The Incidence of Urolithiasis in Cats and Dogs - 2ndChance.info

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The Incidence of Urolithiasis in Cats
and Dogs and the Influence of Diet in
Formation and Prevention of
Recurrence.

Abigail E. Stevenson

Thesis submitted for the degree of Doctor of Philosophy

Institute of Urology and Nephrology
University College London

2002
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ABSTRACT
The two most common minerals found in uroliths from cats and dogs were
calcium oxalate and magnesium ammonium phosphate, identified using accurate
quantitative analytical techniques. Other mineral types included calcium phosphate
and uric acid/ammonium urate. Cystine uroliths were found only in dogs. Trends
towards age, breed and sex for each mineral type are discussed.
The major urinary risk factors for calcium oxalate formation in dogs were
found to be calcium and oxalate, although uric acid concentration was also increased
in some dogs. Although individually these factors differentiated between calcium
oxalate stone-forming dogs and clinically normal dogs, the relative supersaturation of
urine with respect to calcium oxalate more clearly discriminated between the two
groups.
Differences between the urine composition of breeds susceptible to calcium
oxalate formation (Miniature schnauzer, Cairn terrier and Cocker spaniel) were
identified, when compared to a breed with a low risk of calcium oxalate formation
(Labrador retriever). These included a lower urine volume (per kg bodyweight),
higher urine specific gravity and increased calcium concentration. Increased dietary
moisture and sodium were shown to reduce the severity of these differences, thereby
reducing the risk of calcium oxalate crystallisation in susceptible breeds. This thesis
also demonstrated that both dietary calcium and oxalate have to be controlled in order
to minimise the risk of calcium oxalate formation in susceptible breeds.
It was shown that in cats a moderately acidic urine pH within the range of 6-
6.5 could minimise the risk of both calcium oxalate and MAP crystallisation
compared to either a more acidic (5.8) or more alkaline urine pH (6.8). Finally,
dietary potassium citrate supplementation, which is often recommended for the
management of calcium oxalate formation in dogs had limited effects on urine
analytes in the majority of dogs.

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DECLARATION
This thesis represents my own unaided work, except where acknowledged below.

1. All urolith analyses were carried out by the staff at the Department of Chemical
Pathology, University College London Hospitals, Windeyer Building, Cleveland
Street, London, W1P 6DB.

2. All urine and diet analyses were carried out by the staff at the Central Nutritional
Laboratory, Pedigree Masterfoods, Mill Street, Melton Mowbray, Leics., LE13 1BB.

3. In Chapter 4, the typical nutrient analysis program for human foods, and the risk
factor program were supplied by Dr. W.G. Robertson, Institute of Urology and
Nephrology, University College London.

Abigail Stevenson
2002

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ACKNOWLEDGEMENTS
I would like to thank the many people, colleagues, friends and family, who
have assisted me in any way over the past few years, both in collection and analysis of
data and in the preparation of this thesis. Without their help and encouragement much
of this work would have been difficult if not impossible.
Firstly, I would like to thank my two supervisors, Dr W.G. Robertson, from
University College London, and Mr Peter Markwell from the WALTHAM Centre
for Pet Nutrition, for their continued advice and support. I could not have wished for
two more motivating and inspiring mentors!
Particular thanks must also go to Carrick, my three-year-old son and my
husband Phil, firstly, for providing both the motivation to complete this thesis and for
providing a good reason to go home in the evenings, and secondly, for coping so well
without me over the last few months. Along the same lines, huge thanks must also go
to my Mum and Dad for all the help and support they have shown in looking after
Carrick.
I am also very grateful to the WALTHAM Centre for Pet Nutrition who
provided all the funding for this thesis, and special thanks must go to Mr. Bill Fry for
having the belief in my ability to deliver.
Thanks are also due to the many dogs and cats that participated in generating
data for these studies, both at the WALTHAM Centre for Pet Nutrition and in the
home environment. Close relationships were formed with the owners of many of the
clinical cases that were monitored for up to a year, and their co-operation is very much
appreciated.
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Thanks must also go to the animal technicians at the WALTHAM Centre for
Pet Nutrition who assisted in the collection of urine samples and the feeding of the
dogs and cats, with a special thank you to Virginia Frere and Amelia Wagstaff. I am
also grateful to Joy Stevenson for her comments on the statistical methods used to
analyse data in this thesis. I must also thank the staff at the Department of Chemical
Pathology, UCL Hospitals for the urolith analysis work, with particular thanks going
to Dr. Ron Kasidas for his continued support.
Finally, the clinical cases included in this work were predominantly acquired
from the Peoples Dispensary for Sick Animals in Nottingham and Leicester, and
several other veterinary practices in England. I am indebted to the clinicians at these
practices for providing the case material required for this study.

