Servet Clinical Guide. Chronic Kidney Disease

PRESENTATION

BROCHURE NEPHROLOGY CHRONIC KIDNEY DISEASE

SERVET

CLINICAL GUIDE

CHRONIC KIDNEY DISEASE Carmen María Pineda Martos Ignacio López Villalba

SERVET CLINICAL GUIDE

NEPHROLOGY CHRONIC KIDNEY DISEASE

Servet Clinical Guide Chronic Kidney Disease

SERVET

CLINICAL GUIDE

CHRONIC KIDNEY DISEASE Carmen María Pineda Martos Ignacio López Villalba

SERVET CLINICAL GUIDE

This Servet Clinical Guide on chronic kidney disease provides veterinary surgeons with the most up-to-date information on this disease to help them establish diagnosis and select the most appropriate treatment for each patient. Readers are provided with a series of guidelines, presented in a visual and dynamic manner, that will help them develop an effective relationship with the owner and explain the key aspects of their pet’s disease.

TARGET AUDIENCE:

✱ Small animal vets. Internal medicine, Nephrology ✱ Veterinary students FORMAT: 17 × 24 cm RETAIL PRICE NUMBER OF PAGES: 144 NUMBER OF IMAGES: 110 BINDING: hardcover ISBN: 978-84-18020-63-6 PUBLISHING DATE: July 2020

€50

Authors CARMEN MARÍA PINEDA MARTOS Master’s degree in Animal Health, Medicine, and Improvement and PhD in veterinary medicine from the University of Córdoba. Member of several research groups. She currently works at the Internal Medicine Service of the Veterinary Teaching Hospital of the University of Córdoba.

IGNACIO LÓPEZ VILLALBA PhD in veterinary medicine from the University of Córdoba and professor of internal medicine and clinical examination techniques at the Faculty of Veterinary Medicine of the University of Córdoba. Author of over 70 scientific publications in international journals specialising in internal medicine Contributor: María Luisa Suárez Rey

KEY FEATURES:

➜ Comprehensive review of diagnostic and treatment protocols. ➜ Includes guidelines to improve communication with owners of pets with chronic kidney disease. ➜ Information presented in a visual and attractive manner.

Presentation of the book It is my pleasure to write the foreword for the book Servet Clinical Guide. Chronic Kidney Disease. The authors are highly qualified and skilled to develop, write, and edit the contents for this book. They have a good balance between extensive experience in clinics and that in the research environment related to chronic kidney disease (CKD). These experts continue to be on the cutting edge of advances in the understanding of diagnosis and treatment of CKD, as evidenced by their numerous high-quality publications in this area. They are to be congratulated for the publication of this highly useful and informative book on CKD. This hardcover book is primarily intended to help guide primary care veterinarians in first-opinion clinics in the approach to diagnosis and management of CKD in dogs and cats. Much of this information is also appropriate and useful for veterinary students and veterinary nurses. Veterinarians with special interest in nephrology will also benefit from use of this book.

Many advances in nephrology and CKD have occurred over the past 20Â years. Sometimes it is difficult for research findings to find their way into clinical practice. These authors have been successful in getting much of this information into this book in a way that is accessible and understandable to primary care veterinarians.

This book features the approach to the clinical history, diagnostic imaging, and use of clinical pathology laboratory testing (blood and urine) for the initial diagnosis and during follow-up visits during treatment. The staging of CKD using IRIS guidelines (creatinine, proteinuria, systemic blood pressure) is described. Treatment protocols are subsequently detailed by the specific problem, such as anemia, control of systemic hypertension, and control of proteinuria. Dietary modification is discussed in detail as an appropriate first step in the treatment of most patients with stable CKD. This book emphasizes the importance of communication with client owners of dogs and cats with CKD. It provides tips on how to communicate effectively when speaking with clients during the initial diagnostic evaluation and during sequential visits during treatment of CKD. There are several high-quality color figures that allow the reader to immediately recognize the most important concepts of CKD. Pictures of patients with CKD remind us of the consequences of advancing CKD. Strategically placed call-out boxes refer to and summarize the most important concepts discussed in more detail in the text. Well-designed and easy-to-read tables are used to summarize quantitative information, such as that needed to evaluate nutrient intake of a renal diet on an energy density basis.

