Written by Jasna Trbojevic-Stankovic
Reviewed by Change IME
Chronic kidney disease (CKD) is highly prevalent worldwide, with up to 14% of people affected in some regions, and the number of potential or productive life years lost due to premature death or disability is rising, regardless of the underlying cause of renal damage (1, 2). It is estimated that more than 5 million individuals will require renal replacement therapy by 2030, presenting a substantial burden on health services worldwide (3, 4). Despite the efforts to alleviate the burden of CKD, most therapeutics investigated have failed to achieve significant beneficial effects on disease progression in either diabetic kidney disease (DKD) or non-diabetic kidney disease (NDKD), (5-17). There is, therefore, a pressing need for novel renoprotective therapies that would stabilise kidney function and delay the need for renal replacement therapy.
The 2020 ERA-EDTA first fully virtual conference presented an occasion to discuss the latest treatment strategies for DKD, and their possible benefits on CKD progression in both DKD and NDKD patients. At a virtual panel meeting
, moderated by Professor Adeera Levin, Professors Katherine Tuttle and Hiddo Lambers Heerspink shared their views on the possible role of sodium–glucose co-transporter 2 (SGLT2) inhibitors in preserving kidney function.
Insights from SGLT2 inhibitor trials – could the answer be in front of us?
Diabetes is the leading cause of CKD worldwide and was responsible for 42% of CKD cases in 2016 (18).
An estimated 40% of the 476 million adults with diabetes will develop CKD globally (18, 19). The risk of CKD development and progression to end-stage renal disease (ESRD) increases with the duration of diabetes, particularly in patients with an insulin-resistant form of the disease (20). Moreover, the number of deaths due to Type 2 diabetes (T2D) and CKD increased by 94% almost doubled between 1990–2012 (21). All this data accentuates the need for more effective therapies to improve the prognosis for DKD patients.
Several recent randomised controlled clinical trials: EMPA-REG OUTCOME, CANVAS Program, CREDENCE, DELIGHT and DECLARE-TIMI 58, as well as a real-world observational cohort study, CVD-REAL 3, have investigated the effect of SGLT2 inhibitors on the risk of kidney disease endpoints in T2D patients, and demonstrated very promising results (7, 22-29). In EMPA-REG OUTCOME, CANVAS Program, CREDENCE and DECLARE-TIMI 58, SGLT2 inhibitors reduced the risk of progressing to renal composite endpoints, inclusive of: doubling of serum creatinine, a ≥40% fall in estimated glomerular filtration rate (eGFR), progression to ESRD, renal replacement therapy, or kidney death (7, 23, 28, 30-36) . These effects were consistent across a range of baseline urine albumin:creatinine ratio (UACR) and eGFR (37). Furthermore, in these trials and in a real-world population, SGLT2 inhibitors provided long-term stabilisation of eGFR, following an initial reversible decline in kidney function (7, 23, 25, 28, 29, 38, 39). These results were also consistent regardless of cardiovascular status or background therapies, as well as across a range of baseline UACR and eGFR (25, 38). Finally, SGLT2 inhibitors also reduced UACR, prevented progression and increased regression of albuminuria (40). Based on this evidence, the EURECA-m and the DIABESITY working groups of the ERA-EDTA have recently published a consensus statement on the use of SGLT2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for nephroprotection and cardioprotection in patients with diabetes and CKD (Figure 1).