Renal Ettinger Flashcards
What is Carbamylated Hemoglobin?
(dissociated BUN that reacts with Hb) concentrations higher in dogs w/ renal disease (vs control) and higher w/ CRF vs ARF
What is GFR directly related to?
Functional renal mass
How is BUN made?
synthesis in liver via Ornithine cycle from catabolism of ammonia (from catabolism of endogenous and exogenous proteins)
Name 3 things that affect BUN.
Passive reabsorbed in tubules (greater extent when slow tubular flow (like with dehydration)
GI bleeding (increase nitrogenous compounds)
Drugs (increased catabolism with steroids, azathioprine), (decreased protein synthesis with tetracyclines)
How is creatinine made?
nonenzymatic breakdown product of phosphocreatinine in muscle, daily amount based on muscle mass
Which breed has higher creatinine?
Greyhounds (more muscle)
Describe the relationship btwn changes in BUN and creat.
Relationship of BUN or Crea concentration to GFR is a rectangular hyperbola; large changes in the early courses of renal disease cause only small increase in BUN/Crea vs small changes in GFR in advanced renal disease result in large changes
What does it imply when BUN and creatinine are increased?
Incr BUN & Crea implies that at least 75% of the nephrons are not functioning
What is cystatin C?
(small polypeptide protease inhibitor, freely filtered by glomeruli)
○ Filtered cystatin C - almost completely reabsorbed by proximal tubular cells and catabolized to AA
○ Produced at a constant rate = May serve as a marker of GFR
What can affect cystatin C?
inflammation or neoplasia
When does urinary concentrating ability lost?
When 66% of nephrons are lost
When does azotemia occur?
When 75% of nephrons are lost
When is it best to use the creatinine clearance?
When the patient is PU/PD but their BUN and creatinine are normal
Name agents that can be administered for a single injection to estimate GFR?
inulin, iohexol or Creatinine
When is dynamic renal scintigraphic methods with radioisotopes helpful?
When individual renal function information is needed
What is microalbuminuria an indication of ?
§ Humans: Early indication of vascular endothelial damage
Dogs/cats: 15-20% normal animals have an increase, unknown if results in progressive renal dz in vet med
What is the Bladder Tumor Antigen Test and what are problems with it?
latex agglutination dipstick test that detects glycoprotein antigen complex associated with bladder tumors in people
alse + occur w/ marked proteinuria, glucosuria, pyuria, hematuria
§ Good to differentiate neoplasia from normal dogs, but not good in animals with other LUT dz
What is the role of the water deprivation test?
tubular function test, used to decipher between DI vs psychogenic PD
When is the maximal stimulation of ADH release?
With 5% loss of BW!
What is the benefit of the gradual water deprivation test?
use to eliminate diagnostic confusion created by medullary wash out
○ Dogs with pyschogenic PD: Endogenous release of ADH, increased permeability of inner meduallary collecting ducts to urea and restoration of normal gradient of medulalary hypertonicity
Which electrolyte is good for pre renal vs renal disease?
Fractional excretion of Na: Pre-renal animals should have avid Na conservation!
What is the renal threshold for glucose in dogs and cats?
Renal threshold glucose – Cat 300, Dog 180 mg/dL
What ketones are noted on the dipstick?
○ Nitroprusside reagent (dipsticks) - Acetone < acetoacetate (NOT with beta-hydroxy)
What is the renal worm?
Dioctophyma renale
Which breed can get renal telangectasia?
Welsh Corgi
What is a caudate cells?
transitional cells w/ tapered edges that originate from the renal pelvis
Which casts are normal in low number?
Occasional hyaline and granular casts
What is a hyaline cast?
pure proteins precipitates (Tamm-Horsfall mucoprotein and albumin), dissolve in dilute or alkaline urine; Small numbers can be seen with fever/exercise; seen in diseases assoc. with proteinuria
What is a coarsely or fine granular cast?
degeneration of cells in other casts or precipitation of filtered plasma proteins; * suggestive of ischemic or nephrotoxic renal tubular injury
What is a fatty cast?
Fatty cast – type of coarsely gran cast – contain lipid granules; seen with nephrotic syndrome or DM
What is a cellular cast?
Cellular cast – white cell (pyelonephritis ), red cell cast (rare, fragile), renal epithelial cell cast (acute tubular necrosis or pyelonephritis)
What is a waxy cast?
○ Waxy cast – represent the final degeneration of granular casts (stable), suggest intrarenal stasis; brittle casts & often have cracks or sharply broken ends
Which crystals are seen in acidic urine?
Uric acid, CaOxalate, Cystine
Which crystals are seen in alkaline urine?
Struvite, CaPhosphate, Ca Carbonate, amorphous phosphate & ammonium biurate
What is the renal length on rads?
Renal size – L2 ratio (on VD) is 2.5 to 3.5 in dogs & 2.4-3.0 Cats
What is the “halo” sign in ultrasound of the kidney?
○ Ethylene glycol toxicity – renal hyperechogenicity “halo” sign correlated w/ onset of anuria
What is the significance of the medullary rim sign?
○ Medullary rim sign(echogenic line in outer zone of medular and paralleling corticomedullary junction) – ethylene glycol toxicity, acute tub necrosis, hyperCa, FIP, chronic tubulointerstitial nephritis; seen in normal cats (mineralized tubular basement membrane)
What is important for the number of glomeruli in the renal bx samples?
96% of samples contained > 6 glomeruli
What is the main complication with renal bx?
Hemorrhage (Severe hemorrhage in 10% dogs and 17% cats)
Can also see linear infarcts, and hydronephrosis
What is the definition of AKI?
· AKI → > 0.3 mg/dl increase in creatinine or >25% increase from baseline creat
What does RIFLE stand for and how it is used?
RIFLE (Risk; Injury; Failure; Loss; End-stage Renal Disease) classification based on:
1. Changes in creatinine and GFR (take into account preexisting renal disease) 2. Changes in urine output
àNot evaluated in vet med due to unknown baseline creat or urine output
What are the sections that can be effected to cause renal AKI?
o **Can affect any section: Tubular, Glomerular, vascular, interstitium, vessels
Tubular most common: Toxic or ischemic
What is the breakdown of bacterial infections that results in pylonephritis?
□ 74% = Gram negative → E. coli (37-45% of all UTIs)
□ 25-30% = Gram positive
□ Predisposing factors – endocarditis, discospondilitis and pyometra
What is the host of Leptospira interrogans Canicola?
Dogs
What is the host of Leptospira interrogans Icterohaemorrhagiae?
rats
What is the host of Leptospira interrogans Grippotyphosa?
vole, raccoon, skunk, opossum
What is the host of Leptospira interrogans Pomona?
cow, pig, skunk, opossum
What is the host of Leptospira interrogans Hardjo?
Cow
What is the host of Leptospira interrogans Bratislava?
rat, pig, horse?
What is the most common cause of AKI?
toxins!! § Dog → Ethylene glycol, NSAID, cholecalciferol, aminoglycosides
§ Cat → Ethylene glycol, Cholecalciferol, Lillies
What accounts for 70-75% of AKI?
Pre-renal + renal causes
What are the phases of AKI?
- Clinically silent (initiation)
- Extension Phase
- Maintenance Phase
- Recovery Phase
What happens during Clinically silent (initiation) of AKI?
- Clinically silent (initiation): Ischemic or nephrotoxins = if ID problem here and intervene improved outcome
What happens during Extension Phase of AKI?
- Extension Phase: Continued hypoxia and inflammation propagates damage
o Cortical structures (proximal tubule, Loop of Henle) are predisposed to toxic/ischemic since they receive 90% of renal blood flow and are highly metabolic
§ Decreased ATP = Impairing Na-K pump → Cellular swelling and death
§ Loss of brush boarder of apical and basal cells = Likely related to increased cytosolic Ca
o Intervention MAY NOT be helpful here :(
What happens during Maintenance Phase AKI?
- Maintenance Phase: 1-3 weeks, urine output may be affected
o Irreversible damage has occurred
o Urine resembles ultrafiltrate
o Increased/decreased urine output
What happens during recovery phase of AKI
- Recovery Phase: Increased urine output, +/- decreased urine sodium = May take weeks to months
o Extreme Na losses = Volume depletion (delay or stop renal recovery) = Need to replace Na and water
§ Na Loss →Decreased proximal and ascending loop henle sodium/potassium pump function due to reduced # of Na transporters and aquaporin-2 proteins
What are the 2 main mechanisms of decreased GFR in AKI?