This book fills an unmet need for primary care veterinarians to have a single comprehensive resource updating their understanding of the diagnosis, staging, prognosis, and treatment of dogs and cats with CKD. This book will find a prominent place in my library.

Dennis J. Chew, DVM, ACVIM (Internal Medicine) Professor Emeritus The Ohio State University Columbus, Ohio

Servet Clinical Guide Chronic Kidney Disease

Authors Carmen María Pineda Martos Carmen María Pineda Martos received her degree in veterinary medicine (2008), her master’s degree in Animal Health, Medicine, and Improvement (2009), and her PhD in veterinary medicine (2014) from the University of Córdoba. She is a member of the PAIDI CTS-179 Veterinary Internal Medicine research group of the University of Cordoba and the GC-13 Calcium Metabolism and Vascular Calcification research group of the Maimónides Biomedical Research Institute of Córdoba (IMIBIC). She has been a visiting clinician at several prestigious international veterinary centres. Currently, she teaches as an assistant professor in the Department of Medicine and Animal Surgery of the University of Córdoba and works in clinical practice in the Small Animal Internal Medicine Service of the Veterinary Teaching Hospital of the University of Córdoba, focusing in particular on nephrology and urology.

She has authored and co-authored multiple notable scientific publications, book chapters, and communications presented at national and international conferences.

Ignacio López Villalba Ignacio López Villalba received his PhD in veterinary medicine from the University of Córdoba in 2002. He is associate professor of veterinary internal medicine at the Department of Animal Medicine and Surgery of the University of Córdoba, and head of the Small Animal Internal Medicine Service of the Veterinary Teaching Hospital of the University of Córdoba. He has worked as a visiting researcher at several prestigious veterinary hospitals in the United Kingdom, Germany, the United States, and South America. He has worked in clinical practice at the Veterinary Teaching Hospital of the University of Córdoba since 2003 and at the Veterinary Oncology Centre (CIOVET) since 2015.

He is the author of over 70 scientific publications in international journals specialising in internal medicine, and has spoken at more than 130 congresses and national and international postgraduate seminars. He has received numerous awards for his research work.

Contributor

María Luisa Suárez Rey María Luisa Suárez Rey received her degree in veterinary medicine from the Faculty of Veterinary Medicine (Lugo) of the University of Santiago de Compostela, Spain (1991).

In 1997, she was awarded her PhD in veterinary medicine by the same university. She began her teaching career as an associate professor in 1997 and is currently a professor of veterinary clinical medicine at the Faculty of Veterinary Medicine, Lugo. She is AVEPAcertified in internal medicine and works as an internal medicine specialist at the Rof Codina Veterinary Teaching Hospital.

Table of contents 1. Visit to the clinic What is chronic kidney disease?

What is the first sign that the owner observes?

Anamnesis to guide the diagnosis Risk factors Differential clinical signs

Clinical examination protocol Points to which particular attention should be paid

2. Diagnostic protocols Identifying the primary disease Most common laboratory alterations Haematology Blood biochemical analysis Urinalysis Acid–base and electrolyte analyses

Blood pressure measurement Useful diagnostic imaging tests Radiography Ultrasound Computed tomography Magnetic resonance imaging Scintigraphy

Specialised diagnostic tests

Estimation of glomerular filtration rate New markers of renal function How to manage phosphocalcic metabolism disorders Renal biopsy

Staging and diagnostic criteria for CKD

3. Communication with the pet owner How to inform the owner Can an animal with CKD be cured?

Can disease progression be predicted?

CKD prognosis

4. Treatment protocols Medical treatment of the patient Dietary modification as a fundamental pillar of treatment Correction of dehydration and management of acid–base and electrolyte alterations Treatment of gastrointestinal signs Treatment of anaemia Treatment of hyperphosphataemia Treatment of hypertension Treatment of proteinuria

Other treatments

Calcitriol Mesenchymal stem cell therapy Probiotics Calcimimetics

Control of uraemic crisis in cases of exacerbation of CKD Use of replacement therapies

5. Guidelines for the owner: follow-up Owner involvement, a key element in the management of CKD What signs should be monitored once diagnosis is established?

