touchPANEL DISCUSSION

Progress in the management of CKD in patients with type 2 diabetes: How might non-steroidal MRAs change the treatment paradigm?

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Cardiovascular Risk, Diabetes, Chronic Kidney Disease CE/CME ACCREDITED Watch Time: 38 mins

touchPANEL DISCUSSION Progress in the management of CKD in patients with type 2 diabetes: How might non-steroidal MRAs change the treatment paradigm?

Experts discuss the evidence for non-steroidal mineralocorticoid receptor antagonists (MRAs) as an additional treatment option for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).

Prof. Christoph Wanner

University Hospital of Würzburg, Würzburg, Germany

CHAIR

Panelists:
Prof. Janet McGill, Prof. Javed Butler
 
Video Chapters
Introduction

Chair, Prof. Wanner, introduces the expert panel and agenda for this discussion on how non-steroidal mineralocorticoid receptor antagonists might change the treatment paradigm for patients with type 2 diabetes and chronic kidney disease.

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1/4 Next Chapter
 
Why does the treatment landscape for patients with T2D and CKD still require novel therapies?

The panel considers the burden of disease in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) and current treatment approaches to slow CKD progression, limitations of current treatments for T2D and CKD, and the unmet treatment need.

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2/4 Next Chapter
 
Why are non-steroidal MRAs being investigated in patients with T2D and CKD and what do the latest data show?

The panel discusses the rationale for blockade of the mineralocorticoid receptor in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), properties of steroidal versus non-steroidal mineralocorticoid receptor antagonists (MRAs), and the latest data for non-steroidal MRAs in patients with T2D and microalbuminuria/CKD.

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3/4 Next Chapter
 
How might non-steroidal MRAs address unmet needs in T2D and CKD and fit into the current treatment paradigm?

The panel considers trial designs and efficacy and safety outcomes across the FIDELIO-DKD, FIGARO-DKD, DAPA-CKD and CREDENCE trials, how non-steroidal mineralocorticoid receptor agonists might address unmet treatment needs, and how they might be integrated into future clinical practice.

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Overview & Learning Objectives
Overview

In this activity the expert panel will discuss three clinical themes covering unmet treatment needs for patients with T2D and CKD, the rationale and evidence for nonsteroidal MRAs and how they may best be incorporated into the treatment pathway for T2D and CKD.

This activity is jointly provided by USF Health and touchIME.

Target Audience

Endocrinologists, diabetologists, nephrologists, cardiologists and primary care physicians globally, with a focus on the EU, USA, Brazil and Canada.

Disclosures

All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity.  The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Christoph Wanner, MD discloses Advisory Board/Panel fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company and MSD. Grants/Research support from Boehringer Ingelheim (Terminated).

Janet McGill, MD, MA FACE, FACP discloses Advisory Board/Panel fees from Bayer, Eli Lilly and Company (Terminated) and Salix Pharmaceuticals (Terminated). Consultant fees from Boehringer Ingelheim (Terminated). Consultant/Grants/Research fees or support from Dexcom (Terminated). Grants/Research support from Beta Bionics, Medtronic and Novo Nordisk. Speaker’s Bureau fees from Janssen (Terminated).

Javed Butler, MD, MPH, MBA discloses Consultant fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array BioPharma, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Luitpold Pharmaceuticals, Inc., Medtronic, Merck, Novo Nordisk, Relypsa, Seguana Medical and Vifor. Consultant/Speaker’s Bureau fees from AstraZeneca, Janssen and Novartis.

Content reviewer

Christy Thai, PharmD, BCPS has no relevant financial relationships to disclose.

Touch Medical Director

Sola Neunie has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu 

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 01 November 2021. Date credits expire: 01 November 2022.

If you have any questions regarding credit please contact cpdsupport@usf.edu

Learning Objectives

After watching this activity, participants should be better able to:

  • Evaluate the need for new treatment options for patients with T2D and CKD
  • Justify the use of MRAs in patients with T2D and CKD and describe the cardiorenal efficacy and safety of new and emerging nonsteroidal MRAs
  • Appraise how nonsteroidal MRAs can address unmet needs in patients with T2D and CKD and fit into the current treatment paradigm
Faculty & Disclosures
Prof. Christoph Wanner

University Hospital of Würzburg, Würzburg, Germany

Prof. Christoph Wanner is Professor of Medicine and Head of the Division of Nephrology at the University Hospital of Würzburg, Germany.