• Main 2 mechanisms of decreased GFR → Hypoxia (intrarenal vasoconstriction) and tubular dysfunction
• Hypoxia: Poor medullar blood flow most to cortex, Intrarenal vasoconstriction (may be caused by altered endothelin/ decreased NO production - due to sublethal epithelial injury)
• Tubular Dysfunction:
o Obstruction by cellular debris (detached epithelial cells)
o Back-leakage of the tubules
Name other factors that leads to AKI.
ATP delpetion Increased intracellular Ca Reperfusion injury Oxidant injury Intracellular acidosis Phospholipase activation Protease activation Actin Cytoskeleton injury from energy depletion Disruption of cell-substrate attachment
When does mannitol help in AKI?
• ATP depletion (more AMP = energy deficit) causing Na/ K ATPase pump to stop functioning
o Causes Na/K concentration gradient imbalance
o Cell swelling à tubule obstruction, vascular congestion
§ Mannitol helps here (hemodynamic alterations, osmotic diuresis, scavenging hydrozyl ions)
What is the rationale behind using Ca channel blockers in AKI?
• Increased intracellular [Ca] causes mitochondrial swelling, uncoupling of oxidative phosphorlaylation and cell death
o Rational behind use of Ca channel blockers (diltiazem/verapamil) in ARF = Improve renal hemodynamics and stabilize cell membranes
What is essential for renal recovery?
Dependent upon sub-epithelial basement membrane, recovery of sublethally injured cells with recovery of realign (of polarity), migrate and regeneration (of renal cells), removal of necrotic cells/casts.
When there is renal damage what happens with fractional excretion of Na?
Renal damage = Na fractional excretion higher
Why are there false negative ethylene glycol test kits (esp in cats)?
Esp cats dt lower limit of detection of kit (50 mg/dl)
What infectious dz should be considered for AKI?
Lepto, Lyme, RMSF (oliguria RF, vasculitis, polyarthritis, meningitis, mild thrombocytopenia), Ehrlichia canis (glomerular damage)
In s study of dogs with with Hospital-acquire Acute Renal Failure (HARF), what are the most common causes?
□ Nephrotoxicant exposure 72% □ >7yrs old 69% □ chronic heart disease 41% □ preexisting renal disease 35% □ Neoplasia 31% □ Fever 28%
Anesthesia 14%
Volume depletion is VERY important
How are aminoglycosides nephrotoxins?
not metabolized, low molecular weight, water soluble–> urine excretions
□ Ionize and bind anionic sites on proximal tubule–> pinocytosis–> high intracellular concentration (10 X HIGHER)–> tubular epithelial cell damage
□ Increase risk of ARF with aminoglycosides: prolonged use >5days; elevated trough levels, preexisting renal dz, dehydration, hypo-kalemic, calcemia, magnesemia, acidosis
□ Reduce toxicity with less frequent dosing, toxicity more closely associated with [trough]
□ Monitor for proteinuria, casts daily (alert you prior to onset of azotemia)
What are occur if expired tetercyclines are given?
AKI
fanconi-like syndrome–> metabolites in mitochondria in proximal tubules
What happens in AKI from NSAIDs?
o NSAID: COX inhibition leading to Afferent arteriole constriction (reduced prostaglandins), healthy euvolemic minimal risk
§ Higher risk when trying to maintain renal blood flow and counteracting the effects of systemic vasoconstriction
§ COX 1 vs 2; both can be constitutive in kidney so no difference in risk of non-selective COX and COX-2 specific
□ Prognosis favorable if recognized early
What is a CVP?
Central venous Pressure
o CVP: 10 overhydrated
□ Challenge: 2-4 cm H20 rise euvolemic, >4 overhydrated, no change hypovolemic
What is normal urine output?
normal 1-2 ml/kg/hr
What is consider polyruia, oliguria, and anuria?
o Polyuria >2 ml/kg/hr
o Oliguria <1.0 ml/kg/hr
o Anuria-virtually no urine production
What medications can be used if concern about urine output?
Mannitol Furosemide Dopamine Fenoldopam (selective dopaminergic 1 agonist, renal artery dilation, inhibits N/K ATPase, angiotensin II, and ADH, dogs to have renoprotective effects in acute ischemic injury) Diltiazem
What are the average insensible losses per day?
Insensible: average 22 ml/kg/day, ie panting
What is the treatment for ethylene glycol?
4 methylpyrazole or ethanol
What are the typical ECG changes with hyperkalemia?
Bradycardia, tall tented T-waves, prolonged QRS, wide/absent P waves
What electrolyte abnormality is worse with ethylene glycol?
Hypocalcemia
What are the main uremic complications?
Hyperkalemia Metabolic Acidosis Calcium/ Mg Phosphorus Hypertension Hematological changes (anemia and thrombocytopathy) GI disorders Nutritional support Infections
In cats with AKI what did each increase unit of potassium show?
each unit increase in serum potassium, in mEq/L, there was a 57% decrease in chance of survival
What is associated with a negative prognosis in AKI?
Decreased urine output
NOT severity of azotemia
Is everity of azotemia associated with outcome in AKI?
NO!! Only Decreased urine output
What is the overall survival with infectious causes of AKI?
58-100%
What is the overall survival with toxic causes of AKI?
20-40%
Name several dz in which renal transplant is NOT recommended?
-Amyloidosis
-Pyelonephritis
+-Calcium oxalate obstructive disease
+- IBD (variable absorption of Cyclosporin)
-FeLV/ FIV+
-Cardiac disease
-HyperT4
-DM
-Neoplasia
What are the mainstays in immunosupresisve therapy in cats undergoing renal transplant?
Cyclosporine
Prednisolone
What are several long term complications of renal transplant in cats?
Rejection (acute and chronic)
Ureteral Obstruction (stricture)
Neuro signs (dialysis disequilibrium syndrome - Dt rapid osmotic shifts, hypertension?)
Hypertension (unknown reason, vasactive products in kidney?)
Infection (about 25%, bacterial , viral, fungal, protozoal)
Diabetes mellitus
Neoplasia
How long does a transplanted kidney work?
About 3 years in cats
What is the most common neoplasia that feline renal transplant cats get?
LSA
Neoplasia seen in about 10% cats
What syndrome has been reported in cats undergoing renal transplant and in kids?
• Hemolytic uremic like syndrome (3 cats: hemolysis, thrombocytopenia, thrombotic microangiopathy)
○ In kids this is caused by E. coli O157: H7 endotoxin
What is overall outcome of feline renal transplant?
Periop 25% mortality
Survival to discharge: 6 month survival 60-70% (time of highest mortality), 3 year survival-40-50%
What are the problems in canine renal transplant?
combination of immunosuppressive regimens
THROMBOEMBOLIC DZ!!!
What is CKD?
permanent reduction in # functioning nephrons
1. Kidney damage that has existed for at least 3 months (with or without ¯ GFR) 2. ¯ GFR by more than 50% of normal persisting for at least 3 months o Since renal compensatory hypertrophy and improvement in renal function may continue for up to 3 months following acute loss of nephrons
What is acute vs chronic kidney disease?
· “Acute” = potentially reversible (by resolution, adaptive compensatory enhancements, or combo)
· “Chronic” = irreversible and usually progressive loss of kidney function and/or structure, compensatory enhancements have already reached a nadir (about 3 months or longer)
o Clinical Signs: weight loss, polyuria, polydipsia, ¯ appetite, ¯ BCS, ¯ hair quality (3 months or longer)
o Documentation of kidney function (over 3 months): Progressive ↑ Creatinine
o Persistent proteinuria (> 3 months)
o Anemia is characteristic but NOT diagnostic
o Small kidneys (US): Loss of nephrons → replacement with fibrosis tissue
o Rare: Skeletal changes with renal osteodystrophy (esp within jaw)
Why i staging CKD important?
Helpful for establishing a prognosis and managing the patient
During what stage is PU/PD seen in CKD?
Stage 2-4
During what stage is proteinuria seen in CKD?
Stage 1-4
During what stage is UTIs seen in CKD?
Stages 1-4
During what stage is neproliths, ureteroliths seen in CKD?
Stages 1-4
What CS are seen in Stage 3-4 CKD?
Decreased appetite Dehydration Constipation Hyperphosphatemia Metabolic Acidosis Hypokalemia Anemia
During what stage is uremia seen in CKD?
Stage 4
What do you need to stage a dog/cat with CKD?
Need to obtain 2 or more serum creatinine readings when pet is FASTED and well hydrated over several weeks in order to use this staging
What is the threshold for Stage 2 CKD?
hreshold of stage 2 CKD → 1.4 mg/dL (dogs); 1.6 mg/dL (cats)
o Values btwn 1.4 mg/dL and upper RR should be able to concentrate their urine (1.030 (dog) and 1.035 (cat)) if normal kidney function
What are the substaging of IRIS CKD?
