3D Nephrology in small animals

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3D Nephrology in small animals ÓSCAR CORTADELLAS RODRÍGUEZ MARÍA LUISA SUÁREZ REY

3D Nephrology in small animals

3D Nephrology

in small animals ÓSCAR CORTADELLAS RODRÍGUEZ MARÍA LUISA SUÁREZ REY

AUTHORS: Óscar Cortadellas Rodríguez and

María Luisa Suárez Rey.

FORMAT: 22 × 28 cm.

NUMBER OF PAGES: 116.

NUMBER OF IMAGES: 150.

BINDING: hardcover, wire-o.

eBook included

ANIMATIONS INCLUDED

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This book describes, in a way that greatly facilitates learning, the most relevant renal diseases in cats and dogs, with a focus on their pathophysiology and diagnosis, as well as on how they can be treated.

The content not only reflects the latest advances in nephrology, but also shows the kidney in a way rarely seen in veterinary medicine.

Either by navigating through the ebook or by using the QR codes in the printed version, readers will be able to view animations designed to explain the anatomy and physiology of the kidney, the pathophysiology of renal diseases, and certain surgical techniques.

Videos of the most common diagnostic techniques are also included, together with many images, diagrams and 3D illustrations, which turn this book into a very useful resource.

This book will undoubtedly help veterinary surgeons by providing them with very accurate scientific information; it may also be used to aid communication with pet owners.

3D Nephrology in small animals

Presentation of the book Nephrology is a branch of veterinary medicine that may sometimes appear difficult to understand owing to the amount of details involved and the tiny differences between pathologies. A good knowledge of renal physiology is key to a correct understanding of the primary diseases affecting the kidneys, which may be inherited, familial, acquired, or a complication of other diseases. In the past few years, the definition and classification of the different stages of renal diseases, both in their acute and chronic phases, has been greatly improved. However, those who specialise in this branch of internal medicine know well how difficult it can be for veterinary practitioners to catch these diseases at their onset. Yet, catching the disease at an early stage is key to treatment success, when this is possible, and, in some cases, to curing the disease. Starting from these premises, new protocols and new techniques have been developed for both acute kidney injury (AKI) and chronic kidney disease (CKD). This improved knowledge and training of veterinary clinicians as well as the increasing number of veterinary units where extracorporeal therapy is performed in dogs and cats open a new era in the treatment of renal diseases.

Any publications, in particular textbooks, aimed at improving the knowledge and interpretation of the clinical signs of renal disorders, and at explaining how they can be treated, are always welcome. This is all the more true when the publication provides new and up-to-date information. The book 3D Nephrology in small animals, written by Ă“scar Cortadellas and MarĂ­a Luisa SuĂĄrez, represents a new concept of textbook and offers fascinating solutions to facilitate the understanding of renal anomalies and diseases. I really appreciated the quality of the scientific information and how this information is presented to the reader. This book will certainly be of great help to students and veterinarians, as the possibility to view the kidney structure and anomalies in 3D will give them a better insight into nephrology.

Claudio Brovida, DVM, PhD President of the International Renal Interest Society (IRIS)

The authors Óscar Cortadellas Rodríguez Óscar Cortadellas Rodríguez holds a degree in Veterinary Medicine from the University of Zaragoza (1989) and a PhD in Veterinary Medicine from the University of Murcia (2004).

Since 1990, he has worked as a private clinician at the Germanías Veterinary Clinic, Gandía, Valencia (Spain). Since 2016, he has also worked as an internal medicine specialist at the Clinical Veterinary Hospital CEU-UCH, Valencia. His areas of interest within the field of internal medicine include nephrology, cardiology, and infectious diseases.

He has published articles in national and international journals, spoken at numerous national congresses, and has presented papers at various international conferences for internal medicine specialists.

3D Nephrology in small animals

María Luisa Suárez Rey

hkeita/shutterstock.com

María Luisa Suárez Rey holds a degree in Veterinary Medicine from the Faculty of Veterinary Medicine of 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 full professor of Medical Pathology in the Department of Veterinary Clinical Sciences of the Faculty of Veterinary Medicine, Lugo. In addition, she works as an internal medicine specialist at the Rof Codina Clinical Veterinary Hospital, Lugo.

