Nutritional Management of Canine Protein-Losing Enteropathy

Protein-losing enteropathy (PLE) is a syndrome in which plasma proteins are lost into the gastrointestinal (GI) lumen. Any GI disease, if severe enough, can lead to intestinal protein loss; the term PLE broadly encompasses intestinal disorders resulting in GI protein loss so great that hypoalbuminemia results.¹ PLE can be the result of inflammatory enteropathies, infectious enteritis, lymphangiectasia, intestinal neoplasia, or small intestinal dysbiosis.^2,3 Certain dog breeds appear to be predisposed to PLE (BOX 1).

In adult dogs, lymphangiectasia and alimentary tract lymphoma are the most common causes of PLE.⁴ In very young dogs, hookworms and chronic intussusception appear to be more common. If inflammatory bowel disease (IBD) is the cause of PLE, the IBD is typically very severe.⁴

Causes and Mechanisms of Protein Loss

Although many conditions can result in protein loss through the GI tract, there are a limited number of mechanisms by which plasma protein is lost through the GI tract⁵:

• Lymphatic obstruction leading to “overflow” lymph leak (e.g., congenital or acquired lymphatic disease)
• Cellular mediator release affecting vascular permeability, resulting in fluid entering tissues (e.g., eosinophilic gastroenteritis)
• Mucosal inflammation (e.g., IBD)

Pathologic dilation of lymphatic vessels in the small intestine, known as intestinal lymphangiectasia, accounts for roughly half of cases of canine PLE.⁵ Intestinal lymphangiectasia can be congenital; it may also be the result of inflammation and/or hydrostatic pressure changes within veins in the intestine.^6,7 Lymphangiectasia leads to PLE by impairing the flow of lymph, which transports fat (in the form of chylomicrons) through lacteals (intestinal lymph vessels) to the systemic circulation. Lymph protein content increases with dietary fat intake,¹ and lymph flow increases two- to threefold for 4 to 6 hours postprandially. When lymphatic flow is impaired, lacteals balloon with lymph and can rupture, releasing lymph into the intestinal lumen. The intestinal mucosa is then damaged, with even more protein lost through exudation or hemorrhage into the small intestine.

Clinical Signs of PLE

Clinical signs indicative of PLE are listed in BOX 2. Lymphangiectasia signs may be subtle and often wax and wane over several weeks to months before becoming evident. Clinical manifestations are mostly attributable to the loss of lymph elements or to the inherent GI disease.

It is important for veterinary healthcare teams to remember that not all dogs present with GI signs. Progressive weight loss, even if the patient has a good appetite, has been reported often in established cases.¹ Thus, the team should perform a complete nutritional history, along with body condition scoring and muscle condition scoring, initially and on every subsequent visit.

Nutritional Evaluation of Patients With PLE

Every time an animal presents to the hospital, it should be assessed to establish nutritional needs and feeding goals, which depend on the pet’s physiology and/or disease condition. This is especially true for patients with PLE. The role of the veterinary nurse is to establish patient history, score the patient’s body condition, work with the veterinarian to determine the proper nutritional recommendation for the patient, and communicate this information to the pet owner.

Nutritional History

A nutritional history aids in ascertaining the type or types of food being given to the pet as well as the feeding protocol. The veterinary nurse should ask the owner open-ended questions to uncover more information rather than questions that can be answered with a single word, which may not reveal everything that the patient ingests (BOX 3).

The veterinary team member should also ask the owner about the pet’s access to foods, supplements, and medications and how much of each the pet consumes each day. Pets may be fed by multiple family members or receive numerous treats throughout the day. All of these factors play a role in developing a proper nutritional protocol for a patient with PLE.

Body and Muscle Condition Scoring

The healthcare team should document the pet’s body condition score (BCS), muscle condition score (MCS), and weight at every visit as part of the physical examination. The BCS is a subjective assessment that is important when determining whether the patient is at a healthy weight, while the MCS evaluates muscle mass. Assessing muscle condition is important because early identification of muscle loss is beneficial for successful intervention. Together with weight, the BCS and MCS provide consistent measures that can be obtained by all team members.

Client Education

Dogs with PLE do not often have a positive outcome, with only about 50% of cases surviving longer than 4 months.⁸ Thus, it is imperative for the veterinary team to identify, work to correct, and manage the individual risk factors indicative of a poor outcome (e.g., small intestinal diarrhea, vomiting, anorexia, weight loss) to improve the patient’s odds for survival. As the bridge between veterinarian and client communication and education, the veterinary nurse plays a critical role in the management of these patients by educating clients about the serious nature of the disease, the importance of nutritional management, and the modest potential for a positive outcome.