Magnitude of proteinuria and systemic blood pressure
When are animals considered to be proteinuric with CKD?
§ Proteinuric (P) when UPC > 0.5 (dogs) and 0.4 (cats)
When are animals considered to be nonproteinuric with CKD?
What are the stages of hypertension in CKD staging?
Stage 0
What is the prevalence of CKD?
1-3% cats and 0.5-1.5% dogs
What breeds of cats get CKD?
Maine Coon, Abyssinian, Siamese, Russian Blue, and Burmese cats
What happens with the incidence of CKD in dogs?
It increases with increasing age
Name two causes of CKD in cats that are related to virsuses?
FIV
SQ feline herpesvirus 1, calicivirus, and panleukopenia virus vaccines in culture have induced antifeline renal tissue antibodies → Could repeated vaccination play a role
What does renal bx reveal in dogs with CKD?
§ Biopsy Study (37 dogs)
o 58%: Chronic tubulointerstitial nephritis
o 28%: Glomerulonephropathy
o 6%: Amyloidosis
What does renal bx reveal in cats with CKD?
§ Biopsy Study (cats) o 70%: Tubulointerstitial nephritis o 15%: Glomerulonephropathy o 11%: Lymphoma o 2%: Amyloidosis
Name 3 dog breeds that get familial amyloidosis.
Shar-Pei, English Foxhound, Beagle
Name 5 breeds that get familial renal dysplasia.
Shih Tzu, Lhasa Apso, Golden Retriever, Norwegian Elkhound, Chow Chow, Standard Poodle, Soft Coated Wheaten Terrier, Alaskan Malamute, Miniature Schnauzer, Dutch Kooiker
Name a breed that gets familial fanconi syndrome.
Basenjis
Name 5 breeds that get familial glomerulopathy.
English Cocker Spaniel, Doberman Pinscher, Bull Terrier, Soft Coated Wheaten Terrier, Samoyed, Dalmatian, Bullmastiff, Newfoundland, Rottweiler, Pembroke Welsh Corgi, Beagle, Bernese Mountain Dog, Brittany Spaniel
Which breed gets Hereditary multifocal renal cystadenocarcinoma?
GSD
Name 3 breeds that get Polycystic kidney disease
Cairn Terrier, Bull Terrier, West Highland White Terrier
Which breed gets Reflux nephropathy with segmental hypoplasia?
Boxer
Which breed get renal Telangiectasia?
Pembroke Welsh Corgi
What cats get amyloidosis?
Abbysinian, Siamese, and Oriental Shorthair
Which cats get polycystic renal disease?
Persian and Himalayans
What are the prognostic factors for CKD in cats?
- Phosphorus and IRIS stage
- Magnitude of proteinuria
NOT hypertension in cats
What are the prognostic factors for CKD in dogs?
- Cats live longer with CKD than dogs
- Proteinuria: Risk of death associated with CKD increased by 60% for each unit of UPC above 1
- Baseline systolic BP
- BCS (fatter did better, similar to humans)
What are the 3 mechanisms of uremia?
These affect every organ system
- Disturbed excretion of electrolytes and water (more load on remaining nephrons)
- Decrease excretion of organic solutes (uremic toxins)
- Impaired renal hormone synthesis (*calcitriol, *EPO, prostaglandins, kinins, renin)
Are urea and creatinine considered uremic toxins?
No! But act as surrogate for systemic concentration other uremic toxins
What is known about calcitriol in dogs and humans with CKD?
calcitriol in dogs and humans with CKD may slow progression of kidney disease and prolong survival
What are several factors that can lead to impaired urine concentrationsin CKD?
increased solute load per surviving nephron (solute dieresis), disruption of the renal medullary architecture & countercurrent multiplier system, impaired response to ADH
What is the MOA of anemia in CKD?
short RBC life, nutritional abnormalities, EPO inhibitors in uremic plasma, blood loss, myelofibrosis, EPO synthesis (renal peritubular capillary endothelial cells and interstitial fibroblasts likely sources) (a relative vs absolute deficiency in EPO levels)
What is the MOA of thrombocytopathic in CKD?
abnormal PLT function (diminished PLT thromboxane A2 production, abnormal iCa mobilization, increased intracell cAMP) biochem changes in blood itself
What was found in a • Prospective longitudinal study
○ Determine if cats in nonazotemic stage of CKD have increased PTH (as a compensatory mechanism to maintain phosphorus in RR)?
- Plasma PTH was significantly increased in cats that developed azotemia compared to cats that remained nonazotemic
- PTH increased prior to changes in plasma Ca or Phos
- Moderate positive association btwn plasma calcitriol and PTH was noted
- Plasma PTH was associated with: age, urea, creat, total Ca
- Suggests that renal secondary hyperPTH can develop prior to azotemia in cats (even in the absence of hyperP or hypoCa)
What electrolyte is directly linked to increased mortality in humans, cats and dogs with CKD
phosphorus
What is the self perpetuating cycle with potassium in CKD?
excessive urinary K loss and whole body K depletion that is likely to further decrease renal function
Marked hypoK – PU bc decreased renal responsiveness to ADH
What is the MOA of proteinuria resulting in progressive CKD?
mesangial toxicity, tubular overload & hyperplasia, toxicity from specific proteins, MCP-1 (proinflammatory molecules, monocyte chemoattractant protein-1); overload of lysosomal degradative mechanisms
What are risk factors for ACUTE decline in renal function?
Volume depletion urinary obstruction Nephrotoxic drugs ABX NSAIDs ACEi and Angiotensin II receptor blockers IV contrast
What are risk factors for LONG TERM decline in renal function?
Active renal dz Hypertension Inappropriate diet/nutrition Neprholithiasis/ureterolithasis Proteinuria UTI
What is the link with CKD and FIV?
cats with CKD were significantly more likely to have positive test results for serum antibodies against FIV gp40 than cats without CKD
What is recommended for phos in CKD diets?
Phos restriction for Dogs & Cats w/ stage 2,3,4 of CKD
What is true about dogs that were fed a renal diet?
risk of developing a uremic crisis was reduced by 75% in dogs fed renal diet vs adult maintenance diet
What are the current recommendations for feeding renal diets to cats/dogs?
§ Cats – CKD stages 2-4; Dogs 3-4; **Stage 2 CKD in dogs not evaluated critically
§ Any Stage II patient with P exceeding 4.5 mg/dL may benefit from dietary therapy
What is a potential side effect with AlOH on RBCs?
Microcytosis
What is the number one SE of hormone replacement for anemia in CKD?
1 Neutralizing anti-EPO Ab hypertension, seizures reported
What is a potential complication with using lanthanum based phos binders (sevelamer)?
§ Can have effects on clotting dt vit K def
What treatment has been shown to have an equivocal benefit in cats but great benefit in cats?
Calcitriol therapy
When is calcitriol therapy required in dogs? Why is it important?
confirmed the value of calcitriol in reducing mortality in dogs with CKD stages 3 & 4
§ Improvement in appetite, more BAR, more active, longer lifespans
Name factors that result in normal micturition in urinary tract that defend against microbes..
Adequate urine volume
Frequent voiding
Complete voiding
Urinary continence
Name factors that result in anatomic structures in urinary tract that defend against microbes.
Urethral high pressure zones Surface characteristics or urothelium Ureteral peristalis Prostatic sections (antibacterial fraction and Ig) Length of urethra Ureterovesical flap valves Ureteral peristalsis Glomerular mesangial cells: Possible phagocytic and antigen presenting functions Extensive renal blood supply and flow
Name factors that result in antimicrobial properties of urine in urinary tract that defend against microbes.
Extreme high and low pH Hyperosmolality High urea concentration Organic Acids Low MW carbohydrates Tamm-Horsfall mucoproteins Host Defense peptides (defensins)
Name factors that result in systemic immunocompetence factors in urinary tract that defend against microbes.
Cell mediate immunity
Humor-mediated immunity
Name factors that result in mucosal defense barriers in urinary tract that defend against microbes.
Antibody production
Surface layer of glycoaminoglycans
Intrinsic mucosal antimicrobial properties
Exfoliation of urothelial cells
Bacterial interference by commensal microbes of distal urogential tract
Mucosal innate immunity: Toll-like receptors
What are microbial factors to enhance virulence in E. coli?
