How can reading Mark Twain illuminate how chronic kidney disease is treated today?

Introduction

For this Blog, we've had the pleasure of speaking with many nephrologists. We don't often get the perspective of a primary care leader, one with frontline experience in both a large academic system and in surrounding rural communities. A doctor who is also a leader in diabetes care, with tangible insights into its impact on the development of chronic kidney disease. Dr. Eugene Wright provides such a perspective through, as he calls it, a 'lived experience.' An avid reader, I especially appreciated the way he shared his thinking through wonderful and pointed literary quotes and analogies.

Bio

Dr. Wright is an internist with over 40 years of clinical experience as a private practitioner, academic clinician-and-educator, medical administrator, rural physician in Southeast North Carolina, and a volunteer physician.

He specializes and does research in diabetes diagnosis, treatment, and management.

Dr. Wright currently serves as the Medical Director for Performance Improvement at the Charlotte Area Health Education Center (AHEC), with previous work experience as the Chief Medical Officer of the Cape Fear Valley Health System and as Consulting Associate in the departments of Medicine and Community and Family Medicine at Duke.

Since 2009, he has been an active member of the planning committee of the Clinical Conference of the American Diabetes Association (ADA) where he also serves on the Primary Care Interest Group, of which he was the Inaugural Chair.

Dr. Wright also serves and has served on several advisory and editorial boards to include Clinical Diabetes and Diabetes Technology and Therapeutics and is a steering committee member of the "Know Diabetes by Heart" initiative.

He has presented and published nationally and internationally on diabetes related topics and currently serves as a reviewer for several publications, including UptoDate.

"A loaded gun never hurt anyone,
until the trigger was pulled."

1. Since type 2 diabetes is the #1 risk factor for developing chronic kidney disease (CKD), let's start with some questions about diabetes. What are the risk factors for developing type 2 diabetes?

Obesity, genetics*, and the 'lived experience' are factors for developing type 2 diabetes.

There is a worldwide increase in the prevalence of obesity, a primary trigger of and associated risk factor for diabetes. There are also patients who have a genetic predisposition for developing glucose intolerance. And then, we need to factor in the 'lived experience:' what patients eat, how much physical activity they get, etc. Think about it this way: genetics are the bullets in the gun. A loaded gun never hurt anyone, until the trigger (how a patient lives) was pulled.

"We can't let patients read disease progression
as a failure on their part."

1. Does type 2 diabetes progress or worsen over time?

Yes, type 2 diabetes is a disease that progresses over time. And it's important that we communicate about 'progression' in the right way, when speaking with patients.

Patients can 'read' progression as a failure on their part. But the patients are not failing, it's the medications and treatments that are available at that time that are failing. If something is not working, we need to escalate the treatment.

1. Although type 2 diabetes is not curable today, are there any near-in "cures" that are in the works?

For years, we've used bariatric surgery to treat morbid obesity especially when associated with comorbid conditions such as diabetes. After the surgery, some patients can live without medications for a period. Others never have to take medications again. Which, I guess, would be considered a 'cure.'

Now, we also have new medications, and for the first time, the clinical community is talking about diabetes remission. Some of these new therapies are changing the entire dynamic for how patients live with a chronic disease, like diabetes.

1. Do we know why type 2 diabetes is the #1 risk factor for developing CKD?

There are at least three primary reasons why diabetes contributes to the development of chronic kidney disease:

• In the hyperglycemic (high blood glucose) state, the kidneys capacity to handle very high glucose is exceeded and glucose and other substances leak from the blood causing damage to the kidney tissues.
• Many patients with Type 2 diabetes live with hypertension, which causes increased pressure and damage to small vessels in organs, including the kidneys.
• There are inflammatory processes in the kidney and other organs that are triggered by high blood sugar. This inflammatory process leads to kidney (and other organ) damage.

1. In our society, we still seem to be more focused on disease management vs. disease prevention or, at a minimum, early-stage, disease mitigation. This certainly seems to be the case for both diabetes and chronic kidney disease. Do you agree? If so, can you provide some color as to why this is the case?

You hit the nail on the head.

For many years we spent most of our time and energy managing and treating diabetes and its complications after they appeared. We did not have many tools, medications, or resources to do much else.

