Updates on managing chronic kidney disease (Proceedings)

Diagnosing Chronic Kidney Disease

Chronic kidney disease (CKD) is a common clinical diagnosis in middle-aged to geriatric cats and dogs that may significantly affect the quality of life of both the patients and their owners. Although "old age" is not a disease, it is a time when many diseases are more likely to occur, often concurrently. Early disease detection of disease conditions allows earlier intervention and more successful outcomes once treatment has been initiated. Routine monitoring is also helpful to monitor therapy, follow trends and identify any emerging conditions.

The concept of senior wellness exams should be thoroughly explained to clients to increase compliance. Clients need to be educated about the definition of a senior pet and the benefits of detecting disease conditions early. Many pets in the early stages of kidney disease may be asymptomatic, or they may show subtle, non-localized clinical signs often mistaken for age-related changes by owners. Detecting CKD in the early stages is important so that appropriate therapeutic measures may be instituted to minimize the progression of disease and delay the onset of uremia.

The diagnosis of CKD requires a very thorough medical history from the owner in addition to a physical exam and laboratory findings. Owners may report increased thirst, increase urination or accidents in the house. Gradual weight loss, selective appetite, deteriorating haircoat, may all be signs of CKD as well. Physical exam findings of poor body condition, poor haircoat, small kidneys, also indicate chronicity. Many laboratory findings are not that helpful in distinguishing acute from chronic kidney disease, but there are some subtle differences that do occur. For example, a non-regenerative (hypoproliferative) anemia may be found with chronic kidney disease.

The laboratory diagnosis of CKD is based on demonstrating azotemia (elevated BUN and creatinine) concurrently with inadequately concentrated urine. In most cases, urine specific gravity values less than 1.030 in dogs and less than 1.035 in cats in an azotemic patient strongly suggests the diagnosis of primary renal failure. It is important to note that animals with kidney disease do not typically have urine specific gravities less than 1.006. Values below this specific gravity indicate urine-diluting capacity, which requires functional kidneys.

Management of CKD

Conservative medical management of CKD consists mostly of supportive and symptomatic therapy. The goal is to correct or improve deficits and excesses in fluid, electrolyte, acid-base, endocrine, and nutritional balance. Minimizing these changes will hopefully reduce clinical signs, improve the patients' quality of life and slow the progression of the disease.

Dietary modifications in CKD

Diet therapy has been the cornerstone in the management of canine and feline chronic kidney disease (CKD) for decades. In the past, the emphasis has been on reducing the protein content of the diets. Although protein content continues to play an important role in diet formulation, other diet modifications are also important in managing patients with kidney disease. Compared to adult maintenance diets, diets formulated specifically for dogs and cats with chronic kidney disease typically have reduced protein, phosphorus, and sodium content; increased potassium, B-vitamin content and caloric density; a neutral effect on acid-base balance; and an increased omega-3/omega-6 polyunsaturated fatty acid (PUFA) ratio.

Protein

Although the ideal quantity of protein to feed dogs and cats with CKD remains unresolved, a general consensus of opinion supports the fact that reducing protein intake improves clinical signs in animals with advanced kidney disease. Many of the uremic toxins are actually by=products of protein metabolism. When not excessive, limiting protein intake does not appear to have any adverse effects, and it may be easier to initiate treatment with renal diets before the onset of clinical signs of uremia. In addition, protein restriction may delay onset of clinical signs of uremia as renal disease progresses.

Phosphorous

Renal diets are limited in phosphorus content as patients with kidney disease are not able to clear phosphorous from their bodies readily. The increase in serum phosphorous leads to problems with calcium and parathyroid hormone metabolism as well; a syndrome known as renal secondary hyperparathyroidism. Eventually this may lead to bone loss, and mineralization of the kidneys and other organs. Dietary phosphorus restriction has been shown to enhance survival and a slow decline in renal function in dogs with induced renal failure. In cats, dietary phosphorus restriction has been shown to limit renal mineralization. Because protein is a major source for phosphate, it is usually necessary to limit dietary protein to limit diet phosphate content.

Potassium

Hypokalemia is quite common in cats with chronic kidney disease but less common in dogs. Clinical signs of hypokalemia may include muscle weakness and further impairment of kidney function. Renal diets are generally supplemented with potassium, however, some patients still require oral or parenteral administration of potassium salts. Potassium gluconate and potassium citrate are the preferred salts for oral administration; potassium chloride is used parenterally. It is important to avoid administering potassium chloride by mouth as it is likely to induce vomiting. Potassium should not be administered in subcutaneous fluids as it is quite painful in concentrations greater than 4mEq/L (the concentration found in LRS).

