This transcript has been edited for clarity.
Matthew Sparks, MD: Hi. I'm Dr Matt Sparks and welcome to the Medscape InDiscussion Series on chronic kidney disease [CKD]. Today, we'll be discussing screening for CKD. We'll talk about estimated glomerular filtration rate. We'll talk about albuminuria and proteinuria, and we'll talk a little bit about current clinical trials that are underway. First, let me introduce my guest. This is Dr Nisha Bansal, who is a professor of medicine in the Division of Nephrology at the University of Washington. Welcome.
Nisha Bansal, MD: Thank you so much, Dr Sparks. I'm really delighted to be here today.
Sparks: Well, the one thing I like to do on InDiscussion is to give our listeners a little bit of information about who you are and how you got into the field. So first off, can you tell us one thing that you wish you knew about nephrology before you became a nephrologist?
Bansal: Oh, this is a great question. There are so many things I wish I knew about nephrology. It's surpassed my expectations as a clinician, as a scientist, and in terms of looking for a specialty with an inclusive group of colleagues. It's just a wonderful field, dedicated to comprehensive and longitudinal care of patients, and it's one of the most passionate groups of clinicians I've ever encountered. It's a true honor to be part of the nephrology community.
Sparks: Well, now that you've told us about that, I agree, nephrology is the best — there's no other specialty where you can take care of patients at such a critical time in their life, needing to start dialysis or transplantation, but also because of the camaraderie in the field. It's one of the few specialties that I think truly people love and it's their life. Tell us a little bit about yourself. What's one thing that you like to do outside of medicine?
Bansal: Outside of medicine, I love spending time outdoors. I'm originally from Connecticut but have lived on the west coast now for over a decade. And one thing I've really loved about life out here is just the easy access to nature … long hikes, kayaking, biking … I've learned to love it all. It's been fun.
Sparks: Great. Let's talk a little bit about CKD. I'd like to know where we are with that definition and what can a primary care physician do to say, "all right, I have diagnosed somebody with CKD." How can we identify it? And what would you tell a primary care physician about that?
Bansal: Yeah, great question. And it's such important work our primary care docs do every day in terms of identifying diseases in these very complicated patients. Chronic kidney disease, simplistically, I would say is defined as a reduction in GFR [glomerular filtration rate], which we estimate, so eGFR through equations or presence of abnormalities in the urine, either protein or blood. It's a very common condition. It is estimated that maybe around one in eight persons in the United States, unfortunately, is affected by chronic kidney disease and it is often silent in its manifestations. Patients don't have typical symptoms of chronic kidney disease until very advanced stages of disease, which makes the work that primary care doctors do, in terms of identifying disease early in the trajectory, incredibly important. One thing to recognize with chronic kidney disease is that it is a group of diseases; it's not a single entity. And thinking about etiology — what's causing the disease — is critical in terms of management. But the first step is really to identify it and understand that something is abnormal with the kidneys, and that can be accomplished with blood and urine tests.
Sparks: Let's get right to it. I think this is always a confusing area for trainees. What is the difference in proteinuria, microalbumin, albumin-to-creatinine ratio, and 24-hour urine? What should a primary care physician do when deciding and does it matter?
Bansal: Yes, we offer a lot of options in terms of how to measure abnormalities in the urine. There are certainly 24-hour collections, which are quite cumbersome for patients. As a starting point for primary care physicians, I recommend starting with spot urine collections. In that case, a patient simply collects a random specimen of urine, and we can measure spot concentrations of either urine albumin or urine protein. In terms of which one you should order, I would say that most primary care physicians prefer to order urine albumin, but both have merit. If you're in a setting in which urine albumin is not readily available in terms of measurement, urine protein is great as well.
Sparks: So, I've ordered the test and it comes back. How do I interpret that test and what do I do about it?
Bansal: Yes. So, you've measured a urine albumin-to-creatinine ratio from a spot urine sample and it's abnormal. Now we want to look at the quantification. You receive the number of milligrams [of albumin] per gram of creatinine you have in that random urine sample. And based on that, we can determine the severity of albuminuria in that patient. Typically, in an average patient, normal is considered <30 mg/g. We define microalbuminuria as 30-299 mg of albumin/g of creatinine in the urine. And then ≥300 mg/g of albumin is considered macroalbuminuria. That quantification is important because it can give you clues in terms of the etiology of that proteinuria.
