The Continuum of Kidney Disease Care: From Identification to referral

Welcome, everyone, and thank you for joining today's webinar. The Continuum of Chronic Kidney Disease Care from Identification to Referral. I'm Harvey Kaufman, senior medical director at Quest Diagnostics, and I will introduce our speakers and moderate today's question and answer session. You were joined in listen only mode. I am honored to introduce our two outstanding speakers, Dr. Wright, physician and founder of Adventia and Premier Prevention Memphis, and Dr. Rajpal, nephrologist at South West Kidney Institute. Dr. Wright co-founded and currently leads the team at Adventia that partners with corporations, physicians and individuals to implement personalized prevention programs. In 2017, he opened a concierge practice, Premier Prevention Memphis. He serves on speaker panels for the Bale Doneen Method and for Quest Diagnostics and Cleveland Heart Lab, which is owned and operated by Quest Diagnostics. Dr. Wright was recognized for his work in 2012 with the Memphis Business Journal Health Care Hero Finalist Award. Also joining us today is Dr. Rajpal, board certified nephrologist and hypertension specialist at Southwest Kidney Institute. He trained at Cleveland Clinic and convinced all roads lead through Cleveland. Dr. Rajpal has extensive research experience in renovascular hypertension. Hypertension and kidney transplantation and cardiorenal interactions. His publications and poster presentations span a broad range of scientific journals and meetings. And he is a member of numerous medical societies. Before we continue, first, a few housekeeping items. Today's program is being recorded and will be posted on the Quest Diagnostics Education Center as a future On-Demand educational offering so you can review this valuable information in the future and share it with colleagues who couldn't join us for the live program. A link to the recording will be emailed to you in approximately two weeks. Please ask your questions in the Q&A box. and as time allows, we look forward to answering questions in the Q&A portion of the program. Dr. Wright, please take it away. Thank you, Dr. Kaufman. And thanks to each of you who have taken precious time out of your day to be with us. As a primary care physician who has spent the majority of my career seeking to prevent chronic diseases, today's topic on chronic kidney disease or CKD, is especially important. Most diseases of aging have a long preclinical, pre-symptomatic period upwards of 30 years., in most cases. In the 1600s, Sir Thomas Sydenham, the father of English medicine, stated “A man is as old as his arteries.” Wow. We now understand that the most common diseases of aging: diabetes, heart disease, stroke, kidney failure and even dementia at their core are diseases of accelerated arterial aging. This includes both macro and micro vasculature, and this aging is caused by chronic daily injury of the endothelium from a variety of factors such as blood pressure, glucose, lipids and more, which trigger an inflammatory response, accelerating the process. The key to effective prevention is to implement proven strategies as early as possible in order to stabilize, halt and at times even reverse the disease process. The challenge in these diseases is that they are completely asymptomatic for many years, are associated with subtle clues and are therefore often missed until suddenly we have a problem. My primary care colleagues are the crucial link in any effort to prevent the preventable. Today, I will focus on your role in detecting and preventing CKD. While Dr. Rajpal will discuss why early detection matters and when to refer patients with CKD to a nephrologist. Next. The challenge of CKD is that it's hidden. Sadly, over the course of my career, despite the advances in the science of prevention, not much overall progress has been made in preventing the progression of CKD. Most of this is for the reasons already stated. No symptoms, subtle clues. We can do better. And that's what today's presentation is all about. When you realize that 37 million people have CKD and 90% don't, don't know it either because they haven't been told, or maybe their physician hasn't realized that they're in a stage of CKD and a third of adults are at risk for CKD. So it's a huge problem. Next. Each of you are essential in the quest to to reduce the burden of CKD. Our goal is to make your days easier by simplifying the burden of clinical decision making, which patients, which tests. when to refer. Next. At least annually. The groups on this slide should be screened for CKD. It's easy to see that this is a large percentage of the average primary care practice. Additionally, any patients with a history of acute kidney injury, such as your patients who are hospitalized with COVID 19 should be screened. I suspect we'll see an uptick from the pandemic and chronic kidney disease unless we aggressively manage the survivors. Next. There are two tests. The EGFR, or estimated glomerular filtration rate is calculated on every bmp or renal panel and measures actual kidney function. We all do this test regularly, but are you systematically screening the high risk groups at least annually? Also, recall that small changes from normal in serum creatinine represent large changes in the loss of function. 40 years ago on my residency, I was taught the simple rule of dividing one by the serum creatinine to get a feel for the percentage of GFR remaining. So to go from 1 to 1.1 means about 90% is left. To go from 1 to 2. 