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3D Nephrology in small animals ÓSCAR CORTADELLAS RODRÍGUEZ MARÍA LUISA SUÁREZ REY

Table of contents 1. Renal anatomy and physiology Introduction Kidneys Renal irrigation Innervation and lymphatic drainage

Ureters Bladder

Renal amyloidosis Introduction Pathogenesis Clinical presentation Diagnosis Treatment

Nephrotic syndrome Clinical presentation

Urethra

Pathophysiology

Renal physiology

Treatment

Uropoietic function Endocrine functions

2. Hereditary nephropathies

DIAGNOSIS OF GLOMERULAR DISEASE Proteinuria

Introduction

Physiology and classification of proteinuria

Polycystic disease

Practical assessment of proteinuria

Treatment

Renal dysplasia Hereditary nephritis Amyloidosis

Prognostic factor

Kidney biopsy Pre-biopsy considerations Techniques for obtaining kidney biopsies Aftercare and complications

Immune-mediated glomerulonephritis

Processing of biopsy samples

Tubulopathies

Diagnostic utility of the biopsy

Fanconi syndrome Cystinuria Renal glycosuria

3. Glomerular diseases Introduction Glomerulonephritis Classification Pathogenesis Clinical presentation

4. Pyelonephritis Introduction Pathophysiology Clinical presentation Diagnosis Treatment

5. Nephroureterolithiasis

Diagnosis

Introduction

Treatment

Clinical presentation Diagnosis Treatment

6. Hydronephrosis Introduction Aetiology Pathogenesis

Aetiology and pathogenesis Prerenal damage Postrenal damage Intrinsic renal damage

Specific causes of AKI

Clinical presentation

Ethylene glycol poisoning

Diagnosis

Leptospirosis

Ultrasound Radiography

Treatment

7. Renal abcesses Introduction Clinical presentation Diagnosis Treatment

8. Perirenal pseudocysts Introduction Clinical presentation Diagnosis Treatment

9. Idiopathic renal haematuria Introduction Clinical presentation

Nephrotoxicity caused by aminoglycoside antibiotics Nephrotoxicity caused by grapes and raisins Nephrotoxicity caused by lilies Nephrotoxicity caused by NSAIDs Hypercalcaemia AKI secondary to heat stroke

Clinical presentation Diagnosis Treatment

11.Chronic kidney disease Introduction Pathophysiology of CKD Causes of CKD Clinical presentation Diagnosis and classification of CKD Treatment

12.Kidney and bladder tumours Kidney tumours

Diagnosis

Clinical presentation

Treatment

Diagnosis

10.Acute kidney injury Introduction Phases of AKI

Treatment

Bladder tumours Clinical presentation Diagnosis Treatment

3D Nephrology Introduction The urinary system consists of 2 kidneys, 2 ureters, 1 bladder, and 1 urethra. The main functions of the urinary system are carried out by the kidneys, while the remaining organs are responsible for the passage and storage of urine.

The urinary tract is essentially the same in males and females, except for the length of the urethra and its relationship with the prostate in males.

The kidney carries out a variety of important functions.

The most obvious of these is the purification and elimination of organic waste. However, its primary function is the homeostatic regulation of water and ion content. This is achieved by capturing these substances from the blood and excreting them via the urinary system. Another important function is regulation of the acid-base equilibrium. The urinary system also plays an important role in endocrine function: renal cells synthesise erythropoietin, release renin (an enzyme that regulates the production of hormones involved in blood pressure homeostasis and sodium balance), and vitamin D is converted into its active metabolite in the kidney.

The reserve capacity of the kidneys is enormous: it is estimated that a loss in renal function of over 75 % is required before effects on homeostasis are observed.

Many animals with only 1 kidney retain perfectly normal kidney function (Fig. 1).

Figure 1.

Computed tomography in a case of a renal agenesis.

Figure 2. Dog kidney. Medial longitudinal section.

Kidneys The kidneys of the dog and cat are similar in structure and relative size (Fig. 2). Macroscopically, the kidneys are 2 smooth viscera of reddish brown colour located in the roof of the abdominal cavity, on either side of the vertebral column next to the lumbar vertebrae, in a retroperitoneal position (the dorsal aspect of the kidneys is not covered by peritoneum).

They are usually surrounded by abundant fibro-fatty tissue, which protects against the pressure and friction of other adjacent structures. The kidneys are bean-shaped. The renal vessels, nerves, and ureters enter and leave via the hilum, a deep depression in the centre of the concave medial border.

The right kidney is located slightly more cranially, at the level of vertebrae T13 and L2. It is bordered cranially by the renal fossa of the caudate lobe of the liver and the right adrenal gland, ventrally by the right lobe of the pancreas and the ascending colon, and medially by the caudal vena cava and the right ureter (Fig. 3). The location of the left kidney is more variable, and depends on the degree of repletion of

2

Figure 3.