How often should periodic check-ups be performed?

How often should a patient with CKD visit the veterinary clinic?

What should we do when the disease progresses to terminal stages?

6. Appendix Suggested treatment protocols according to IRIS CKD stage

Recommended reading

How long can an animal live with CKD? What factors influence survival time?

Guidelines to follow once diagnosis is established

Plaza Antonio Beltrán Martínez, 1 Centro Empresarial El Trovador planta 8, oficina 50002 Zaragoza, Spain

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+34 976 461 480

NEPHROLOGY CHRONIC KIDNEY DISEASE

SERVET

CLINICAL GUIDE

CHRONIC KIDNEY DISEASE Carmen María Pineda Martos Ignacio López Villalba

SERVET CLINICAL GUIDE

SERVET CLINICAL GUIDE

NEPHROLOGY

MEDICAL TREATMENT OF THE PATIENT The objective of chronic kidney disease (CKD) treatment is to minimise the clinical signs of uraemia, delay the progressive loss of renal function, and preserve the nutritional status of the animal (Fig. 1).

It is recommended to establish the most appropriate treatment in order to: ➤ Control the electrolyte balance. ➤ Control vomiting and inappetence. ➤ Provide hormone replacement (e.g. erythropoietin and calcitriol). ➤ Control hypertension and proteinuria.

CHRONIC KIDNEY DISEASE

In addition to medical treatment, dietary management is critical in the treatment of CKD.

TREATMENT GOAL

MINIMISE CLINICAL SIGNS OF URAEMIA

DELAY THE PROGRESSIVE LOSS OF KIDNEY FUNCTION

If the cause of the kidney disease is reversible it should be treated (e.g. pyelonephritis, hypercalcaemia, or obstructive nephropathy)

PRESERVE THE ANIMAL’S NUTRITIONAL STATUS

Concurrent urinary tract infections should be treated with appropriate antibiotics

Figure 1. Main objectives of the treatment of chronic kidney disease.

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DIETARY MODIFICATION AS A FUNDAMENTAL PILLAR OF TREATMENT Dietary modification is a fundamental pillar in the management of CKD in both human and veterinary medicine. Of all the therapies used to treat CKD in dogs and cats, renal diets have the greatest benefit and are supported by the largest body of evidence.

The following can result in reduced food intake and deterioration of body condition, both of which are common in CKD: ➤ Physical changes. ➤ Alterations of the senses of smell and taste. ➤ Metabolic changes that suppress appetite. ➤ Dietary interventions that negatively affect food consumption.

The diet must provide levels of nutrients sufficient to ensure good quality of life and reasonable body condition (Fig. 2).

AVOID WEIGHT LOSS AND ANOREXIA

AVOID THE DEVELOPMENT OF SECONDARY HYPERPARATHYROIDISM

DIETARY MANAGEMENT OF CKD

MAINTAIN ADEQUATE GLOMERULAR FILTRATION

LIMIT THE PRODUCTION OF URAEMIC TOXINS

Figure 2. Main objectives of dietary management in chronic kidney disease.

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NEPHROLOGY

CHARACTERISTICS OF RENAL DIETS In the past, a reduction in dietary protein content was considered a fundamental aspect of dietary treatment of CKD. However, it is now known that other dietary modifications are both important and effective.

CHRONIC KIDNEY DISEASE

Diets specifically designed for dogs and cats with CKD (Table 1) have the following characteristics: ➤ Reduction of protein content by 30–50 %. ➤ Reduction of phosphorus content by 70–80 %. ➤ Other features include: ➤ Sodium restriction. ➤ Increased caloric density and soluble fibre. ➤ Supplementation with vitamin B, alkalis, antioxidants, and omega-3 fatty acids. ➤ Potassium supplementation (in the case of cats with CKD).

Table 1. Ranges of dietary components in commercial renal diets for small animals.

