Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana

Abstract

Chronic kidney disease (CKD) is a global health burden with a continuously increasing prevalence associated with an increasing incidence of diabetes and hypertension in aging populations. CKD is characterized by low glomerular filtration rate (GFR) and other renal impairments including proteinuria, thus implying that multiple factors may contribute to the etiology this disease. While there are indications of ethnic differences, it is hard to disentangle these from confounding social factors. Usually, CKD is detected in later stages of the disease when irreversible renal damage has already occurred, thus suggesting a need for early non-invasive diagnostic markers. In this study, we explored the urine secretome of a CKD patient cohort from Ghana with 40 gender-matched patients and 40 gender-matched healthy controls employing a kidney injury and a more general cytokine assay. We identified panels of kidney-specific cytokine markers, which were also gender-specific, and a panel of gender-independent cytokine markers. The gender-specific markers are IL10 and MME for male and CLU, RETN, AGER, EGFR and VEGFA for female. The gender-independent cytokine markers were APOA1, ANGPT2, C5, CFD, GH1, ICAM1, IGFBP2, IL8, KLK4, MMP9 and SPP1 (up-regulated) and FLT3LG, CSF1, PDGFA, RETN and VEGFA (down-regulated). APOA1—the major component of HDL particles—was up-regulated in Ghanaian CKD patients and its co-occurrence with APOL1 in a subpopulation of HDL particles may point to specific CKD-predisposing APOL1 haplotypes in patients of African descent—this, however, needs further investigation. The identified panels, though preliminary, lay down the foundation for the development of robust CKD-diagnostic assays.

Free Bilirubin Induces Neuro-Inflammation in an Induced Pluripotent Stem Cell-Derived Cortical Organoid Model of Crigler-Najjar Syndrome

“…After performing the cytokine array with non-treated and BF-treated organoids, the hybridizations of the cytokine arrays were scanned with the Fusion FX instrument (PeqLab, Erlangen, Germany) and read into the FIJI/ImageJ software version 1.53c, Java 1.8.0_172, where the spots were quantified as described in our previous publication by Wruck et al [ 24 , 25 ]. The spots were associated with the cytokine identifiers provided by the manufacturer (Proteome Profiler Array from R&D Systems, Human XL Cytokine Array Kit, Catalog Number ARY022B).…”

“…The Robust Spline Normalization from the R/Bioconductor package lumi was applied to the data [ 27 ]. The expressed and differentially expressed cytokines were determined as described previously [ 24 ]. The differential expression was tested via the moderated t -test from the Bioconductor package limma, adjusted for the false discovery rate via the method of Benjamini and Hochberg [ 28 , 29 ].…”

Unconjugated bilirubin induces neuro-inflammation in an induced pluripotent stem cell-derived cortical organoid model of Crigler Najjar Syndrome

“…After performing the cytokine array with nontreated and UCB treated organoids, hybridizations of the cytokine assays were scanned and read into the FIJI/ImageJ software , where spots were quantified as described in our previous publication by Wruck et al [17,18]. Spots were associated with cytokine identifiers provided by the manufacturer (Proteome Profiler Array from R & D Systems, Human XL Cytokine Array Kit, Catalog Number ARY022B).…”

“…The Robust Spline Normalization from the R/Bioconductor package lumi was applied to the data [20]. Expressed and differentially expressed cytokines were determined as described before [17].…”

Healthcare Seeking Behaviour of Patients with Chronic Kidney Disease in the Tamale Teaching Hospital, Ghana

“…Ghana has a 13.3% prevalence rate and the epidemiological transition is blamed on the adoption of Western lifestyles with changes in nutrition, growing urbanization, coupled with the aging population [7,12]. Though a number of CKD patients may progress to a severe stage that will require them to use dialysis, a number of patients die as a result of associated cardiovascular diseases [13][14]. Considering CKD is a chronic condition, it necessitates ongoing monitoring and treatment, and all healthcare workers, particularly nurses, have critical responsibilities in providing care and education to patients, and they must encourage patients to take an active role in their disease treatment [10,[15][16].…”