Computed tomography image showing the more cranial position of the right kidney in a dog.

the stomach. It occupies a slightly more caudal position, at the level of vertebrae L2–L4. It is bordered cranially by the left lobe of the pancreas and the left adrenal gland; dorsally by the pillars of the diaphragm and the quadratus lumbar, transversus abdominis, and psoas muscles; caudally by the descending colon (and the mesovarium in females); and

3D Nephrology Renal anatomy and physiology

Ultrasound of a normal dog kidney

Anatomy of the kidney

medially by the aorta, the left ureter, the descending colon, the mesocolon, and the ascending duodenum. In feline species the kidneys are more mobile, and are located more caudally, generally at the level of vertebrae L1–L4 on the right and L2–L5 on the left (Fig. 4).

In unipyramidal or unilobular kidneys, like those of carnivores, the kidney consists of a single lobe formed by fusion during development of several lobes. Examination of a longitudinal section of the kidney reveals that they are covered by a fibrous capsule closely connected to the parenchyma that prevents expansion of the organ. In cats, the capsular veins converge at the renal hilum on this capsule (Fig. 5).

The parenchyma is formed by the cortex, which is reddish brown in colour and has a granular appearance due to the presence of the renal corpuscles and the contiguous tubules, and the medulla, which is usually paler and has a striated appearance owing to the presence of the loop of Henle and the collecting duct system. The renal medulla is organised into triangular sections called renal pyramids, delimited by the interlobar vessels. The apices (papillae) of each pyramid merge into a common central ridge (renal crest). This crest in turn is intimately associated with the renal pelvis (a dilated portion of the ureter), which is located in the renal sinus in the area of the hilum.

The functional unit of the kidney is the nephron. The number of nephrons varies between species and is higher in canine than in feline species.

Figure 4. Radiograph showing the position of the kidneys in the

cat.

Figure 5. Capsular veins in a cat kidney.

On average, a medium-sized cat has about 200,000 nephrons per kidney, while a medium-sized dog has about 700,000.

Mammalian nephrons are composed of a renal corpuscle (formed by the glomerulus and the glomerular capsule), tubules (proximal convoluted tubule, loop of Henle, and distal convoluted tubule), and the collecting ducts, which collect the filtrate from several nephrons and empty into the papillary ducts (Figs. 6 and 7).

Two types of nephrons are identified based on the location of their glomeruli and the depth of penetration of the loop of Henle into the medulla: • Cortical nephrons: the glomeruli are located in the outer or middle zone of the cortex, and the loop of Henle extends to the point at which the cortex meets the medulla, or slightly into the outermost region of the medulla.

Figure 6. Histological image of the renal cortex.

• Juxtamedullary nephrons: the glomeruli are located in the proximal region of the medulla and the loop of Henle extends very deep, almost reaching the renal pelvis.

These nephrons are responsible for maintaining the osmotic gradient between the outer and inner part of the medulla. The percentage of this type of nephron varies between species, and reaches almost 100 % in cats.

3

Kidney with amyloidosis

30

3D 3DNephrology Nephrology Glomerular Glomerular diseases diseases Renal Renalamyloidosis amyloidosis Introduction Introduction The The term term amyloidosis amyloidosis refers refers to to a set a set of of clinical clinical manifestations manifestations thatthat occur occur as as a consequence a consequence of of alterations alterations in protein in protein metabmetabolism, olism, which which cause cause normally normally soluble soluble protein protein compounds compounds to to acquire acquire a characteristic a characteristic spatial spatial disposition disposition (in(in thethe form form of of a a folded folded beta-sheet), beta-sheet), rendering rendering them them insoluble. insoluble.

This This results results in in thethe extracellular extracellular deposition deposition of aoffibrillar a fibrillar protein protein material material called called amyloid. amyloid.

Amyloidosis Amyloidosis cancan bebe local local (when (when alterations alterations affect affect a single a single organ/tissue) organ/tissue) or or systemic systemic (affecting (affecting different different viscera, viscera, conconnective nective tissue, tissue, or or blood blood vessels). vessels).

It can It can bebe primary primary (with (with nono apparent apparent cause) cause) or or secondary/reactive secondary/reactive (i.e.(i.e. a complication a complication of of a pre-existing a pre-existing disease), disease), andand cancan bebe classified classified as as hereditary hereditary or or acquired. acquired.

The The most most common common form form of of amyloidosis amyloidosis in dogs in dogs andand cats cats is reactive is reactive or or secondary secondary amyloidosis, amyloidosis, which which cancan also also occur occur as as an an acquired acquired disease disease (associated (associated with with inflammatory inflammatory or or neoneoplastic plastic diseases, diseases, although although thethe cause cause is not is not always always evident) evident) or or as as a familial a familial disease disease in certain in certain dogdog (e.g. (e.g.

