Chronic kidney disease (CKD) is associated with generalized inflammation. The presence of CKD-related (non-traditional) cardiovascular disease (CVD) risk factors such as inflammation, oxidative stress Show more
Chronic kidney disease (CKD) is associated with generalized inflammation. The presence of CKD-related (non-traditional) cardiovascular disease (CVD) risk factors such as inflammation, oxidative stress and uraemic toxins worsen the CVD. A distinct form of lipoprotein alteration known as uraemic dyslipidaemia, characterized by normal low-density lipoprotein (LDL), reduced high density lipoprotein (HDL) and elevated triglyceride and lipoprotein (a) has been described in CKD. The combination of all these factors increase the cardiovascular risk in CKD patients. We evaluated the relationship of lipoprotein and inflammatory biomarkers to atherosclerotic vascular disease (AsVD) among stage 3 CKD, end stage kidney disease (ESKD) patients on continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD) and kidney transplant recipients (KTRs). This was a cross-sectional study of 40 adult (18-65 years) non-diabetic stage 3 CKD patients, 40 CAPD and 40 HD patients, 41 KTRs and 41 age- and sex-matched healthy controls. Socio-demographic and cardiovascular risk factors were documented and serum samples were analysed for inflammatory and lipoprotein markers. Echocardiography was performed and carotid intima media thickness (CIMT) was measured in all participants. The overall prevalence of AsVD was 52.8% in the study population, with the highest burden of inflammation present in CAPD patients. Significantly increased levels of hsCRP, pentraxin-3, Lp(a) and Lp-PLA2 were seen in CAPD, compared to controls. Older age, male gender, reduced high-density lipoprotein (HDL-C) and elevated Lp(a) levels were independently associated with AsVD. The burden of inflammation and lipoprotein abnormalities was greatest among end stage kidney disease (ESKD) patients and was the highest in CAPD patients. Lipoprotein(a) independently predicted AsVD. Show less
Mice that lack the genes for IL-27, or the IL-27 receptor, and infected with The molecule IL-27 is critical in limiting the immune response to the parasite
Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and f Show more
Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene−metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene−metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10−8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach. Show less