1
Q
With conventional ultrasonography and Doppler mode which indexes can be used to evaluate and detect hemodynamic changes that can affect renal function in cats ?
A
Resistivity index and pulsatility index.
They are calculated from the systolic and diastolic velocity values obtained by the wave spectrum, and represent the resistance of the vascular wall to blood flow during organ perfusion. These indexes have been used in the evaluation of renal perfusion in humans and dogs, as well as horses and cats.
Ref : JFMS Nov 2022, Evangelista, Evaluating feline lower urinary tract disease: Doppler ultrasound of the kidneys
2
Q
In which disease resistivity index (RI) and pulsatility index (PI) of the kidneys (calculated in conventional ultrasonography and doppler mode) can be significantly increased in comparison with healthy cats ?
A
Feline lower urinary tract disease (FLUTD).
Cats with FLUTD showed significantly higher values in the assessment of RI (P = 0.027 and P = 0.034, respectively) and PI (P=0.044 and P=0.048, respectively) of the right and left kidneys, compared with control group.
Ref : JFMS Nov 2022, Evangelista, Evaluating feline lower urinary tract disease: Doppler ultrasound of the kidneys
3
Q
What are the 3 main types of glomerular disease in dogs ?
A
Immune complex glomerulonephritis, amyloidosis and glomerulosclerosis
4
Q
Name three dog breeds predisposed to familial renal amyloidosis
A
Beagle, English Foxhound and Shar Pei
5
Q
What type of familial glomerulopathy suffers the soft coated wheaten terrier ?
A
Podocytopathy
6
Q
How many dogs with glomerulonephritis and amyloidosis do not have azotemia at initial diagnosis (respectively)?
A
53% and 26%
7
Q
How many dogs with glomerulonephritis and amyloidosis have hypoalbuminemia at diagnosis (respectively)?
A
60% and 70%
8
Q
How many dogs with glomerulopathies have immune complex glomerulonephritis ?
A
48,1%
9
Q
Among dogs with renal biopsies for suspected glomerulopathy, how many have membranoproliferative glomerulonephritis?
A
26%
10
Q
What are the histopathologic characteristics of membranoproliferative glomerulonephritis?
A
Light microscopy: thickened capillary loops and mesangial hypercellularity
IFM: immune complex deposition of a combination of C3 IgM/IgA/IgG in the glomerular basement membrane
TEM: immune depositis
11
Q
What is the most common glomerular disease in cats ?
A
Membranous Nephropathy
12
Q
How many dogs with biopsies for glomerular disease suffer from membranous Nephropathy?
A
26%
13
Q
What defect results in hereditary nephritis in dogs ?
A
Basement membrane collagen IV defect
14
Q
Name 3 breeds of dog predisposed to renal agenesia
A
Beagle, Doberman pinscher and Shetland sheepdog
15
Q
What type of sympathetic and parasympathetic receptors are present in the canine ureters ?
A
Alpha-1, alpha-2 and beta adrenoreceptors and muscarinic cholinergic receptors
16
Q
In how many cats medical management of obstructive ureterolith is successful?
A
8-13%
17
Q
What is the survival rate to discharge following SUB placement in cats ?
A
94%
18
Q
How many ureteroliths in dogs are successfully treated by shock wave lithotripsy?
A
80% with 50% dogs necessitating at least 2 treatments
19
Q
How many cats with renal transplant will experience ureteral obstruction secondary to retroperitoneal fibrosis ?
A
21%
20
Q
Of recurrent uroliths in dogs, how many are attributable to a nidus of suture ?
A
9,4%
21
Q
What is the recurrence rate of calcium oxalate urolith in dogs at 2 years ?
A
50%
22
Q
How many cats presented for lower urinary tract signs are diagnosed with urolithiasis ?
A
7-28%
23
Q
What is the percentage of clinical response of female dogs suffering from USMI to phenylpropanolamine ?
A
75-90%
24
Q
What is the percentage of clinical response of male dogs suffering from USMI to phenylpropanolamine ?
A
43%
25
Does castration increases risks for prostatic tumor development in dogs ?
