ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Diabetes Care. 2018;41:128-135

Renal damage and kidney failure are amongst the most detrimental co-morbidities of T1DM. In order to be able to prevent renal disease in the first place and treat progression of diabetic renal disease to kidney failure, the mechanisms that lead from high blood glucose levels to damage of the vascular bed of the glomerulus and to end stage renal dysfunction need to be fully understood.

In this study, the very large data sets from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were used to explore the long term interrelationship of inflammation and progression of diabetic kidney disease during a 28 year long time period. To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association, traditional biomarkers of inflammation (C-reactive protein and fibrinogen), and interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), as well as markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]) were measured. Plasma markers of inflammation, endothelial dysfunction, and fibrinolysis were indeed related to the progression of kidney dysfunction during both short-term and long-term follow-up of patients with in T1DM.

These data show that the mechanisms, by which chronic high blood glucose levels lead to damage to the glomerular vascular bed, involve inflammatory processes and that these are characterized by early vascular dysfunction in the kidneys. These findings may well lead to new treatment concepts, whereby early anti-inflammatory intervention may be considered in order to prevent endothelial damage particularly in the kidney.