplant patients from APOL1 RRV genotype donors and administration of interferon treatment led to collapsing FSGS [3,4,11,52–60]. Riella et al described a new regulatory pathway mediated by adenosine deaminase acting on RNA (ADAR) aimed to reduce APOL1 gene expression and balance the direct interferon stimulatory effect on APOL1 expression [61 ▪▪ ].…”

Section: Crosstalk Of Apol1 and Innate Immune System: Brakes And Indu...mentioning

confidence: 99%

APOL1 nephropathy – a population genetics success story

Tabachnikov,

Skorecki,

Kruzel-Davila

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review More than a decade ago, apolipoprotein L1 (APOL1) risk alleles designated G1 and G2, were discovered to be causally associated with markedly increased risk for progressive kidney disease in individuals of recent African ancestry. Gratifying progress has been made during the intervening years, extending to the development and clinical testing of genomically precise small molecule therapy accompanied by emergence of RNA medicine platforms and clinical testing within just over a decade. Recent findings Given the plethora of excellent prior review articles, we will focus on new findings regarding unresolved questions relating mechanism of cell injury with mode of inheritance, regulation and modulation of APOL1 activity, modifiers and triggers for APOL1 kidney risk penetrance, the pleiotropic spectrum of APOL1 related disease beyond the kidney – all within the context of relevance to therapeutic advances. Summary Notwithstanding remaining controversies and uncertainties, promising genomically precise therapies targeted at APOL1 mRNA using antisense oligonucleotides (ASO), inhibitors of APOL1 expression, and small molecules that specifically bind and inhibit APOL1 cation flux are emerging, many already at the clinical trial stage. These therapies hold great promise for mitigating APOL1 kidney injury and possibly other systemic phenotypes as well. A challenge will be to develop guidelines for appropriate use in susceptible individuals who will derive the greatest benefit.

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The changing landscape of HIV-associated kidney disease

Diana,

Naicker

2024

Nat Rev Nephrol

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Apolipoprotein L1 gene variants and kidney disease in patients with HIV: a systematic review and meta-analysis

Cited by 4 publications

References 34 publications

Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience

Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience

APOL1 nephropathy – a population genetics success story

The changing landscape of HIV-associated kidney disease

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