Nutritional Management of Patients With PLE

Energy balance is an important concept in managing dogs with PLE. Ideally, an animal’s energy intake and expenditure should be equal. However, in dogs with PLE, impaired intestinal absorption of protein lowers the amount of energy obtained from food, often leading to a severe negative protein and energy balance—that is, energy expenditure is higher than energy intake. These animals have subsequent ongoing weight loss and a decrease in lean body tissue as well as fat, making nutritional support essential. Dietary fat intake should be controlled, and, to offset intestinal losses, providing food with a higher protein content may be of benefit.

Digestibility

Feeding highly digestible foods (fat and soluble carbohydrate ≥ 90% digestibility; protein ≥ 87% digestibility¹) provides several advantages for managing lymphangiectasia in dogs. Nutrients—especially the energy-supplying nutrients (e.g., fat, carbohydrates, protein)—in highly digestible foods are more readily and completely absorbed in the proximal gut. Highly digestible foods are also associated with:

• Reduced osmotic diarrhea associated with fat and carbohydrate malabsorption
• Reduced intestinal gas production associated with carbohydrate malabsorption
• Decreased antigen loads
• Energy Density and Fat

Nutritional management of intestinal lymphangiectasia focuses on reducing lymphatic pressure by lowering chylomicron formation. This can be achieved through reducing the patient’s fat consumption.⁶ In many pet foods, fat content comes from long-chain triglycerides. After digestion and lymphatic absorption, long-chain triglycerides are reconstituted into chylomicrons, which are transported from the mucosal epithelium through lacteals as previously described. Because lymph protein content is increased by long-chain triglyceride absorption and lymph flow increases postprandially, it is sensible to limit dietary fat intake (≤ 15 g/1000 kcal) to minimize lymph flow, reduce lacteal and lymphatic distention, and minimize protein loss.^1,6

In addition to being balanced, highly digestible, and low fat, diets for dogs with PLE must have sufficient energy density (> 3.5 kcal/g).¹ Veterinary teams must remember that patients with PLE may be cachectic; thus, it may be beneficial to include medium-chain triglycerides (MCTs) as a source of calories. MCTs are water soluble and are hydrolyzed readily and rapidly. If MCT oil is warranted, it should be incorporated as an ingredient of a therapeutic food rather than added as a supplement, as the supplement negatively affects palatability. MCT oils do not contain essential fatty acids; thus, the veterinary team must ensure adequate intake of essential fatty acids when MCT oils are used for prolonged periods.

Protein

A PLE patient’s diet should contain enough high-biologic-value proteins to support hepatic protein synthesis and replace depleted tissue proteins.¹ Overall, the protein content of food for canine PLE patients should be at least 80 g/1000 kcal. It has been shown that feeding high-protein or all-meat foods without other appropriate dietary alterations does not support a successful outcome for patients with PLE.^1,9,10

If severe IBD is the underlying cause of PLE, the veterinary team should consider the use of a low-fat elimination diet containing lower levels of highly digestible, novel protein sources or a hydrolysate-based food. Similarly, if intestinal lymphangiectasia is suspected to be secondary to a food allergy, alternative nutrition strategies such as feeding novel, hydrolyzed, or amino acid protein sources can be implemented.

Tryptophan

Tryptophan, an essential amino acid in dogs, is important in energy metabolism. It is a precursor for kynurenine, serotonin, and melatonin. A small proportion of tryptophan makes its way to the colon, where it is metabolized by luminal bacteria into indole, skatole indicant, and tryptamine, which aid in reducing intestinal inflammation; these metabolites are essential for the induction of anti-inflammatory cytokines such as interleukin-22.¹¹ In dogs with chronic enteropathies, serum amino acids are frequently decreased.⁸ In dogs with PLE, tryptophan appears to be the only amino acid to be decreased in serum.¹² These lower serum tryptophan concentrations correlate with lower serum albumin and poor outcome in dogs with PLE.¹² Tryptophan supplementation may have benefit in some PLE cases, but additional research is needed before this becomes standard protocol.