Component

Renal diet

Minimum recommended amount (FEDIAF)*

Renal diet

Dog Protein (g/1,000 kcal)

Minimum recommended amount (FEDIAF)*

Cat

25–55

45

58–82

62.50

Phosphorus (g/1,000 kcal)

0.40–1.20

1

0.80–1.35

1.25

Sodium (g/1,000 kcal)

0.40–1.20

0.25

0.50–1.00

0.19

Potassium (g/1,000 kcal)

0.80–2.10

1.25

1.40–2.60

1.50

Omega-3 fatty acids EPA + DHA (g/1,000 kcal)

32–1,200

–

31–1,910

–

* Nutritional Guidelines for Complete and Complementary Pet Food for Cats and Dogs, FEDIAF (2018): adult animal, maintenance diet.

FEDIAF, The European Pet Food Industry Federation; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

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CHARACTERISTICS AND MAIN BENEFITS OF RENAL DIETS IN SMALL ANIMALS 1. Protein restriction: ➤ The ideal amount of dietary protein for dogs and cats with CKD is not definitively established. ➤ Limiting the consumption of dietary proteins improves clinical signs associated with uraemia. Clinical studies support the use of renal diets in IRIS stages III and IV in dogs and IRIS stages II–IV in cats. ➤ Renal diets appear to reduce the severity of proteinuria and are therefore recommended in patients with proteinuric kidney disease. ➤ Recommending renal diets in IRIS stage II and early stage III makes it easier to initiate the transition to the renal diet long before the onset of clinical signs of uraemia. ➤ Control of body condition, weight, and calorie consumption is recommended. ➤ Protein restriction as the sole dietary change does not appear to protect against the progression of kidney disease in dogs and cats with advanced CKD. 2. Phosphorus restriction: ➤ Restricting the amount of dietary phosphorus (P) is the most important therapeutic intervention in dogs and cats with CKD since this slows disease progression and prolongs survival. ➤ Restriction of dietary P levels is indicated for dogs and cats in IRIS stages II–IV. ➤ Renal diets normalise serum P levels in most patients in IRIS stage II and in many patients in stage III. In advanced stage III and stage IV, administration of a P chelator is usually necessary. ➤ Restriction of dietary P reverses secondary hyperparathyroidism and can reduce the severity of renal disease, improve the glomerular filtration rate, and prolong survival.

3. Others: ➤ To maintain body condition, nonprotein calories are provided in the form of carbohydrates and fats. ➤ Supplementation with omega-3 polyunsaturated fatty acids has renoprotective effects: reduced inflammation and hypertension, antithrombotic effects, and lipid profile alterations. ➤ While the ideal concentration of sodium (Na) in the diet of animals with CKD is not clearly defined, moderate restriction is recommended. ➤ The administration of antioxidants (vitamins C, E, and β-carotene) may favour the reduction of oxidative stress associated with CKD. ➤ The benefits of prebiotics and probiotics are not fully understood.

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TRANSITION TO A RENAL DIET Renal diets are less tasty than maintenance diets (in part due to the lower protein and phosphorus content). This often leads to poor adherence, which can be further aggravated by inappetence in patients with more advanced kidney disease.

RECOMMENDATIONS AND TIPS TO ENSURE CORRECT TRANSITION TO A RENAL DIET AND IMPROVE CONSUMPTION ➤ ➤

CHRONIC KIDNEY DISEASE

➤

➤ ➤ ➤ ➤ ➤ ➤

The diet should be introduced as early as possible in IRIS stage II. Gradual transition to the new diet will increase acceptance; the new diet can be served in the animal’s usual food bowl, or alternatively served alongside/ mixed with a ration of the former diet. The proportion of the former diet should be reduced while increasing that of the renal diet over 4–8 weeks.

If the patient rejects the renal diet provided, an alternative renal diet can be offered. There is a wide variety of commercial renal diets available, and some animals find certain diets tastier than others.

Heating food before serving may be useful.

Stimulate feeding using positive reinforcement (e.g. by stroking the animal).

The use of home-prepared diets can improve palatability. However, the diet should adequately fulfil the animal’s nutritional requirements.

Choice of diet: moist renal diet > dry renal diet > homemade renal diet > wet geriatric diet > dry geriatric diet.