50% is left. It's a good guide. We lose about one mil per minute per year, starting in our thirties and early forties. This should be slow enough that end stage renal disease should essentially never happen, at least not from the aging process. The National Kidney Foundation wants CKD stages one and two together as they are relatively low risk for progression to dialysis. I would encourage you to follow that trend as a simple way to follow arterial aging throughout the vasculature. Even in these early stages, and to be sure, the major CVD and CKD risk factors are being controlled. The urinary albumin creatinine ratio, which used to be called the micro albumin creatinine ratio, defines kidney damage. This is the missing piece for most of us in systematically and comprehensively managing our patients at risk. Think of the albumin creatinine ratio as the canary in the coal mine. The earliest and easiest test to detect damage to the glomerulus, to the endothelium lining the kidney. The majority of CKD is due to microvascular endothelial glomerular damage. And remember the arterial tree is a unified whole. Damaged in one arterial bed is a signal that all the other vital organ arterial beds are at risk. Prevention targeting CKD will benefit all organs. Next. This is the National Kidney Foundation heatmap and is incorporated into the new Quest CKD report. The Matrix uses both the EGFR on the left hand side of the chart and the albumin creatinine ratio across the top to categorize the severity of kidney disease and to suggest the frequency of testing and to guide when to refer to nephrology and to help your patients understand where they stand. Let's take a look at the CKD lab report. Next. This screenshot shows the entirety of the CKD report that you and your patient can see. This is an overview and we'll take a closer look in the next few slides and even discuss its use in a real patient. At the top there's a summary of results. And next steps. Next are the medical guidelines summaries in the middle or the actual results. And at the bottom is the risk map that we referred to. Next. At the top of the report is this gray box that has a concise summary of the CKD stage comparison to the most recent prior test and suggestions for either confirmatory testing of renal function or referral to a nephrologist. There are times when an additional test such as a Cystatin C or an actual clearance measurement is needed to confirm the stage that a patient is in. There are reasons where the estimated GFR are inaccurate and so confirmatory tests might be indicated. Next. This is an important table and it makes it very simple for you to stay current with the guidelines. Once you know the stage of kidney disease your patient is in, this shows you exactly which tests are needed to monitor progression and for complications and how often to do them. And and typically a brief comment on why the test is needed. This, this is invaluable as as a busy primary care practitioner to know, Oh yes. Here are the tests I need to do. Tell your medical assistant to be sure they get done and move on to the next patient. Next. As with all Quest reports, the color coded results table helps you to easily and quickly identify what the problem areas are and the trends. For example, on this patient, we see on the right hand side, the historical result of his micro albumin was in a high risk range. Non optimal, and now it's improved. It's gone below that high risk cut point. So the color code helps both you and the patient to to quickly see where they stand. Next. The National Kidney Foundation risk map is essential to your clinical decision making. This is at the bottom of the test report. It's color coded from the light beige to the dark, darker red from upper left to lower right. And each of those correspond on the left hand side to the different stages of CKD. Stages one and two at the top, stage, five at the bottom. And then across the table are the micro albumin creatinine ratios for normal, moderately increased and severely increased. The boxes contain important information. The digit recommends how often to retest each year: 1, 2, 3 or 4 or more times a year, depending on the stage of chronic kidney disease. The letter recommends either the confirmatory testing I mentioned with Cystatin C or a clearance test, or when to refer to a specialist. There's a box that's highlighted here on the left that shows up on your report that explicitly states these recommendations for you. It makes it simple for you to make decisions, and that's the core of this report. Next, let's look at a patient. Daniel, 56 years old and for his annual wellness visit. Probably like patients you see each and every day in your office. He's 5’10”, weighs 260 pounds, is on meds for hypertension. And when you calculate his BMI, which I hope everyone is doing regularly, make that easy. It's 37. So he has two risk factors indicating the need for at least annual screening. He's obese and he's hypertensive. The recommendation from the guidelines is to use both tests. The estimated glomerular filtration rate and the urinary albumin creatinine ratio test. Let's look at his results. Next. Daniel's results indicate he is at high risk for kidney damage. Yes, he's in stage two, so that's an early stage. But remember, that means he has already lost a significant portion of renal function and is headed towards stage three or beyond. His albumin creatinine ratio is strikingly high. In fact, he's in the severe range. And you'll notice that that puts him in that upper right hand box that says we ought to test at least twice a year and he should be referred to a specialist. Despite a creatinine that's not that impressive at 1.1, his albumin tells us that kidney damage is significant and referring to a special is specialist is essential. In fact, any time the the albumin creatinine ratio is above 300, the guidelines recommend referral. I'm going to refer excuse me, I'm going to turn it over now to Dr. Rajpal to discuss further why early intervention isn't critical and recommendations for management to prevent progression to end stage renal disease. Dr. Rajpal. Thank you, Dr. Wright, for the excellent presentation. Thank you, Dr. Kaufman for giving me this opportunity to present. Hello, everybody. We'll get on right with the presentation. Let's go to the next slide, please. All