JMIR Publications

ABSTRACT

Background:

The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Indeed the rate of cardiovascular disease is much higher in people with both diabetes and kidney dysfunction than in those with either alone. By the time these people are identified in current clinical practice proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease. This in turn would provide targeted intervention to improve patient outcomes.

Objective:

We investigated a cross-sectional study of people with diabetes and chronic kidney disease (CKD) to identify potential biomarkers associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers were explored, namely, DNA methylation profiles in blood lymphocytes, metabolomic profile of blood-derived serum and urine, as well as the gut microbiome.

Methods:

One hundred and twenty-one people with diabetes and varying stages (stages I-V) of chronic kidney disease were recruited into this cross-sectional study. Data collection occurred only at one time point and included blood, urine and faecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities and medications.

Results:

Data collection commenced in January 2018 and was completed in June 2018. Hundred and twenty one patients were recruited at submission of manuscript.There were 83 participants in the early diabetes-associated CKD group with a mean eGFR of 61.2 ml/min/1.73m2 (early CKD group consisting of stage 1, 2 and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 ml/min/1.73m2 (late CKD group, consisting of stage 3b, 4 and 5), P<0.001. We have successfully obtained DNA for methylation and microbiome analyses using this detailed protocol and are currently analysing these results together with the metabolome of this cohort of individuals with diabetic CKD.

Conclusions:

There has been an upsurge in the understanding and knowledge of the epigenome, metabolomics and the gut microbiome and its influence on the incidence of many diseases, such as cancer, particularly in association with specific environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. The current study will provide insight into the fundamental understanding on the pathophysiology of chronic kidney disease in individuals with diabetes, especially in relation to novel areas such as epigenetics, metabolomics and the kidney-gut axis.