The evolving story of apolipoprotein L1 nephropathy: the end of the beginning

Abstract

Genetic coding variants in APOL1 , which encodes apolipoprotein L1 (APOL1), were identified in 2010 and are relatively common among individuals of sub-Saharan African ancestry. Approximately 13% of African Americans carry two APOL1 risk alleles. These variants, termed G1 and G2, are a frequent cause of kidney disease — termed APOL1 nephropathy — that typically manifests as focal segmental glomerulosclerosis and the clinical syndrome of hypertension and arterionephrosclerosis. Cell culture studies suggest that APOL1 variants cause cell dysfunction through several processes, including alterations in cation channel activity, inflammasome activation, increased endoplasmic reticulum stress, activation of protein kinase R, mitochondrial dysfunction and disruption of APOL1 ubiquitinylation. Risk of APOL1 nephropathy is mostly confined to individuals with two APOL1 risk variants. However, only a minority of individuals with two APOL1 risk alleles develop kidney disease, suggesting the need for a ‘second hit’. The best recognized factor responsible for this ‘second hit’ is a chronic viral infection, particularly HIV-1, resulting in interferon-mediated activation of the APOL1 promoter, although most individuals with APOL1 nephropathy do not have an obvious cofactor. Current therapies for APOL1 nephropathies are not adequate to halt progression of chronic kidney disease, and new targeted molecular therapies are in clinical trials.

Apolipoprotein L1 Genetic Variants in Cameroonians with chronic kidney disease: A case control study

“…There is correlation between the prevalence of hypertension and the zones of APOL1 genetic risk variant distribution in Africa [16]. It is no longer in doubt whether APOL1 risk variants are susceptibility factors to non-diabetic CKD as it has been reported across many studies and we have also shown the same results in the Cameroonian population [17]. What remains yet to be established is a causal relationship between the APOL1 variants and non-diabetic CKD.…”

A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

“…Reports indicate that a history of amputation or ulceration, 68 peripheral edema, 69 foot pressure, 70 plantar callus formation, 71 nephropathy, 72 poor glucose control, 73 ischemia, 74 retinopathy 75 and prolonged diabetes 76 is an important predisposing factor leading to the development of DFUs. Recent studies have reported that diabetic wounds exhibit a prolonged inflammatory phase due to impairment of phagocytes and macrophages, resulting in the excessive release of MMPs (matrix metalloproteinases), causing degradation of collagen and extracellular matrix (ECM).…”

Host factors predisposing to kidney disease in people with HIV

“…However, most people with APOL1 kidney-risk genotypes, including those with HIV, do not develop CKD, suggesting other genetic or environmental factors are likely to be required. The best recognized are immunodeficiency, HIV viraemia and hepatitis C co-infection or other infections such as parvovirus B-19 and coronavirus disease 2019 (COVID-19) which result in interferon-mediated activation of the APOL1 promoter, although most individuals with APOL1 nephropathy do not have an obvious cofactor [36 ▪▪ ].…”