Yes : 8 times increased risks for prostatic transitional cell carcinoma and 2.1 times increased risks for prostatic adenocarcinoma
26
What is the prevalence of metastasis at the diagnosis of prostatic tumor ?
80%
27
Who does excrete a small amount of creatinine in urines?
Male dogs
28
What clinically may cause overestimation of dehydration in uremic pets ?
Xerostomia
29
Which biomarker is associated with development of azotemia, progression of CKD or death in cats ?
FGF23
30
What are the 3 layers of the filtration barrier of the glomerulus ?
- Highly fenestrated endothelium
- Glomerular basement membrane (including collagen IV, laminin, heparan-sulfate bound proteoglycans)
- Podocytes (visceral epithelial cells)
31
Which components of the glomerulus are mainly responsible for the charge selectivity ?
Glycocalyx, GBM and slit diaphragms
32
Which component of the glomerulus is mainly in charge of the size selectivity?
The GBM
33
What specific ICGN has been associated with Borrelia burgdorferi?
Membranoproliferative Glomerulonephritis
34
Which breeds of dogs and cats may have more commonly medullary amyloid deposition?
Abyssin and Shar-Pei
35
What is type III cystinuria?
Cystinuria affecting intact male dogs with unknown genetic origin
36
What is type I cystinuria?
Autosomal recessive mutation of Slc3a1 affecting Newfoundland, Labrador and Landseer
37
What is the main mechanism of urate stones formation in Dalmatian ?
Decreased uric acid transport through hepatic membrane (decreased conversion), decreased proximal tubular reabsorption and distal tubular secretion (mutation Slc2a9)
38
What is the main mechanism of ureteral peristaltism ?
Myogenic peristaltism (urine enters -> initiate electrical impulses -> smooth muscle contractions)
39
Name a risk factor for calcium phosphate stones in dogs.
Hyperparathyroidism
40
Name three types of stones associated with male sex in dogs.
Silica, Urate, Cystine
41
What type of urolith is associated with size >10mm, ovoid or pyramidal shape in dogs?
Struvite urolith
42
Name the contre-indications of renal biopsies
- IRIS stage IV
- Primary tubulo-interstitial disease
- Hydronephrosis
- Hemostatic disorders
- Hypertension
- Infection/renal abcess
43
Name biological abnormalities in nephrotic syndrome
Hypoalb
HyperChl
proteinuria
Hypercoagulable state (89% cases) risk of thrombotic disease
44
What are the 2 type of baroreceptors able to stimulate AVP secretion?
- High pressure arterial baroreceptors (in aortic arch & carotid sinus)
- Low pressure volume receptors (in atria & pulmonary system)
45
What is the consequence on renal blood flow and GFR of :
- ↑resistance in afferent arteriole (= vasoconstriction)?
- ↓resistance in afferent arteriole (=vasodilatation)?
- ↑resistance in efferent arteriole (= vasoconstriction)?
- ↓resistance in efferent arteriole (=vasodilatation)?
- ↓GFR ↓RBF
- ↑GFR ↑ RBF
- ↑GFR ↓RBF
- ↓GFR ↑ RBF
46
What is the consequence on afferent and efferent arteriole of
- Norepinephrine
- Angiotensin II
- PGE2/PGI2
- AINS
- Kinins
- IECA
- Endothelin
- Thromboxan
- NO
- Adr, Noradr
- corticosteroids
- cyclosporine
- Theophylline
- Norepi: vasoconstriction aff vasoC eff (↓GFR)
- Thromboxan: vasoC aff >vasoC eff (↓GFR)
- cyclosporine: vasoC aff vasoC eff
- corticosteroids: No effect aff vasoC eff (↑GFR)
- AINS: vasoC aff No effect eff (↓GFR)
- Adr, Noradr: vasoC aff No effect eff (↓GFR)
- PGE2/PGI2: vasoD aff vasoD eff (↑GFR)
- Kinins: vasoD aff vasoD eff (↑GFR)
- NO, prostacyclin: vasoD aff vasoD eff (↑GFR)
- IECA: No effect aff vasoD eff (↓GFR)
- Theophylline: vasoD aff No effect eff (↑GFR)
47
What are the main etiologies for tubulointerstitial nephritis in cats?