His research in the field of diabetic kidney disease, lipid disorders and rare kidney diseases has been published in more than 800 PubMed-referenced scientific papers and articles (Hirsch Index 92). He was Principal Investigator on the 4D study and steering committee member of the SHARP and REVEAL trials. He is also steering committee member of the EMPA-REG Outcome, EMPEROR and EMPA-KIDNEY studies, as well as the CARMELINA trial and the FIGARO-/FIDELIO-DKD studies aimed at slowing the progression of kidney disease and improving cardiovascular outcomes. read more

He is a member of several editorial boards of kidney journals and has been Associate Editor of the Clinical Journal of the American Society of Nephrology, as well as Editor-in-Chief of the Journal of Renal Nutrition, until recently.

In 2012, he received a doctorate honoris causa from the Charles University of Prague. He has received the 2016 Award from the European Renal Association-European Dialysis and Transplant Association for Outstanding Clinical Contributions to Nephrology, and in 2018, the Franz Volhard medal, the highest award from the German Society of Nephrology. Prof. Wanner is President of the European Renal Association, being in office from June 2020–2023.

Christoph Wanner, MD discloses Advisory Board/Panel fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company and MSD. Grants/Research support from Boehringer Ingelheim (Terminated).

Prof. Janet McGill

Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

Janet McGill is Professor of Medicine in the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine, and attending physician at Barnes-Jewish Hospital in St. Louis, Missouri.

She is currently the principal investigator of the National Institutes of Health (NIH)-funded GRADE study and the Insulin-Only Bionic Pancreas Pivotal Trial. She is a sub-investigator on the RADIANT study, which hopes to discover genetic causes of diabetes with atypical features through deep phenotyping and genotyping. read more

Prof. McGill has conducted over 220 clinical trials in type 1 and type 2 diabetes, studying new treatments and complications such as hypertension, hyperlipidaemia, nephropathy, neuropathy and retinopathy. She was the Principal Investigator (PI) of the NIH-funded PERL study, “Preventing Early Renal Loss in Type 1 Diabetes” and a continuous glucose monitoring sub-study, also the WISDM and recently published MOBILE studies. She led the Washington University site for the T1D Exchange clinic registry, and was the PI for several T1D Exchange clinical trials and registry studies. Prof. McGill has served on steering committees and data safety and monitoring boards for long-term outcome studies, both NIH- and industry-sponsored, and leads data safety committees locally for investigator-initiated studies.

Prof. McGill has published over 200 peer-reviewed articles, numerous commentaries and editorials, 25 book chapters, and she has edited four books, including the recently published books, Atypical Diabetes and the Washington Manual, Endocrine Subspecialty Consult, fourth edition. She has served on the editorial boards of several journals, and has lectured nationally and internationally on diabetes and related topics.

Prof. McGill served on the board of directors of the American Association of Clinical Endocrinology and the American College of Endocrinology, and is active in the Endocrine Society and the American Diabetes Association. She is a member of the Alpha Omega Alpha Honor Medical Society, and has received the Distinguished Clinician Award, the Alumni Achievement Award and the Endocrine Fellows’ Teaching Award from her peers at Washington University.

Janet McGill, MD, MA FACE, FACP discloses Advisory Board/Panel fees from Bayer, Eli Lilly and Company (Terminated) and Salix Pharmaceuticals (Terminated). Consultant fees from Boehringer Ingelheim (Terminated). Consultant/Grants/Research fees or support from Dexcom (Terminated). Grants/Research support from Beta Bionics, Medtronic and Novo Nordisk. Speaker’s Bureau fees from Janssen (Terminated).