Shar Shar PeiPei andand probably probably thethe Beagle Beagle andand English English Foxhound) Foxhound) andand catcat (e.g. (e.g.

Abyssinian) Abyssinian) breeds. breeds.

Renal Renal amyloidosis amyloidosis is aiscommon a common cause cause of of glomerular glomerular disease disease in dogs in dogs and, and, according according to to one one study, study, may may account account forfor upup to to 23 % 23 % of of cases. cases.

It isItless is less common common in cats. in cats.

Pathogenesis Pathogenesis In most In most cases cases amyloid amyloid consists consists of of 3 components: 3 components: • •Amyloid Amyloid P: this P: this is aisnon-fi a non-fi brillar brillar protein protein identical identical to to a nora normalmal circulating circulating plasma plasma globulin globulin called called serum serum amyloid amyloid P. ItP. It is thought is thought to to actact as as a basic a basic skeleton skeleton onon which which thethe fibrillar fibrillar proteins proteins areare deposited. deposited.

• •Amyloid Amyloid fibrillar fibrillar proteins: proteins: these these areare generally generally formed formed from from fragments fragments of of precursor precursor proteins proteins that that undergo undergo parpartialtial proteolytic proteolytic cleavage. cleavage.

• •Components Componentsof ofthetheextracellular extracellularmatrix: matrix:these theseareare mainly mainly glycosaminoglycans glycosaminoglycans such such as as heparan heparan sulfate sulfate andand dermatan dermatan sulfate, sulfate, andand areare non-covalently non-covalently bound bound to to thethe fibrils. fibrils.

Their Their function function is not is not clear, clear, butbut they they appear appear to to exert exert a fiabrinogenic fibrinogenic effect effect onon certain certain precursor precursor proteins proteins of of amyloid amyloid fibrils. fibrils.

Renal Renal amyloidosis amyloidosis

canine feline species, protein responsible In In canine andand feline species, thethe protein responsible development renal amyloidosis is the forfor thethe development of of renal amyloidosis is the AAAA amyloidprotein, protein,formed formedby bypolymerisation polymerisationof ofthethe amyloid amino terminal portion acute phase protein amino terminal portion of of an an acute phase protein called serum amyloid A (SAA). called serum amyloid A (SAA).

Synthesis SAA liver is induced cytokines Synthesis of of SAA in in thethe liver is induced by by cytokines (IL-6, IL-1β, TNF-α), which turn produced (IL-6, IL-1β, andand TNF-α), which in in turn areare produced by by macrophages in response tissue damage.

In normal conmacrophages in response to to tissue damage.

In normal conditions serum concentration is around mg/dl, ditions its its serum concentration is around 0.1 0.1 mg/dl, butbut when a tissue injury occurs value increases between when a tissue injury occurs thisthis value increases by by between 100 1,000 fold, remains elevated 100 andand 1,000 fold, andand remains elevated forfor 3636 to to 4848 hours if the cause inflammatory process disappears. hours if the cause of of thethe inflammatory process disappears.

However, if the inflammation persists, levels remain However, if the inflammation persists, thethe levels remain high continuously.

This implies that a chronic persistent high continuously.

This implies that a chronic andand persistent stimulus is required animal develop amyloidosis. stimulus is required forfor an an animal to to develop amyloidosis.

However, given that very animals with chronic inflamHowever, given that very fewfew animals with chronic inflammatory processes develop amyloidosis, it seems likely that matory processes develop amyloidosis, it seems likely that other coexisting hereditary acquired predisposing other coexisting hereditary or or acquired predisposing fac-factors must also contribute process. tors must also contribute to to thisthis process.

In the pathogenesis amyloidosis, several phases In the pathogenesis of of amyloidosis, several phases cancan bebe distinguished. initial predeposition phase in which there distinguished.

AnAn initial predeposition phase in which there is an increase in the concentration SAA (which also is an increase in the concentration of of SAA (which cancan also persist during deposition phase), a subsequent deppersist during thethe deposition phase), andand a subsequent deposition phase.

In turn, deposition process is divided into osition phase.

In turn, thethe deposition process is divided into 2 stages: rapid stage, characterised a rapid increase 2 stages: thethe rapid stage, characterised by by a rapid increase in in amount of amyloid; plateau phase, in which very thethe amount of amyloid; andand thethe plateau phase, in which very changes in amyloid deposition occur.

In the Shar fewfew changes in amyloid deposition occur.

In the Shar Pei,Pei, thethe predeposition phase is characterised recurrent episodes predeposition phase is characterised by by recurrent episodes fever inflammation tibiotarsal joint. of of fever andand inflammation of of thethe tibiotarsal joint.

