B- CRF : Measurement of renal function
D- Diabetes type 2 with CV complications
D- Diabetes type 2 with other complications
Non-proteinuric pathways in loss of renal function in patients with type 2
diabetes
Dr Esteban Porrini, MD ; Piero Ruggenenti, MD ; Carl Erik Mogensen, MD ; Drazenka Pongrac Barlovic,
MD ; Manuel Praga, MD et al
Journal : The Lancet Diabetes & Endocrinology
Year : 2015 / Month : May
Volume : 3
Pages : 382–391
DOI: http://dx.doi.org/10.1016/S2213-8587(15)00094-7
ABSTRACT
Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease
has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, and
macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset
of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of
early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can
start to decline before progression to overt nephropathy. In addition to proteinuria, other risk factors might
contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in particular
hypertriglyceridaemia), hypertension, and glomerular hyperfiltration, at least in a subgroup of patients. This
phenomenon could explain why patients with type 2 diabetes can have renal insufficiency even before the
onset of overt nephropathy, and might also suggest why the heterogeneous phenotype of type 2 diabetic
renal disease does not necessarily associate with typical histological lesions of diabetic renal disease,
unlike in type 1 diabetic renal disease. Patients with renal insufficiency but without albuminuria are usually
excluded from randomised clinical trials in overt nephropathy, thus optimum treatment for this group of
patients is unknown. The wide inter-patient variability of the disease probably needs individually tailored
intervention.
COMMENTS
This review conducted by experts of the EDTA-ERA Association document risk factors of chronic renal
insufficiency that could not be reflected by the specific target of diabetic glomerulopathy and may control, in
some part, the event of end-stage renal disease at least in diabetes type 2.
RAS inhibitors do not seem to prevent or delay progression of renal disease in type 2 diabetes as
effectively as they do in type 1 diabetes or in non-diabetic proteinuric nephropathies. A plausible
interpretation of these findings is that in type 1 diabetes and in non-diabetic proteinuric nephropathies,
proteinuria has a central role in progression of the disease and proteinuria reduction mediates a large part
of the renoprotective effects of RAS inhibitors, whereas pathways additional to proteinuria can sustain renal
function loss in type 2 diabetes, in particular before progression to overt nephropathy.
Here, the authors present evidence supporting the notion of a non-proteinuric phenotype and discuss
possible risk factors and pathways associated with type 2 diabetes, since progressive renal function loss
can be noted at any stage of renal involvement and is greatly accelerated with the onset of
macroalbuminuria or overt proteinuria. Several factors have been associated with the pathogenesis of the
disease, including hypertension, hyperglycaemia, insulin resistance, proteinuria, advanced glycation end
products, and oxidative stress. For easy understanding, they propose the following schematic
presentation :
Evolution of renal function in the classic versus non-proteinuric phenotype of diabetic renal disease.
Increase and subsequent decrease of glomerular filtration rate in patients with type 2 diabetes and
normoalbuminuria, microalbuminuria, or proteinuria.
In summary, the evidence they describe supports the existence of a non-proteinuric phenotype of diabetic
renal disease predominantly seen in patients with type 2 diabetes Such a phenotype has to be taken into
account for preventing premature decline in renal function that is usually triggered by proteinuria and
hypertension.
Pr. Jacques CHANARD
Professor of Nephrology