§ O-antigen (outer polysaccharide, marker of virulence in humans)
§ K-antigen (capsule, may inhibit phagocytosis and complete mediated bactericidal activity; increase resistance to inflammation favors persistence of bacteria in tissue)
§ Adhesive Fimbriae (pili; proteinaceous filamtous organelles that protrubed form bacterim; may enhance capacity to adhere to urothelium (p-fimbriae)
§ Hemolysin (Increases amount of free iron available to bacteria; tissue damage)
§ Aerobactin (iron binding protein)
§ R-plasmids (promote antibacterial resistance)
§ Resisatnce to bactericidal activity
§ Short generation time in urine
Which bacteria make urease and what is the role?
Proteus/ Staph/ Klebsiella (some)
Hydrolosis of urea to ammonia (causing epithelial damage)
Promote Struvite (magnesium ammonia phosphatase) formation
What are the most common micrboes isolated from UTIs?
○ 33-50% E. coli
○ 25-33%: G+ cocci: Staph/ Strep/ Enterococcus
□ Cats: Staph felis unique pathogen
○ Others: Proteus, klebsiella, Pasteurella, Pseudomonas, Corynebacterium
What uropathogen is unique to cats?
Staph felis
What is the breakdown of isolates in urine cultures (numbers)?
Single pathogen 75%, 2 pathogens 20%, 3+ 5%
What cultures are used for urine?
Blood agar-support growth
MacConkey-colony morphology
What is the biggest risk factor for UTI when a U cath is in place?
The duration that the u cath is in place
What antibiotics should be used as “first-line” in UTIs?
Amoxi, cephalexin, TMS (consensus says TMS and Amoxi only)
What is defines as a complicated UTI?
intact dogs, most cats, animals with identified predisposing factor (DM, Cushing’s dz, hypert4, CKD), upper urinary infection
What is a relapse in a UTI and what are potential causes?
Recurrence of UTI with SAME bacteria
◊ use of an inappropriate antimicrobial agent
◊ administration of an appropriate antimicrobial agent at an inappropriate dosage, frequency, or duration
complicating factors such as a permanent breach in urinary tract defenses, particularly those that allow a nidus of infection to form and prevent complete penetration of drugs
What is a reinfection of a UTI?
Recurrence of UTI with DIFFERENT bacteria within 6 months of prior UTI
What is defined as recurrent UTI?
3 or more UTIs in 12 months
What is a superinfection?
Infection with new bacteria while on ABX for previous UTI
What is a refractory UTI?
Persistence of + UC result during treatment
Name two antiseptics for UTIs?
Methenamine (turns to formalin in acidic environment)
Tris-EDTA
What is polypoid Cystitis?
○ Polypoid Cystitis: epithelial proliferation from chronic inflammation
□ Differences from neoplasia (cannot truly differentiate without histopath): Polyp-more in apex, more commonly botryoid, not grossly vascular
□ Proteus most commonly associated with polyps
□ Lesions may resolve with therapy, but may be faster if cystectomy performed
What is a microbe commonly associated with polypoid cystitis?
Proteus
What are 4 common complications of UTIs.
Polypoid cystitis
Emphysematous Cystitis
Struvite stones
Pyelonephritis
What microbes are associated with emphysematous cysitits and why?
□ Most commonly E. coli, others-proteus, clostridium, Aerobacter
Most commonly associated with DMdue to high [ ] of fermentable substrate
What microbes make struvite stones?
□ Urease producing bacteria-Proteus, Staph, others-Corynebacterium, Klebsiella, Ureaplasma
What protects the kidneys from pyelonephritis?
vesicoureteral flap valves
Long ureters
Relative hypoxic environment of the medulla
What is the most common fungal cause of UTIs?
Candida
What disease are commonly associated with fungal UTIs?
DM
LUT neoplasia
Urinary tract stoma (cystotomy tube)
What is the treatment for fungal UTIs?
Fluconazole 6-8wks, +/- intravesicular clotrimazole or amphotericin B
What are the 3 layers of filtration in the glomerulus?
Fenestrated Endothelium
Glomerular basement membrane
Visceral Epithelial Cells (podocytes) - Slit diapgragm (cell junctions btwn podocytes)
What is the passage of the filtrate?
Endothelium fenestrae
Permeates GBM (size -selective barrier)
Through filtration slits of epithelial cells
Urinary space
What are the major determinates of filtrate?
Molecular size
Charge (since there is a negative charge barrier - negatively charged glycoprotein)
Which breeds are over represented for glomerular dz?
Labs and Goldens (could be related to popularity of breeds)
Which breeds has familial amylodosis?
Beagle, English Foxhound, Shar-Pei
Which breed has mesangiocapillary glomerulonephritis?
Bernese Mountain Dogs
Which breeds have a herditary nephritis?
Bull terriers, English Cocker Spaniels, Dalmation, Samoyed (rare)
Which breed has glomerulosclerosis an dcystic glomerular atrophy?
Doberman, Welsh Corgi
Which breed gets glomerular vasculopathy and necrosis?
Greyhound
Which breed gets glomerulosclerosis?
Newfoundland
Which breed gets atrophic glomerulopathy?
Rotties
Which breed gets proliferative and sclerosis glomerulonephritis?
Soft Coated Wheaten Terrier
What is the hallmark of glomerular disease?
PROTEINURIA
UPC > 0.5
Which glomerular dz has the highest UPCs?
amyloid and membranous nephropathy
Which glomerular dz has the lowest UPCs?
Tubulointerstital dz
What is glomerular imbalance?
Renal azotemia with intact concentrating ability - seen in glomerular dz
How many animals with develop hypoproteinemia with glomerular dz?
60% with glomerulonephritis and 70% with amyloidosis
What is nephrotic syndrome?
Hypoalbuminemia, proteinuria, hypercholesterolemia, and edema
PATHOGNMONIC for glomerular dz
Only 10% with glomerulonephritis
Imcomplete (w/o edema) common 49% dogs
Which disease are more likely to have nephrotic syndrome?
Amyloidosis, membranous nephropathy, hereditary nephritis, minimal change disease = HEAVY proteinuria with these conditions
What is nephritic syndrome?
CS that develop secondary to acute renal inflammation (mainly in human med)
Hematuria, RBC casts, subnephrotic proteinuria, edema, hypertension, azotemia, oliguria
CONSIDER: Acute lyme nephritis in dogs
What are the 3 samples needed for renal bx?
- Formalin
- For EM in gutaraldehyde
- For Ig samples: Frozen or in Michel’s solution (IgM, IgG, IgA, C3)
Which stain is good to asses the GBM?
Periodic Acid-Schiff (PAS)
Which stain is good for tubules, glomeruli, adn Bowman’s capsule?
Methenamine Silver
Which stain is good for mesangium and Ig?
Trichrome
Which stain is good for amyloid?
Congo red
What is crescent glomerulonephritis?
2 or more layers of cells in Bowman’s capsule = SEVERE injury; 50% glomeruli have cresecents in them (uncommon in vet med)
What happens when there is glomerular injury?
IC deposition that leads to glomerular damage fromcell mediate immune mechanisms = INFLAMMATION
Leads to activation of complement, coagulation, resident cells
Influx of neutrophils, monocytes, platelets, release of proteolytic enzymes, cytokines and growth factors and pro-inflammatory mediators
What is the most common glomerular disease in dogs?
membranoproliferative glomerulonephritis (20-60% cases), but also most likely to be called when incomplete elevation has occurred (maybe over-represented in dogs)
Which breed has familial membranoproliferative glomerulonephritis?
Bernese Mountain Dog
Membranoproliferative glomerulonephritis is fatal in association with which infectious dz?
Borrelia burgdorferi
What is Type I MPGN (membranoproliferative glomerulonephritis)?
Mesangiocapillary glomerulonephritis
Induced by infectious dz!
Immune complex deposition on subendothelial side of GBM
Which breed gets Type I MPGN (membranoproliferative glomerulonephritis) with congenital C3 deficiency?
Brittany Spaniels
What is Type II MPGN (membranoproliferative glomerulonephritis)?
Dense Deposit Disease
Intramembranous dense deposites (NOT Immune complex) - unknown origin
NOT associated with infectious dz
Rare in dogs
Activation of alternative pathway of complement (humans - hypocomplementemic GN)
Why are antiplatelets needed in MPGN?
Since activation of platelets involved in pathogensis
What is the prognosis of MPGN?
Unknown
What is the most common glomerular dz in cats (second most common in dogs)?
Membranous Nephropathy
- Young cats
-More common in males
MASSIVE proteinuria
What is the terminal completment complex?
