Kyle Wood, MD

 It can be. When you look at the big picture, you can say, “Well, the majority of patients with enteric hyperoxaluria have had bariatric surgery.” So if we look at a global prevention strategy, or a national prevention strategy, it would address the obesity epidemic and other factors outside the surgical means. It would be dietary recommendations and weight loss clinics. In addition, if a patient is choosing to have a bariatric surgery, you can try to do another type of surgery, different from the malabsorptive surgeries—although they’ve been shown to be the most beneficial for patients with weight loss. You can consider gastric bands, which is a restrictive procedure. There are obviously treatment options and management strategies that can prevent enteric hyperoxaluria once we identify these patients. With Crohn disease, if you treat the active disease form, you may prevent the patient from having the malabsorptive state. There are various ways to treat the conditions that they have and understanding the population. This avoids malabsorption by gastric bypass if that’s a concern. These patients are often managed with bariatric surgery for obvious reasons—for health benefits—and this is the sequel of those procedures. But there are ways to prevent enteric hyperoxaluria.

You mentioned therapies. What are some treatment options for this disease?

 I break it down into 4 categories. That’s the way I like to view it. The first 1 is dietary management. Obviously, if you persuade them to take a lower-oxalate diet, which is hard to do, they’ll understand oxalate content in the things they’re eating, which is obviously less oxalate burden to the gut and, therefore, less absorption. The other thing is because of a fat malabsorptive state. If you focus on low-fat foods so that the patient has less fat malabsorption, that can be beneficial. You can talk to them about a high-calcium diet. In the pathophysiological processes, the calcium is being saponified, so if you get them to have a higher-calcium diet—giving them calcium supplements or calcium in their diet—you can bind to more of the oxalate and reduce the oxalate load to the kidneys. As with all kidney stone formers, increased fluids—if you persuade them to drink more fluids—will dilute their urine and make kidney stone formation less likely. That’s the dietary approach that I usually take. The second category is looking at oxalate binders.

I alluded to it, but the use of calcium supplements—giving patients prescription calcium—to increase the amount of calcium that can bind to oxalate will lower oxalate in the urine. Magnesium can be used the same way. The third category we think about is bile acid sequestrants [resins]. This is a malabsorptive process of fat and bile acids. If you use cholestyramine [Questran], or other medications to reduce the bile acids, you may reduce the saponification to calcium, and thus reduce the oxalate load that’s getting absorbed.

The fourth category is for newer ideas that are coming out in clinical trials, which are the oxalate-degrading enzymes or bacteria. We’ve known about Oxalobacter formigenes for quite some time. It’s a normal, gram-negative bacteria that may colonize in the gut and degrade oxalates. The newer novel therapies, currently in phase studies, are looking at degrading oxalate by using enzymes or modifying bacteria. None of those have been approved by the FDA, but those are things we can think about for treating our patients.

Videos

Kyle Wood, MD, reviews current therapies and strategies for the management of enteric hyperoxaluria.

Treatment Options for Enteric Hyperoxaluria

What are the symptoms of enteric hyperoxaluria?

 High oxalate levels in the urine may not have symptoms. Just because they have hyperoxaluria does not mean that they’ll have symptoms because of the high oxalate. However, with high oxalate comes the increased risk of forming kidney stones, so some of the presenting symptoms for enteric hyperoxaluria may be kidney stone related or kidney stone event related. In addition, the symptoms that the patients may experience that lead to thinking about enteric hyperoxaluria may have to do with the malabsorptive process. They may present, say after a bariatric surgery, with signs of malabsorption—increased bowel movements, diarrhea—and those may lead you to believe that they have a malabsorptive process in their gut that could be explaining their enteric hyperoxaluria. A lot of the symptoms are unrelated to the actual levels of oxalate but have to do with the consequences, or sequela, of having high oxalate. Kidney stone events and chronic kidney disease may result. In severe cases, you can have oxalate deposition in other tissues. That could be a manifestation as well.

 You mentioned the malabsorption. How can that lead to enteric hyperoxaluria? What are some of the diseases that cause malabsorption absorption?