Fiber

Increased levels of insoluble fiber are not typically recommended when managing PLE nutritionally; rather, a total dietary fiber level of 15 g/1000 kcal is recommended.⁶ Fiber-containing foods do not seem to be directly damaging for patients with PLE, as there are cases in the veterinary literature in which a high-fiber food was successfully fed; however, the food had a low fat content.^1,6,13,14

• Dietary fiber at the recommended level of 15 g/1000 kcal is responsible for¹:
• Binding digestive enzymes and bile acids
• Decreasing pancreatic secretion of lipase
• Reducing pancreatic enzyme activity

These actions decrease intraluminal fat digestion and micelle formation, which inhibits long-chain fatty acid absorption.¹³ Consequently, fiber is believed to play a secondary role in reducing long-chain fatty acid absorption, thereby decreasing lymphatic flow and subsequent loss of lymph. However, increased levels of fiber reduce the caloric density and digestibility of a food, which are both considered important to the appropriate management of patients with PLE.¹ The recommendation for these patients is lower fiber levels, which support higher caloric density and improved digestibility.

Vitamins

Hypocobalaminemia has been identified to be of similar prognostic importance as hypoalbuminemia in dogs with chronic enteropathies.¹⁵ Supplementation with cobalamin can reverse the risk of hypocobalaminemia.¹⁵ Cobalamin can be supplemented through weekly subcutaneous injection or orally.

If a commercially prepared food is being fed, vitamin supplementation should not be necessary. In addition, healthy dogs and cats generally have stores of vitamins A, D, E, and K in the body that can last several months. However, as always, the veterinary team needs to continually monitor the patient. If steatorrhea persists, parenteral supplementation with fat-soluble vitamins may be warranted. In cases of long-term fat malabsorption, supplementation of fat-soluble vitamins may be necessary.

Minerals

When fed foods containing higher levels of fat, dogs with an impaired ability to absorb fat may lose increased levels of divalent cations (e.g., calcium, magnesium, zinc, copper) due to intraluminal saponification. Severe hypocalcemia can lead to muscle twitching and contractions (tetany). A decrease in ionized serum calcium concentrations has frequently been reported in dogs with PLE.^8,16 Multiple canine PLE studies found ionized hypocalcemia in approximately 10% of all cases.⁵ One study reported twitching episodes in approximately 60% of Yorkshire terriers with PLE.^8,16 These same dogs were found to have significant hypocalcemia and hypomagnesemia, with an accompanying increase in serum concentration of parathyroid hormone.¹⁶ Intravenous calcium supplementation should be instituted in dogs with PLE if hypocalcemic tetany develops.¹

Likely causes of low serum magnesium levels in dogs with PLE appear to be anorexia and malabsorption, which is further complicated by the use of magnesium-free fluids. If needed, the use of appropriate intravenous fluids to replace magnesium should be considered. Supplementation of other minerals should be carried out if a specific deficiency is found.¹

Continuing Care

Following discharge from the hospital, patients with PLE need close monitoring to assess progress or lack thereof. As the owner will need to bring their pet in for these visits at least once a week, the veterinary nurse needs to ensure the relationship between team and owner remains open and honest and, if possible, to teach the owner how to properly weigh their pet and assess BCS and MCS (BOX 4). Each clinical reexamination should include assessment of body weight, BCS, and MCS. A complete nutritional history should be performed at every visit. As part of providing consistent education and client support, the veterinary nurse should be available at these visits to answer questions and aid in explaining any diet or other changes recommended by the veterinarian based on the patient’s progress.

If the patient’s condition improves, nutritional therapy should be maintained until the underlying enteropathy is resolved; however, complete resolution is rare. Most often, dietary management continues for the lifetime of the pet. With time, it may be possible to increase dietary fat intake; if this is recommended, it should be done gradually and cautiously and only in patients that are not able to maintain ideal body weight or dogs demonstrating evidence of essential fatty acid deficiency.

Summary

PLE in dogs can be a debilitating disease that can be painful for the patient and frustrating for the pet owner and the healthcare team. Nutritional management of PLE is focused on reducing lymphatic pressure by lowering chylomicron formation through reduced fat consumption. Feeding highly digestible foods is advantageous, and the nutritional profile of these foods should support hepatic protein synthesis and replace depleted tissue proteins as well as provide sufficient energy. In cachectic PLE patients, this may include adding MCTs as a source of calories. Dietary fiber, vitamins, and minerals should also be assessed and adjusted as needed. Client education and support are paramount in helping manage patients with PLE, which may require lifelong nutritional therapy.