To avoid aversion to food, medication should be administered mixed with an alternative, tastier meal.

Dietary changes should not be introduced while the animal is hospitalised or clinically ill (e.g. nausea).

Malnutrition is an important cause of morbidity and mortality in dogs and cats with IRIS CKD stages III–IV.

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HOW CAN THE PATIENT’S NUTRITIONAL NEEDS BE FULFILLED? ➤ For owners, food consumption is a key indicator of their animal’s quality ➤

➤

➤

➤

of life.

The specific nutritional objectives required to maintain body weight and body condition should be established before beginning nutritional therapy.

Maintaining caloric intake is the highest priority in patients with CKD. These patients must consume enough calories to maintain a body condition score of between 4/9 and 5/9.

Factors that promote weight loss and malnutrition (anorexia, vomiting, nausea, hormonal and metabolic disorders, and catabolic factors related to uraemia, particularly acidosis) should be addressed.

Placement of a feeding tube (oesophagostomy or gastrotomy) can be very useful to maintain nutrition and hydration in the long term, particularly when the nutritional intake is inadequate and/or when owners become frustrated by their inability to effectively administer their animal’s medication (especially in cats) (Fig. 3).

Placement of a feeding tube can improve the nutrition and quality of life of animals with CKD, and should not be considered as a last resort.

a

b

Figure 3. Placement of a feeding tube (oesophagostomy) in a cat (a and b).

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HOMEMADE DIETS FOR DOGS AND CATS WITH CKD Some owners may prefer to prepare homemade diets for their pets. It is possible to resort to the use of homemade diets when the animal has difficulty Table 2. Example of a balanced homemade diet with reduced protein and low phosphorus levels for an 18-kg adult dog with chronic kidney disease.

CHRONIC KIDNEY DISEASE

Ingredients

Quantity (grams)

Cooked white rice Can be seasoned with meat broth during cooking

237

Cooked beef (with fat intact)

78

Large boiled egg

20

White bread

50

Vegetable oil

3

Calcium carbonate

1.5

Iodised salt (sodium chloride)

0.5

Total

390

Add vitamin-mineral complex for adults

1 tablet per day

Nutritional analysis - Dry matter Dry matter (%)

41

Energy (kcal/100Â g)

445

Protein (%)

21.1

Fat (%)

13.7

Linoleic acid (%)

1.8

Raw fibre (%)

1.4

Calcium (%)

0.43

Phosphorus (%)

0.22

Potassium (%)

0.26

Sodium (%)

0.33

Magnesium (%)

0.091

Table adapted from Hand et al., 2010.

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consuming or rejects a commercial renal diet. Homemade diets should be balanced in terms of nutritional requirements.

Examples of homemade diets for dogs and cats with CKD are shown in Tables 2 and 3.

Table 3. Example of a balanced homemade diet with reduced protein and low phosphorus levels for a 4.5-kg adult cat with chronic kidney disease.

Ingredients

Quantity (grams)

Cooked white rice (can be seasoned with meat broth during cooking)

98

Cooked chicken liver

21

Cooked chicken meat

21

Vegetable oil

7

Calcium carbonate

0.7

Iodised salt (sodium chloride)

0.5

Salt substitute (potassium chloride)

0.5

Total

149

Add vitamin-mineral complex for adults Add taurine (500-mg tablets)

½ tablet per day ½–1 tablet

Nutritional analysis - Dry matter Dry matter (%)

37.8

Energy (kcal/100 g)

458

Protein (%)

24.4

Fat (%)

17.5

Linoleic acid (%)

7.9

Raw fibre (%)

0.85

Calcium (%)

0.54

Phosphorus (%)

0.29

Potassium (%)

0.66

Sodium (%)

0.42

Magnesium (%)

0.09

Table adapted from Hand et al., 2010.

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CORRECTION OF DEHYDRATION AND MANAGEMENT OF ACID–BASE AND ELECTROLYTE ALTERATIONS In addition to filtering and eliminating waste products, the kidneys are responsible for maintaining the volume and composition of body fluids by promoting the elimination or reabsorption of water and solutes as needed to maintain the equilibrium of the internal environment. Every day the kidneys process and reabsorb large quantities of water and electrolytes. Therefore, a marked loss of renal function will result in

The main objective of this section is to provide several guidelines to avoid dehydration in animals with CKD, as well as measures aimed at controlling metabolic acidosis and the loss of important electrolytes such as potassium.