Today, we have various 'tools' in our toolkit. We know that if we treat diabetes aggressively, and early, we can prevent or delay cardiovascular and renal complications.

Those results were clear in both the DCCT and the UKPDS studies, where tight glycemic control demonstrated patient benefit, extending out multiple years.

"Is there such a thing as being pre-pregnant?
Well, I'm not sure there's 'pre' diabetes either."

1. Should our focus be on prediabetes or does early care in diagnosed type 2 diabetes patients suffice? Is the answer different when discussing the mitigation of developing chronic kidney disease cases?

Very interesting question.

I'll start with this: Is there such a thing as being pre-pregnant? Not really, right? Same thing applies here.

When I think about prediabetes, I think about where it falls along a continuum. Some clinicians and researchers believe that 'prediabetes' is stage 1 or stage A, not some pre-stage. It's hard to say for certain when diabetes starts, as the glucose level upon which the diagnosis is made was decided based on consensus opinion. It was and still is recognized that the impact of blood sugars that have not risen to the level of a diabetes diagnosis have consequences.

We know that when we look at blood sugars at less than 126 but greater than 100, in the fasting stage, it is not normal. We also know, that when we look at A1c in the 'prediabetes' range, it may not yet register as a diabetes diagnosis, but can still be indicative of a high-risk patient for diabetes and its complications.

The net: whatever we call it, if a patient has metabolic syndrome or prediabetes, they are at an increased risk for chronic kidney disease, cardiovascular disease, and liver disease. The earlier we address changes in the patient's lifestyle and behavior and, potentially add certain medications, the greater the opportunity to reduce those risks.

1. CKD is typically called the "silent killer" because it is asymptomatic in its early stages. Can you talk about other ways it might also be silent, for example, from a racial bias standpoint?

Yes, early in CKD there are no symptoms, or the symptoms are not typically recognizable until later stages, when at least 40-50% of kidney function has already been lost.

I like to think about it this way - 'Where there is smoke, there is fire.' When you see early signs of smoke, you may not see a fire yet, but it's coming if you do nothing. And it is best to act early and aggressively to get to the flames before they burn the house down.'

And yes, there is certainly 'silence' given the significant bias that has existed for decades. However, many have been trying to address this bias in new CKD screening equations. In fact, some health systems and laboratories have already removed race, also known as "The Race Modifier", from these equations. The "Race Modifier" has for many years caused a person's kidney function, as calculated by the risk equation, to appear to be better than it is based on their race. This led to under diagnosis and under treatment of CKD in Black patients. While others have not yet removed it, they are reviewing whether they should.

"We have two ears and one mouth so that
we can listen twice as much as we speak."

• Dr. Wright, quoting Epictetus, a Greek philosopher

1. If you were King for the Day, how would you change the healthcare ecosystem to break the silence in CKD?

• Follow the Guidelines. I would incentivize annual screenings of eGFR and UACR. Approximately 1/2 of patients with type 2 diabetes are still not getting appropriately screened for CKD.
• Improved patient engagement. I often hear patients say that they would have changed their lifestyle earlier if they had known and understood that it would have improved their health. We may think that we are communicating clearly with our patients, but that's not always the case. That's why I always paraphrase Epictetus when speaking with Interns and learners… 'you have two ears and one mouth, use them in that proportion. Listen to your patients and assess what they understand, and both of you will be well served.'
• Team-based coordinated care. In this approach, a patient benefits from a 360-care model. The PCP and patient are supported with a full team, including specialty care in cardiology, nephrology, endocrinology, etc.

"PCPs are multi-specialists."

1. As a primary care leader, can you speak to the reasons why primary care is not more focused on this disease? Is it because they are inundated with being at the frontline for many more illnesses than just CKD? Or do they feel that they must prioritize something else? Or is it a lack of training?

Yes, yes, and yes.

In my opinion, primary care practitioners (PCPs) are under-appreciated for all that they do. PCPs are "multi-specialists" as they are clinicians who don't have the luxury of following one set of guidelines. Primary care clinicians are challenged with taking care of the entire patient with all the interconnected systems. The challenge is to figure out how to address many guidelines within their clinical workflow.