 That’s a great question. Pathophysiologically, let’s say you have bariatric surgery and you have a malabsorptive process that’s created to help with weight loss. But in the process of that, you can have fat malabsorption and bile acid malabsorption. What happens is the bile acids and the fats saponify, or bind, to the calcium in the gut. In that process, the calcium can no longer bind to the oxalate, so the gut oxalate is free to be absorbed through the gut, into the bloodstream. That higher level of oxalate that gets absorbed into the bloodstream gets excreted in the kidneys, causing high oxalate in the urine. That’s the main pathophysiological process. The other thought is in these malabsorptive states. You may have increased gut permeability, which allows for more oxalate to be absorbed as well. We have mentioned some diseases that cause this. Any bariatric surgery will purposely create a malabsorptive state. Gastric bypass—Roux-en-Y gastric bypass—a duodenal switch, or biliopancreatic diversion, can all cause malabsorption processes. Some disease states, like inflammatory bowel diseases—like Crohn disease—can cause a malabsorptive process that can cause enteric hyperoxaluria. Cystic fibrosis, has issues with pancreatic enzymes, thus the malabsorptive process can present with enteric hyperoxaluria as well. Anytime you’re looking at the bowels or anything that’s causing a malabsorptive state, or if there’s been surgical removal of the small intestine, these conditions can lead to the same process. You could have enteric hyperoxaluria.

Kyle Wood, MD, comments on the presenting signs and symptoms of enteric hyperoxaluria and complications of untreated disease.

Clinical Presentation of Enteric Hyperoxaluria

What’s the prevalence of enteric hyperoxaluria in the United States?

That’s a tough question to answer. Enteric hyperoxaluria is still a disease that we may not be diagnosing, or that we’re underdiagnosing. If you look at the most common causes of enteric hyperoxaluria—that being bariatric surgery—we have some idea of the number of procedures being done and the number of people who will have hyperoxaluria when they’ve had these procedures. When you look at a bariatric surgery, there are over 100,000 bariatric surgeries being done annually within the United States. Some studies suggest that upward of 75% of those individuals will have at least one 24-hour urinalysis showing hyperoxaluria. If you look at those large numbers, you can imagine a large population of at least 75,000 cases per year who are having this surgery, resulting in hyperoxaluria. Obviously, those populations are living longer. The accumulation of each of those years and populations estimate that there’s about 250,000 patients with enteric hyperoxaluria and kidney stones. About 100,000 of those patients are recurrent kidney stone formers. Enteric hyperoxaluria isn’t just caused by bariatric surgery. It also can be a manifestation of Crohn disease, cystic fibrosis, or other bowel surgeries. It may be a result of gut permeability, or—for some of the idiopathic hyperoxaluric patients—it may be explained by an enteric cause if we look further into it. The population is much larger than we’ve come to realize. It probably represents hundreds or thousands of people in the United States.

 It really stems from a good history and a physical exam. Understanding what those patients have had done and, by surgical procedures, whether they’ve had bariatric surgery, and getting a good feel of both their dietary intake and their bowel habits. That’s the initial phase: taking our kidney stone formers and doing a good history and a physical exam. If you follow the AUA [American Urological Association] Guidelines, a lot of these individuals would require a metabolic work-up, which would be a 24-hour urinalysis. That’s how we would diagnose hyperoxaluria—greater than 40 mg of oxalate per day with an accurate collection. That’s the work-up that we do to determine whether they have an oxalate issue, and whether the patient has enteric hyperoxaluria.

With the diagnostic process, do you think community providers are aware of the need to diagnose hyperoxaluria?

 There’s a disconnect, as I had mentioned before. The community providers and academic centers sometimes treat kidney stones as an episodic event. The patient comes in, and we may treat them surgically, or we may not further work them up on why they’re forming stones. There’s a disconnect. We need to do better, as providers, to start working up our patients. The hallmark is that metabolic work-up of a 24-hour urinalysis. Blood work is not needed for the diagnosis of that. However, blood work, in the setting of 24-hour urine analysis, can help understand why a stone former might be forming stones for other reasons.

I know you mentioned the disconnect, but what are the challenges in diagnosing hyperoxaluria?

 Some of the challenges are the physicians themselves—us ordering the tests. Some of it’s the vendors we use for the 24-hour urine test. It’s not a complex study, collecting urine for 24 hours, but it’s an inconvenience for the patient. There are compliance issues with the actual collection of the order, so if we order a 24-hour urine test, seeing it to completion is sometimes difficult. In addition, as I had mentioned previously, another challenge is the accuracy of the collection. Despite us ordering the 24-hour urine test and the patient collecting it, they may not collect it accurately, meaning it may not be a full 24-hour urine. It may be an under- or overcollection, which can make results difficult to determine, and whether to diagnose them with hyperoxaluria. Those are some of the issues that we run into. It comes down to actually placing the orders for the patients, getting them to complete their 24-hour urine test, looking at the results in a very practical way, understanding if they are hyperoxaluric and the causes of that, and then recognizing patients who are enteric.