FIV, morbillivirus
HT4, dental disease
Cardiac disease
Stress, vaccine, diet
Ischemia, hypoxia &other
48
Which intracellular interstitium accumulation contributes to tubular cell death in feline CKD?
Tubular lipids
49
Name 2 uremic toxins
Indoxyl sulfate & p cresylsulfate
50
Name the anorexigen substance than can accumulate in cases of CKD
Leptin, CCK, obestatin, desacylghrelin
51
In which disease is capromorelin contre indicated?
Acromegaly
careful with DM
52
What are the prognosis factors in dogs and cats with CKD?
Cats: FGF23, P, uremic toxins, body weight, anemia
Dogs: FGF23, P, uremic toxins, BCS, muscle mass, proteinuria, HTA, increase CaxPo4
53
Which molecule has a role in glomerular perm selectivity and when lost in urine lead to protenuria and hyperlipemia aggravation in glomerulonephritis ?
Orosomucoid (also called alpha-1-acid glycoprotein)
## Footnote
orosomucoid loss also contribute to hyperlipidemia by indirectly
causing decreased hepatic production of heparin sulfate, a cofactor needed in normal
lipoprotein lipase function.
54
What is the formula of glomerular filtration rate
Kf(Pression hydrostatique capillaire glomerulaire-Pression hydrostatique bowman)-(Pression oncotique capillaire glomerulaire - pression oncotique bowman)
55
In which condition is phosphate binder contreindicated?
Hypercalcemia
Aluminium hydroxide
Lanthanum carbonate
Ca carbonate & chitosan
Sevelamer carbonate
56
Name 7 markers of proximal tubular injury
NAG
Alpha1 and B2 microglobulin
Cystatin C
RBP
GGT
Inosine
(ALP LDH)
57
Name a marker of distal tubular injury
Interleukin18
58
Name a marker of generalized nephron injury
NGAL
Clusterin
59
Which breed is predisposed to atrophic glomerulopathy?
Rottweiler
60
Name 3 causes of calcium oxalate formation in cats and 3 risk factors in dogs
Cats : primary hyperoxaluria (genetic), Vitamine B6 deficiency, acidic diet
Dogs: Idiopathic hypercalciuria, genetic predisposition, hypercalcemia
61
Which channels are responsible for Ca reabsorption in the kidney
TCP : Claudin 2
TAL : Claudin 16&19
TCD : TRPV5/6, NCX1, PMCA1b (calbindin for intracellular translocation)
62
Is there a better name for feline idiopathic cystitis?
‘bladder pain syndrome’, as used in human medicine
63
What is the area of the brain that responds to threat with activation of various nervous and endocrine systems and can become sensitised by epigenetics, genetics and life experiences?
Central threat response system
Idioapathic cystitis : bladder’s response to persistent activation of the central threat response system
64
What medication can be used for refractory cases of feline idiopathic cystitis?
Analgesia is strongly recommended as this is a painful condition.
Amitriptyline may be considered in refractory cases
and fluoxetine has been shown to decrease urine spraying
Urinary retention has been reported with fluoxetine
65
Name uncommon uroliths in cats
urate, cystine, calcium phosphate (apatite),
compound and mixed
Solidified blood
uroliths of the antiviral nucleoside analogue GS-441524
66
What are the risk factors for struvites formation in cats?
female >male
Indoor lifestyle
Can be associated with infection with urease-producing
bacteria (uncommon in cats)
Breed: Himalayan, Ragdoll, Chartreux, Oriental Shorthair, Siamese
67
What are the risk factors for oxalates formation in cats?
mean age 7 years
Persian, Himalayan, British Shorthair, Ragdoll
Diets low in sodium or potassium
Dietary acidification
68
Which bacteria is more likely to be present in urinary tract in cats with subclinical bacteriuria or as part of a polymicrobial infection?