right. So this is a study which tells us early referral versus late referral, and what are the consequences? Early referral refers to getting a nephrologist involved with stage 3B with even slight amount of proteinuria and later for mean stage 4, if patients were involved with a nephrologist early on, they see lesser overall mortality, one year mortality, frequency of hospital admissions, their serum albumin and hematocrit, which in turn corresponds with morbidity and mortality, are also better if they are involved with nephrologists early on. Next slide, please. So the cost of chronic kidney disease and its progression to ESRD is immense. From last we know it's above 81 billion and probably rising every time a patient moves on a stage of CKD, either 3 to 4 or 4 to 5. The cost rises. The cost is most when the patient moves on to dialysis. So if we can stop that progression to dialysis in a patient's lifetime, there's enough money to be saved to be used reasonably for other patients. Next slide, please. So when to get a nephrologist involved, if there is a sudden drop in GFR, also called as acute kidney injury, if the GFR is in stage 3B or beyond, if there is persistent albumin in the urine greater than 300 milligrams per gram, if the albumin is between 30 to 300, you can consider based on the rapidity of GFR decline, if any. Always remember there will be atypical progression of CKD, especially in later stages. So just that the GFR has dropped slowly over the last ten years does not mean it can drop suddenly. This mostly happens when patients are at the end of CKD stage 3B and beginning of CKD stage 4, which usually means dialysis may not be that far. If you see blood in the urine, you have to consider is it coming from the kidney and not just from the bladder or kidney stones? Kidney blood usually called glomerular hematuria can indicate a nephritis, which, if treated in time, can preserve somebody's kidney for life. Hypertension is a key contributor to chronic kidney disease and ESRD. And if it's refractory, a nephrologist should hopefully be involved when we start seeing potassium problems or other electrolyte problems, sodium and bicarbonate, a nephrologist may be needed. And if there is extensive nephrolithiasis prevention with a nephrologist is needed. Family history of kidney disease is also an indication to get nephrologist involved. Next slide, please. The heat map again, the green is the good area. Mostly people will be fine with follow up once a year. The light yellow is actually the controversial area because this may be just okay a GFR of 45 to 59 sounds good, but if you start seeing other problems or some in some people, this GFR may not be a good representation because you know it may be lower than what the GFR is calculating for us. So this is an area where we should review the history, review the risk factors and make sure we eliminate anything which can decline this GFR further. When we get to the orange area, which is stage 3B all with the proteinuria Albuminuria above 30, we should get a nephrologist involved. Red areas should be managed by nephrology regularly. Next slide please. So this is a page taken from the NKF GFR calculator. It is just to indicate that a serum creatinine of 1.3 in a 60 year old male non-African-American may not sound bad and the GFR with CKD epicalculation, that's the most current calculation that we are using is only 59. So 59 is not that bad. But now we plug in a albumin creatinine ratio of 300 mg per gram and suddenly this patient is very high risk for progression to ESRD and will need a nephrology follow up and labs three times a year. Next slide. This is a good way of presenting our labs in this patient. The GFR is 44, his age is 45. A male with albumin greater than 30 but less than 300. So at two years he has 1.91% risk of progression to ESRD, and at five years his risk of progression is 5.85. Next slide. We have actually done good with incidence of ESRD, but the prevalence of ESRD continues to rise and we are trying to prevent transplant as much as possible. So in the last ten years things have improved slightly but not enough to reduce the healthcare burden. Next slide. Of course, when a patient gets diagnosed at a younger age, there is higher risk they will end up on dialysis versus if they get diagnosed later on in life, chances of dialysis are less as death will proceed dialysis. Next slide. This is the look at per month cost per patient right before they start dialysis. So six months before they start dialysis, the cost is around $1000 to $6000 per month for per patient. When they start dialysis, this cost jumps to close to $40,000 per month per patient. And then once the dust settles and the patient is now permanently on dialysis, they still end up spending about $20,000 per month. It's a health care cost. This is from Medicare data. Please. Next slide. This is the most important slide of today, which which focuses on why we need to have this presentation in the first place. Two in five patients with chronic kidney disease stage 4 are not seeing a nephrologist. One out of three patients in stage 5 have not seen their nephrologist in the past six months. 