The diagnosis of CKD is often delayed due to the lack of early symptoms and the lack of disease awareness. It's only been recently, the last 5 - 7 years, where labs have even consistently reported eGFR, a measure of kidney function. What's assumed, by many clinicians, is that if eGFR is greater than 60, it's a normal reading. But we know from multiple studies, that a patient can have a "normal" eGFR of 100 or 130, but in the presence of albuminuria, it's not normal kidney function. The presence of albumin in the urine may be the "Smoke that precedes the Fire". So, that can be confusing.

Further, when Guidelines are developed, they tell a clinician what to do. They don't tell him/her how to do it. For example, 'When do I use the screening tools?' 'For which patients?' and 'How do they fit within my workflow?' While PCPs are accountable for early recognition and diagnosis, they need the resources, tools, guidelines and care pathways to make it happen.

Mark Twain's words might help us understand why many doctors are not diagnosing or treating early CKD. He wrote: 'It ain't what you don't know that gets you into trouble. It's what you know for sure that just ain't so.' Confidently held misinformation is the key to the issue here. Many clinicians believe that for CKD prevention, there is little to no additional benefit beyond treating blood sugar, blood pressure and lipids.

"In Diabetes, we are still following
a treat-to-failure paradigm."

1. It seems that we should have translatable learnings from other 'silent diseases,' like hypertension and cancer. What are your thoughts here?

I think that the analogies you draw from hypertension and cancer are very useful.

Over the last 20 years, recognition and treatment of blood pressure has really changed. Today, it's hard to find a diagnosed patient who is not on two blood pressure medications from the start. That's because we know what patient metrics we're trying to hit, and multiple medications help us reach those goals.

With cancer too, we use overlapping and complementary medications to improve the chances of remission.

In Diabetes, many are still following a treat-to-failure paradigm. We start with one medication and, when it fails, we add another one. When that fails, we add a third one or the so called "Treat to Failure" paradigm. It takes years to determine each medication's success or failure. In that time, patients are exposed to excess glycemic burden and all its potential complications.

That said, the paradigm is shifting. Due to growing evidence, more practitioners are focused on early and aggressive treatment, with the goal of preventing or delaying these complications. The ADA promotes Patient Centered Care with the goals of Prevention of Complications and Optimizing the quality of life.

1. So… are additive medications for diabetes treatment the new standard of care?

Yes, the ADA guidelines maintain that when diabetes is first diagnosed, patients should be assessed for cardiovascular and kidney risk and disease and the treatment paradigm should be directed accordingly. We add certain agents to the treatment mix to mitigate the development of and the progression of these and other diseases. Not everyone has adopted these new guidelines in their practices, but we're moving in the right direction.

"Could CKD screening tests
be automatically ordered?"

1. To better ensure that these diagnostic tests are conducted, could there be an automatic flag on the patient's electronic health record indicating that it needs to get done?

Yes, there are some automatic flags, though not for early kidney disease yet. And PCPs often suffer from 'flag fatigue,' not necessarily knowing which 'flags' (of the many) to prioritize.

So, what if we switched it up? Instead of being flagged as 'something to do,' why not just have the tests automatically ordered based on patient profile and established guideline directed criteria? In this case, every relevant patient would get the screening needed unless the doctor said 'no' for some reason.

1. Is this automatic opt-in being discussed somewhere? Or is this just one of your dream scenarios?

I'm sure it is. This is something we did for influenza nearly twenty years ago. For that, if a patient met certain criteria, and he hadn't received a shot, he would receive a letter saying that it was time to come into the office to get one. A similar approach could be used for eGFR and UACR for CKD screening.

"If you save me time or make me money, I will listen.
If you do both, I'm all in."

1. Switching gears, I'd love your thoughts on the question of therapeutic inertia in type 2 diabetes. How do you think that we can change this dynamic at the PCP level?

As you've said, there's a lot that's been written about therapeutic inertia. Based on my experience, here are some observations:

• A PCP is looking for opportunities that will save her time and/or reward her behavior with additional resources. I used to say, 'If you save me time or make me money, I will listen. If you do both, I'm all in.'
• A PCP may act in a way that conflicts with the behaviors that are favored by the large health system she may be working within. Many large systems and some payors are motivated by cost savings and risk mitigation.
• The "sweet spot" is to find a way to align the incentives of the PCP with the incentives of the health systems and payors.

1. Are there any risk assessment tools that can reduce therapeutic inertia? Would blood-based biomarkers be something that could facilitate action and compliance?