Enterococcus faecalis
69
To which antibiotics enterococcus species are intrinsically resistant ?
Beta-lactams
Cephalosporins
Trimethoprim sulfonamide
Fluoroquinolones
70
What combination of clinical abnormalities are strongly correlated with severe hyperkaliemia (potassium concentration >8 mmol/L) in cats?
The combination of bradycardia (heart rate <140 beats per minute [bpm]) and hypothermia (<35.5°C)
71
What is the role of terbutaline in hyperkaliemia?
Active NaKATPase
May cause tachycardia
72
Why is oral diazepam not recommended in cats for antispasmodic therapy?
is associated with idiosyncratic hepatic necrosis
73
What is the aetiopathogenesis of post-obstructive diuresis?
- loss of osmotic solutes into the urine
- accumulation of excess diuretic solutes (eg, urea) during the period of obstruction
- reduced collecting duct responsiveness to antidiuretic hormone
- progressive reduction in medullary concentration gradient
74
What can be used in cases of failed urethral catheterization?
intraurethral atracurium besylate (neuromuscular blocking agent that causes skeletal muscle relaxation)
75
If a cat fails to urinate after a urinary catheter is removed, what should be suspected?
recurrent obstruction is possible, but detrusor atony
should be excluded
76
Which MRI sequence was found to provide the clearest visualization of urethral wall layers in dogs?
T2- weighted (T2W) sequence
77
How did post-contrast T1-weighted (post-T1W) MRI improve the evaluation of the bladder wall and tumors?
Post- T1W sequence enhanced bladder wall layer visualization, improving anatomical boundary
conspicuity and aiding in tumor invasion detection.
78
What are the main advantages and limitations of contrast-enhanced CT compared to MRI in assessing the lower urinary tract?
CT allowed rapid imaging with minimal motion artifacts but provided limited soft- tissue detail
79
Name other treatment than ECAi, ARBs and amlodipine for systemic hypertension in cats
- Hydralazine :direct arterial vasodilator, hypertensive
emergencies in cats, 2.5 mg/cat Po or SC, q24h or q12h.
- Nitroprusside, acepromazine and fenoldopam, although there is a lack of data to support recommendations for their use at present
80
which HIF target gene lead to fibrosis in CKD? lead to inflammation?
TGFbeta
EPO
IGF1
Other factors of profibrotic state : hyperphosphataemia,
chronic inflammation, and ageing
Proinflammatory : Inducible nitric oxide synthase & VEGF
81
Proposed mechanims of kidney hypoxia in CKD?
- loss of peritubular capillaries & endothelial injury
- Decreased O2 diffusion --> interstitial fibrosis
- Reduced peritubular capillaries blood flow (rarefaction)
- Oxidative stress
- Increased O2 consumption due to tubular hypertrophy
- reduced red cell mass
- Vascular changes, vascular calcification
82
What is the main gut microbial composition modification in colon in cases of CKD? What is the cause?
↑ aerobic bacteria
↓ anaerobic bacteria (they synthesize SCFA)
↑ genera Klebsiella and Clostridium
↓ genus Ruminococcus
Because of an increase in the luminal pH
83
Define dialysis disequilibrium syndrome
Excessive intracellular fluid shifts into the central nervous system predisposes brain edema and increased intracranial pressure, leading to a variety of neurological signs
The risk for DDS increases with the intensity of the dialysis treatment and primarily determined by animal size, the degree of azotemia, the urea clearance rate, and presence of comorbid factors such as electrolyte abnormalities, acid-base status, bleeding tendency, hypertension, and preexisting
neurologic abnormalities
May be fatal and should be prevented by prescribing a
treatment intensity inversely proportional to the severity of the azotemia and directly proportional to the size of the patient.
Severely azotemic animals and small animal size, especially cats, are at a highest risk for disequilibrium complications.
84
Which products of fermentation in the colon, are considered deleterious to the gut by inducing inflammation and decreasing motility ?
