Andrew Frankel, consultant physician and nephrologist at Imperial College Healthcare NHS Trust (London, UK), writes to set out the process behind the new guideline from the UK Guideline Group on sodium glucose co-transporter 2 inhibitors (SGLT2i) in kidney disease treatment, which will be presented on at UK Kidney Week (5–7 June, Newport, UK).
At this year’s UKKW event, Will Herrington (University of Oxford, Oxford, UK) will be presenting on the EMPA Kidney study at a plenary session, and will be referencing how this study has influenced the new UK Guideline Group recommendations on how SGLT2i should be used in the treatment of chronic kidney disease (CKD), on which I was also an author.
Over the last 20 years there has been year-on-year growth in the number of people with CKD progressing to end-stage kidney failure and requiring either a kidney transplant or dialysis. The response must be to identify those individuals earlier and optimise their therapy with interventions that reduce the progression of their kidney disease. The factors that have proven to be central to optimisation and treatment of CKD include better glucose control, blood pressure control and the use of inhibitors of the renin aldosterone angiotensin system (RAASi). In addition, careful attention to cardiovascular risk is important to reduce the increased cardiovascular complications associated with CKD.
These treatments have been augmented by publications that have demonstrated the significant benefit that SGLT2i have on progression of CKD and, additionally, their benefits in relation to prevention of heart failure progression. In response to this important information, in September 2021 the UK Kidney Association (UKKA) published evidence-based guidance on the use of these agents in people with kidney disease.
However, the field has been rapidly changing with the publication of two further important large trials in 2022: DELIVER, which investigated the use of the SGLT2i dapagliflozin in people with heart failure with preserved or mildly reduced ejection fraction, and EMPA-KIDNEY, which investigated the use of empagliflozin in people with CKD including people with and without diabetes and people with and without albuminuria. The results from these trials and an additional meta-analysis of the totality of evidence has greatly expanded our understanding of the uses of SGLT2i and have increased the strength of evidence on which to make recommendations for use. Because of this an early update of the UKKA Guidance was required and has now been delivered.
The updated guideline maintains its original structure but has now also been published in the format of an interactive PDF which makes it much easier to navigate the guideline in order to find both the information on treatment recommendations and also to review the rationale and evidence to support the recommendations within that guideline.
The latest data has resulted in a broadening of the recommendations covering the groups of people who would benefit from the use of SGLT2i. The updated guideline extends the use of these agents to people both with and without diabetes and evidence of kidney disease. For people with diabetes and any evidence of kidney disease—or indeed high cardiovascular risk—there is stronger evidence to support the use of SGLT2i. In regard to people without diabetes and CKD (people with a glomerular filtration rate [GFR] that is <60 and/or proteinuria), the guideline has extended the recommendations to use SGLT2i in those with lower degrees of proteinuria based on the evidence that SGLT2i slows the rate of decline in GFR thereby delaying the requirement for end-stage kidney failure treatment for this group of individuals.
These benefits are in addition to their general benefits in relation to prevention of heart failure. There is also now evidence to support the use of SGLT2i in people with lower degrees of kidney function and, although the grade of evidence is not as strong as for people with GFR>20, the guideline suggests that consideration is given to the use of SGLT2i in people with GFR<20.
Implementation of the recommendations from these guidelines should have a significant effect on the long-term risk of CKD and provide significant population benefit as well as improving the long-term outlook for many individuals with CKD. The implementation of these recommendations will become a priority for the healthcare community in discussion with those individuals with CKD.