HIV-associated nephropathy: Protocol and rationale for an exploratory genotype phenotype study in a sub-Saharan African population
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Date
2021-04-06
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS ONE
Abstract
Background
HIV-positive persons of African descent are disproportionately affected by chronic kidney
disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to
CKD in HIV positive patients, and the pathophysiology of progression to ESKD.
Objectives
We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD
in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene
expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria.
Methods
We will consecutively screen 150 HIV-positive adults (�18 years of age) attending the HIV
clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and
elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral
(ARV) regimen. In the first group (n = 16), we will determine differential gene expression
markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse
transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based
approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases.
Results
Our exploratory study will provide valuable information on the potential roles of differential
expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population.
The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches.
Conclusion
Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.
Description
Keywords
HIV-positive persons, Musa Babashani, Aminu Zakari Mohammed, Donna J. Ingles, ACE: Genetic Medicine, University of Ghana, WAGMC
Citation
Yusuf AA, Musa BM, Galadanci NA, Babashani M, Mohammed AZ, Ingles DJ, et al. (2021) HIV-associated nephropathy: Protocol and rationale for an exploratory genotype-phenotype study in a sub-Saharan African population. PLoS ONE 16(4): e0249567. https://doi.org/10.1371/ journal.pone.0249567