Diabetic kidney disease: the onset of a new era?
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EDITORIAL
Diabetic kidney disease: the onset of a new era? Paola Fioretto1
© Italian Society of Nephrology 2020
Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) worldwide [1, 2], affecting approximately 40% of patients with diabetes. DKD in both type 1 and type 2 diabetes is associated with increased mortality and cardiovascular risk; indeed the majority of patients with DKD die of cardiovascular complications before reaching ESRD [3]. Thus, DKD is a major burden for the person with diabetes and also for the health care systems. Currently, there is no reliable test to predict who will develop DKD and by the time increased albuminuria and/or reduction in GFR are detected the burden of renal and cardiovascular risk is already very high. Better control of glycemia and blood pressure, including renin-angiotensin system blockade (RASB) [4, 5], are effective in slowing DKD progression rate but have failed to substantially decrease the annual incidence of new cases of ESRD due to diabetes. Despite multifactorial interventions, including tight control of glucose, blood pressure, lipids and lifestyle modifications, the residual risk of progression towards ESRD remains high among patients with type 2 diabetes [6]. Thus, there is an unmet need for better treatment options, starting as early as possible to prevent the development and slow progression of DKD in high risk patients. This sad scenario is likely to rapidly change with the use of new glucose-lowering classes of drugs that have been shown to have nephroprotective effects. In particular SGLT2 inhibitors, as a class, reduce GFR loss and ESRD, as demonstrated in cardiovascular outcome trials, where this class of drugs significantly decreased major adverse cardiovascular events, hospitalization for heart failure, and renal events [7–9]. The nephroprotective effects have been confirmed in ‘renal’ studies performed in patients with advanced CKD (CREDENCE trial, performed in patients with type 2 diabetes [10], and in
* Paola Fioretto [email protected] 1
Department of Medicine, Clinica Medica 3, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
DAPA-CKD, performed in both non diabetic and diabetic patients [11], and stopped early in March 2020 after overwhelming efficacy. The results of this trial will be presented at the European Heart Association meeting on August 31st). SGLT2 inhibitors, in addition to slowing GFR loss, have a potent antiproteinuric effect, which is additive to that provided by RAS blockade. In patients with abnormal albuminuria at baseline, all trials have shown a significant reduction in urine albumin to creatinine ratio (UACr) levels of about 30–40% [7–10]. Thus, SGLT2 inhibitors undoubtedly substantially slow progression towards ESRD in patients with DKD; the question is whether these agents may completely change the natural history of renal complications in diabetes and whether they are effective also in primary prevention. A reduction in the risk of developing new onset microalbuminur
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