Clinical Clinical presentation presentation

Animals Animalswith withrenal renalamyloidosis amyloidosisareareusually usuallyof ofmedium/ medium/ advanced advanced age, age, although although young young animals animals cancan alsoalso bebe affected affected in in cases cases of of familial familial disease. disease.

The The clinical clinical signs signs observed observed areare nonnonspecific specific andand include include anorexia, anorexia, lethargy, lethargy, weight weight loss, loss, polyuria/ polyuria/ polydipsia, polydipsia, vomiting, vomiting, andand diarrhoea. diarrhoea.

Some Some animals animals present present thethe classic classic manifestations manifestations of of a nephrotic a nephrotic syndrome, syndrome, while while those those In human In human medicine, medicine, more more than than 2525 proteins proteins have have been been impliimpli- with with very very advanced advanced disease disease usually usually present present with with uraemic uraemic synsyncated cated in the in the development development of of amyloidosis. amyloidosis.

Depending Depending onon thethe drome. drome.

Another Another possible possible reason reason forfor seeking seeking veterinary veterinary assisassisnature nature of of thethe individual individual proteins proteins involved, involved, different different types types of of tance tance is paralysis is paralysis or or severe severe dyspnoea dyspnoea caused caused by by thromboemthromboemamyloidosis amyloidosis willwill arise. arise. bolism. bolism.

In In thethe Shar Shar Pei,Pei, recurrent recurrent fever fever andand inflammation inflammation of of

3131

3D Nephrology Sulfosalicylic acid test Proteinuria can also be evaluated using the sulfosalicylic acid (SSA) test. Equal amounts of urine and 3–5 % sulfosalicylic acid solution are mixed, and the resulting turbidity evaluated (Fig. 13). This test enables semiquantitative detection of protein from 5 mg/dl, and detection of Bence Jones proteins.

False positives can result from the presence in urine of radiological contrast agent, some antibiotics (penicillins and cephalosporins), and the preservative compound thymol.

Determination of microalbuminuria The presence of proteins in urine can also be estimated by measuring microalbuminuria. A patient is considered microalbuminuric when 1–30 mg/dl of albumin is detected in the urine. Currently microalbuminuria can be measured semiquantitatively in the clinic using certain urine analysers, or quantitatively (in an external laboratory) by measuring either microalbuminuria or the albumin/creatinine ratio.Theoretically, the determination of microalbuminuria allows earlier detection of proteinuria, since the aforementioned techniques are not sufficient to detect proteinuria in all cases. Several studies have shown that a relatively large percentage of healthy patients can present microalbuminuria. Furthermore, other studies have demonstrated a relationship between microalbuminuria and various systemic diseases without renal involvement (tumours, inflammatory or immune diseases, endocrine disorders), and urinary tract infections. Given these findings, together with the poorly described relationship between microalbuminuria and kidney disease in dogs and cats, current guidelines for microalbuminuria patients who are classified as non-proteinuric (see protein/creatinine ratio) simply recommend monitoring the evolution of the condition (Fig. 14).

Protein/creatinine ratio From a practical point of view, the best method to estimate the severity of proteinuria is to calculate the urine protein/ creatinine ratio (UPC).This is a quantitative technique that has shown good correlation with the “reference method” (quantification of the amount of protein excreted in urine over 24 hours), and can be performed in the clinic (this test can be incorporated into some biochemical testing equipment) or in external laboratories. It should be noted that results obtained using different techniques may differ. To avoid false positive results, unless there is a strong suspicion of proteinuria of renal origin, it is advisable to rule out potential causes

38

Positive SSA test

Figure 13. Evident turbidity in the sulfosalicylic acid test for denaturation and precipitation of proteins.

Negative SSA test

Microalbuminuria

Sulfosalicylic acid

Test strips

0

5

10

15

20

25

30

35

40

Figure 14. Proteinuria concentrations detected using different analytical methods (mg/dl).

of prerenal proteinuria (blood and urine protein profile) and postrenal proteinuria (sample collection by cystocentesis and evaluation of urine sediment) before calculating the UPC. In any case, it is important to remember that some patients with familial glomerular disease (e.g. purebred Abyssinian cats) may present with proteinuria together with haematuria or pyuria (Fig. 15). Thus, even if there is clinical suspicion of proteinuria of renal origin it should be quantified using the UPC, even in cases of active urinary sediment.

Creatinine excretion occurs steadily throughout the day and measurement of any parameter in urine should be performed relative to the creatinine concentration to eliminate the effect of dilution or concentration of the urine.