57% of dialysis patients who get started on dialysis did not see their nephrologist in the last year, and 25% of all ESRD therapy starts without ever seeing a nephrologist and may be patient never even knowing that they need to start dialysis. And I'm pretty sure because of because of the pandemic, many people have deferred their regular care. So this data will be worse, not better after COVID 19. Next slide. How can how can we control progression of chronic kidney disease in our primary care office? The goal of blood pressure after sprint and accord is less than 130 by 80. We do have to focus on the subset of chronic kidney disease, which did not do so well with intense blood pressure control. Of course, with intense blood pressure control requires more medications, more side effects, more electrolyte abnormalities, and also more drop in GFR. That being said, we should still aim for 130 by 80, except in in our patients who have very low diastolic patients or a very low diastolic blood pressure or in those who have symptoms from low blood pressure in those are more individualized approach is needed is an ARB are still our go to for proteinuria and blood pressure control provided we can manage their electrolytes especially potassium. Next slide. When should we start ACE and ARB? Almost every time a patient with chronic kidney disease has proteinuria, we should consider ACE or ARB. In our fragile patients with advanced age, we need to consider if that's really needed. If GFR drops more than 25 or serum creatinine increases by 25%, we may need to stop this. Other contraindications before not starting ACE or ARB might be renal artery stenosis. We always have to remember that a low sodium diet has to be followed. Diuretics are almost always needed, but we still want to avoid volume depletion in our patients with chronic kidney disease, especially on ACE and ARB. Next slide. The new development in chronic kidney disease in the last ten years has been the importance of SGLT-2 inhibitors. The trade names are in Invokana, Jardiance, Farxiga. The most pivotal trials were the credence trial that recently came out and the DAPA trial. Both these trials had to be stopped early on because SGLT-2 inhibitors had significant renal protective effect. They they work by reducing the reabsorption of glucose and sodium. So in turn they actually help with blood sugar control, blood pressure control, and even volume control in some patients. But most most important, they help reducing or slowing the progression of chronic kidney disease. So so this is one take home point. Every diabetic chronic kidney disease patient should be started on one of these agents if possible. The doses the renal doses are different, Invokana it's 100 milligrams. For Farxiga it is 5 to 10 milligrams. Next slide please. Of course, primary care doctors should aim for avency of seven whenever possible and avoid hypoglycemia while doing it. This is the best when it can be done, but side effects have to be managed as well. Next slide. Of course, for cardiovascular risk prevention, everything that can be done should be done. You should always remember CKD is a cardiovascular disease risk factor and a cardiovascular disease equivalent. Smoking cessation, exercise, weight reduction, lipid lowering and aspirin for secondary, but not primary prevention are the keys. Next slide. Anemia goals have to be targeted if if hemoglobin is low and TSAT is less than 30% and ferritin less than 500, make sure to start iron whether oral or iron or IV appropriate needs to be initiated after iron therapy or when iron saturation is good when hemoglobin is less than ten. But we have to remember to stop procrid if hemoglobin is greater than 11.5. Bone mineral density is the key. Are vitamin D levels. We are, we are trying to approach 40 when possible, but in many cases regular vitamin D2 or B3 may not work. We need to start activited vitamin D called calcitrial to to manage our rise in PTH so we have to check PTH once a year. If it is rising, we have to try to manage it with either vitamin D or activated vitamin D and so on. Phosphorus needs to be controlled with the diet, mostly dark drinks and phosphate binders like Tums or Fossil, or maybe initiated. If if calcium is not high. Next slide. Metabolic acidosis is usually ignored until a patient sees a nephrologist. So the goal serum bicarbonate has to be above 22, please initiate sodium bicarbonate tablets. 650 once or twice a day in chronic kidney disease patients. If the bicarbonate is less than that, the or the most the biggest concern is are we going to cause edema or hypertension with sodium bicarbonate? And most studies have indicated that's not the case. So feel free to start sodium bicarbonate in a hypertensive or a CHF patient. You should not see volume gain or blood pressure rate or raised. Hyperkalemia is mostly a dietary concept when GFR is low. Of course ACE and ARBs contribute, but NSAIDs cox inhibitors, potassium sparing diuretics like electon also contribute. Next slide. The role of plant based diet in chronic kidney disease is becoming more and more prevalent. Of course, it has not been proven in randomized large trials, but from observational studies in multiple countries we believe the more plant based the diet is, the less the progression of CKD. Remember Dash diet, which we are, which which has been proven to be good for hypertension, is essentially a high plant based diet, which is a bit low salt. Next slide, next slide. If CKD leads to a lot of medication errors because most doses end up being toxic, so doses have to be changed. Electrolytes have to be managed and multidrug resistant infections, recurrent hospital admissions, they end up causing the burden in our CKD population. Next slide. The diagnostic tests which contribute to acute kidney injury and chronic kidney disease are a contrast based test which can cause acute kidney injury. The gadolinium from MRI does not cause acute kidney injury, but can cause a rare syndrome called Nephrogenic systemic fibrosis. It is extremely rare but extremely fatal. So avoid gadolinium if CKD greater than stage 4 is present. Phosphate enemas can lead to disaster, so avoid that if possible. And then most patients with advanced chronic kidney disease don't get their angiograms on time, so they sometimes don't get proper management. Of course, fluid is always a concern for advanced CKD patients Next slide. A couple of drugs that need to be altered. Allopurinol, the dose needs to be reduced to 100. In chronic and chronic kidney disease stage 4 I'd like to reduce gabapentin to less than 300 milligrams per day. Reglan, narcotics and Digoxin toxicity is a big concern in advanced CKD, as we do not dialyze digoxin. And