BCFAs
they account for a minor fraction of the total SCFA production and result from the microbial fermentation of
branched-chain amino acids (valine, leucine, isoleucine) in the colon, mainly by the genera Bacteroides and Clostridium
85
Among secondary bile acids, which have positive/protective effect on gut and which can be cytotoxic ?
Protective & antiinfl : UDCA ursodesoxycolic acid
cytotoxic : DCA LCA (deoxycholic acid and lithocholic acid)
86
What are the advantages of SDMA?
higher sensitivity than creatinine for detecting a 30 % decrease of GFR of healthy geriatric cats
concentrations increase prior to creatinine in most cats that develop azotaemic CKD
87
What are the IRIS recommendations for the diagnosis of stage 1 and early stage 2 (non-azotaemic) CKD?
- Persistently increased serum SDMA concentrations >14 µg/dL (top-end of the laboratory RI)
- Increasing serum creatinine/SDMA concentrations over time within the laboratory RI without an identifiable pre-renal cause
- Abnormal renal imaging
- Persistent renal proteinuria
- Loss of urine concentrating ability
88
What could be the role of betaine in non azotemic CKD?
betaine id a trimethylated derivative of the amino acid glycine and methyl donor
betaine supplementation to IRIS stage 1 and 2 CKD cats
could help to increase total body mass and to decrease uraemic toxins (including 3-indoxyl sulfate)
89
List the actions of angiotensin II when acting on AT1-R in the circulating RAAS
constriction of the efferent glomerular arteriole --> increasing intraglomerular pressure --> GFR↑
↑ adrenal gland secretion of aldosterone --> additional renal sodium retention and expansion of circulating volume
Pro-oxidation
Pro-inflammation
Pro-fibrosis
90
What are the mechanisms regulating renin release?
systemic BP
renal perfusion pressure
sodium chloride concentration of the renal tubular fluid in the distal convoluted tubule
β1-adrenergic stimulation
Direct negative feedback of AngII on renin release via AT1R (controversial)
91
List the actions of angiotensin II when acting on AT2-R
vasodilation
natriuresis & diuresis
anti-inflammatory
Anti-fibrosis
anti-oxidation
92
What is the role of Angiotensin 1-7? From which molecules is it created and which enzymes are involved?
Interacts with angiotensin 1–7/Mas receptor (MasR) or the AT2R
--> antihypertensive, anti-inflammatory, and anti-fibrotic
can be generated
from angiotensin I (by neprilysin)
from angiotensin 1-9 (by ACE and neprilysin)
from AngII (by ACE2)
(Angiotensin 1-9 is created from angiotensin I by ACE2)
93
WHere are expressed AT1R and AT2R?
both AT1R and AT2R are expressed by the kidney
94
What stimulates the intrarenal renin-angiotensin system? What is the difference between the tissular and circulating systems?
- stimulated by angiotensin II --> creating a self-enhancing feed-forward loop (through production of angiotensinogen mRNA and protein)
Tissular : angiotensinogen is the major determinant of intrarenal angiotensin II production
Circulating : renin is.
--> angiotensin II concentrations in the kidney << circulating RAAS activity and can be regulated independently from it
95
What is the method of measurement for angiotensin peptides and aldosterone?
liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based protocol (RAS-Fingerprint™)
(recently introduced)
96
What is the rate limiting step of angII production?
By which factors is the concentration of Angiotensinogen regulated?
Historically : renin release
Now : production rate is likely determined by the availability of renin and the concentration of angiotensinogen
Angiotensinogen is regulated by its production and
release by the liver, which occurs relatively slowly
--> limited role of angiotensinogen in AngII production compared to renin availability, as the latter is regulated on a minute-to-minute basis
97
Where is angiotensinogen produced? ECA?
Liver
lung
98
With what kidney lesions is intrarenal angII correlated to?
Glomerulosclerosis
intrarenal ang II immunoreactivity : positively correlated with worsening histopathological scores for glomerulosclerosis and cellular infiltration in cats with CKD
99
What changes occur in intrarenal angiotensinogen, ACE, and angiotensin I/II levels in cats with CKD?
in circulating SRAA in dogs ?