3D Nephrology Glomerular diseases Depending on the protein/creatinine ratio in urine, patients can be classified as: • Non-proteinuric: UPC <0.2.

• Potentially proteinuric: UPC between 0.2 and 0.4 (cat)/0.5 (dog).

• Proteinuric: UPC >0.4 (cat)/0.5 (dog)

Prognostic factor As regards the role of proteinuria as a prognostic factor in CKD, it has been demonstrated that proteinuria severity is directly related to a decrease in survival. For example, a study of dogs with azotaemic CKD reported greater deterioration of renal function in dogs with UPC ≥1.0, together with a 3-fold increase in the risk of uraemic crisis and death. Moreover, in cats with CKD, the risk of death or euthanasia is increased 2.9 and 4 fold in patients with UPC values of 0.2–0.4 and >0.4, respectively, as compared with cats with a UPC <0.2.

Finally, although it is accepted that proteinuria contributes to the progression of kidney disease in humans, this remains unclear in dogs, and even more so in cats. Although there is evidence indicating a direct relationship between severe proteinuria and inflammation and fibrosis that can directly contribute to the formation of tubulointerstitial lesions, it has not been demonstrated that “low-grade” proteinuria (the form observed in most cats with CKD) directly promotes the progression of kidney disease (Fig. 16).

Kidney biopsy Figure 15. Renal haematuria.

The UPC value can be used to try to establish the origin of the proteinuria. Although there are some exceptions, UPC values >2 are associated with glomerular disease, while values in the range of 0.4–2.0 can be indicative of tubular involvement or a less severe glomerular process.

Determination of protein concentration by electrophoresis In laboratories in which it is available, polyacrylamide gel electrophoresis with sodium dodecyl sulphate (SDS-PAGE) allows determination of the origin of proteinuria. This technique separates the different proteins present in urine based on their molecular weight, and thus can be used to establish whether proteinuria is of glomerular or tubular origin and identify the presence of Bence Jones proteins in patients with multiple myeloma.

In the majority of renal patients, evaluation of the clinical history together with the results of the physical examination, laboratory tests, and diagnostic imaging tests allows definition of various “categories” of kidney disease (glomerular disease, acute kidney injury, chronic kidney disease, or exacerbation of prior CKD). Generally, this allows the clinician to establish an adequate treatment regimen, even if the exact nature of the renal lesion has not been established. However, in certain situations a definitive diagnosis is required to establish a specific treatment and an adequate prognosis. This requires a renal biopsy. Moreover, histopathological results can provide information on whether the lesion is reversible or irreversible.

In general, renal biopsy is indicated in cases in which the histological diagnosis influences the treatment of the patient.

The majority of scenarios in which this occurs involve patients with glomerular disease or acute kidney injury. In CKD patients, as the severity of the disease increases, the likelihood that histology provides information relevant to the management of the case decreases.

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3D Nephrology 2

a

1

b

8

9

3

4

5

6

7

11

c

10

d

12

13 1.

2.

3.

4.

5.

Bowman's capsule Endothelial cell Mesangial cell Podocyte Bowman's space

Figure 16. Progression of renal disease.

40

14 6. Parietal epithelial cell 7. Glomerular basement membrane (GBM)

8. Fibrin

15 9. Cells (neutrophils, lymphocytes)

10. Plasma proteins 11. Spaces in the GBM caused by glomerular damage

12. Parietal epithelial cell proliferation

13. Macrophage infiltration 14. Interstitial fibroblasts 15. Fibrosis

3D Nephrology Glomerular diseases Pre-biopsy considerations Before proposing a renal biopsy to a pet owner, a complete diagnostic evaluation should be carried out to rule out any cause of kidney disease that can be treated without the need for a biopsy. A posteriori, it is difficult to justify a biopsy if the definitive diagnosis could have been reached using noninvasive techniques.

Box 2 lists the scenarios in which biopsy is contraindicated. Performing biopsies in animals with only one kidney is controversial, although it can be done if there are no other contraindications and the appropriate technique is used.

The owner should be informed that samples are usually obtained under general anaesthesia, although in critical patients deep sedation can be used, depending on the risk associated with anaesthesia and the technique to be used. In dogs it may be easier to obtain samples from the right kidney; given its anatomic location it tends to move less during the procedure. However, access is complicated in dogs with a deep thorax. In these cases the left kidney is preferred, although it moves more. In cats, both kidneys are easily located and remain immobile, facilitating the procedure.

In some patients with suspected neoplasia, fine-needle aspiration can be diagnostic, but in most cases veterinary surgeons prefer to use disposable (and reusable) pre-loaded devices (16 G–18 G) that can be operated with one hand and allow extraction of good quality samples (Fig. 17).

