Evidence Based Decisions for Chronic Kidney Disease

Transcription

1 Evidence Based Decisions for Chronic Kidney Disease Todd L. Towell, DVM, MS, DACVIM Hill s Pet Nutrition, Inc. A variety of treatments may be helpful for patients with chronic kidney disease. However the only one shown to improve survival in cats with CKD is therapeutic food. In dogs there are only 2 treatments therapeutic food and calcitriol. Nutritional management has been documented to improve the quality and quantity of life for cats and dogs with chronic kidney disease. But how do you decide which foods to recommend? When to treat: Chronic kidney disease (CKD) is the most common disease affecting the kidneys of dogs and cats. Historically, a variety of terms have been used to define the severity of renal dysfunction including renal insufficiency, renal failure and uremia. However, there has never been a consensus on definitions of these terms. The International Renal Interest Society (IRIS) recommends replacing these terms with a scheme to classify severity of CKD into four stages based on stable serum creatinine concentrations (Figure 1). This classification scheme requires that the presence of CKD is confirmed and that azotemia, if present, is localized as renal in origin. This classification scheme incorporates the continuum of severity of renal injury from patients with kidney damage but without azotemia (stage 1 CKD), to progressively more severe CKD and resultant increases in serum creatinine concentration for stages 2 to 4. Use of the staging criteria makes it possible to better understand, communicate and apply management guidelines for patients in each stage. Although management of individual cases may vary IRIS recommends instituting treatment for all patients with Stage 2 CKD and for proteinuric or hypertensive patients with Stage 1 CKD (Figure 2). More detailed information on the IRIS staging criteria can be found at There is general agreement that nutritional management of CKD should be instituted when overt signs exist; however, the role of nutritional intervention during earlier stages of CKD is less well defined. Thus, in a sense, the question is not whether to use nutritional management but when should it be initiated. Because detection of CKD in its early stages is difficult and there appears to be no harm in nutritional intervention during earlier stages, nutritional management should be considered by stage 2 CKD and is clearly indicated when serum creatinine exceeds 2 mg/dl (179 µmol/l). 1,2 Similarly, significant and persistent renal proteinuria, even in the absence of azotemia, reflects marked renal damage and signals the need for nutritional management regardless of the CKD stage. How to treat: The goals of managing patients with CKD are to: 1) control clinical signs of uremia, 2) minimize disturbances associated with fluid, electrolyte and acid-base balance, 3) support adequate nutrition and 4) modify progression of CKD. 3 Nutritional management plays a role in all of these goals and is indicated to address the etiopathogenic mechanisms that occur in CKD. (Table 1) The use of an appropriately formulated commercial veterinary therapeutic renal food is the only treatment that has been shown in randomized, controlled clinical studies to prolong survival time and improve quality of life in dogs and cats with CKD. 1-4 Therefore, nutritional intervention should be considered a critical component of managing patients with CKD. Nutritional Management The kidney is susceptible to self-perpetuating injury and the extent of damage may be modified by therapeutic nutrition. Self-perpetuating injury results from the nature of the organ's response to disease. With chronic kidney disease decreased glomerular filtration rate leads to increased single