then I have other drugs for you to refer to later. Next slide. So key points. CKD patients are at high risk of drug related adverse events. Several classes of drugs are renally eliminated. Renal a GFR and not just serum creatinine should be considered when prescribing drugs. Minimize pill burden because they get a lot of pills from multiple specialists. Of course, a history of NSAID should be asked and they should be stopped every time. Avoid adding ACE and ARB at the same time. They do not help and that has been shown in multiple studies. Any med with greater than 30% renal clearance needs to be dose adjusted. Avoid bisphosphonates if GFR is less than 30. Metformin can be given till GFR is 30, but not below as risk of metabolic acidosis is high. Avoid glyburide and avoid gadolinium. Next slide. Serum creatinine does not always reflect the GFR because we have non GFR determinants of creatine which include race, sex and age. We are working on new guidelines on how to incorporate it, but at this point a 24 year old African-American male with a creatinine of 1.3 is not the same as a 59 year old Caucasian woman with a creatinine a 1.3. The GFR difference can be huge. Next slide. We'll skip it. Next slide. All right, so this is again indicating that we do not always see a regular decline in GFR. Thus the decline of GFR starts around age 45 at one mL for a minute or a year. And then we can of course see a faster decline which will take us towards ESRD, just like Dr. Wright mentioned in his slides. So if we are seeing a rapid decline in GFR, I would say a reevaluation and a nephrology consult is needed. Next slide. So how can we be more cost effective? The best approach is to avoid progression on CKD and ESRD. We should screen the serum creatinine and micro albumin are now urine albumin creatinine ratio on time. We should have close monitoring once we are in those risk groups. Just like the heat map. Dr. Wright mentioned a timely referral in stage 3B, specialist intervention and coordinated care with with the primary doctor, nephrologist and nutritionist and and other providers. The next slide. All right. Thank you. I move on to questions and Dr. Kaufman, if you have any words. There I go. Well, thank you very much for those two wonderful presentations. I think we all learned a lot from each of them. And I invite participants to enter questions in the Q&A box at the bottom of your screen. I'm going to start with a few questions that have come in. First one, one of the hot topics in kidney disease is the CKD epi equation for EGFR that includes a race based coefficient. What's happening and how are you reacting in your practice? Dr. Wright, Want to go first? That's a great question. And we know from the mounting evidence and the papers that have been published in recent years that the the race based adjustment is actually underestimating the burden of disease in the African American population, which means they get referred later to nephrologists, that they are even later to transplant when that when that's needed. Currently we have to go by the guidelines. We don't have a a solution just yet, but we know that the experts are working on a unified equation that can take that into account. In my own practice, what I do is I look at the African-American adjustment and and actually go down at least a few points from that, especially if they're on the edge of one of the different CKD stages. Thank you, Dr. Rajpal. So, you know, disparities in health care need to be addressed for sure. We do, however, want to answer the question in two ways. We don't want to over diagnose and overtreat either. So So when the CKD epi equation was analyzed back in the day in 2009, it did show a good effect of mortality and morbidity when it was adjusted for race. But that being said, I totally agree with Dr. Wright that we don't want to underdiagnose and undertreate, especially stage 3A and stage 4 where around GFR of 20 because these are the patients when they would be referred to transplant and when they would be active on the transplant list. GFR we have to remember, is a small but a very important marker. So I agree that improvement in the guidelines and hopefully the ACE and NKF task force with come up with will come up with a good solution very soon. Great. And the Quest Diagnostics position on this that we're going to be patient and wait for the National Kidney Foundation, the American Society of Nephrology, to issue their final report and look forward to implementing following that recommendation. If I may add one more thing. Sure. If in doubt, the cystatin C based guideline does not use race into account. So if we if we are in doubt, we can always do cystatin C creatinine, which will at least reduce our bias by half. So that's one technique that that can be used as well along with what doctor I mentioned. Thank you. Perfect. Thank you. Dr. Rajpal, first. So why is it that CKD is so common but so poorly recognized? What's keeping patients from interventions that can slow disease progression and increase appropriate referral to nephrologist? First question I ever get asked by a patient when they come to my office is why am I here? And and that tells me a lot. CKD is so silent. It is a number based disease. And patients, you know, especially at that age, are waking up four or five times every night to go to the restroom. So so they're like, my kidney's working overtime. What are you talking about? So, number one, it's a silent disease. Number two is a lot of it gets blamed on age. Number three is early CKD does not get the respect it deserves. And most importantly, you know, there are as we improve other other health care scenarios, sometimes a kidney being the filter of the body gets ignored. So we have to do a better with our diabetes, hypertension, our nephrotoxins. People have to be better at taking care of their health with the obesity exercise and so on. And then nephrologists have to do a better