C5b-9 membrane attack complex = Part of the membranous nephropathy
What is the classic histopath signs of membranous nephropathy?
GBM thick = Deposition of immune complexes in subepithelial space (beading along GBM - spikes) - There are 4 stages
What is the treatment for membranous nephropathy?
- Tx underlying dz
- IMMUNOSUPPRESSION
- Humans: Steroids, alkylating agent (cyclophosamide, chlorambucil), cyclosporine
- Manage proteinuria!
What is the prognosis in dogs and cats with membranous nephropathy?
Progression may be slow (live normal lives)
• CATS:
○ Long term survival: Only IgG, C3, or both
○ Shorter term survival: IgM or IgA; Stage III/IV
• DOGS:
○ Spontaneous remission
What is Proliferative
Glomerulonephritis?
endocapillary and/or mesangial cell proliferation **>4cells per mesangial region
= Immune complex dz
What is known about Proliferative
Glomerulonephritis in humans?
Immune complex dz
• Humans: Anti-GBM antibodies (not in vet med)
After strep infections
What is the tx for Proliferative
Glomerulonephritis?
NONE
• Eliminate source of immune complexes
What is the prognosis for Proliferative
Glomerulonephritis?
Unknown in dogs
Poor prognosis if renal failure or cresecents in glomeruli on histopath
What is IgA Nephropathy?
Part of proliferative GN
IgA on IFA (trapped in mesangium) = PROLIFERATION
Can have co-deposits of IgG. IgM, and C3
What is diseases is IgA nephropathy seen in dogs?
- Male, young to middle age dogs
- Dogs with Enteric dz (excessive formation of IgA)
- Dogs with liver dz (decreased clearance of IgA)
What is the tx of IgA nephropathy in dogs?
Tx underlying systemic inflammation
• Control hypertension
• Fish oil (omega 3) - No change in proteinuria
What is the prognosis of IgA nephropathy in dogs?
Poor prognosis: Co-deposits of IgG, IgM, both; uncontrolled hypertension
What causes amyloidosis?
• Reactive amyloidosis (NINs) - 35-53%
• Serum amyloid A (SAS)
○ Made by hepatocytes dt Il-1, IL-6, TNF
• Dogs = Glomeruli
EXCEPTION = Shar Peis MEDULLA
Light-extracellular expansion of acellular fibril eosinophilic proteinatious material (beta-pleated sheets),
***CongoRed + (red and birefringent under polarizedlight)
What is Shar Pei fever?
Shar Pei Fever (Swollen Hock Syndrome)
• Females
• MEDULLA (only 64% in glomeruli)
• 23-43% proteinuria (LESS)
• CS: Due to deposition in other organs (LIVER)
• Familial Mediterranean Fever in Humans (defect in pyrin - decreased mediators of inflammation)
• IL-6
What is unique about amyloidosis in cats?
Abyssinians • MEDULLA (some in glomeruli) • Uncommon marked proteinuria • Medullar fibrosis and papillary necrosis = CRF Siamese • LIVER = Rupture and hemorrhage
What is the tx of amyloidosis?
- Cholchicine: Impaired release of AA from hepatocytes (microtubular binding)
- Needed during predeposition phase (fever/swollen hocks)
- DMSO = Controversial
- Anti-inflammatory
What is the prognosis of amyloidosis?
POOR!!
• 58% died or euthanized at diagnosis
• Only 8.5% survival of 1 year or longer
What stain is best for amyloidosis?
***CongoRed + (red and birefringent under polarized light)
What is Hereditary Nephritis?
***EM (required!)-multilaminar splitting and fragmentation of GBM
Pathogenesis-defect of Type IV collagen (primary collagen of GBM)
• Autosomal Recessive: English Cocker Spaniel
• Autosomal Dominant: Dalmatian and Bull Terrier
• X-Linked: Samoyeds
Bull Terrier: Concurrent hearing and ocular problems (anterior lenticonus)
What is the treatment for Hereditary Nephritis?
NONE!
• Early renal diet and ACEi
What is the prognosis for hereditary nephritis?
• Progressive of dz PREDICTABLE in Samoyeds and Cockers = renal failure by 2 yrs
Variable in Bull terrier and Dalmatian
What is minimal change disease?
Pathogenesis-loss of anionic charge (increased lymphokines from dysfunctional T cells = increased GBM permeability) and foot process thickening/effacement (is it primary loss of podocyte function that causes this??)
* SELECTIVE proteinuria = ALBUMIN * ONLY 1 dog in literature
Light-unremarkable
IFA-unremarkable
***EM-podocyte foot process effacement
What is the treatment for minimal change disease?
***Usually Steroid responsive (humans) - 80-90%
What is the prognosis for minimal change disease?
Unknown in dogs
• Humans - Can have relapses
What is Glomerulosclerosis?
Histo-glomerulosclerosis,
**Big thing look for is it focal and segmental or global/generalized
Focal and Segmental Glomerulosclerosis likely different disease
Pathogenesis-glomerulosclerosis from any renal injury
• End stage lesion
• Increased with age
• Humans - Diabetes (seen in some dogs with DM)
Why is control of proteinuria essential?
Proteinuria induced tubular damage and progressive nephron loss (obstruction of tubules with protein casts, inflammation = Tubulointerstitial lesions from glomerular dz
NOT established in dogs BUT it exists
What are the 3 main areas of treatment for glomerular disease?
- Tx underlying cause (need renal bx)
- Reduce proteinuria
- Manage uremia and other complications of renal failure
What is the standard of care for reducing proteinuria?
ACEi +/- losaratan
Manage hypertension
Inhibit platelets
Dietary protein restriction (enhanced omega 3, Na and Phos restriction)
What is the MOA of ACEi?
Decreased efferent glomerular resistance which leads to decreased glomerular hydraulic pressure and decreased proteinuria
What are common SE with ACEi?
Azotemia (unlikely), HYPERKALEMIA
What can be added onto an ACEi?
Angiotensin receptor blockers (LOSARTAN) - works better with ACEi than as monotherapy
What is the day to day variation with UPC?
It is present
Esp when UPC >4 - Need pooled UPC
What are some complications of glomerular dz?
Edema formation Hypertension Thromboembolic dz Hyperlipidemia Increased risk fo infection Altered pharmacokinetics Malnutrition Muscle Wasting Endocrine changes
What % of dogs with glomerular dz will have hypertension?
80%, MOA increased plasma vol from Na retention
What % of dogs with glomerular dz will have thromboembolic dz?
5% dogs with GN
14% with amyloid
PTE MOST common
Is loss of AT levels correlated with thrombus?
NO!
low albumin associated with PLT aggregation, hypercholerstolemia causes PLT hypersensitivity, increased fibrinogen concentrations (often seen with nephrotic syndrome)
Why is warfarin NOT a good choice for thromboembolic disease with glomerular dz?
Highly protein bound
What is the MOA of hyperlipidemia in glomerular dz?
HypoAlb stims hepatic protein synthesis which leads to incr cholerstol; *Orosomucoid (normally maintains glomerular permselectivity) is lost – results in decreased hepatic heparin sulfate synthesis (that is needed for normal lipoprotein lipase function)
What is Orosomucoid?
plays an important role in the maintenance of glomerular permselectivity, is lost in the urine of patients with glomerular disease. Urinary losses of orosomucoid exacerbate proteinuria but also contribute to hyperlipidemia by indirectly causing decreased hepatic production of heparin sulfate, a cofactor needed in normal lipoprotein lipase function
What is the prognosis in dogs with nephrotic syndrome?
Median survival was significantly shorter for NS (12.5 days) versus NNGD dogs (104.5 days). When subgrouped based on serum creatinine (
What is the main stimulus for prostatic function?
• DHT (dihydrotestosterone) main stimulus for function
Intraprostatic conversion of Testosterone to DHT via 5α reductase & activation androgen binding receptor (ABR)
What portion of seminal fluid is prostatic in origin?
About 90%, the third fraction is exclusively from the prostate
Is PSA good in dogs?
PSA activity not good for dogs bc enzyme could not be measured in the serum or seminal plasma of normal dogs or dogs with prostatic disease
What is Canine Prostate Specific Esterase?
• CPSE (canine prostate specific esterase) – not an accurate test for prostatic disease in dogs
Levels were higher in BPH than normal patients, but no difference between BPH and other dz
Which breed is more severely affects by BPH?
Scotties
What is the main mediator of prostatic growth?
DHT
What are the treatment goals with BPH?
Goal = reduce prostate size and decrease chances of complications
What are several options to tx BPH?