2 nephron glomerular filtration, increased hydrostatic pressure within the glomerular capillaries, and increased glomerular size. These changes are referred to as glomerular hyperfiltration, hypertension, and hypertrophy, respectively. These glomerular functional and structural changes appear to be maladaptive, leading to further renal injury. In addition disruption of renal homestatic mechanisms may result in systemic hypertension and hyperphosphatemia which also damage the kidney, further contributing to the vicious cycle of inherent progressive renal injury. Some proposed etiopathogenic mechanisms for progression of kidney disease include renal hypoxia, glomerular hypertension, renal secondary hyperparathyroidism, hypokalemia, metabolic acidosis, proteinuria, renal oxidative stress, systemic hypertension and tubulointerstitial inflammation leading to fibrosis. Pharmacologic agents are often considered the most effective therapy to address these metabolic alterations in patients with CKD. However, nutritional therapy provides many of the same benefits. Table 1 outlines some pharmacologic therapies indicated for the proposed etiopathogenic mechanisms and the corresponding nutritional therapy. Nutritional therapy incorporates more than simply avoiding protein excess. Renal oxidative stress causes renal injury and may contribute to the progression of chronic kidney disease. Increased intake of dietary antioxidants has been documented to decrease DNA damage associated with oxidative stress in cats with chronic kidney disease. 5 Dietary intake of some nutrients has a direct effect on the magnitude of the complications of kidney disease. For example, ingestion of a diet with moderate phosphorus content (0.9% phosphorus on a dry weight basis) will have few, if any, consequences in a normal animal; in contrast, in animals with chronic kidney disease this level of dietary phosphorus intake worsens hyperphosphatemia and hyperparathyroidism and leads to progressive declines in renal function. 6 Given these benefits of individual nutrients appropriately formulated veterinary renal therapeutic foods for dogs and cats generally contain less protein, phosphorus and sodium and have increased fat, omega-3 fatty acids and buffering capacity compared to typical maintenance pet foods. Feline renal foods contain increased potassium to help prevent hypokalemia. In addition to key nutritional factors, it is important to consider available evidence supporting effectiveness of specific veterinary therapeutic renal foods and other treatments for CKD (Table 2). Only two foods have grade 1 evidence from a randomized controlled clinical trial in client owned animals to improve quality of life and prolong survival time. Getting picky patients to eat 1. Educate Owners: Owners who understand that nutritional management has been proven to prolong survival time and improve quality of life in patients with kidney disease are more likely to succeed in transitioning their pets. For treatment to succeed, owners must commit their time and money, which is more likely to occur if they understand the benefits of their efforts. 2. Begin nutritional management sooner rather than later: Current evidence supports feeding a veterinary therapeutic renal food when serum creatinine is 2 mg/dl. Waiting until later (e.g., when there are signs of uremia) is not advised because patients with more advanced disease may be less likely to accept a change in treatment and therefore will not receive optimal benefits of a renal therapeutic food. 3. Transition gradually: Probably the single most important thing you can do to increase patient acceptance of a veterinary therapeutic renal food is gradually transition to the new food. The transition period should be a minimum of seven days; however, some patients (especially cats) need a transition of three to four weeks or longer. It is critical to discuss the need for this transition with pet owners, otherwise, they are likely to buy a new food, go home and switch from the old food to the new food at the next meal. In this scenario, many patients will refuse to eat the new food, which results in an unhappy owner and a patient that will likely not receive the benefits of nutritional

3 management. One option for transitioning to a renal food is to mix the old and new food, gradually adding more of the new food over time. Another approach is to provide both foods (old and new) in side-by-side food dishes. This technique assists with gradual transition and also allows cats to express their preferences. For more information, visit for The Indoor Cat Initiative. If transitioning cats from dry to moist food, use a flat food dish (e.g., saucer) instead of a bowl. This avoids rubbing the cat s whiskers on the food dish, which could affect acceptance of new food. 4. Prevent food aversions: Avoid offering veterinary therapeutic renal foods in stressful environments (e.g., sick and/or hospitalization, during force-feeding); a food aversion may develop causing decreased acceptance of the food when the patient is feeling better. Stated another way, while patients are hospitalized, do not feed them (especially cats) the food you want them to eat for the rest of their lives. In this situation, one option would be to feed a maintenance food that avoids excessive protein, phosphorus and sodium until the patient is feeling better and then gradually transition to a therapeutic renal food. 5. Use fresh food at room temperature: Some patients may eat refrigerated food that is warmed, but others will only eat food from a newly opened container. Some patients may eat food that has been refrigerated and stored in a plastic container vs. food stored in the original can. 6. Offer foods with different textures (e.g., minced formulas) or form (dry vs. moist). Some pets may prefer dry or moist food all their lives and when they develop kidney disease, their preferences may switch (e.g., a cat that has eaten dry food all its life may eat moist food after kidney disease occurs and vice versa). Add flavor enhancers (low-sodium chicken broth or tuna juice) or a small amount of maintenance food to encourage the patient to eat all the veterinary therapeutic food. Excessive use of other foods will likely decrease the beneficial effects of the veterinary therapeutic renal food; therefore, the smallest amount possible should be used. 7. Try a different brand: If you have followed the steps above and there is still reluctance to eat a veterinary therapeutic renal food, switch to a different brand. Although commercially available renal foods have general features in common, they are not the same. In addition, individual pets may express a preference for one brand over another. Avoid giving the owner samples of several different brands of foods at once; this could result in a food aversion to all veterinary therapeutic renal foods, especially if owners offer each sample at successive meals or on consecutive days. Summary Chronic kidney disease is common is dogs and cats and the frequency of diagnosis increases with age. A variety of compensatory and adaptive responses are involved in the pathogenesis and progression of naturally occurring CKD. The goals of managing patients with CKD are to improve quality and quantity of life. Nutritional management plays a key role in both of these goals. Although there are many available treatments, veterinary therapeutic renal food is the only one that has been shown to prolong survival time and improve quality of life for dogs and cats with CKD. Therefore, nutritional intervention is a critical component of managing patients with CKD. When designing a therapeutic regimen for dogs and cats with CKD, it is helpful to consider key nutritional factors (water, protein, phosphorus, omega-3 fatty acids, antioxidants, sodium, chloride and potassium). In addition to key nutritional factors, it is important to consider available evidence supporting effectiveness of specific veterinary therapeutic renal foods as well as other treatments for CKD. Individual patient needs and responses and owner preferences must also be considered to design an optimal therapeutic regimen. Transitioning to a therapeutic renal food often requires a team approach and effective communication involving the owner and health care team. There are many strategies that can be used to increase therapeutic success and thus improve the lifespan and quality of life for dogs and cats with CKD.

