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Renal Risk Reduction in T2D

CE / CME

Navigating the Latest Evidence and Strategies for Renal Risk Reduction in T2D

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Released: December 23, 2024

Expiration: December 22, 2025

David M. Charytan
David M. Charytan, MD, MSc
Jennifer B Green
Jennifer B Green, MD
CME/CE Information

Activity

Progress
1 2
Course Completed

Diabetes Statistics in the United States

Jennifer B. Green, MD:
In the United States, 38 million people have diabetes. That correlates to 1 in every 10 adults. Unfortunately, 1 in 5 people do not even know they have diabetes. This means there is certainly a diabetes screening and education gap. 

An even bigger problem is the fact that there are 98 million US adults with prediabetes. This correlates to more than 1 in 3 adults having prediabetes and more than 8 in 10 adults not knowing that they have prediabetes. Even though prediabetes does not yet meet the criteria for diabetes, it is undoubtedly a key step toward its progression and is likely associated with a risk of kidney disease and other complications.1

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Common Risk Factors for CKD

Jennifer B. Green, MD:
There are many risk factors for CKD. Some of these risk factors are modifiable and some are not. Age, for example, is not a modifiable risk factor, but many others are. In the United States, diabetes and hypertension are among the most common contributing factors to the development and progression of CKD. Other contributing factors include obesity, smoking, dyslipidemia, environmental factors, and other toxic exposures.2 

Also, women who have experienced adverse pregnancy outcomes, such as pregnancy-related hypertension or an acute kidney injury, are at an increased risk for the development and progression of CKD. Some of these contributing factors for CKD can be mitigated and others cannot.3

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Kidney Disease Is an Early and Common Complication of T2D

Jennifer B. Green, MD:
Kidney disease is an early and common complication of T2D. This slide shows that among people with T2D, approximately 50% have evidence of CKD. This means these patients have either albuminuria or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, or both.4 

When looking at the likelihood of a person developing microalbuminuria or more advanced degrees of albuminuria over time, after approximately 15 years, almost 30% of people with T2D will have some degree of albuminuria.5

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Prevalence and Overlap of Cardiac, Renal, and Metabolic Conditions in US Adults, 2015-2020

Jennifer B. Green, MD:
On the left-hand side of this graph, which shows data between 2015 and 2020, are the percentages of US adults affected by cardiovascular disease, kidney disease, or metabolic diseases such as diabetes. 

Toward the right-hand side of the graph, the bars represent the percentages of individuals who have more than 1 of those conditions. This graph may make things look better than how they are regarding the prevalence and overlap of cardiovascular, kidney, and metabolic conditions in US adults. For example, if you were to restrict these data to only individuals with diabetes in the United States, the percentages of people with cardiovascular disease, kidney disease, or both would be much higher than what is shown.6

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Overlapping Pathophysiology of Diabetes, CKD, and Heart Failure

Jennifer B. Green, MD:
There is an overlapping pathophysiology in the development of T2D, CKD, and cardiovascular diseases, including heart failure. Because of this overlap, these conditions commonly occur in the same individual. Some reasons for this are oxidative stress, endothelial dysfunction, and chronic inflammation. Multiple pathophysiologic mechanisms may be present in one person and contribute to the development and worsening of these comorbidities.

There are many opportunities to intervene and mitigate the drivers of progression of CKD and diabetes. Some known contributors of progression of CKD are hyperglycemia and hemodynamic dysregulation. However, there is an increasing appreciation for the role that inflammation has to play in the development and progression of cardiovascular and kidney diseases.7

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Medications Used to Delay CKD Development and Progression

Jennifer B. Green, MD:
Listed on this slide are the classes of available drugs that are used to help reduce the risks related to the drivers of diabetic kidney disease (DKD) progression. The RAAS inhibitors, SGLT2 inhibitors, and nonsteroidal mineralocorticoid receptor antagonists (nonsteroidal MRAs) all favorably affect hemodynamic dysregulation. Those same classes, as well as GLP-1 RAs, may all reduce systemic and/or organ-specific inflammation. 

The GLP-1 RAs and other antihyperglycemic agents can minimize hyperglycemia and its toxic effect on the kidneys.8

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Metabolic Effects of GLP-1

Jennifer B. Green, MD:
This slide shows the effects that the endogenous hormone GLP-1 has in our body. GLP-1 is an incretin hormone. It is released from the small intestine almost immediately after taking a bite of food. In turn, GLP-1 decreases appetite through central mechanisms and through slowing gastric emptying to feel fuller. 

GLP-1 also stimulates insulin secretion and suppresses glucagon secretion from the pancreas. This process helps keep our blood sugar from rising into an abnormal range after eating. 

These are all normal, crucial physiologic mechanisms of action that GLP-1 exerts in the body, helping to maintain normal glucose levels and overall metabolic function.9

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Proposed Mechanisms of Actions of GLP-1 RAs

Jennifer B. Green, MD:
It is important to note that although the primary use of GLP-1 RAs has focused on their mechanisms of action and benefits regarding reducing glucose levels and weight, GLP-1 receptors actually are present throughout the body on various organs, tissues, and cells. 

Because of the implications throughout the body, when receiving a GLP-1 RA, there is the potential for agonism or stimulation to have favorable effects elsewhere. For example, there could be effects on the kidney to increase diuresis and natriuresis. These agents also have the effects of decreasing gluconeogenesis and hepatic steatosis and have beneficial effects on the cardiovascular system and endothelium. All of these mechanisms may help to mitigate the risks associated with cardiovascular disease, kidney disease, and diabetes.10

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Potential Cardio-Nephroprotective Mechanisms of GLP-1 RAs

Jennifer B. Green, MD:
GLP-1 RAs are agents that stimulate or mimic the effects of our body’s own systemic GLP-1. There is a variety of potential cardioprotective and nephroprotective mechanisms that these drugs may induce. 

These favorable effects may be both direct and indirect. The indirect ways in which GLP-1 RAs act include improving glycemic control, increasing insulin sensitivity, and inducing weight loss. They can also lower blood pressure, improve lipid levels, improve left ventricular wall motion, and reduce neointimal formation in the vasculature. 

More direct effects that are theorized to be of benefit in mitigating the risks of cardiorenal disease include induction of natriuresis, improvement in tubulo-glomerular feedback in the kidney, reductions in kidney-specific and systemic inflammation, decreased oxidative stress, reduced renal hypoxia, and reduced glomerular atherosclerosis.

These are several theorized mechanisms through which these drugs exert their beneficial clinical effects on cardiorenal disease.11

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