Prof. Javed Butler

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

Javed Butler, MD, MPH, MBA, is the Patrick H. Lehan Chair in Cardiovascular Research, and Professor and Chairman of the Department of Medicine at the University of Mississippi Medical Center in Jackson, MS. He is also Professor of Physiology. Prior to joining the University of Mississippi, he was Charles A. Gargano Professor and Director of the Division of Cardiovascular Medicine and Co-Director of the Heart Institute at Stony Brook University, New York. He had served as the director for heart failure research at Emory University and director of the heart and heart-lung transplant programs at Vanderbilt University prior to that. read more

He received his medical degree from the Aga Khan University and then completed residency training at Yale University, cardiology fellowship and advanced heart failure and transplant fellowships at Vanderbilt University, and cardiac imaging fellowship at the Massachusetts General Hospital at the Harvard Medical School. He has completed a Master of Public Health degree from Harvard University and a Master in Business Administration from Emory University.

Prof. Butler is board certified in cardiovascular medicine, advanced heart failure and transplant medicine. His research interests focus on clinical trials in patients with heart failure. He serves on several national committees for the American College of Cardiology, American Heart Association, National Institutes of Health, US Food and Drug Administration, and the Heart Failure Society of America. He is the recipient of the Simon Dack Award by the American College of Cardiology, as well as the Time, Feeling, and Focus Award by the American Heart Association.

Prof. Butler has authored more than 700 peer-reviewed publications. He serves on the editorial board of several peer reviewed cardiovascular journals. He has been cited numerous times in America’s Best Doctors list.

Javed Butler, MD, MPH, MBA discloses Consultant fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array BioPharma, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Luitpold Pharmaceuticals, Inc., Medtronic, Merck, Novo Nordisk, Relypsa, Seguana Medical and Vifor. Consultant/Speaker’s Bureau fees from AstraZeneca, Janssen and Novartis.

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Question 1/4
Your patient, aged 62 years, was diagnosed with T2D 11 years ago. He is currently taking metformin combined with exercise and dietary changes for glycaemic control, and no other medication. At his latest visit, his A1c was 8.1%, eGFR 56 mL/min/1.73 m2, UACR 120 mg/g, BMI 28.4 kg/m2 and blood pressure 145/90 mmHg. Which of the following modifications to his treatment regimen would you consider?

A1c, glycated haemoglobin; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide-1 receptor agonist; SGLT2i, sodium–glucose cotransporter-2 inhibitor; T2D, type 2 diabetes; UACR, urine albumin-to-creatinine ratio.
Correct

KDIGO guidelines recommend that glycaemic management for patients with T2D and CKD should include lifestyle therapy and first-line treatment with metformin and an SGLT2i for patients with an eGFR ≥30 mL/min/1.73 m2. Additional drug therapy can be added as needed for glycaemic control, with GLP-1 RAs generally preferred. Treatment with an ACEi or an ARB should be initiated in patients with albuminuria and hypertension, and dual antiplatelet therapy used in patients after acute coronary syndrome or percutaneous coronary intervention.

Abbreviations

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide-1 receptor agonist; KDIGO, Kidney Disease: Improving Global Outcomes; SGLT2i, sodium–glucose cotransporter-2 inhibitor; T2D, type 2 diabetes.

Reference

Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. Kidney Int. 2020;98(Suppl. 4):S1–115.

Question 2/4
KDIGO guidelines state that patients with T2D with albuminuria and hypertension should receive antihypertensive therapy with an ACEi or ARB to reduce the risk of CKD progression or cardiovascular disease. In such patients, a limitation of long-term ACEi or ARB treatment includes an increased risk of:

ACEi, angiotensin-converting enzyme inhibitor; ARB angiotensin II receptor blocker; CKD, chronic kidney disease; CV, cardiovascular; KDIGO, Kidney Disease: Improving Global Outcomes; T2D, type 2 diabetes.
Correct

The KDIGO guidelines for diabetes management in CKD state that patients with diabetes and CKD should be treated with a comprehensive strategy to reduce the risk of kidney disease progression and cardiovascular disease. Treatment with an ACEi or an ARB should be initiated in patients with diabetes, albuminuria and hypertension, and these medications be titrated to the highest approved and tolerated dose.1

In cardiorenal disease, aldosterone overactivates mineralocorticoid receptors, resulting in fibrosis and inflammation. Blockade of the renin–angiotensin system (RAS) with ACEis or ARBs is reno-protective, with the benefits ascribed to a reduction in systemic and intraglomerular blood pressure and proteinuria, and a reduction in aldosterone. However, long-term treatment is often followed by aldosterone breakthrough or escape, either because of insufficient blockade of RAS or concomitant increases in potassium (hyperkalemia).2

Abbreviations

ACEi, angiotensin-converting enzyme inhibitor; ARB angiotensin II receptor blocker; CKD, chronic kidney disease; KDIGO, Kidney Disease: Improving Global Outcomes.