Kidney biopsy

a

Regardless of the biopsy technique used, it is important that the samples obtained correspond to the renal cortex, for 2 main reasons: • If the needle passes through the corticomedullary junction, this increases the risk of damaging important blood vessels and causing severe bleeding during the procedure. Furthermore, there is an increased risk of damaging the renal parenchyma as a consequence of ischaemia or infarction in the area.

Box 2. Contraindications for biopsy.

• • • • • • • • •

Severe coagulopathy.

Severe anaemia.

Creatinine values >5 mg/dl.

Patients who have been treated with NSAIDs in the previous 5 days.

Hydronephrosis.

Uncontrolled hypertension.

Large renal cysts.

Abscesses.

Severe pyelonephritis.

• In almost all renal processes, the structures of interest (e.g. glomeruli) are found in the renal cortex.

To reduce the risk of damaging the renal medulla, it is important that when the device is activated, the cannula does not penetrate beyond the location of the needle tip. This should be taken into account when introducing the needle.

Techniques for obtaining kidney biopsies Ultrasound-guided percutaneous biopsy This is the technique of choice, especially in dogs of over 5 kg and in cats. After performing a global ultrasound examination of the kidney to select the biopsy site, the patient is placed in lateral decubitus on the opposite side and the area is shaved and prepared aseptically. Next, an incision is made in the skin to allow insertion of the needle tip into the renal capsule.

Once the needle is inserted, the device is activated and the sample acquired (Fig. 18).

b

c

Figure 17. (a) Disposable and (b) reusable devices for obtaining biopsies. (c) Extraction of a kidney biopsy sample.

41

3D Nephrology

Figure 6. Ultrasound image showing severe

dilation of the renal pelvis.

Figure 7. Ultrasound image showing dilation of the cranial ureter caused by a calculus, detected by the presence of an acoustic shadow.

When examining an animal with a dilated renal pelvis, it is recommended to follow the ureter to determine whether it is dilated and to investigate the possible cause. The ureters are usually not identified by ultrasound unless they are abnormally dilated (Figs. 6–8).

Radiography Hydronephrosis is only identified as a renal enlargement and it is not possible to differentiate it, by means of simple radiography, from other causes of nephromegaly, such as: • Acute renal failure.

• Amyloidosis.

• Feline infectious peritonitis.

• Polycystic disease.

• Primary or metastatic renal neoplasm.

• Perirenal pseudocysts.

• Perirenal or subcapsular haematoma.

• Pyelonephritis.

Radiography allows detection of ureteral calculi, which may be the cause of the obstruction and consequent hydronephrosis (Fig. 9).

In cases of hydronephrosis, when the cause of the obstruction cannot be identified by ultrasound, ultrasound-guided antegrade pyelography or computed tomography (CT) are recommended (Figs. 10 and 11). Antegrade pyelography helps identify the presence of a partial or complete obstruction. With ultrasound guidance, a needle connected to an extension line and a 3-way stopcock is inserted into the renal pelvis. If possible, urine from the dilated renal pelvis is collected before contrast injection, and is used for culture. The volume of injected contrast agent should be equivalent to 75–100 % of the volume of urine removed. Abdominal radiography is performed immediately, 5 and 15 minutes after injection.

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Figure 8. Ultrasound image showing severe

pyelectasis caused by an intraluminal mass in the left ureter that causes marked dilation.

Degrees of renal pelvic dilation

• Pelvic dilation of 0–4 mm: this is considered a normal finding if the patient does not show other abnormalities, or can be associated with increased diuresis (polyuria/ polydipsia, diuretics, fluid administration), pyelonephritis, or kidney disease.

• Pelvic dilation of 4–8 mm: may be due to pyelonephritis or obstructive hydronephrosis. Should be correlated with other clinicopathological findings.

• Pelvic dilation of 8 mm: most likely due to obstructive hydronephrosis, but can also be caused by severe pyelonephritis. Should be correlated with other clinicopathological findings.

• Pelvic dilation >13 mm: always associated with obstruction.

Ultrasound showing hydronephrosis in a patient with ureteral ectopia and obstruction of the ureter in its extravesical insertion point

Ultrasound showing hydronephrosis in a elderly patient with ureteral obstruction caused by soft tissue, without histological confirmation

Ultrasound of both kidneys showing dilation of the renal pelvis of varying severity and ureteral distension (hydroureter). Under normal conditions the ureters cannot be usually visualised by ultrasound

3D Nephrology Hydronephrosis Treatment

Figure 9. Radiograph showing ureteral

calculi in several locations in the ureter.