job in coming up with new and novel ideas to prevent a progression of CKD. Another thing I hear, especially from doctors, is, you know, but nothing much can be done to prevent progression of chronic kidney disease. I don't exactly agree with that idea. Multiple things can be done, and if done at the right time, they can lead to a cascade of GFR slowing down enough that dialysis is not needed in a person's lifetime. And I think that's a job well done. Dr. Wright, do you want to add? A great, great conversation there, Dr. Rajpal And what I would add is that as a busy primary care doctor with lots of patients in lots of rooms, you see that early stage disease and if you either are uncomfortable with remembering the guidelines for what to do next and who to refer, or you feel like, Oh, I've just opened a can of worms that I don't really know how to even have the conversation. It's easy to kick that can down the road. I know that I used to be that way as well, but the point of the Quest Report is to make that conversation easy, to facilitate that so that you can feel confident and competent to have the conversation and make the patient aware and show them on the heatmap. Here's where you're at. What would you like to do about it? And they're going to be all ears for what next steps are. Thank you. Next question. If a mother and a son each have a cyst, this is family medicine, both seen on imaging studies and both have CKD. Does this warrant further testing and if so, what testing? And I referred to the the Bosniak classification of cyst. Welcome the panelists to add their commentary. We get a lot of consults for cysts and you know cysts are usually part of life. There are specific guidelines on number of cysts at what age if you are going to consider it genetic. Polycystic kidney disease disorder, chronic kidney disease can run in families and association with the cyst may not always be there. Actually, most of the times the association is not there with the cyst. But of course, if the cyst is growing or is on the higher Bosniak classification, then we should make sure that it's not a malignancy and further testing with imaging and a urology consult may be needed, but I don't usually make a cyst and CKD, especially if those cyst burden is too low in the same equation. Great. Next one's a little long. Magnesium is noted to be a powerful vitamin D cofactor. Unfortunately, its least recommended mineral to prevent bone depletion. More unfortunate, it's usually the wrong magnesium level. It should be the magnesium RBC and also replacement should be chelated for or for or of magnesium rather than the commonly recommended oxide form. So either panelist want to take on magnesium? Well, you know, a problem is in our chronic kidney disease patients, magnesium gets accumulated. And most people I see have been taking magnesium either for cramps or something else. And we deal with hyper magnesemia more in our chronic kidney disease patients, number one. Number two is every time we see hypo magnesemia is basically below 1.6, we do recommend magnesium replacement. Magnesium oxide has been a good cheap replacement. Of course, it has the side effects of diarrhea, which in some cases actually end up treating two things. But, you know, like I said, magnesium should be checked. And if the level is below 1.6, it should be replaced. But, you know, that's what I would give answer. Dr. Wright, if you want to add something, I would add that in the primary care office, your role is to be that early detection system. And so I think these are great points for those early either normal GFR in the 90, you know, above 90 or they're starting to get into stage 2 chronic kidney disease that that there is potential benefit. But you do have to watch the magnesium level closely because hyper magnesemia here can be a lethal outcome. But yes, I think in early stage primary care practice, there's absolutely a role. Thanks for that question. Great. When to start an ARB instead of an ACE2 inhibitor? So my bias and again I'll be interested to hear Dr. Rajpal's thoughts but my bias is to always go with the ACE inhibitor first. They've been around longer. We have more safety data. We have lots of trials. The hope trial obviously was foundational in bringing ACEs to cardiovascular prevention, let alone chronic kidney disease prevention. So my preference is to go with the tried and true ACE inhibitors, especially Ramipril In my own practice. For those 10% of folks that get the cough, then then I'll move to an ARB at that point. So that's my strategy. But I'd love to hear Dr. Rajpal. During my fellowshipm this was actually one of the things I looked at and from what I found by systematic review that the difference between ACE and ARB prescribing may be just that ACEs are used more in clinical trials and ARBs are used less. It's now, I think, in my opinion, a matter of preference of whether somebody wants to start an ACE or a ARB. I have not seen clinically significant differences between the two. I think most things that we get with ACE, we get with ARB as well. But yeah, I mean, there's nothing wrong in starting an ACE first. And if we see a cough move on to an ARB, but in terms of which is more efficacious, I have yet to see a big difference between ACE and ARB. Thank you. What is the link between obesity and CKD, and is this related because of the hypertension and diabetes, or is there a direct link between obesity and CKD? Dr. Wright if I may take this, You know, yes, obesity, hypertension, diabetes, you know, they are all risk factors for CKD, but obesity, it, per say, can lead to kidney scarring or FSGS. It is a known cause of secondary FSGS. The way I think of it is, you know, a kidney is a filter and if you give it a bigger body to filter, there's higher chances of scarring that will happen. So yes, there is a direct cause of obesity, bypassing hypertension, diabetes and other other things as well. Of course there is high