Diabetic kidney disease (DKD) remains an important clinical problem with substantial medical comorbidity despite many recent medical advances (1,2). More focus on the earlier identification of patients with type 2 diabetes who are at risk for developing chronic kidney disease (CKD) is needed, especially with regard to biomarkers, genetics, and high-risk phenotypes. Another key area of opportunity is the need for better clinical care models to eliminate socioeconomic and racial disparities.

Fortunately, in the past few years, new therapeutic opportunities have been discovered, and more are being considered, for possible use in improving clinical outcomes. Angiotensin receptor blockers were the last major advance for the treatment of DKD, in 2001 (3,4). The serendipitous observations of improved cardiovascular and renal outcomes with sodium–glucose cotrans-porter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists in cardiovascular outcomes trials were a major surprise (5–7). These observations were followed by the improved cardiorenal outcomes in two large renal protection trials in patients with DKD: the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial (8) using the SGLT2 inhibitor canagliflozin and the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) study (9) using the novel and not-yet-approved selective nonsteroidal mineralocorticoid receptor antagonist finerenone.

As more therapeutic opportunities become established, we need an improved understanding of the mechanisms underlying the progression of diabetic vascular disease and target organ damage so that newer and traditional therapeutic options can be used together most efficiently to improve clinical outcomes. We need to consider the therapeutic index of these treatments and appreciate the massive amount of pharmacopeia that patients with diabetes and CKD consume on a daily basis. Thus, to enhance the precision of therapy, we need more knowledge of the mechanisms of kidney and cardiovascular disease progression in type 2 diabetes.

The results of newer clinical trials are another important area for discussion, as well as trials that are planned or are currently underway. The newer clinical trials have been conducted in patients who are already on optimal medical therapy, including improved blood pressure control, highest tolerated doses of renin-angiotensin system blockers, and lipid-lowering therapy.

Ultimately, we need more precision in guiding pharmacotherapy given the many new therapeutic options available. This compendium will provide an updated opportunity to gauge our progress in the efforts underway to improve longer-term outcomes for patients who have diabetes and CKD.

See references starting on p. 34.

The opinions expressed are those of the authors and do not necessarily reflect those of AstraZeneca, Bayer, or the American Diabetes Association. The content was developed by the authors and does not represent the policy or position of the American Diabetes Association, any of its boards or committees, or any of its journals or their editors or editorial boards.

Editorial and project management services were provided by Debbie Kendall of Kendall Editorial in Richmond, VA. M.R.W. is supported by National Institutes of Health grants R01 HL-127422, U01 DK-16095-01, U01 DK-106102, and R01 DK-120886. R.A. is supported by National Heart Lung and Blood Institute grant R01 HL126903 and U.S. Veterans Administration grant I01 CX001753. P.R. is supported by Novo Nordisk Foundation grant PROTON Personalized Treatment of Diabetic Nephropathy (NNF14OC0013659).

Dualities of Interest

M.R.W. has served on a clinical trial steering committee for Vifor and on advisory boards for AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, and Vifor.

R.A. has received consulting fees from Akebia, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, Diamedica, Merck, Reata, Relypsa, and Sanofi and has received royalties from UpToDate.

P.R.'s institution has received honoraria from his teaching and consultancy activities from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Merck, Merck, Sharp, & Dohme, Mundipharma, Novo Nordisk, Sanofi, and Vifor.

J.B. serves as a consultant for Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, V-Wave Limited, and Vifor.

K.C.N. has been a consultant to Atlantis Health Care, served on an advisory board for ESRD Network 3, and been a board member of the Forum of ESRD Networks.

S.D.-J. has received research grants from the National Institutes of Health, and his institution has received funding for clinical trials in which he was an investigator from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; he has served as a consultant or advisory board member for AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Merck, and Sanofi; and he is a stock shareholder in Aerami Therapeutics and Jana Care.

G.L.B. has been a consultant to Alnylam, AstraZeneca, Bayer, Ionis, KBP Biosciences, Merck, and Vifor and has served on clinical trial steering committees for Bayer, Novo Nordisk, and Vascular Dynamics.

No other potential conflicts of interest relevant to this compendium were reported.

Author Contributions

All authors researched and wrote their respective sections. Lead author M.R.W. reviewed all content and is the guarantor of this work.

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