New opportunities to tackle the global burden of CKD – the role of SGLT2i

Good afternoon, everybody. I'd like to introduce this session on SGLT2 inhibitors and the global burden of kidney disease.

These are my disclosures. I do have grant support, have been on advisory steering committees, as well as on ISN research working groups.

I wanted to start out by acknowledging that 850 million people worldwide have some form of kidney disease. In context, 750 million people inhabit Europe, so it's really quite a burden. In 2017, CKD as a cause of years of life lost was number 16, and we have the dubious honor of being expected to be number 5 by 2040.

Importantly, this slide shows to you the productive years of life lost due to premature death and disability in those with chronic kidney disease in 1990 and in 2017. You can see not only is there an increase, but it's irrespective of the cause of kidney disease, be that diabetes type 1 or 2, non-diabetic kidney disease, glomerulonephritis, and in the age group between the ages of 45 and 70 are where the greatest increases are. This is quite important burden to a vital group of people.

This is our classification system from 2012, and as you know, there's a graded risk of eGFR in urine ACR, and importantly, this is part of the way that we actually assess risk and determine benefit. This risk profile has been looked at and quantified with respect to a number of different outcomes, all-cause mortality, cardiovascular mortality, acute kidney injury, progressive kidney disease, and importantly, kidney failure. You know there's an independent risk between urine ACR and GFR, and these outcomes are important for us to measure both.

The costs of treatments are not always highlighted to policymakers, and I think this is something that as a community we need to do, identifying people at high risk and preventing CKD and cardiovascular are much more cost-effective than putting people on dialysis or transplantation.

We do now have a changing landscape in nephrology, and it's very exciting for those of us that are old enough to remember this. There are landmark approvals in nephrology after a decade of nothing. Now a number of disease-specific, as well as process-specific things, including potassium binders, SGLT2 inhibitors, which are the focus of today, and nonsteroidal MRAs.

There are a number of different renal and extrarenal mechanisms of action that the SGLT2s actually have. They're depicted on this slide. Importantly, not only do they affect glomerular hemodynamics and tubular protection, but also probably change the metabolism within the renal parenchyma. The extrarenal things include blood pressure control, volume control, reduction of uric acid, and weight loss, which obviously are a benefit in a number of different ways. This is a slide done by one of our speakers, Dr. Jardine, which is an evidence review of the cardiovascular and kidney benefits as of 2021. Importantly, you can see that whether you do or don't have diabetes, the kidney and cardiovascular outcomes are significantly impacted in a positive way in those on SGLT2 inhibitors in a number of different trials.

This is a summary of the benefits in different populations of whether you have type 2 diabetes, kidney disease, or heart failure. There are both cardiovascular and kidney benefits. The 2023 KDIGO guidelines are now able for the first time, not only to describe and discuss some new diagnostic tools, et cetera, but also can now incorporate this new data so that we can manage people to the best of our ability and that's an exciting evolution from 2002. This is a slide that you will see again, however, this describes for you the evolution since 2015 of the large SGLT2 inhibitor trials, and shows you that we have either addressed kidney disease, heart disease, or both with diabetic populations and non-diabetic populations, so the totality of evidence in this field is really growing, and I'll let the other speakers speak to this more fully. With that, I'd like to end, and thank you very much for your attention.