Hyperkalemia is more often encountered with acute oliguric kidney injury, or in stage 4 CKD when the function of the kidneys is severely compromised. Increased potassium may also be seen in animals receiving angiotensin receptor blockers such as enalapril or benazepril. Typically the hyperkalemia associated with these medications is mild and does not require intervention, however, if the potassium continues to rise or is significantly elevated, the medications may have to be discontinued, or the dosage decreased. In addition, choosing a diet with less potassium may also help to control the values.

Dietary Buffering

Animals with kidney disease are often not able to clear acids effectively in urine. They also tent to lose bicarbonate. The net result is a state of metabolic acidosis. Several clinical signs have been associated with metabolic acidosis including increased protein catabolism, anorexia, nausea, vomiting, lethargy, muscle wasting, and malnutrition. Therapy for metabolic acidosis should be considered when the blood bicarbonate concentration serum total CO2 concentration or consistently remains below 17mEq/l on consecutive determinations.

Treatment options for metabolic acidosis include alkalinization using diet, sodium bicarbonate, or potassium citrate. Most diet formulated specifically for animals with renal failure are designed to be neutral to slightly alkalinizing. Often, early acidosis may be controlled with diet alone. However, if the acidosis persists or worsens, oral alkalinization with sodium bicarbonate or potassium citrate should be considered. Response to therapy should be assessed after 10-14 days with a blood bicarbonate concentration. Ideally the sample should be collected just prior to administration of the drug. The dosage of medication should be adjusted to maintain the blood bicarbonate concentration within the normal range.

Omega-3 polyunsaturated Fatty Acids

The optimum quantity of omega-3 PUFA supplementation and ratio of omega-3/omega-6 PUFA appropriate for renal diets have not been conclusively established. Beneficial effects of omega-3 PUFA's have been demonstrated in a study looking at dogs with induced renal failure, but have not yet been evaluated in dogs with naturally occurring disease. Published data supporting the use of omega 3 polyunsaturated fatty acids in cats is limited to a single retrospective study of cats with spontaneous CKD in which cats surviving the longest were receiving the diet with the highest omega-3 PUFA concentration. The general consensus is that diets supplemented with omega-3 PUFA's are unlikely to cause harm and may be beneficial. Most renal diets do contain supplemental omega-3 PUFA's and additional supplementation is usually not required.

Hydration

It is very important that patients with kidney disease always remain well hydrated. Patients with kidney disease are particularly at risk for dehydration when they are not feeling well or have had limited access to water (ex. if their water bowl becomes empty during the day) or they are not eating or drinking. Their kidneys no longer have the ability to conserve water when intake is low, so they continue to lose water through their urine. It is important to continue to keep a fresh supply of water available for pets at all times.

Patients that develop recurrent episodes of signs consistent with dehydration are candidates for intermediate-to long-term fluid support. For example, many cats with kidney disease present frequently to the veterinarians office for constipation. This may indicate chronic low grade dehydration. If simple management techniques (water fountains, flavoured water, multiple water bowls, etc.) do not provide adequate hydration, an enteral feeding tube or subcutaneous fluid therapy should be considered. Normal saline or lactated Ringer's solution are the fluids most commonly used for home subcutaneous fluid therapy. They are well tolerated by most cats and dogs and appear to be reasonable choices for most patients. However, chronic administration of lactated Ringer's solution or normal saline may contribute to the progression of kidney disease because of the associated salt load. Unfortunately there is no way to administer free water to a patient via SQ fluids. By necessity, SQ fluids must be an electrolyte balanced solution. We recommend that patients requiring long term fluid support receive an enteral feeding tube. Esophagostomy tubes are well tolerated long term by both dogs and cats, and allow for the administration of free water in addition to providing a means to supplement nutrition and administer medications.

Diet Therapy-Evidence from Clinical Trials

The importance of feeding a renal diet must be stressed to owners. Clinical evidence exists in both cats and dogs demonstrates that animals with CKD that are fed a diet formulated for renal disease live longer, with fewer complications than those fed a maintenance diet. In the dog study the risk of developing a uremic crisis was reduced by approximately 75% in dogs fed the renal diet compared with dogs fed an adult maintenance diet, and the median interval before development of uremic crisis in dogs fed the renal diet was twice as long as that observed in dogs fed the maintenance diet. Likewise, cats fed the maintenance food had a significantly greater number of uremic episodes compared to cats fed the renal food. A significant reduction in renal-related mortality, occurred in cats fed the renal food.

How can diet therapy be successfully implemented?