Sparks: So, 30 and above is microalbuminuria. And it's interesting because our VA [Veterans Administration hospital] calls the albumin-to-creatinine ratio … they just call it the microalbumin test, which has always been a source of confusion. I just want to make sure our listeners understand it's the same thing but just named differently. [A value of] 30-300 would be microalbumin and then 300 and above is macroalbumin. And what I've really loved using, in the last several years, is this kidney failure risk equation. What is that and how can that be useful for our primary care physicians?
Bansal: Yes, it's a very important question. So, we've developed these equations in nephrology. The primary one we use is the kidney failure risk equation, which uses eight common variables that are measured clinically, including eGFR [estimated GFR], albuminuria, and some metabolic parameters to predict the risk of developing kidney failure over a 2- or 5-year time period. And I think this is a really important tool to consider for use because the question we're asking is, "all right, so someone has chronic kidney disease. What is their risk of progressive loss of kidney function?" And unfortunately, the result of progressive loss of kidney function is development of kidney failure. If we can better prognosticate the trajectory of disease in patients, we can make more informed counseling decisions with our patients in terms of understanding their preferences and tailoring treatments to best address their risk of kidney failure.
Sparks: You can go to kidneyfailurerisk.com to access that calculator. And I do agree, it's a very useful tool that has been validated to give you a rough estimate. I mean, no test is perfect, no calculator. But this gives you an idea about how worried you should be and gives you a little bit of guidance on who might need a referral to nephrology. Now let's go back a little bit — what patients need to have albuminuria or albumin-to-creatinine ratio and creatinine in the serum measured? All patients or are there certain patients that need it? Or are we still debating this topic?
Bansal: The idea of screening for chronic kidney disease certainly has been a hotly debated topic over the years. We can agree that there are certain subgroups of people that would benefit from screening for chronic kidney disease with measurement of serum creatinine and urine ACR (albumin-to-creatinine ratio).
The people that I would consider most appropriate for screening for chronic kidney disease would include those with elevated blood pressure or hypertension, those with diabetes, and those with preexisting cardiovascular disease. I would seriously consider screening for chronic kidney disease in other individuals who have other potential unique risk factors for chronic kidney disease. Those would include people with a significant family history or concern for genetic disorders. For example, those who've had recent acute kidney injury and you're monitoring their kidney function over time, and potentially patients who've had unique exposures to certain medications or nephrotoxins that might make you concerned about development of chronic kidney disease. While the idea of screening remains debated, I think there is certainly benefit in these high-risk patients.
Sparks: It's always interesting to me that we have this debate, yet insurance companies use albuminuria as a screening tool to get long-term insurance. So, they've found that it's useful. And as a nephrologist, it's often that you do see a patient who had an abnormal screen for that purpose and comes to your clinic. I do know that that is being debated in some of the big taskforce guideline committees right now. There are a lot of individuals [in the groups] that you named off who qualify for screening. But for the general population, we're still in a gray area.
Bansal: I agree. In a disease such as chronic kidney disease, which is so asymptomatic or silent until very late stages, to me, that highlights the potential importance of screening early. That's when you want to potentially offer therapies, think about additional diagnostics, anything you can to give the patient a chance in terms of better outcomes. I'm very curious to see where the next few years take us in terms of this ongoing debate about screening.
Sparks: That leads us to a perfect segue into what we do about it. And this is a great time because we are really gaining a lot of therapeutics. It used to be renin-angiotensin system blockade (RAS) with ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers) and now we've got mineralocorticoid receptor antagonist (MRAs) and SGLT2 inhibitors and maybe more down the pipeline. Obviously, if we're going to move the needle in diminishing the number of individuals in this country who need dialysis or transplant, we're going to need primary care physicians to start deploying these therapies. I want to give them an opportunity to hear from an expert about the comfort of starting these, because they come with some unique things you need to do. And we'll start with an oldie but goodie: ACE inhibitors and ARBs. When you have a patient with a little bit of albuminuria, let's say right in that 300 range, and you want to start them on this medication … they have diabetes and you want to start them on an ARB. How do you do that?