An expert endourologist describes the prevalence and diagnostic processes of
enteric hyperoxaluria, as well as common challenges faced in making a diagnosis.

Diagnosis of Enteric Hyperoxaluria

 video series titled “Enteric Hyperoxaluria, Understanding the Disease.” I’m Kristie Kahl, vice president of content for 

®. We have Dr Kyle Wood, an assistant professor in the department of urology at the University of Alabama at Birmingham, with us today. Thank you for joining us, Dr Wood. Let’s get started. Dr Wood, can you start by defining what hyperoxaluria is?

 Sure. Hyperoxaluria is based on 24-hour urine collections. First, we need to be focused on collecting 24-hour urine and following the AUA [American Urological Association] Guidelines. Once we get the 24-hour urine data, we need to ensure that it’s an accurate collection. That’s done by looking at creatinine excretion throughout that 24-hour time frame. Hyperoxaluria is defined as oxalate levels 40 mg or greater, per day, in that collection. There are some data, and there are some publications that suggest you can look at 45 mg as the cutoff. But most people look at about 40 mg per day as the cutoff that defines hyperoxaluria.

 The 3 types of hyperoxaluria are broken down into primary hyperoxaluria. There are 3 known conditions. They’re all monogenetic causes. They’re all involved in the glyoxylate-oxalate pathway within the liver. Each has to do with a mutation of a gene that’s involved in that process, which results in increased oxalate excretion in the urine because of increased endogenous production. Idiopathic, or secondary hyperoxaluria, are those patients who have high oxalate in the urine without a known cause. It’s not a genetic mutation, nor is it enteric hyperoxaluria. Those are probably a combination or a multifactorial process, which may include dietary indiscretion, some component of enteric hyperoxaluria, or some other unknown cause. Enteric hyperoxaluria has to do with fat malabsorption processes. Fat malabsorption in the gut and saponification of calcium are done by bile salts or fat. You have increased oxalates, which can be absorbed because they’re not binding to calcium, and thus you have increased urinary oxalate excretion through the kidneys. That’s really the hallmark of enteric hyperoxaluria—the most common of which is gastric bypass procedures, and bariatric, or bariatric surgery, procedures.

Can you discuss the need for education to help others understand this disease?

 If we talk about the state of hyperoxaluria as a whole, it’s important to understand that there are multiple reasons why an individual can have high oxalate in their urine, and that the pathophysiology of each of those causes can lead to various treatment options. It also really focuses on, or teaches us, that we need to have a good history and physical exam, because knowing the patient’s history may lead you to 1 of these diagnoses or causes of hyperoxaluria.

Who should be screened for hyperoxaluria?

 If you follow the AUA Guidelines, any recurrent kidney stone former or first-time kidney stone former who’s interested in a work-up should have a metabolic evaluation, which would include these 24-hour urines. In my practice, what all urologists should be focusing on is if you have a recurrent stone former or a high-risk stone former, all of them should be evaluated for hyperoxaluria. That would be done by a 24-hour urinalysis. Those first-time stone formers who desire a work-up should also receive a 24-hour urinalysis and be screened for hyperoxaluria.

How often do patients with kidney stones see a doctor?

 There are individuals who can pass their kidney stones without seeing a physician. But for the most part, when they have an acute event, they present to the emergency department, a primary care physicians, or a urologist. Many times, they require intervention with a urologist. Those kidney stone formers are really the population that we should be treating and evaluating for hyperoxaluria. What’s interesting is the disconnect between what the patients desire and what the urology community is doing. If you look at patients, or if you ask a kidney stone former whether they would want to be further worked up, greater than 90% of them say that they would want to be further worked up and try treatment—or medical, or dietary options—to prevent stones. Yet when you look at urology, there are published data that suggest we order 24-hour urine analyses in only about 7% to 8% of our population. There is that disconnect between greater than 90% of patients desiring treatment, and us ordering 7% to 8% in the studies or of the population. Stone formers present in many ways. But at least from urology, the contact point is usually to discuss surgical interventions. Most stone formers probably present because of the pain and issues that are afflicted during a stone event.

Kyle Wood, MD, provides insight on the types of hyperoxaluria, the importance of disease education, and who should be screened for the disease.

Kyle Wood, MD

Articles

Treatment Options for Enteric Hyperoxaluria

Clinical Presentation of Enteric Hyperoxaluria

Diagnosis of Enteric Hyperoxaluria

Overview of Hyperoxaluria