output, congestive heart failure, but again, that's a secondary cause. FSGS is probably the direct relation. I would add that the other factor that's important is most people that are obese have high visceral fat content. And remember that visceral fat is inflammatory. It drives interleukin 6 levels, which drives the inflammatory cascade. The HSCRP that you measure is actually a surrogate marker for IL 6 activation of the liver. So anything that increases visceral fat is driving inflammation, which as I said earlier, is going to drive arterial aging, especially accelerated arterial aging. So obesity is very important indeed. Dr. Rajpal, we talked earlier about SGLT-2 inhibitors. What is their role in patients with CKD but without diabetes? So the DAPA trial, especially for Farxiga, is a, you know, it is showing some promise that it could be started even in patients without diabetes with CKD for prevention. I have yet to use it in my clinical practice. I mean, I find it hard to convince a patient to start a anti-diabetic with no indication for for diabetes. But the indication is there at this point. And since there is good benefits seen in congestive heart failure, I think in the near future it may be clinical practice to start these agents if patients have CKD. So the evidence is there. I think it needs to be looked at closely before it's used in clinical practice. And again, as a primary care doc, I think that's our role is we'd rather not have to send people to Dr. Rajpal, right? I mean, and he would rather not have the the inundation of patients. Absolutely. And so I think that's where each of you it's incumbent on you to get comfortable with the literature. So the DAPA trial, please read through that. Become comfortable with the SGLT-2 inhibitors and then be able to have that conversation of, yes, this is a diabetic drug. But the great news for you is we've found it can help you prevent progression. So really the primary care folks, again, you’re front line and I would encourage you to get up to speed on when and how to use those two drugs. Right. One of our participants is protesting about EGFR values that are over 60 but are still, let's say, below 90. And it feels like this is a gut punch to patients to suddenly learn that they're in stage 3A. So what is the best way to communicate to patients who have values of 60 to 89? Dr. Wright? Want to take that first? I love the question and that's spot on and that's what I alluded to in my opening comments of the fact that we do want to detect people at the earliest possible stage to have the best chance of prevention. And so that's where the heatmap can really help you to show that that when your GFR starts to go below 90 and as it approaches, it certainly as it approaches 60, they've already lost a significant amount of kidney function. And so it is important to have that conversation. Remember, these stages are stages of chronic kidney disease. So you'll notice that a GFR of 91 isn't in the table, right? Because that's normal. So my approach is that, yes, have the conversation about stage 1 and 2 chronic kidney disease. And just explain. Great. Thank you. Someone wants to confirm that they heard that CKD is a risk equivalent to heart disease. In other words, we know that type two diabetes is a risk equivalent. Should we treat CKD in the same way for our patients? Amen. Amen. Amen. Again, it gets back to this is an, typically it's an arterial disease. It starts out that way. If it starts out as a primary renal disease, that's going to end up as an arterial disease because of the CKD. So it does go in both directions. But yes, it's this is a window into the arterial tree and the arterial tree is a unified whole. So chronic kidney disease equates to chronic heart disease, chronic cerebrovascular disease. Thank you. What's the data say about metformin that it should not be used for patients with EGFR below 30? Many patients still need this to control A1 C levels. Well, I do have quite a few patients that show up in my office with the GFR less than 30 who are still on metformin and they swear by it. The risk of metabolic acidosis, especially sudden metabolic acidosis requiring dialysis is there. So that's something that we should always keep in mind. And but you know, the data clearly indicates that once you get to GFR 30 or less, that may be a time to transition off to something different at that time. But yeah, I try to minimize metformin use less than 30, so the data is quite clear on that. Good. It's amazing. We have about 30 questions left, so we're going to try to go through as many as we can as quickly as we can. Next question is many patients come to have their labs drawn fasting in order to have a appropriate lipid panel in glucose. How much does hydration impact in terms of serum creatinine? And then the calculation of EGFR? And sort of related to that is why do we need to verify diagnoses with specimens drawn three months apart? So hydration does help, even though the the difference is not significant. We also have to remember that the GFR, the EGFR is not the measured GFR and there is a chance of wide variability with or without hydration, number one. That's why, you know, since it's a calculated and not a measured correlation, we should do frequent labs depending on how low it is to make sure we are in the ballpark range. Usually we like to stay within stages and not try to, you know, focus more on the GFR number. So if you are in the same stage and we see a decline of five, that could just be that the EGFR was a, you know, a different we can just check it again in three months and we should be okay. So that's the answer pretty much for both. It's a calculated measure. It has some error built in, but it is better than just simply using the creatinine at this point. And I always tell my patients for fasting lab that they can drink water and in fact should, because we've all had folks that come in dry and you can't draw