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CONTENTS
TITLE PAGE ................................................................................................................ 1
ABSTRACT .................................................................................................................. 2
DECLARATION ........................................................................................................... 3
ACKNOWLEDGEMENTS .......................................................................................... 4
CONTENTS .................................................................................................................. 6
FIGURES .................................................................................................................... 14
TABLES ...................................................................................................................... 16

CHAPTER 1. GENERAL INTRODUCTION ............................................................ 20
1.1 Definition of urolithiasis ..................................................................................... 20
1.2 Historical perspective......................................................................................... 20
1.3 Anatomy of the canine and feline urinary tract .................................................. 22
1.3.1 Kidney ..................................................................................................... 22
1.3.2 Renal pelvis and ureter ........................................................................... 23
1.3.3 Urinary bladder and urethra .................................................................... 24
1.4.The physiology of urine formation ..................................................................... 25
1.5 Urolithiasis in cats and dogs ............................................................................... 29
1.5.1 Prevalence ............................................................................................... 29
1.5.2 Anatomical occurrence ........................................................................... 30
1.5.3 Mineral composition of uroliths ............................................................. 31
1.5.3.1 Cystine urolith formation .............................................................. 32
1.5.3.2 Uric acid / urate urolith formation ................................................ 34
1.5.3.3 Magnesium ammonium phosphate and calcium urolith formation 37
1.6 Theories of urolith formation .............................................................................. 38
1.6.1 ‘Free-particle’ theory of urolith formation.............................................. 39
1.6.2 Fixed-particle’ theory of urolith formation ............................................. 40
1.6.3 Modifiers of crystallisation .................................................................... 41
1.6.3.1 The ‘Promoter’ theory .................................................................... 42
1.6.3.2 The ‘Inhibitor’ theory ..................................................................... 44
1.6.3.2.1 Low molecular weight polyanions ........................................ 44
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1.6.3.2.2 Macromolecular polyanions ................................................. 48
1.6.4 The concept of urinary supersaturation ................................................... 50
1.6.4.1 Zones of urinary supersaturation .................................................... 52
1.6.4.1.1 Zone of undersaturation ........................................................ 52
1.6.4.1.2. Zone of metastable supersaturation ...................................... 52
1.6.4.1.3 Zone of oversaturation .......................................................... 53
1.6.5 Methods for measuring urinary relative supersaturation ........................ 54
1.6.5.1 The relative supersaturation ratio (RSS) ........................................ 54
1.6.5.2 Activity product ratio (APR) .......................................................... 56
1.6.6 Composite theories of urolith formation ................................................. 57
1.7 Factors influencing the urinary supersaturation in cats and dogs ....................... 59
1.7.1 Magnesium ammonium phosphate (MAP) ............................................. 59
1.7.1.1 Age, breed, sex and sexual status ................................................... 59
1.7.1.2 Urine pH ......................................................................................... 59
1.7.1.3 The role of urinary tract infections (UTIs) ..................................... 60
1.7.1.4 Increased urine volume .................................................................. 61
1.7.1.5 Dietary magnesium and phosphorus .............................................. 62
1.7.2 Calcium oxalate ...................................................................................... 63
1.7.2.1 Age, breed, sex and sexual status ................................................... 63
1.7.2.2 Increased urine volume .................................................................. 64
1.7.2.3 Calcium .......................................................................................... 65
1.7.2.3.1 Calcium metabolism .............................................................. 65
1.7.2.3.2 Urinary calcium excretion ..................................................... 66
1.7.2.4 Oxalate ........................................................................................... 67
1.7.2.4.1 Oxalate metabolism ............................................................... 67
1.7.2.4.2 Urinary oxalate excretion ...................................................... 69
1.7.2.5 Other dietary factors ....................................................................... 71
1.7.2.5.1 Protein .................................................................................. 71
1.7.2.5.2 Fibre ..................................................................................... 72
1.7.2.5.3 Vitamin B ............................................................................ 72
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1.7.2.5.4 Vitamin C .............................................................................. 73
1.8 Rationale and aims of the study ......................................................................... 74

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CHAPTER 2. MATERIALS AND METHODS....................................................... 75
2.1 Housing conditions ............................................................................................. 76
2.1.1 Cat housing specifications ...................................................................... 76
2.1.2 Dog housing specifications ..................................................................... 76
2.2 Urinalysis ............................................................................................................ 77
2.2.1 Urine pH ................................................................................................. 77
2.2.2 Urine volume and specific gravity .......................................................... 77
2.2.3 Urinary relative supersaturation (RSS) ................................................... 78
2.2.2.1 Sample collection ........................................................................... 78
2.2.2.2 Sample analysis .............................................................................. 78
2.3 Dietary nutrient analysis .................................................................................... 80
2.4 Data analysis ...................................................................................................... 81