References

  1. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. Kidney Int. 2020;98(Suppl. 4):S1–115.
  2. Frimodt-Møller M, et al. Curr Opin Nephrol Hypertens. 2020;29:145–51.
Question 3/4
In patients with T2D and CKD, what is the rationale for novel treatment approaches that target the mineralocorticoid receptor?

CKD, chronic kidney disease; T2D, type 2 diabetes.
Correct

The mineralocorticoid receptor belongs to the superfamily of nuclear hormone receptors, and is predominantly expressed in the heart and kidneys, as well as the vasculature, brain, gut and myeloid cells. Overactivation of the mineralocorticoid receptor, implicated in chronic pathophysiological disease states such as T2D and CKD, leads to high levels of inflammation and fibrosis, and subsequent end-organ damage in cardiorenal disease. Inhibition of mineralocorticoid receptor overactivation reduces its deleterious effects by reducing proinflammatory and profibrotic gene expression, with the aim of slowing CKD progression.

Abbreviations

CKD, chronic kidney disease; T2D, type 2 diabetes.

Reference

Agarwal R, et al. Nephrol Dial Transplant. 2020;doi:10.1093/ndt/gfaa294.

Question 4/4
Your patient is a 60-year-old woman with T2D who was recently diagnosed with stage 3a CKD. When discussing treatment options to slow the progression of CKD, the patient mentions having heard about an agent called finerenone (a non-steroidal MRA), and asks about its suitability for her. Based on the results of the FIDELITY meta-analysis, how would you advise her?

CV, cardiovascular; CKD, chronic kidney disease; MRA, mineralocorticoid receptor antagonist; T2D, type 2 diabetes.
Correct

The FIDELITY prespecified meta-analysis evaluated individual data from two trials (FIDELIO-DKD and FIGARO-DKD) of finerenone therapy in patients with T2D and CKD.1 Eligible patients in FIDELIO-DKD had a UACR 30–<300 mg/g and eGFR 25–<60 mL/min/1.73 m2, or UACR 300–5,000 mg/g and eGFR 25–<75 mL/min/1.73 m2.2 Eligible patients in FIGARO-DKD had a UACR 30–<300 mg/g and eGFR 25–90 mL/min/1.73 m2, or UACR 300–5,000 mg/g and eGFR ≥60 mL/min/1.73 m2.3 Over 13,000 patients were evaluated in the meta-analysis, with a median follow-up of 3 years.1

The primary composite endpoint was onset of time to CV death, nonfatal MI, nonfatal stroke or HHF, and its relationship with UACR/eGFR. Finerenone reduced the risk of this outcome by 14% versus placebo (HR 0.86, p=0.0018).1

The secondary composite endpoint was onset of time to kidney failure, sustained ≥57% eGFR decline for ≥4 weeks or renal death, and its relationship with UACR/eGFR. The risk of this outcome was reduced by 23% with finerenone versus placebo (HR 0.77, p=0.0002).1

Abbreviations

CKD, chronic kidney disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; HHF, hospitalization for heart failure; HR, hazard ratio; MI, myocardial infarction; T2D, type 2 diabetes; UACR, urine albumin-to-creatinine ratio.

Reference

  1. European Society of Cardiology. Finerenone benefits patients with diabetes across spectrum of kidney disease [Press Release]. 2021. Available at: www.escardio.org/The-ESC/Press-Office/Press-releases/Finerenone-benefits-patients-with-diabetes-across-spectrum-of-kidney-disease (accessed 14 October 2021).
  2. Bakris G, et al. N Engl J Med. 2020;383:2219–29.
  3. Pitt B, et al. N Engl J Med. 2021; DOI: 10.1056/NEJMoa2110956.
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