Blood-based markers - used as a risk assessment tool - could be beneficial in a variety of ways.

First, patients will benefit from knowing their own level of risk before the onset of symptoms. We have done this with high-risk patients for certain types of breast cancers.

Second, by focusing resources on those patients at greatest risk, and treating them earlier, costs would be reduced within health systems over the long term.

And, from a clinician perspective, a risk assessment tool could be a simple way for a PCP to identify 'priority patients' (those at greatest risk for progression to kidney failure) and implement the most appropriate care earlier than we might otherwise if we waited on symptoms.

1. We have exciting new medications - SGLT2inhibitors - proven to slow the progression of CKD. But we've heard that some doctors are hesitant to use them and have trouble explaining the initial downward slope that occurs when a patient takes them? How would you suggest a PCP explains it?

PCPs are all about safety, efficacy, and accessibility, in that order.

Originally SGLT2i's were used to improve glycemic control or to lower blood glucose levels. It hasn't been that long since they've also been used for the treatment of CKD. So, many doctors, understandably, are a bit cautious.

That said, we have all seen the results of various clinical trials that demonstrate both cardiovascular and renal benefits from these medications.

If they are proven to be safe and effective, why are PCPs still not prescribing them more?

It comes down to our clinical training. We've been trained that the lower the eGFR, the worse the kidney function. So, if you start with an eGFR of 50, for example, and it drops 5 - 10%, both the doctor and the patient are concerned. We as PCP's now know to expect a slight decrease in the eGFR with any medication that lowers blood pressure. We also now know that a slight decrease in eGFR is expected with age (~1-2 ml/yr) therefore we need to look at the trajectory (rate of fall) over time. When you do, you'll see that the 'rate of fall' is less than without the medication.

1. Have you seen any visual aids or educational materials that effectively explain this dynamic for clinicians or patients?

No, and that's a big challenge. Many of the package inserts for newer medications specify that a clinician should expect to see anywhere between a 10 - 30% initial drop in a patient's eGFR and that >30% drop is significant and should be addressed. But many PCPs don't have the time to read the fine print.

1. On the patient side, since CKD is largely asymptomatic in its early stages, how can we get patients to even care about their kidneys and engage in treatment?

Interesting question.

Well, we are starting to see some large-scale awareness campaigns from pharmaceutical companies.

I do think that fear is a significant motivator for change. Many patients with diabetes are concerned about or afraid of 'death, dialysis, and amputation.' Speaking to those risks can be motivating in terms of patient engagement and prevention. Further, messaging around all the new 'tools' that we have today, and our excitement that we can treat patients and this disease like never before, will also be a great incentivizer.

1. What differences do you see in patients with type 2 diabetes and CKD when they're at Duke vs in the more rural areas that you serve? Are there inequities between the two?

The greatest difference is in access to support systems and resources.

In rural areas, a patient may not have access to certified diabetes educators or specialists, like nephrologists, cardiologists, endocrinologists, etc. If they have access, it may take months to get an appointment, especially if the patient is not in an acute situation.

Collaborative team care is also very different in an academic institution vs a rural environment. For example, at Duke and other like places, there are Cardio-Renal Clinics where patients can be jointly seen by multiple specialties. This doesn't happen elsewhere. Telehealth could close some of the gaps here, but we're behind in that implementation.

1. I've read that you enjoy traveling internationally with your wife. Which of the places that you've traveled to - or others around the world - do a better job of managing diabetes and CKD?

Internationally, some places are much better at using tools to diagnose disease early.

Places like the United Kingdom and Sweden test early at a rate of 60 - 70%.

The United States is around 50%.

Some of this is the result of different models of healthcare.

While there are costs associated with these early diagnostic tests, other countries have figured out that there's a cost benefit associated with early diagnosis.

1. The differences in screening test rates make sense to me…since it seems that the U.S. is more focused on chronic illness management and specialty care, where other countries are more focused on preemptive and primary care. Is that true?

You're right. I'm thinking of a story that a patient, who has type 2 diabetes and end stage kidney disease, told me. He said, 'By the time you need dialysis, you are provided many resources to assist with your disease management. You have dieticians, nurses, even transportation to appointments. Imagine what it would be like if even some of those resources were re-assigned to someone before he developed end stage kidney disease?'

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