CHRONIC KIDNEY DISEASE

HEALTHY INDIVIDUAL

CHRONIC KIDNEY DISEASE

hydroelectrolytic imbalance, which mainly give rise to dehydration (Fig. 4).

Figure 4. Electrolyte and acid–base

H2O

H2O H+

H

+

imbalances in patients with chronic kidney disease (CKD). At least one third of the total population of nephrons must be functional in order to generate concentrated urine.

In patients with renal insufficiency, loss of more than two thirds of functional nephrons results in deficient urine concentration and a decreased ability to maintain the normal state of hydration. Because a large amount of acidic substances are eliminated via the urine, CKD increases the likelihood of accumulating acids and consequent development of metabolic acidosis.

INTERNAL ENVIRONMENT

CONCENTRATED URINE (DENSITY >1.030)

DILUTED URINE (DENSITY = 1.008–1.016)

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FLUID THERAPY IN ANIMALS WITH CKD The administration of intravenous fluids in patients with CKD is only necessary in cases of decompensation (i.e. in dehydrated and anorexic animals). The management of these animals is similar to that of animals with acute kidney damage and will be addressed in the section on the management uraemic crisis.

Figure 5. Sources of running water are an effective means of stimulating daily water consumption, especially in cats.

Patients with compensated CKD (i.e. those in which clinical dehydration is absent and appetite is preserved) should always be provided with ad libitum access to potable water. In the case of cats, daily consumption of water can be stimulated by using sources of running water (Fig. 5).

However, the excessive production of diluted urine in most of these patients, together with digestive losses, frequently results in subclinical dehydration. To correct this subclinical dehydration in small dogs (less than 10 kg) and cats, small volumes of fluids can be administered subcutaneously every 1 or 2 days (Fig. 6). Subcutaneous fluid administration can be done by the owners, who should be taught how to do so by their veterinary surgeon. The types and volumes of fluids administered are shown in Table 4.

Figure 6. Administration of subcutaneous fluid therapy in a dog of less than 10 kg. To administer the serum comfortably, the animal can be placed on the lap of the veterinary surgeon or owner.

The goal of fluid therapy in animals with compensated CKD is not to increase renal function per se, but to prevent the subclinical dehydration that usually occurs and thus avoid further exacerbation of azotaemia due to prerenal causes.

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MEASURES TO ENCOURAGE CONSUMPTION OF WATER IN DOGS AND CATS WITH CHRONIC KIDNEY DISEASE ➤ ➤ ➤ ➤

➤ ➤ ➤ ➤

CHRONIC KIDNEY DISEASE

➤ ➤

Use moist and palatable canned food.

Offer small meals several times throughout the day. It is thought that water consumption increases significantly with increasing frequency of meals.

It is important to provide easy access to water at all times. Cats are nocturnal animals and may prefer to drink at night.

Cats prefer a bowl with a large surface from which to drink; rubbing of their highly sensitive whiskers against the walls of the bowl can cause irritation.

Preferences in terms of the type of container used (glass, ceramic) can vary.

The water bowl should always be kept clean and filled with fresh water.

It may be useful to offer different types of water: filtered, distilled, bottled, hot or cold tap water, rain water.

The water can be flavoured or flavoured ice cubes (tuna, meat) added.

Do not sweeten the water.

Sources of running water are an effective means of stimulating daily water consumption, especially in cats.

In cats it is important to keep food and water containers away from the litter box area.

It is recommended not to share the receptacle with other pets (especially when different species live in the same house).

Table 4. Subcutaneous fluid therapy: fluid types and volume of administration in small animals.

Types of fluid recommended

➤ Isotonic fluids (Ringer’s lactate or isotonic saline) ➤ Avoid solutions containing glucose or hypertonic

solutions

Administration volume

➤ Dog: 10 ml/kg/day ➤ Cat: 75–100 ml/cat/day

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