Abstract
BackgroundIndividuals with two copies of the apolipoprotein-1 (APOL1) gene risk variants are at high risk (HR) for non-diabetic kidney disease. The presence of these risk variants is highest in West Africa, specifically in Nigeria. However, there is limited availability of dialysis and kidney transplantation in Nigeria, and most individuals will die soon after developing end-stage renal disease. Blocking the renin angiotensin aldosterone system with angiotensin-converting enzyme inhibitors (ACEi) is a well-recognized strategy to slow renal disease progression in patients with diabetes mellitus with chronic kidney disease (CKD) and in patients with HIV-associated nephropathy. We propose to determine whether presence of the APOL1 HR genotype alters or predicts responsiveness to conventional therapy to treat or prevent CKD and if addition of an ACEi to standard combination antiretroviral therapy (ART) reduces the risk of kidney complications among non-diabetic Nigerian adults.Methods/designWe will screen 2600 HIV-positive adults who have received ART to (1) determine the prevalence of APOL1 risk variants and assess whether APOL1 HR status correlates with prevalent albuminuria, estimated glomerular filtration rate (eGFR), and/or prevalent CKD; (2) assess, via a randomized, placebo-controlled trial (RCT) in a subset of these participants with microalbuminura (n = 280) whether addition of the ACEi, lisinopril, compared to standard of care, significantly reduces the incidence or progression of albuminuria; and (3) determine whether the APOL1 HR genotype is associated with worse kidney outcomes (i.e. eGFR slope or regression of albuminuria) among participants in the RCT.ConclusionsThis study will examine the increasing prevalence of kidney diseases in HIV-positive adults in a West African population, and the relationship between these diseases and the APOL1 high-risk genotype. By evaluating the addition of an ACEi to the care of individuals with HIV infection who have albuminuria, our trial will provide definitive evidence to guide strategies for management and clinical care in this population, with the goal of reducing HIV-related kidney complications.Trial registrationClinicalTrials.gov, NCT03201939. Registered on 26 August 2016.
Highlights
Individuals with two copies of the apolipoprotein-1 (APOL1) gene risk variants are at high risk (HR) for non-diabetic kidney disease
The reported prevalence of chronic kidney disease (CKD) in Human immunodeficiency virus (HIV)- positive antiretroviral therapy (ART)-naïve patients ranges from 6% to 48% across sub-Saharan Africa, with the highest prevalence reported in Nigeria [5,6,7,8,9,10]
A paucity of research, has focused on the cause, progression, and prevention of CKD in this region [9]. This is of particular concern, given that Nigeria has the second largest number of people living with HIV (PLHIV) globally, among whom only ~ 30% are receiving ART [11, 12]
Summary
Individuals with two copies of the apolipoprotein-1 (APOL1) gene risk variants are at high risk (HR) for non-diabetic kidney disease. Genovese et al described two risk alleles in the Apolipoprotein-1 (APOL1) gene [22], Kopp et al and others showed that carriage of these two alleles (APOL1 high-risk (HR) genotype) confers sizeable risk (with odds ratios ranging from 3.1 to 89) for FSGS and hypertension-attributed end-stage renal disease (ESRD) [15, 21, 22, 28]. These variants are present only on African-origin chromosomes, with frequency of these risk alleles highest in West Africa, in Nigeria [29, 30]. Even when HIV replication is suppressed, APOL1 HR individuals remain at greatly increased risk for FSGS and ESRD, similar to HIV-uninfected APOL1 high-risk individuals [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
