Abstract

The burden of chronic kidney disease (CKD) in Africa remains poorly characterized, due partly to the lack of appropriate diagnostic strategies. Although in recent years the diagnostic and prognostic utility of microRNAs (miRNAs) have gained prominence in the context of CKD, its value has not been evaluated in African populations. We investigated the expression of whole blood miRNAs (miR-126-3p, -30a-5p, -1299, -182-5p and -30e-3p) in a total sample of 1449 comprising of 13.3% individuals with CKD (stage 1–5) and 26.4% male participants, as well as the association of these miRNAs with prevalent CKD, in a community-based sample of South African adults. We used Reverse Transcription Quantitative Real-Time PCR (RT-qPCR) to analyze miRNA expression. There was an increased expression in whole blood miR-126-3p, -30a-5p, -1299 and -182-5p in individuals with CKD, compared to those without (all p ≤ 0.036), whereas miR-30e-3p showed no significant difference between the groups (p = 0.482). Only miR-126-3p, -182-5p and -30e-3p were independently associated with increased risk of CKD (all p ≤ 0.022). This study showed for the first time that there is a dysregulation of whole blood miR-126-3p, -30a-5p, -1299 and -182-5p in South Africans of mixed-ancestry with CKD. More research is needed to ascertain their role in CKD risk screening in African populations.

Highlights

  • Chronic kidney disease (CKD) is a major health concern globally, affecting approximately 8–16% of the adult population worldwide, with more than three quarters of these people residing in low-to-middle-income countries (LMICs)[1]

  • Despite the fact that Africa has the greatest genetic diversity compared to any other region in the ­world[24], there are as yet no existing studies that have examined the expression of miRNAs in African populations, the present study aimed: (1) to characterize the expression level of whole blood miRNAs, previously associated in the literature with kidney function or kidney disease pathophysiology, namely miR-126-3p19, -30a-5p25, -129926, -182-5p27 and -30e-3p28, and (2) to investigate the association between these miRNAs and prevalent chronic kidney disease (CKD), in a community-based sample of adult South Africans

  • Of the 1989 individuals recruited for the Vascular and Metabolic Health (VMH) study, only 1449 samples were included in the present analysis

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Summary

Introduction

Chronic kidney disease (CKD) is a major health concern globally, affecting approximately 8–16% of the adult population worldwide, with more than three quarters of these people residing in low-to-middle-income countries (LMICs)[1]. There are various limitations to the equations, for example the predominant use of serum creatinine for estimation of glomerular filtration rate which may be affected by factors such as age, sex and body m­ ass[8] These prediction equations, were derived and validated in high income countries with predominately Caucasian. These equations are biased and need to be validated in African populations for correct estimates of CKD burden The limitations of these equations have stimulated interest for novel diagnostic markers with improved diagnostic/prognostic accuracy for CKD. Since their discovery in 1­ 9939, microRNAs (miRNAs) have attracted immense attention in biomedical science as possible biomarkers for early detection and prognosis for various diseases such as c­ ancer[10], cardiovascular diseases (CVDs)[11] and kidney ­diseases. Despite the fact that Africa has the greatest genetic diversity compared to any other region in the ­world[24], there are as yet no existing studies that have examined the expression of miRNAs in African populations, the present study aimed: (1) to characterize the expression level of whole blood miRNAs, previously associated in the literature with kidney function or kidney disease pathophysiology, namely miR-126-3p19, -30a-5p25, -129926, -182-5p27 and -30e-3p28, and (2) to investigate the association between these miRNAs and prevalent CKD, in a community-based sample of adult South Africans

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