Many owners (and veterinarians!) are reluctant to use a renal diet as they feel that reduced palatability will adversely affect the patients food intake and nutritional status. There are some "do's and don'ts" that are helpful to remember when recommending a diet change. While some patients easily transition from one diet to another, others (especially cats) are very selective and may require more coaxing to induce diet change. In general, it is probably best to recommend that diet changes be made very slowly rather than abruptly. Most patients can be transitioned onto a new diet in two by gradually mixing the new diet into the old diet. In my experience, cats are more likely to accept a new diet if transitioned over 3 weeks. Clinical signs of uremia should be controlled prior to the introduction of a new diet. Attempting to introduce a new diet when an animal is nauseated is likely to result in food aversion.

In general, it is best to start by using the same form of diet the patient is used to eating (i.e. dry food versus canned food). Often the addition of flavour enhancers (low sodium chicken broth, tuna juice, etc, encourage food consumption. It is best to avoid additives that contain excessive protein, phosphorus, or salt.

It is important to consider metabolic causes for anorexia before assuming that poor appetite is diet-related. A variety of metabolic causes may be associated with poor appetite in dogs with renal insufficiency including: 1) anemia, 2) uremic gastritis, 3) dehydration, 4) metabolic acidosis, 5) hypokalemia, and 6) renal secondary hyperparathyroidism. Most of these conditions can be managed with appropriate therapy.

Providing frequent small meals may be helpful in increasing calorie intake in patients that are partially anorexic. Medications should not be mixed with the food as they may alter taste resulting in food aversion. If the patient is showing a progressive decline in body condition, an enteral feeding tube (esophagostomy or gastrostomy) should be recommended for longer-term nutritional support.

High Blood Pressure

Hypertension has become a well-recognized complication of CRF in both cats and dogs. It is very important that pets with CKD have their blood pressures measured frequently. Although many animals do not show clinical signs associated with hypertension, some may be dramatic. Often cats present with an acute onset of blindness If left untreated, hypertension could damage the kidneys, heart, and brain. Perhaps the most obvious clinical sign of severs hypertension, especially in cats, is acute blindness due to detachment of the retinas. Immediate and aggressive control of the blood pressure may allow the retinas to reattach and the pet may regain some vision.

Blood pressure measurements should ideally be done by the same individual in a quite room, after the animal has been allowed to acclimate to the surroundings. Blood pressure equipment is also very important as the accuracy and precision of many machines is questionable. The current recommendation is that blood pressure be determined using an oscillometric technique in both cats and dogs. Several readings should be obtained and the cuff size and location should be consistent. Studies have demonstrated that hypertension is a risk factor for shortened survival times in dogs with CRF and the same is likely true of cats.

Amlodipine (a calcium channel blocker) currently is the drug of choice for managing hypertension in cats. It has been shown to be effective in at least one clinical trial in lowering blood pressure. In contrast to amlodipine, ACE inhibitors and Beta-blocking drugs have not appeared to be as effective in lowering blood pressures in cats. Hypertentsion in dogs may be managed successfully with calcium channel blockers, ACE inhibitors or a combination of the two. If blood pressure control is not attained, combination therapy recommended.

Anemia

It is very common for patients with chronic kidney disease to eventually develop anemia as the kidneys are no longer able to make enough of the hormone called erythropoietin. Erythropoietin (EPO) is a hormone that is normally produced by the kidneys when they sense that the body requires more red blood cells. Once produced by the kidneys, EPO travels to the bone marrow where it stimulates the production of new red blood cells. As functional kidney mass decreases, the levels of EPO produced also decrease, and red blood cell production falls. To correct the anemia, we must supply the missing hormone, much like a diabetic requires insulin. EPO is commercially available as Epogen® or Procrit®. However, because these products are designed to replicate the human version of the protein we may run into problems in dogs and cats. The human version of the protein may be recognized as foreign and the pet's immune system may try to clear the EPO from their system. If this immune response develops, the EPO will become ineffective.

There is a new synthetic version of the hormone (darbopoietin; Aranesp®) available that seems to be very promising in dogs and cats. Aranesp has several features that are likely to make an immune reaction less likely and therefore we prefer this drug over traditional EPO. Compared with rHuEPO, darbepoetin has a longer half-life and greater potency, enabling clinical efficacy with less frequent administration. Although not yet proven by clinical trial, anecdotal reports suggest that darbepoetin has similar efficacy and safety to erythropoietin, with the significant benefit of decreased incidence of antibody production.

Patient Monitoring

Patients with renal insufficiency often require frequent monitoring. Frequent evaluations allow for the early detection and management of many complications associated with CKD. Frequent monitoring also encourages owner compliance, thereby improving the quality of care between office visits as well. The frequency of monitoring varies with the stage of kidney disease and the severity of their clinical signs, however, even patients with stages 1 and 2 CKD should be evaluated 2-4 times each year.