Figure 11. CT image from a patient

with ectopic ureters showing generalised ureteral dilation caused by dehiscence of the ureter following its surgical reimplantation. Contrast leak is evident at the level of the trigone.

Figure 10. CT image showing pyelectasis

in the left kidney accompanied by generalised dilation throughout the trajectory of the left ureter.

There is no specific treatment for hydronephrosis. Instead, the cause of the obstruction should be corrected and any complications caused by kidney failure should be treated.

A ureterotomy may be necessary if there are ureteral calculi in the proximal portion of the ureter (Fig. 12). If ureteral calculi are located in the distal portion of the ureter, removal by partial ureterectomy and ureteroneocystostomy may be necessary. If the ureter has been accidentally ligated, removal of the ligature with or without ureteral reimplantation may improve the function of the affected kidney.

The recovery of renal function is inversely proportional to the duration of the ligature/obstruction. Moderate hydronephrosis can improve fairly quickly once the obstruction is removed. More severe hydronephrosis may improve, but kidney function will probably not return to normal.

Unilateral nephrectomy may be necessary in severe cases of unilateral hydronephrosis if the other kidney is functional, as determined by intravenous urography or by CT analysis (Fig. 13). Bilateral hydronephrosis with evidence of renal failure has a poor prognosis.

Figure 12. Image of a hydroureter taken mid-surgery. Corresponds to the ultrasound image showing dilation of the renal pelvis caused by an intraluminal mass in the left ureter (Fig. 8).

Ultrasound showing hydronephrosis caused by a ureteral injury in which the pelvic recesses are clearly visible

CT image of an 8-year-old male Shar Pei with a fully atrophied left kidney with no contrast uptake and mild hydronephrosis of the right kidney.Abnormalities caused by ectopic ureteral insertion into the prostate

Figure 13. Total nephrectomy in a cat with unilateral hydronephrosis. Image taken mid-surgery.

Reconstruction of axial cuts (3D CT scan) showing mild hydronephrosis associated with hydroureter

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3D Nephrology Introduction The term perirenal pseudocyst is used to describe a group of conditions caused by an accumulation of fluid around the kidney (Fig. 1). This accumulation can be unilateral (60 %) or bilateral and tends to occur progressively, such that a unilateral perirenal pseudocyst can be followed by the development of another in the other kidney.

The term pseudocyst is used because the structure in question lacks the fibrous epithelial lining of a true cyst, since the renal capsule is composed of elastic connective tissue derived from mesenchymal tissue (Fig. 2).

Figure 1. Ultrasound image of a renal pseudocyst. A large

amount of anechoic fluid is evident between the renal parenchyma and the capsule.

Ultrasound of a pseudocyst

It is usually anchored to the kidney at the level of the poles, in the area of the hilum, or in multiple areas (Figs. 3 and 4).

Three types of perirenal pseudocysts are described: • Subcapsular pseudocysts: transudate accumulates between the capsule and the parenchyma of the affected kidney. This is the type most commonly described in veterinary medicine, and predominantly affects cats.

• Extracapsular pseudocyst: a pseudocyst is produced by the accumulation of transudate between the renal capsule and the retroperitoneal lining (perirenal fascia).

• Perirenal urinoma: this is produced by the filtering of urine from the renal pelvis, resulting in an inflammatory response in the adjacent tissue that leads to the formation of a fibrous wall around the site of the leak. This type of pseudocyst has been described in dogs and cats after trauma to the urinary tract. It should be differentiated from other forms of pseudocyst, since the appropriate management strategies differ. Treatment of urinoma involves identifying and eliminating the origin of the urine leak.

The formation of a perirenal pseudocyst has been linked to underlying kidney disease, but the exact mechanism by which fluid accumulates is unknown.

The pseudocyst fluid, usually transudate, can come from the capsule or the parenchyma. It is suspected that deterioration of the lymphatic or venous drainage of the capsule or renal parenchyma is the mechanism responsible for pseudocyst formation. In cats, a significant proportion of the venous drainage of the renal parenchyma occurs via the capsular veins. This anatomical peculiarity may be implicated in the formation of pseudocysts, and may make cats more

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Figure 2. Histological image of the kidney of a cat with a renal

pseudocyst.The pseudocyst wall contains scattered aggregates of lymphocytes and plasma cells.The absence of an epithelial lining of the cyst wall is also evident.

Figure 3. Renal pseudocyst in a cat in which the fluid contained

between the capsule and the renal reflection of the peritoneum has already been removed. Microscopy reveals the presence of membranoproliferative glomerulonephritis, as well as multifocal subacute tubulointerstitial nephritis.

Perirenal pseudocysts

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