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26 Cardio Diabetes Medicine 2017

Glucose is Not Always Sweet

Diabetic Kidney Disease: Can we Make it

“SWEET” Again?

Prof. Luigi Gnudi, MD., PhD., FRCP., FASN.,
Head, Unit for Metabolic Medicine,
Cardiovascular Division, King’s College London School of Medicine & Life Sciences,
Department of Diabetes and Endocrinology,
Guy’s and St Thomas Hospital NHS Foundation Trust, London, UK

Abstract on metabolic (glycaemic and lipid control) and hae-
Diabetic nephropathy (DN) is currently the most modynamic (blood pressure) control.
feared chronic microvascular complication of diabe- In some patients, the diabetes-driven renal damage
tes. DN is characterised by a progressive decline in is so minimal that clinically these individuals do not
glomerular filtration rate, that ultimately leads to end experience any evidence of kidney disease during
stage renal disease (ESRD) and is often paralleled by their lifetime.
an increase in cardiovascular morbidity and mortality.
The prevention and management of diabetes and its This supports the idea that hyperglycaemia alone is
chronic complications remains a huge global chal- not sufficient to cause renal damage and other fac-
lenge, as the global number of diabetic patients is tors should be required for its clinical presentation.
expected to increase from 415 million (today) to 642 The interaction between metabolic (hyperglycaemia)
million by 2040. The epidemic of type 2 diabetes, and haemodynamic (hypertension) perturbations is
particularly in newly industrialized and developing an important driver of DN. Hyperglycaemia-mediat-
countries, translates into a dramatic increase of di- ed increase in vascular nitric oxideand reactive oxy-
abetic renal disease and its related increase in car- gen species, have been implicated in vasodilation of
diovascular morbidity and mortality, that results in an both afferent and efferent glomerular arteriolae. Hy-
unbearable growth of social and economic burden. perglycaemia also stimulates the local (e.g. glomeru-
lar) excess production of angiotensin-2. In diabetes,
To face this health-related catastrophe enormous ef-
forts have been devoted to implement new tools to the documented higher sensitivity (likely related to
prevent/treat this disease. Optimized metabolic and a more abundance of angiotensin-2 receptors) of
blood pressure controls remain the cornerstone of the efferent (versus the afferent) glomerular arteri-
treatment. Renin Angiotensin Aldosterone System ole to the vasoconstrictive action of angiotensin-2,
(RAAS) inhibitors have proven very successful in contributes to the imbalance in arteriolar tone which
delaying the progression of kidney disease and in then results in higher glomerular capillary pressure.
preventing ESRD. Data have shown that diabetic kid- As a result, in diabetes, a disproportionate systemic
ney disease can be reversed and recent studies have pressure is transmitted to the glomerular circulation
suggested a potential renoprotective role of different resulting in glomerular hypertension and activation
new molecules (e.g. SGLT2 inhibitors and GLP-1 ago- of the cellular mechanisms that lead to glomerular
nists). Future studies will answer whether these new damage.
therapeutic approaches can improve renal outcome In diabetes, the severity of insulin resistance relates
in patients with diabetes. to the development and progression of kidney dis-
ease. Patients withtype 1 diabetes (T1DM)and microal-
Diabetic kidney disease: pathophysiology (1) buminuria are characterised by increased insulin re-
Chronic kidney disease (CKD) presents in approxi- sistance,and in patients with type 2 diabetes(T2DM)
mately 40% of patients with diabetes, and patients and normal renal function, insulin resistance relates
with diabetes and CKD are at increased risk for car- with the development of microalbuminuria. Insulin re-
diovascular disease. Current treatments rely mainly sistance has been implicated in the development of

GCDC 2017