Castration – 50% reduction w/in 3 weeks; 75% in 3 months
Finasteride - 50-70% decrease in 2-4 wks (involution)
Osaterone acetate (can decrease coritsol - Addison’s)
Gestagens (megesterol acetate)
GnRH agonists desloreline and nafarelin
Estrogens (DES) - NOT recommended
Anti-estrogens (tamozifen)
What the MOA of finasteride?
synthetic steroid that inhibits prostatic type II 5α-reductase that blocks conversion of testosterone to active form DHT
§ Decrease semen volume w/out change of quality or libido
§ Most asymptomatic w/in 4 weeks
§ 50-70% decrease in volume by 2-4 weeks
® Involution by apoptosis
What is the MOA of osaterone?
synthetic testosterone analogue w/ anti-androgen and progesterone effect. It blocks absorption of testosterone into the prostate and competitively inhibits prostatic DHT receptors
□ *Can decreased serum cortisol concentrations & could interfere w/ ACTH response & induce adrenocortical insufficiency
What is a form on non-selective chemical castration?
GnRH agonists desloreline and nafarelin – down regulate receptors &suppress testosterone & estradiol concentrations
What are the most common bacteria for prostatitis?
E coli (70%) > Staph, Klebsiella, Proteus, Mycoplasma canis, Pseudomonas aeruginosa, Enterobacter, Strep, Pasterullae, Hemophilus
What are tx options for bacterial prostatitis?
o consider a complicated UTI
o castration/chem. Or sx after acute phase*
Surgical castration is not recommended in the immediate acute phase
What ABX have good prostatic pentration?
need non-ionized, highly lipid soluble drug that are not protein bound to enter prostate; basic Abx (pKa > 7, like TMS) easily diffuse from blood to prostatic fluid (normal prostatic fluid acidic – ionize drugs & trap in prostate)
Examples:
Fluroquinolones, TMS, chloramphenicol
What is a potential peoblem with chronic prostatits or abscesses?
*blood prostate barrier not disrupted in chronic infections and abscesses
NEED: Fluroquinolones, TMS, chloramphenicol
What is the #1 CC from chronic bacterial prostatitis patients?
1 presenting complaint – recurrent UTI w/ same pathogen
What is the #1 prostatic neoplasia?
Adenocarcinoma
Do canine prostatic neoplasia express androgen receptors?
• Most canine prostatic neoplasia do NOT express Androgen receptors & are hormonally independent;
Do Not respond to androgen deprivation
Which breeds have a predisposition with prostatic neoplasia?
Mixed breed, Shetland sheepdog, Scottie, Airedale, Dobermans
What is the prognosis with prostatic neoplasia in dogs?
• At dx visceral mets up to 80% - sublumbar & iliac lnn, lung, bone (lumbar and pelvis)
o Pyuria found in 62% of dogs
MST short; Piroxicam (COX-1 specific) beneficial in carcinoma, RT did not improve survival significantly, palliative RT for bone lesions
In what conditions is prostatomegaly described in cats?
RARE
only in association with neoplastic lesions, bacterial prostatitis, paraprostatic cysts, and a prostatic abscess
What is the onset of renal failure in renal dysplasia?
3 months – 3 years (peak onset 1 year)
What is the onset of renal failure with Polycystic kidney dz/amyloidosis?
3 – 7 years
What is renal dysplasia?
young dogs,
○ Disorganized development of renal tissue caused by abnormal differentiation
○ Biopsy asynchronous differentiation of nephrons-immature glomeruli and tubules within radial bands adjacent to normal formed glomeruli
○ Main breeds-Shih tzu, Lhasa Apso
Pathogenesis-unknown
What are the main breeds that get renal dysplasia?
Shih tzu, Lhasa Apso
What is the pathogenesis of primary glomerulopathies?
often young, proteinuric
○ Basic pathogenesis: Abnormal formation of Type IV Basement membrane collagen
§ a 3-4-5 network very important in GBM structure
Similar to Alport syndrome in humans
Which gene is noted in the X-linked nephropathy in Samoyeds
COL4A5 gene (collagen IV alpha 5 sub-unit)
Which gene is noted in English Cocker (autosomal recessive) and Bull terrier/Dalmatian (autosomal dominant)?
COL4A4
Also identified in English Springer Spaniels (different mutation in COL4A4)
Which breed develops autosomal dominant polycystic kidney dz?
Bull terrier Australia,
>= 3 cysts in both kidneys on AUS
Liver cysts NOT seen
Which breed develops autosomal recessive polycystic kidney dz?
Westie, Carin Terrier
Affected by 2 months of age, Cysts in kidney AND liver!
What are the 3 main types of familial glomerulonephritis in dogs?
○ Soft-coated Wheaton terrier:
§ Combined PLE/PLN
§ Female> male, Mean age of onset 6y
§ Likely start as food hypersensitivity and increased intestinal permeabilityà lead to glomerular nephritis
§ ~12% thromboembolism
§ Light microscopy:
□ membranous to membranoproliferative glomerulonephritis, progressing to sclerosis
§ IMF
□ IgA, IgM and complement deposits
○ Bernese Mountain Dogs
§ 2-7 years of age
§ Suspected autosomal recessive inheritance
§ Resembles Human Type I membranoproliferative glomerulonephritis
□ Electron dense deposits on subendothelium
§ Mainly IgM and complement
§ Most dogs had high B burgdrferi titers
○ Brittany Spaniels
§ C3 deficiency
What is Basenji Fanconi?
§ Pu/PD/glucosuria/mild proteinuria and aminoaciduria
§ Generalized impairment of reabsorptive function in proximal tubule
□ May develop hyperchloremic acidosis and/or hypokalemia
§ Aggressive medical management
□ Supplement with bicarb, AA, vitamins and minerals
Which breed gets multifocal renal cystadenocarcinoma, and nodular dermatofibrosis?
GSD § Characterized by □ Bilateral renal tumors □ Skin/subcutis nodules □ Uterine leiomyomas
Which breed gets a familial dz that results in hematuria leading to anemia?
○ Pembroke Welsh Corgi: telangiectasia
What is the kidney’s role in acid/base?
H secretion, HCO3 reabsorption, HCO3 formation (Urinary buffer system)
What is the urinary buffer system?
Phosphate, Ammonia/NH4 (in Prox tubule – glutamine synth to (2) NH4 -> 2 HCO3 absorbed)
Why does cystinuria occur?
• Inherited Proximal Tub defect: reabsorption of particular nonessential aa fails
§ Cystine insoluble in urine -> crystal formation at acidic pH
Which breeds get cystinuria?
70 breeds; increased risk breeds – Aus cattle/shep, Basenji, Bulldog, Bassett, Dachshund, ChiChi, Staff Terrier, Mastiff, Newfoundland, Scottie, Welsh corgi
What gene is affect in Newfies that get cystinuria?
Slc3a1 gene (similar in labs) - carriers have normal AA in urine
What gene is affect in Min Pin that get cystinuria?
slc7A9 - Different type in which the carriers get the stones
What are the pH and X-ray properties of cystinuria?
Acidic pH
Radiolucent (need US)
What is the tx of cystinuria?
Protein restricted diet
Alkalization therapy (Hill u/d; +/- K citrate)
Increase water consumption
Drugs
o D-penicillamine;
o **2-MPG (mercaptopropionylglycine)
Forms a disulfide bond with cysteine, making the cystine more soluble
Which -uria has been reported in dogs with cystinuria?
Carnitinuria
What is a potential consequence of chronic Carnitinuria?
o Chronic increased excretion may result in cardiomyopathy (DCM)
Name 3 breeds with Hyperuricosuria?
Excess uric acid in the urine - • Caused by abnormal purine metabolism or excretion
Dalmatians, English Bulldogs, and Black Russian Terriers
In the dalmatian what are the mechanisms for urate production?
- Abnormal urate metabolism (abnormal uric acid transport across the hepatic membrane which limits uric acid metabolism)
- Abnormal excretion (less proximal tubular resorption AND active distal tubular secretion of urates as a result of a membrane transport defect)
What is the inheritance of Hyperuricosuria in dalmatians?
□ Autosomal recessive, carried by all Dalmatians
® Clinical manifestations in 25% of males (males are more frequently clinical)
What type of disease can result in Hyperuricosuria?
Hepatic disease = Reduced conversion of uric acid to allantoin and ammonia to urea
What is the medical management for Urate stones?