Bansal: These are great practical questions of what we do in real life. I love this. I would recommend starting at a low dose of an ACE or ARB and then titrating up from there. And the things that I think about when I'm titrating is, one, what is their blood pressure? You want to look at their starting blood pressure, what the change in blood pressure is, because in addition to having these kidney-protective effects, these are also blood pressure–lowering agents. We have to be careful that we don't drop the blood pressure too much. The other parameters that I consider in terms of initiation and titration of RAS inhibitors or ACE inhibitors and ARBs is the metabolic panel. Specifically, we're looking at the levels of potassium because these agents can cause hyperkalemia. And we're also following the eGFR. It can be tricky but there is this slight decline in eGFR that's expected and quite protective in patients with chronic kidney disease who are started on RAS inhibitors. We would expect to see a slight decline in eGFR somewhere in the 25% range, which is quite acceptable and would not be an indication to stop therapies now.
Sparks: Okay, so that's ACE inhibitors and ARBs. You need to check the creatinine; you check the potassium. SGLT2 [sodium-glucose cotransporter 2] inhibitors seem like they learned all their lessons from ACE and ARBs. Do you look at them similarly in how you start the medications or are there any other things that primary care physicians should think about?
Bansal: Great question. So SGLT2 inhibitors also need some monitoring. The things that I look for, again, are monitoring the kidney function after initiation. And like RAS inhibitors, you do expect to see some decline in eGFR, but that is again protective and not harmful. That should not be a deterrent in terms of stopping the medication. The other things you want to look for are risk of infections, particularly in the urinary tract, and that's been reported. If you have a patient who is at higher risk, I'd be cautious and just monitor for adverse effects. In terms of glucose-lowering [effects], people do get worried that you could drop the glucose a lot with these agents, but in fact their glucose-lowering properties are quite mild. It's rare to develop hypoglycemia in relationship to these medications. And for SGLT2s, like ACE inhibitors or ARBs, I like to start at low doses and then titrate up as tolerated. I never go to a high dose to start.
Sparks: We've got two really great medications that have been proven in many clinical trials to lead to great outcomes for the kidney, but not only that … also for the heart. The question I have is when should a primary care physician start these and when should they refer to nephrology to start these? Any thoughts on that?
Bansal: I'd love to see our primary care physicians getting comfortable with these medications and starting them as much as possible. Primary care docs are our frontline doctors: they're seeing most of our patients. But I would say that if there are concerns about how best to start or titrate, or if it's a patient with reduced kidney function where you're on the fence about whether it's safe to titrate or initiate a medication, it's okay to refer to nephrology. I do want to add that the SGLT2s have been approved for use when the GFR rate is as low as about 25 mL/min. Below that range, we don't have great data yet in terms of supporting safety and efficacy. If you're getting to those lower eGFR ranges and you're getting a little nervous, I think it's totally reasonable to refer to nephrology.
Sparks: Is there a certain amount of albuminuria that would signal you to send to nephrology or anything you want to say on that?
Bansal: If you're starting medications, all these wonderful therapies that we've been discussing — RAS inhibitors, SGLT2 inhibitors, MRAs — and you're finding that the patient continues to have high levels of proteinuria and you're not budging or making a difference, I think that's a reasonable time to refer to nephrology. The other thing that I would consider is thinking about a nephrology referral if the etiology of the disease remains unclear. If it's a patient who has had type 2 diabetes for 20 years, they've had clear progressive diabetic kidney disease, and you feel comfortable with the diagnosis and everything seems to be behaving in a very typical natural history, as we would expect, I think it's great to keep a patient like that under your care. However, if you feel that there's something off, there is this persistent proteinuria that you just can't get under control, there's a rapid decline in eGFR that seems off their natural trajectory, there's new blood in the urine, or anything that feels off, that is the time to refer to nephrology. It may require a little bit more investigation in terms of what's going on in the kidney.
Sparks: We didn't talk much about mineralocorticoid receptor antagonists (MRAs). We mentioned it. Where do they fall into the schema of RAS inhibitors and ACE and ARBs and SGLT2 inhibitors? At what point do you deploy those?