their blood, you know, there they are hard stick, so to speak. So. So please tell them to drink water. Absolutely. One of our participants is concerned about African-Americans risk for CKD. Why is it so prevalent and more prevalent in African-Americans than it is in non-African-Americans? And what's the cause? What can we do to improve this? As a primary care doc, and again, I'll be interested to hear Dr. Rajpal's perspective in the folks he sees, but I'm in Memphis, Tennessee. We are smack dab in the middle of the diabetes, hypertension, cardiovascular disease belt. And and what the reality is that the care that's available to based on socioeconomic class, not not race, but socioeconomic class is different. And so the factors that are there tend to be untreated for longer, that that's a local perspective. Again, I'll look to Dr. Rajpal's perspective as well, though. Yeah, there is a big disparity between minorities in America and throughout the world and the prevalence of chronic kidney disease, both for African-Americans and Asians. So, yes, I do agree that socioeconomic status and, you know, approach to health care, you know, access to health care, those are key. You know, I don't want to lump the EGFR calculation in it because that's a very small component. You know, most patients who are not referred to transplant on time is not because their GFR was not 20 at the time. So I think this is a more social problem than than a medical problem at this point. So my suggestion would be, you know, wider access to health care, early labs, early albumin creatinine ratio, better control of blood pressure, everything that our primary doctors do at this point. So the answer is not a simple answer, and it will require many aspects of our social life and not just medicine at this point. Thank you. Next question, comment comes from someone who's asked asking about renal artery stenosis. One, how do we make this diagnosis? How do we use plasma renin activity in that diagnostic journey? And then further they ask if a in a patient with renal artery stenosis, normal sized kidneys and well-controlled hypertension with low dose ARB, would you recommend opening the artery or do you feel comfortable watching the renal size with EGFR in a urine albumin creatinine ratio? A lot of things, yes. And how big that question? Renal artery stenosis intervention for renal artery stenosis usually only helps in young females with uncontrolled hypertension and maybe in in people with rapidly declining GFR when the when one kidney is for some reason atrophied and the kidney that's good has the renal artery stenosis. So so so both kidneys are not functioning at the same level but in a patient with blood pressure, well-controlled, GFR well-controlled, if there is a incidental finding of renal artery stenosis, I would just leave it alone. Number one. So plasma renin activity has been looked into to to see if it can aid in the diagnosis of renal artery stenosis. And it has in some local studies, but nothing of which can indicate intervention is needed based on either image finding or a plasma renin activity. So at this point, intervention is focused on if hypertension is uncontrolled or if there are recurrent hospitalizations for flash pulmonary edema and so on. So. Great. Thank you. How do we differentiate acute kidney injury from chronic kidney disease? I'll take I'll offer my perspective. First of all, it's an acute change by definition. So suddenly there's a fall within the last three months. And and typically there is an inciting cause that's that's pretty easily identified. So I think the key is looking at prior and noticing that abrupt change. Dr. Rajpal, is is there a percent change that you use to define that? So, yes, acute kidney injury is a 25% decline in GFR suddenly, or if there is a persistent decline over the last few months. So, you know, pretty much the difference has to be compared to the old labs, to the new labs. And if you see a 25% decline, then all doubling of serum creatinine to 24% decline GFR or a doubling of serum creatinine that does qualify as acute kidney injury. And it should, you know, you should look into whatever is needed in terms of history medications or a referral to a nephrologist at that time. Great . Dr. Wright. I'm going to give you 30 seconds to provide a closing remark and then Dr. Rajpal will follow. My comment would be do what you do best in the primary care world. Be an advocate for your patients. Be diligent in following the guidelines, using the screening tools that we have and really be on top of arterial disease. We've talked about chronic kidney disease today, but this is for the entire vasculature. We need you to be to be the the conduit for better care. Thank you, Dr. Rajpal. Thank you so much for being present and listening to our presentation. I really do want to pass on that early diagnosis, early treatment, early referral, early correction, also risk factors, whether it be obesity or, you know, exercise or medications or the sooner we can get on it, the better. There should be no hesitation in involving the patient. And I understand these are delicate questions that sometimes patients don't want to hear negative news, but, you know, involving the patient, educating the patient early on saves us a lot of time and effort later on. So that's what I would I want to. Thank you so thank you for both of our speakers and for sharing your knowledge and perspectives about CKD with us today, also to the many participants. And thank you for joining us in providing so many excellent questions. If you registered with Zoom, you'll receive an email next week with a link to the online survey that we will use to develop a future webinar Topics that are of interest to you. If you're registered on behalf of a group of colleagues, please forward that survey link to them when you receive it. So I'm wishing you a good day and one in which we can each apply new knowledge. Thank you.