§ Diet: purine-restricted
§ Drugs: XO inhibitor (allopurinol)
□ May cause formation of xanthine or hypoxanthine stones
® Only other cause has been reported in a family of CKCS and wirehaired dachsunds
§ Urine alkalinization
□ NaHCO3
□ Reduced renal tubular production of ammonia
® Diminishing amount of ammonium ions that can complex with urate
What is a potential complication with use of allopurinol?
xanthine oxidase inhibitor = □ May cause formation of xanthine or hypoxanthine stones
What other breeds have xathine stones been noted in?
family of CKCS and wirehaired dachsunds
What breeds get primary renal glycosuria?
Scottie, Basenjis, Norwegian Elkhound, mixed breeds
What is the definition of Fanconi Syndrome?
Proximal tubular defect -> glucosuria, aminoaciduria, proteinuria, phosphaturia, hypophosphatemia
Can be inherited or acquired
What is the most common breed to get Fanconi syndrome?
Basenji
Others: Lab Ret, Border terrier w/ renal dysplasia, Yorkie, Whippet
Which breed gets Fanconi Syndrome with renal dysplasia?
Border terrier
What is acquired Fanconi syndrome?
○ Acquired – Proximal tubular injury
Drugs –Gentamycin/Amoxicillin/cephalospins/cisplatin/others
Primary hypoparathyroidism
Food additives – 4-pentenoate & maleate
Copper hepatopathy
Chicken jerky treats ( MOA unknown, FDA 2007, AVMA 2010 – warning statements)
What is the treatment for Fanconi syndrome?
Supportive! Aggressive monitoring and management of secondary lyte abnormalities and metabolic acidosis
GONTO Protocol
Consider Kcitrate
What are renal tubular acidosis?
tubular disorders that lead to Hyperchloremic metabolic acidosis
What is Type I RTA?
• Type 1 (Classic) – Distal tubular disorder
○ Impaired urine acidification due to inability to secrete H in the distal tubule ( H ATPase pump intercalated cell)
○ Metabolic acidosis more severe than type II;
§ Hyperchloremic metabolic acidosis w/ urine pH > 6
What is Type II RTA?
• Type II – Proximal tubular disorder (note – Can occur as part of Fanconi syndrome)
○ Proximal defect in basolateral membrane Na-HCO3 co-transporter causing leakage of HCO3 into urine
○ Metabolic acidosis is self limiting due to distal tubules ability to excrete acid
§ Oral HCO3 -> amt presented to distal tubule increase, overwhelms distal buffering system -> marked bicarbonaturia
○ Dx – based on
o FE HCO3 > 15%
o hyperchloremic M acidosis
o Acidic urine pH
o Identification of concurrent proximal defects
What is treatment for distal RTA?
Type I - ○ Tx – Alkali source (K and Na citrate)
What is Type IV RTA?
ype IV – Distal tubular disorder (Addisons or aldosterone antagonism)
○ Acidosis due to loss of aldosterone on H secretion and Na resorption
○ *Not characterized in Vet Med; consider with Hyperchloremic metabolic acidosis and hypokalemia
What is the difference in hypokalemia and urine pH with proximal and distal RTA?
Hyperchloremic metabolic acidosis
Proximal RTA: Mild hypokalemia; Acidic urine (pH 6)
in which dz has distal RTA been described in cats?
Pyelonephritis
Hepatic lipidosis
What is congenital neprhogenic DI?
Congenital absence of ADH receptors
What is the tx for congenital neprhogenic DI?
§ Chlorthiazide diurectic
§ Low Na/low protein diet
o Reduces the amount of solute that needs to be excreted by the kidneys
Which biomarker is increased indicative or proximal tubular injury?
N-acetyl-B-D-glucosamidase (NAG)
What are risk factors for LUT dz in cats?
overweight, dry diet, multi-cat household, indoor only
What are the 2 forms of feline idiopathic cystitis?
Ulcerative and non-ulcerative (more common, >90% cases)
What are the bladder abnormalities that occur with feline idiopathic cystitis?
□ Increased permeability
□ Decreased urinary GAG and specific GAG (CGP-51)
□ Afferent neurons increased excitability to mechanical and chemical stimuli
® May be very important as SNS release of Norepi may be a mechanism of stimuli for Nitrous oxide release increasing permeability more.
What are some of the systemic abnormalities that are seen in cats with feline idiopathic cystitis?
® Stress exacerbated
® Increased tyrosine hydroxylase immunoreactivity in the locus coeruleus (TH is rate limiting step of catecholamine formation)
® Increased serum NE and enhanced stress-induced release of NE from the bladder
This may cause downregulation of a2-receptors
Are there any infectious diseases that may be related to feline idiopathic cystitis?
Virus associated (Calici) but NOT supporting evidence
Which sex gets the obstructive form of feline idiopathic cystitis and what are they obstructed with?
MALES Ureteral plugs (matrix more similar to serum proteins (albumin and breakdown products)
What 2 initial treatment factors were noted in recurrence rats of Obstructive Feline Idiopathic Cystitis?
□ Relapse rate were lower at 24h and 30d if prazosin was used over phenoxybenzamine
Relapse rate at 24h was lower when 3.5 F was used over 5F
NOTE: No relation btwn length of catheterization and relapse of obstruction
1/4 cats reobstructed at 30 days
What % of cats with FIC will resolve without tx?
~85% of cats with FIC resolve signs with no treatment in 2-3 days
What is the #1 diagnostics in cats with FLUTD and suspected FIC?
Urine Culture
What is the rate of recurrence of FIC?
Recurrence about 50% of cases within 1 year, 39% in another study of cats on dry food
What is recommended during an acute episode of FIC?
® Ab’s rarely indicated
® Anelgesics-buprenorphine, +- tramadol +-NSAID
® +-Drugs to alter bladder/ urethra tone: Acepromazine, prazosin, phenoxybenzamine, bethanechol
What is recommended for chronic FIC?
® Study: 46 cats with MEMO reduced occurrences, severity, fearfulness, resp signs over 10 months
® +- anti-psychotic drugs (fluoxetine, clomipramine, amitriptyline)
® *Diet change: consider change to canned diet to increase water intake
◊ Acidifying diets have not shown any benefit
*Pheromones: Feliway- trend to reduce frequency of occurrence
What are the result of Multimodal Environmental Modification in cats with FIC?
46 cats with MEMO reduced occurrences, severity, fearfulness, resp signs over 10 months
What was the result of use of Feliway in FIC?
*Pheromones: Feliway- trend to reduce frequency of occurrence
What was the result of use of acidifying urine in FIC?
No benefit
What was the result of use of GAG replacer in FIC?
No improvement
What was the result of use of intravesical lidocaine and bicarbonate (for 3 days) in FIC?
No benefit
What does crystaluria mean in cats?
Crystaluria does not mean a cat is at risk of urolithiasis, it is not a disease and needs NO treatment.
Which stones are radiolucent and not seen on rads?
Ammonia urate and cysteine
What is the size limit for Voiding urohydropropulsion in cats?
Stones usually cannot exceed 2 to 3mm for the procedure to be successful
What is the % of uroliths in cats?
stones usually cannot exceed 2 to 3mm for the procedure to be successful
What is an oxalate degrading bacteria?
Oxalobacter formgenes
Why is potassium citrate recommended in oxalate management?
Hypocitraturia may be a risk factor for calcium oxalate stone formation in humans because citrate can become chelated to calcium, forming a more soluble salt than CaOx
What is the most common signalment and breed with urate urolithiasis in cats?
Neutered cats
Siamese (over represented)
What % of cats with FLUTD signs have UTI?
About 4%
What are risk factors for UTIs in cats?
Older (>10 yrs), DM, Hyper T4, CKD, female, Persians, decreasing weight
What is the MOA of prazosin?
Alpha-adrenergic antagonist: Inhibitsα1-adrenergic receptors
What is the MOA of phenoxybenzamine?
Alpha-adrenergic antagonist: Inhibitsα-adrenoceptors
What is the MOA of bethanechol?
Synthetic parasympathomimetic
Stimulates primarily muscarinic receptors
What is potassium citrate (Urocit-K) used for?
Alkalizing uine: Citrate oxidized to HCO3−and urine pH can increase
What is the MOA of allopurinol?
Xanthine oxidase inhibitor: Inhibits the enzyme xanthine oxidase, which is responsible for the conversion of oxypurines to uric acid
What is the most common cause of LUTDs in cats?
FIC
What is the innervation of internal urethral sphincter?
Sympathetic , Alpha, L1-L4 – hypogastric nerve
What is the innervation of external urethral sphincter?
Skeletal muscle, Somatic, S1-S3 pudendal nerve
What is the innervation of detrusor muscle?