CHAPTER 3. QUANTITATIVE ANALYSIS OF UROLITHS SURGICALLY
REMOVED FROM CATS AND DOGS .................................................................... 83
3.1 Introduction ......................................................................................................... 83
3.2 Materials and Methods ........................................................................................ 85
3.2.1 Urolith analysis ....................................................................................... 85
3.2.2 Patient information ................................................................................ 85
3.2.3 Data analysis .......................................................................................... 86
3.2.3.1 Mineral type .................................................................................. 86
3.2.3.2 Age profiles ................................................................................... 86
3.2.3.3 Gender distribution ....................................................................... 86
3.2.3.4 Breed distributions ........................................................................ 87
3.3 Results ................................................................................................................. 87
3.3.1 Canine urolith analysis across all countries ............................................ 87
3.3.1.1 Mineral composition ...................................................................... 88
3.3.1.2 Sex distribution .............................................................................. 88
3.3.1.3 Age distribution ............................................................................ 88
3.3.1.4 Breed distribution .......................................................................... 89
3.3.2 Feline urolith analysis across all countries ............................................ 90
3.3.2.1 Mineral composition ...................................................................... 90
3.3.2.2 Sex distribution .............................................................................. 90
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3.3.2.3 Age distribution ............................................................................ 90
3.3.2.4 Breed distribution .......................................................................... 91
3.3.3 Comparison of uroliths removed from cats and dogs in Hong Kong,
Italy, Netherlands and Great Britain ..................................................................... 91
3.3.3.1 Mineral type ................................................................................... 91
3.3.3.2 Sex distributions ........................................................................... 92
3.3.3.3 Age distributions ........................................................................... 92
3.3.3.4 Breed distributions ........................................................................ 92
3.3.3.4.1 Dogs ...................................................................................... 92
3.3.3.4.2 Cats ....................................................................................... 94
3.4 Discussion ........................................................................................................ 107
3.5 Conclusions and clinical relevance .................................................................. 116

CHAPTER 4. DIFFERENCES IN NUTRIENT INTAKE AND URINE
COMPOSITION BETWEEN CALCIUM OXALATE STONE-FORMING DOGS
AND NORMAL HEALTHY DOGS ........................................................................ 120
4.1 Introduction ....................................................................................................... 120
4.2 Materials and methods ...................................................................................... 124
4.2.1 Dogs ...................................................................................................... 124
4.2.1.1 Stone-formers (SF) ....................................................................... 124
4.2.1.2 Control group (N)......................................................................... 124
4.2.2 Dietary history ...................................................................................... 124
4.2.3 Study design .......................................................................................... 126
4.2.4 Urinary measurements .......................................................................... 127
4.2.5 Blood samples ....................................................................................... 127
4.2.6 Statistical analysis ................................................................................. 127
4.2.7 Risk factor analysis ............................................................................... 128
4.3 Results ............................................................................................................... 128
4.3.1 Dietary compliance and urine sample collection .................................. 128
4.3.1.1 SF group ....................................................................................... 128
4.3.1.2 N group ........................................................................................ 129
4.3.2 Nutrient intakes ..................................................................................... 129
4.3.2.1 Comparison between SF and N on FC ......................................... 129
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4.3.2.2 Comparison between SF and N on S diet .................................... 129
4.3.2.3 Comparison of FC and S diets within the SF group .................... 129
4.3.2.4 Comparison of FC and S diets within the N group ...................... 130
4.3.3 Urinary measurements .......................................................................... 131
4.3.3.1 Calcium oxalate RSS ................................................................... 131
4.3.3.2 Urine specific gravity ................................................................... 132
4.3.3.3 Urinary concentrations ................................................................. 132
4.3.3.4 Urinary excretions (per mmol creatinine) .................................... 136
4.3.5 Blood samples ....................................................................................... 136
4.3.6 Risk factor analysis ............................................................................... 137
4.4 Discussion ......................................................................................................... 143
4.5 Conclusions and clinical relevance ................................................................... 148

CHAPTER 5. THE EFFECT OF BREED ON URINE PARAMETERS IN DOGS 151
5.1 Introduction ....................................................................................................... 151
5.2 Materials and Methods ...................................................................................... 153
5.2.1 Dogs ...................................................................................................... 153
5.2.1.1 Phase 1 ......................................................................................... 153
5.2.1.2. Phase 2 ........................................................................................ 154
5.2.2 Study design .......................................................................................... 154
5.2.3 Housing details ..................................................................................... 155
5.2.3.1 Phase 1 ......................................................................................... 155
5.2.3.2 Phase 2 ......................................................................................... 155
5.2.4 Urine measurements ............................................................................. 155
5.2.4.1 Phase 1 ......................................................................................... 155
5.2.4.2 Phase 2 ......................................................................................... 156
5.2.5 Blood samples ....................................................................................... 156
5.2.6 Statistical analyses ................................................................................ 156
5.2.6.1 Phase 1 ......................................................................................... 156
5.2.6.2 Phase 2 ......................................................................................... 157
5.3 Results ............................................................................................................... 157
5.3.1 Food intake and bodyweight maintenance ............................................ 157
5.3.2 Dietary mineral intakes ......................................................................... 157
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