Cats
↑angiotensinogen, angiotensin I
↓ ACE
==> activation of the intrarenal RAS in cats with naturally occurring CKD
Dogs
↑PRA, Ang I, Ang II, aldosterone
100
True or false : activation of the intrarenal RAS can occur independently of circulating RAAS status
True
101
Which dysfunction of the autonomic nervous system can lead to severe overflow urinary incontinence?
dysautonomia
102
What is recommended as the initial treatment for USMI in male dogs?
an alpha agonist (PPA)
103
Why are term reflex dyssynergia or detrusor urethral dyssynergia discouraged? What term should be used instead?
because DUD specifically describes functional urethral obstruction resulting from CNS disease in humans and a
definitive diagnosis of DUD requires urodynamic testing
term instead : idiopathic Functional Outflow Obstruction
104
What are the factors associated with decreased detrusor contractility?
- decreased muscarinic receptor density
- decrease in smooth muscle cell myofilaments
- weak contractions of hyperplastic cells
- decreased propagation of action potentials through the detrusor muscle secondary to intercellular (tight junction) disruption
105
What is hyperthyroidism doing to renal biomarkers?
Increase CysC
Decrease FGF23
Increase L-FABP (Liver-type fatty acid-binding protein)
F2-Isoprostanes
VEGF
106
What is the initiation of renal secondary hyperparathyroidism?
hyperphosphatemia and diminished renal mass →
reduced renal production of calcitriol →
development of renal secondary hyperparathyroidism
107
Name 2 independent predictors of FGF23 concentration
Calcium (ionized and total)
Phosphore in stage 2-4
108
What is FGF23 independently associated with?
FGF-23 concentration is independently associated with CKD disease progression.
FGF-23 concentrations are higher in cats with progressive disease than in those with stable disease.
109
Feeding a moderately phosphorus-restricted diet can
............................ FGF-23 concentrations.
decrease
110
What could assist in identifying cats with stage 1 CKD
and better identify and stage cats with CKD with muscle
atrophy?
serial measurement of SDMA concentrations
111
By which cells is FGF23 produced? What size? What forms?
osteoblasts and osteocytes
251 amino acid peptide
an active (intact) form or inactive (C-terminal) form
112
Name the factors influencing FGF23 secretion at different
stages of CKD
- Relative iron deficiency
- Anaemia
- Chronic systemic inflammation (IL-1β and IL-6)
- Hypomagnesaemia
- α-klotho deficiency
post-translational processing is physiologically very important in regulating FGF23
113
What is calciprotein?
calcium and phosphate ions can exist in blood in a colloidal form as calciprotein particles
114
What are the effects of phosphorylation and O-glycosylation on FGF23 protein?
Phosphroylation --> marks it out for proteolysis
O-glycosylation --> protects it from proteolysis
115
Name the extrarenal impacts of FGF23 (humans and models)
- left ventricular hypertrophy
- endothelial dysfunction
- vascular calcification and atherosclerosis
- impairment of immune response
In kidney : tubular stress
116
What is burosumab?
monoclonal antibody that binds circulating FGF23 and prevents it from activating receptors
has been trialled in human patients with genetic disorders or tumours (i.e. X- linked hypophosphataemia [XLH]) leading to excess FGF23 secretion
improve nephrocalcinosis
117
FGF23 is an independent predictor of what?
the development of hypertension
aldosterone may enhance FGF23 secretion
118
In which conditions SDMA concentration can be influenced?
DM
Neoplasia (lymphoma)
Thyroid status
119
which eggs can be found in urine?
- capillaria plica
- dirofilariosis
- dictophyma renale
- stephanurus dentalus
120
Name the formulas of
- GFR
- urine clearance
- plasma clearance
- fractional excretion
- GFR : Kf(PhG - PhB) - (PoG - PoB)
- urine clearance : U(mL/min)x[X]u/[X]p
- plasma clearance C=D/AUC
- fractional excretion 100x solute urine x creatinine plasma / (solute plasma x creatinine urine)
121
Name a biomarker of distal tubular injury
IL18