Parasympathetic – S1-S3 pelvic nerve (contraction);
o Sympathetic, Beta – L1-L4 hypogastric nerve (facilitates relaxation; Storage phase)
What is a urethral pressure profile used for?
Confirm Dx of urethral incompetence
What is the Cystometrography used for?
Dx detrusor instability
What is a prerequistite for urolith formation?
urine needs to be supersaturated
What is growth of crystal in a pure solution called?
hemogenous nucleation
What is Growth of crystal on the surface of another called?
epitaxial growth
What are the 3 causes of urolith formation?
§ Promoting nucleation
§ Promoting crystal growth/aggregation
§ Retention of urolith in the urinary tract
What is RSS?
§ Relative supersaturation (RSS)
□ Takes into account the [ ] of various analytes and pH
□ Ratio of these products to the Ksp yields the RSS
If RSS1 = oversaturated
Which imaging modalilty over -estimate urolith size in dogs?
Ultrasound - Overestimated!
What are methods of urolith removal?
- Cystotomy
- Laparoscopic Assisted Cystotomy
- Voiding Urohydropropulsion
- Retrograde Urohydropulsion (for urethral obstruction, flush into bladder)
- Catheter-Assisted Retrieval
- Stone Baskets
- Electrohydraulic Lithotripsy (fragment stones)
- Laser Lithotripsy (more effective, holmiun laser)
- Extracorporeal Shock Wave Lithotripsy (fragment using shock waves then voiding urohydropropulsion)
What breeds are at an increased risk of Ca oxalate stones?
Min Sch, Lhassa, Yorkie, Bichon, Pomeranian, Shih Tzu, Cairn, Maltese, Min poodle, Chihuahua
What breeds are at a decreased risk of Ca oxalate stones?
Goldens, GSD, Cocker spaniels
What type of diet increase risk of Ca oxalate in dogs?
Low Phosphorus
What endocrine dz is associated with Ca oxalate stones in dogs?
HAC - glucocorticoids decreases tubular reabsorption of Ca -> hyperCalciuria
What is the tx for Ca oxalate stones?
Mechanical removal
Why is prevention of Ca oxalate stones important?
recurrence rates up to 50% w/in 3 years of initial diagnosis (recommend q 6 month radiographs)
What is recommended for preventation of Ca oxalate stones in dogs?
Diet (increased water intake) Potassium citrate (conflicting reports) Thiazide diuretics in humans
What is the pathogensis of struvite stones in dogs?
o Urease producing bacteria – Staph spp most common urease producing; sterile struvite Cocker Spaniels
§ Other (less common) – Pseudomonas, Klebsiella, Corynebactium urealyticum ( can manifest as plaques of struvite crystals and necrotic debris), Ureaplasma
□ Urea à Ammonia + bicarbonate (which increases pH)
Which breed of dogs gets sterile struvite stones?
Cocker spaniels
Name the urease producing bacteria?
STAPH
Pseudomonas, Klebsiella, Corynebactium urealyticum Ureaplasma
What happens with Corynebactium urealyticum that can form struvites?
can manifest as plaques of struvite crystals and necrotic debris
What are the tx options for struvites in dogs?
Medical dissolution (diet + Abx) and mechanical
Diet: s/d or SO
Prevention diet: SO or c/d
What is a competitive & noncompetitive enzyme inhibitor of urease?
Acetohydroxamic acid (AHA, Lithostat) - NOT recommened in dogs due to common SE (hemolytic anemia, anorexia, v, hyperbili)
What is the average time for dissolution of struvite stones in dogs?
3 months
What is the metabolic pathway of purine metabolism?
Purine -> Hypoxanthine (Xanthine oxidase) -> Xanthine (xanthine oxidase)-> Uric acid (Uricase) -> Allantoin
What is the mutation in dalmatian for the urate stones?
SLC2A9
Same in English Bulldogs
What is the tx for purine stones (urates) in dogs?
Medical and sx
Diet: Low purines
Aalakine urine (u/d)
Allopurinol (xanthine oxidase inhibitor)
What is a risk of using allopurinaol in dogs?
Formation of xanthine stones
What other AA may be lost with cystine (if defect)?
COLA - cystine, ornithine, lysine, arginine
What is the msot common breed with cysteine stones?
Newfoundland SLC3A1
Same mutation in Labs
What is the tx for cysteine stones in dogs?
Dilute urine
Diet: Protein restricted (u/d), alkalinzation (avoid methionine)
D-penicillamine or N-2 mercaptopropyionyl-glycine (2 MPG) – “tiopronin”
What is the tendency of stone formation of cysteines with age?
Tendency to develop stones will decrease with age
What are 2 predisposing factors for Ca phosphate uroliths in dogs?
Excessive alkalinazation (>7.5) Primary hyperPTH
What is the recommended tx for Ca phosphate uroliths in dogs?
Sx removal
Spontaneous resolution is reported
Which breeds are at risk for silica uroliths?
high prevalence in Kenyan dogs
GSD, OES at increased risk when pure silica
Which drugs can result in uroliths in dogs?
Sulfonamides and tetracyclines
What is the conservative management of ureteroliths?
§ IV fluids+Diuretics+a-adrenergic antagonists+amitryptyline
What is reflex dyssynergia?
failure of coordination a urethral relaxation with detrusor contraction
What is a prolfierative process that can lead to urinary tract obstruction in dogs?
proliferative (“granulomatous”) urethritis
What is polypoid cystitis?
inflammation, epithelial proliferation & development of a polypoid mass or masses w/out histopathological evidence of neoplasia
o More commonly occur in the cranioventral portion of the bladder (vs TCC à trigone)
o Likely secondary to chronic UTI
o More common in females
What is the classic location of polypoid cystitis in dogs?
cranioventral portion of the bladder
What chemo drug can induce a sterile hemorrhagic cystitis and why?
Cyclophosphamide induced cystitis
urinary excretion of acrolein (metabolite of cyclophosphamide) - Use Lasix + mesna!
What organism can result in parasitic cystitis?
Capillaria plica
What are cause of urinary incontinence?
Urethral incompetence Ectopic ureters Neurologic dz Urge incontinence (secondary to infections/uroliths) Idiopathic detrusor instability Paradoxical (overflow) incontinence Ureterocele Pelvic Bladder Ureterovaginal or urethrorectal fistula Patent urachus
What is urethral incompetance or USMI?
Urethral sphincter mechanism incompetence) – Females
§ Frequently occurs in combination with ectopic ureters
Changes with spay time
What is the tx for USMI?
PPA effective for 85-90% of females; Estrogen (increased urethral closure pressure by increasing the density and responsiveness of alpha-adrenergic receptors in urethral smooth muscle) effective in ~ 50-65% of female dogs (DES)
Other tx:
Bulking agents; hydraulic urethral occluder; sx
What is the treatment for urinary incontinence in male dogs?
What breeds get ectopic ureters?
Siberian husky, Lab, Golden, Newfie, Eng Bulldog, WHWT, Fox terrier, Skye terrier, Min Toy Poodle
FEMALES>males*
What does Dr. Vaden think is concurrent with ectopic ureters in some dogs?
USMI
What is known about ectopic ureters in male dogs?
§ Male dogs were similar to females in breed, presenting complaint, age of onset, and bilateral nature
§ After sx, urinary continence was not in 82% dogs
What is a ureterocele?
cystic dilation of terminal portion of the ureter that often protrudes into the bladder lumen
Can cause incontinence, functional urinary retention
What is a urethral prolapse and which breed gets it?
Acquired, males, Eng Bulldog, excessive sexual excitement/stranguria or urolithiasis
What is a Vesicourachal Diverticula and what are they predisposed to?
outpouching of the bladder wall near the bladder apex, seen on scope, recurrent UTI (34%)
What is a Persistent Urachus?
remnant urachal canal btw apex of bladder and the umbilicus
What is a persistent urachus?
urachal canal remains patent, from apex of bladder to umbilicus
dribbling urine through umbilicus
Needs sx!
What is a pelvic bladder?
Blunt-shaped trigone, with the trigone located in an intrapelvic location associated with a shortened urethra
What are the stages of IRIS AKI?
Based on creatinine:
Grade I: 0.3 increase creat within 48 hrs, or oliguira or anuria)
Grade II: 1.7-2.5 mg/dl
Grade III: 2.6-5.0 mg/dl
Grade IV: 5.1-10 mg/dl
Grade V: >10 mg/dl
Subgrade: 1. NO (non-oliguria) or O (oligoanuria)
2. Requireing renal replacement tx
What diseases have been associated with microalbuminuria?
Cushing's Neoplasia Infecitous LUT dz HWD Poor health