Bansal: Yes, great question. We have our steroidal MRAs, which are our traditional ones that have been around for quite some time, including spironolactone and eplerenone. And then we have these newer nonsteroidal MRAs that we've recently started using, and these include agents such as finerenone. The question is when should we use an MRA in addition to a RAS inhibitor, such as an ACE and an ARB, plus an SGLT2 inhibitor? I would say that you're really layering on medications. You may start one and then depending on the response and the safety profile of the initial medication, you may layer on another one if the patient continues to have proteinuria, for example. Ideally, I'd love to see an approach someday where we have everyone on all three of these agents successfully, but I recognize that it can be challenging in some patients. We're learning more about how to use these newer agents collectively in a single therapeutic approach. Right now, I would say it is largely individualized.
Sparks: This is something that you have special interest in. And I want to give you a little opportunity to talk about it. When you think about kidney disease, you very often think about cardiovascular disease. Can you tell the primary care physician who's listening or a trainee or anyone, what is that link? And when you see a patient, what goes through your mind?
Bansal: Oh, yes, Dr. Sparks, you're talking about something near and dear to my heart, for sure. What I find particularly interesting is that patients with kidney disease are often more likely to die of heart disease than to develop kidney failure in their lifetime. And the mechanisms that lead to that cardiovascular disease differ from that seen in patients without kidney disease. So, it's certainly true that patients with kidney disease have a higher prevalence of what I would consider traditional cardiovascular risk factors, things like high blood pressure, and they're older. However, we think that the kidney disease itself is linked with what I think of as kidney-specific risk factors for cardiovascular disease. And these include abnormalities in minimal metabolism markers, things like vitamin D and parathyroid hormone, all which have been potentially linked with cardiovascular disease. There are connections between uremic solutes themselves with development of cardiovascular disease as well. Because of these unique risk factors and this combination of these kidney-specific risk factors and traditional risk factors, we see that cardiovascular disease develops earlier in patients with kidney disease than we would expect in age-matched controls. The natural history is way more aggressive. The presentation of disease can differ. And because of this, the therapeutic response to traditional cardiovascular disease also differs. I'm always on the lookout for cardiovascular disease risk factors in patients with kidney disease, knowing that they may not have the same symptoms — of chest pain, for example — as a patient who does not have kidney disease. To be honest, a lot of the symptoms of kidney disease overlap with that of cardiovascular disease. A classic example would be symptoms of heart failure, which remains largely a clinical diagnosis when patients come in with shortness of breath and edema. And if you talk to a lot of my colleagues, they'll tell you that every single CKD patient I see has shortness of breath and edema. Does that mean they all have heart failure? It's just a matter of keeping it in the back of your mind. Does this patient have cardiovascular disease risk factors that I should be investigating further and treating more aggressively?
Sparks: I totally agree. I want to go through our three key points for today and wrap this up. But first, thank you so much. Definitely, kidney and cardiovascular disease are intertwined. And the good news is these medications treat both. So key point one is that screening for kidney disease is vital. Without it, we will be unable to detect it because as you mentioned, it's a silent disease and we cannot deploy a therapy unless we know it exists. Currently, as you mentioned, high-risk individuals — those who have hypertension, diabetes, a family history or history of acute kidney injury, and many others — are considered high risk. But we're still debating on whether the general public should be screened. The second key point is that the management of CKD is individualized. So, when you see a patient, you need to think about whether they are following the natural trajectory of whatever you think they may have? Do they need referral to a specialist? What is the etiology? Always keep this in mind. The third key point is that this really is a transformational time in nephrology. We just mentioned three new therapies but many more are on the horizon. And so those are our three key points. Thank you so much. Today we've had a national expert, Dr. Nisha Bansal from the University of Washington, discussing screening for CKD and eGFR cutoffs, albuminuria, and how to use some of the current medications that are approved for chronic kidney disease. Thank you so much for joining us. This is Dr Matthew Sparks for Medscape InDiscussion.
Resources
Estimated GFR Can Widely Diverge From Measured GFR
Kidney Failure Risk Equation Works Without Race Adjustment
The Kidney Failure Risk Equation
Don't Routinely Stop RAS Inhibitors in Advanced Kidney Disease
What Is the Role of Mineralocorticoid Receptor Antagonists (MRAs) in the Treatment of Proteinuria?
What Is the Role of SGLT2 Inhibitors in the Treatment of Chronic Kidney Disease (CKD)?
Sodium-Glucose Cotransporter 2 Inhibitors: Safety Concerns
Cardiovascular Disease in Chronic Kidney Disease
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Cite this: Primary Care Screening and Treatment of Chronic Kidney Disease - Medscape - Dec 14, 2022.
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