A LECAMWASAM1,2,3, T MANSELL1,5, E I EKINCI2,4, R SAFFERY1,5, K M DWYER3
1Murdoch Children’s Research Institute- Epigenetics Research, Melbourne, Australia, 2Austin Health- Department of Endocrinology, Heidelberg, Australia, 3Deakin University- Department of Medicine, Waurn Ponds, Australia, 4University of Melbourne- Department of Medicine, Melbourne, Australia, 5University of Melbourne- Department of Paediatrics, Melbourne, Australia
Aim: We investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early or late diabetes associated chronic kidney disease (CKD), inclusive of stages 1-5 CKD, to identify potential metabolomic profiles between the two groups.
Background: Small molecule metabolites provide a window into the integrated physiologic phenotype associated with CKD progression and cardiovascular risk.
Methods: This cross-sectional study recruited 119 adults. Metabolomic biomarkers were quantified in 119 non-fasted plasma and 54 urine samples using a high-throughput proton Nuclear Magnetic Resonance (NMR) platform. Analyses were conducted using R with the ggforestplot package. Linear regression models were minimally adjusted for age, sex, and body mass index and p-values were adjusted for multiple comparisons using the Benjamini-Hockberg method with a false discovery rate of 0.05.
Results: Apolipoprotein A1 concentration (ApoA1) was reduced (adj. p = 0.04) and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) was increased (adj. p = 0.04) in late CKD compared with early CKD. Low-density lipoprotein triglyceride (LDL-TG) had an increased concentration (adj. p = 0.01), while concentrations of high-density lipoprotein cholesterol (HDL-C) was reduced (adj. p = 0.04) in late CKD compared to early stages of disease.
Conclusions: Our results highlight the presence of abnormal lipid metabolism namely significant reduction in the protective ApoA1 and significant increase in atherogenic ApoB/ApoA1 ratio. The study also demonstrates significantly elevated levels of triglyceride-rich lipoproteins such as LDL-TG. We illustrate the significant reduction in protective HDL-C in individuals with diabetic CKD. This study provides an in-depth analysis of lipid profiles from early to late diabetic CKD. The study of complex metabolite profiles may provide additional data required to enable more specific diagnoses and cardiovascular risk stratification.
Ashani Lecamwasam is a specialist physician in Nephrology. She undertook her undergraduate medical degree at the University of Adelaide and did her internship at the Royal Adelaide Hospital. She moved to Melbourne for her basic and advanced physician training. Ashani was awarded her fellowship in 2015 and currently does public work at Northern Health and some private practice. She has an interest in research, specifically in Diabetic Chronic Kidney Disease and is undertaking her PhD, through Deakin University in collaboration with the Murdoch Children’s Research Institute and Austin Health. She has multiple international and national publications.