4 Figure 1: IRIS Staging Criteria Figure 2 Algorithm for Staging of Chronic Kidney Disease in Cats

5 Table 1. Diet and pharmacologic therapies for etiopathogenic mechanisms in chronic kidney disease Factor Diet Therapy Drug Therapy Renal Hypoxia Avoid excess Na EPO / ACE Inhibitors Glomerular Hypertension Renal Secondary HPT Avoid excess protein /Na N3 FA Limit dietary phosphorous ACE inhibitors Intestinal phosphate binders Calcitriol Hypokalemia Potassium enriched foods Potassium Supplementation Metabolic Acidosis Proteinuria Renal Oxidative Stress Systemic Hypertension Tubulointerstitial inflammation/ fibrosis Avoid excess protein Alkalinizing foods Avoid excess protein Increase N3 FA Avoid excess protein, phosphorous and Na N3 FA / antioxidants Avoid excess Na Avoid excess protein /phos N3 FA Alkalinizing agents ACE inhibitors ACE inhibitors Calcium-channel antagonists (amlodipine)

6 Table 2. Summary of evidence for treatments of chronic kidney disease 3,4 Dogs Strength of evidence Therapy Benefit (documented or proposed) Grade 1 Hill s Prescription Diet k/d Canine Prolonged survival and increased quality of life when SCr > 2 mg/dl Calcitriol Prolonged survival ACE inhibitor (enalipril)* Reducing proteinuria Grade 2 ACE inhibitor (enalipril)* Delaying progression Grade 3 Recombinant human EPO Correcting anemia Dietary phosphorous restriction IRIS stage 3 &4 N-3 Fatty Acid Supplementation IRIS stage 3 &4 Grade 4 Therapeutic renal foods Delaying progression when SCr < 2 mg/dl Subcutaneous Fluid therapy Maintaining hydration ACE inhibitors (non proteinuric patients) Delaying progression Phosphate binders Control hyperphosphatemia Alkalinizing therapy Control academia Cats Strength of evidence Therapy Benefit (documented or proposed) Grade 1 Hill s Prescription Diet k/d Feline Prolonged survival and increased quality of life when SCr > 2 mg/dl ACE inhibitor (benazepril)* Reducing proteinuria, increasing appetite in cats with UP:Cr 1 Grade 2 Grade 3 None Waltham Veterinary Diet Whiskas Low Prolonged survival time Phosphorous, Low Protein Dietary phosphorous restriction IRIS stage 3 &4 Recombinant human EPO Correcting anemia Amlodipine Correcting hypertension Potassium supplementation Correcting hypokalemia Grade 4 Therapeutic renal foods Delaying progression when SCr < 2 mg/dl Subcutaneous Fluid therapy Maintaining hydration ACE inhibitors (non proteinuric patients) Delaying progression Phosphate binders Control hyperphosphatemia Calcitriol therapy *Combined with feeding a veterinary therapeutic renal food; ACE = angiotensin converting enzyme, IRIS = International Renal Interest Society, SCr= Serum Creatinine,

7 References 1. Jacob F, Polzin DJ, Osborne CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic renal failure in dogs. J Am Vet Med Assoc 2002;220: Ross SJ, Osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc 2006;229: Roudebush P, Polzin DJ, Adams LG, et al. An evidence-based review of therapies for canine chronic kidney disease. The Journal of small animal practice 2010;51: Roudebush P, Polzin DJ, Ross SJ, et al. Therapies for feline chronic kidney disease. What is the evidence? J Feline Med Surg 2009;11: Yu S, Paetau-Robinson I. Dietary supplements of vitamins E and C and beta-carotene reduce oxidative stress in cats with renal insufficiency. Veterinary research communications 2006;30: Brown SA, Brown CA, Crowell WA, et al. Beneficial effects of chronic administration of dietary omega-3 polyunsaturated fatty acids in dogs with renal insufficiency. The Journal of laboratory and clinical medicine 1998;131: