Novel effective drugs for diabetic kidney disease? or not?
BACKGROUND
Diabetes mellitus is increasingly common worldwide and is expected to affect 592 million people by 2035. The kidney is often involved. A key goal in treating diabetes is to reduce the risk of development of kidney disease and, if kidney disease is already present, to delay the progression to end-stage renal disease (ESRD). This represents a social and ethical issue, as a significant proportion of patients reaching ESRD in developing countries do not have access to renal replacement therapy.


METHODS
The present review focuses on novel therapeutic approaches for diabetic nephropathy (DN), implemented on the basis of recent insights on its pathophysiology, which might complement the effects of single inhibition of the renin-angiotensin-aldosterone system (RAAS), the cornerstone of renoprotective interventions in diabetes, along with glycemic and blood pressure control.


CONCLUSIONS
Although a plethora of new treatment options has arisen from experimental studies, the number of novel renoprotective molecules successfully implemented in clinical practice over the last two decades is disappointingly low. Thus, new investigational strategies and diagnostic tools - including the appropriate choice of relevant renal end points and the study of urinary proteome of patients - will be as important as new therapeutic interventions to fight DN. Finally, in spite of huge financial interests in replacing the less expensive ACE inhibitors and angiotensin II receptor blockers with newer drugs, any future therapeutic approach has to be tested on top of - rather than instead of - optimal RAAS blockade.
IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Center for Rare Diseases "Aldo e Cele Daccò" , Villa Camozzi, Via Giambattista Camozzi 3, 24020, Ranica, Bergamo , Italy +39 03545351 ; +39 0354535371 ; giorgio.gentile@marionegri.it.
Giorgio
G
Gentile
Daniela
D
Mastroluca
Piero
P
Ruggenenti
Giuseppe
G
Remuzzi
D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D012084:Renin-Angiotensin System / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
albuminuria; chronic kidney disease.; diabetic nephropathy; investigational drugs; renin-angiotensin-aldosterone system