Abstract
The consensus management of diabetic nephropathy (DN) in 2015 involves good control of glycaemia, dyslipidaemia and blood pressure (BP). Blockade of the renin–angiotensin–aldosterone system using angiotensin-converting enzyme inhibitors, angiotensin-2 receptor blockers or mineralocorticoid inhibitors are key therapeutic approaches, shown to be beneficial once overt nephropathy is manifest, as either, or both, of albuminuria and loss of glomerular filtration rate. Some significant additional clinical benefits in slowing the progression of DN was reported from the Remission clinic experience, where simultaneous intensive control of BP, tight glycaemic control, weight loss, exercise and smoking cessation were prioritised in the management of DN. This has not proved possible to translate to more conventional clinical settings. This review briefly looks over the history and limitations of current therapy from landmark papers and expert reviews, and following an extensive PubMed search identifies the most promising clinical biomarkers (both established and proposed). Many challenges need to be addressed urgently as in order to obtain novel therapies in the clinic; we also need to examine what we mean by remission, stability and progression of DN in the modern era.
Highlights
Worldwide diabetes mellitus (DM)65.9 million 68.9 million 6.8 million macroalbuminuria (2.8 %/year) and to end-stage kidney disease (ESKD) (2.3 %/year) [19]
D to examine what we mean by remission, stability and progression of diabetic nephropathy (DN) in the modern era
The European Renal Association (ERAEDTA) registry data showed that ten countries across Europe had an increase of 11.9 % per year of type 2 diabetes mellitus (DM) (T2DM) patients starting renal replacement therapy (RRT) [5]
Summary
65.9 million 68.9 million 6.8 million macroalbuminuria (2.8 %/year) and to ESKD (2.3 %/year) [19]. Both metabolic (hyperglycaemia) and haemodynamic perturbations interact synergistically [22, 23] and have been reported to activate local RAAS resulting in increased angiotensin-2, reactive oxygen species (ROS), inflammation, expression of transforming growth factor-β (TGF-β) and dysregulation of different vascular growth factors such as the VEGF-A (upregulated in the initial phase of the disease) and the angiopoietin/Tie-2 system (with excess of angiopoietin-2 over angiopoietin-1) [24] (Fig. 1) This would otherwise be known as the classical pathway of DN where the hallmark features of thickening of the glomerular basement membrane, mesangial expansion and glomerulosclerosis are classically seen on renal biopsy [25] in combination with albuminuria and GFR decline. The effects of aliskiren alone have not been assessed as trials conducted with new agents currently act as adjuncts to RAAS blockade rather than alternatives to ACEi/ARB
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