small animal med- diagnostic eval. of the urinary tract

what are biomarkers of glomerular filtration rate?

1. urea (BUN)

2. creatinine

3. symmetric dimethylarginine (SDMA)

4. urine specific gravity (USG)

what is a biomarkers of tubular injury?

cystatin B

what is a biomarker of phosphorus overload?

fibroblast growth factor 23 (FGF23)

what is azotemia?

elevated BUN, creatinine, and/or SDMA in blood

how is urea made in the body?

1. digestion of proteins makes ammonia

2. ammonia synthesized to urea by the liver

where is urea excreted in the body?

-urea excreted by the kidneys and intestines

-urea freely filtered through glomerulus and reabsorbed by passive diffusion in proximal tubule at rate dependent on flow rate

what are 4 causes of elevated BUN?

1. increased protein catabolism

2. high protein intake

3. pre-renal azotemia

4. kidney dysfunction (reduced GFR)

what are causes of increased protein catabolism leading to elevated BUN?

fever, infection, starvation, hyperthyroidism

what are sources of high protein intake leading to elevated BUN?

high dietary protein intake or severe (large volume) blood loss into GI tract

how does pre-renal azotemia result in an elevated BUN?

decreased urine flow rate and increased passive diffusion out of the urine into systemic circulation

causes: dehydration, hypovolemia, hypotension

is BUN a reliable marker of GFR?

no, it is a poor marker of GFR (and kidney disease); non-specific

have to evaluate BUN in conjunction with other markers of kidney function (creatinine, SDMA, USG)

is creatinine a sensitive marker of GFR?

no

how much of a reduction in functional kidney mass is needed to see an elevation of creatinine on a serum chemistry panel in cats with kidney disease?

60-75%

what non-renal factors can affect creatinine levels?

1. muscle mass

2. age and breed

3. may vary with timing of blood collection to meal

how does change in muscle mass affect serum creatinine levels?

muscle atrophy falsely decreases creatinine

how does age/breed of animals affect serum creatinine levels?

1. birman cat and greyhound higher creatinine in health

2. small breed dogs have lower creatinine than large breed dogs

3. higher in young pets (creatinine declines with age due to age-related sarcopenia)

what is SDMA? how much is excreted by the kidneys?

methylated form of arginine that is released into circulation during protein catabolism

90% excreted by kidneys

is SDMA a specific to kidney disease?

it is a marker of GFR but not specific to kidney disease

have to rule out pre-renal and post-renal azotemia

how does SDMA differ from creatinine when identifying animals with renal dysfunction?

can be elevated before creatinine becomes elevated above RI in pets with early renal dysfunction

SDMA is less influenced by muscle mass than creatinine

how are SDMA results interpreted?

used in combination with clinical suspicion and other diagnostic testing to identify kidney disease

what is the normal range for SDMA?

reference range: 0-14ug/dL

gray zone: 14-18ug/dL (may have kidney dz, recheck in 2-3 months)

>18ug/dL = pet may have kidney dz, investigate further

what is urine specific gravity? what is it used for?

measures solute concentration in urine

used to assess tubular function (ability of tubules to dilate or concentrate urine)

why is USG essential for interpretation of BUN/creatinine/SDMA?

to decipher between pre-renal (dehydration) and renal azotemia

what is the USG of pre-renal and renal azotemia?

pre-renal USG: >1.030 in dogs, >1.035 in cats (hypersthenuric)

renal USG: 1.008-1.018 (isosthenuric)

what is cystatin B?

small intracellular protein that is released into urine when tubular epithelial cells are damaged or die

--> marker of tubular injury

what does elevated cystatin B indicate?

if elevated, signifies active/acute kidney injury

what is FGF-23?

phosphatonin hormone secreted by bone in response to phosphorus overload

promotes phosphorus excretion in urine

what does elevated FGF-23 indicate?

biomarker of phosphorus overload

increases before overt hyperphosphatemia

used to decide whether cats with early-stage CKD and normal phosphorus requires dietary phosphorus restriction

what are the 3 categories of proteinuria?

pre-renal

renal

post-renal

what are the 2 main diagnostic tests used to screen for and diagnose proteinuria?

1. colorimetric biochemical reagent urine dipstick

2. urine protein-to-creatinine (UPC) ratio

what are indications for running a colorimetric biochemical reagent urine dipstick test?

first-line screening test, has good sensitivity, but poor specificity

highest sensitivity for albuminuria

what is a normal urine protein-to-creatinine (UPC) ratio?

normal <0.2

what are indications to run a UPC ratio?

used when you suspect renal proteinuria

preferably performed on sample w/o gross hematuria and pyuria

what are limitations of a UPC ratio test?

large day-to-day variation: with treatment, focus on monitoring trends rather than a single timepoint

test UPC on pooled urine sample (2-3 samples) to get a reliable estimate of proteinuria (for dogs)

how is renal proteinuria diagnosed?

diagnosed after exclusion of pre- and post-renal causes of proteinuria

what are causes of pre-renal proteinuria?

IV hemolysis causing hemoglobinuria, or muscle damage causing myoglobinuria

what are causes of post-renal proteinuria?

hemorrhage or inflammation anywhere between renal pelvis and distal urethra/genitalia

does tubular proteinuria or glomerular proteinuria cause hypoalbuminemia?

glomerular proteinuria

what is the importance of a urinalysis?

vital to interpretation of azotemia

what is included in a urinalysis?

includes USG, dipstick, and micropscopic sediment evaluation

-assesses tubular function (USG)

-glomerular and tubular function (proteinuria, urine casts)

-urine pH

-detection of bacteriuria

what are markers of tubular injury seen on a UA?

1. urine casts (sloughing of tubular epithelium)

2. glucosuria in absence of hyperglycemia

what are hyaline urine casts? are these clinically significant?

result of solidification of tamm-horsfall mucoprotein secreted by renal tubular cells

least important, can be normal in small amounts in healthy patients

what do granular urine casts suggests?

suggests stasis in tubules or associated tubulointerstitial disease

what are epithelial urine casts? what do these suggest?

serious pathologic finding associated with acute tubular necrosis

only occurs when epithelium is sloughing

what do RBC urine casts suggest?

diagnostic of glomerulonephritis or vasculitis and associated with glomerular disease and renal infarction

what do waxy urine casts suggest?

suggests renal stasis or tubular obstruction

what is the purpose of urine cultures?

to confirm bacteriuria, and identifies bacterial species

cystocentesis is preferred sample method

what is MIC stand for?

minimum inhibitory concentration

what is MIC?

lowest concentration of an antibiotic that inhibits growth of the specific strain of bacteria from your patient

lab determines MIC for each antibiotic

can the MIC number of one antibiotic be compared to the MIC number of another antibiotic?

no

what is MIC interpretation based on?

based on published antibiotic breakpoint standards specific to species, drug and bacterial species

what does it mean if an organism is sensitive to an antibiotic?

organism is inhibited by the serum drug concentration that is achieved using the usual dosage

what does it mean if an organism is has intermediate sensitivity to an antibiotic?

organism inhibited if the drug concentrates at site of infection (urine) or only by maximum recommended dose

what does it mean if an organism is resistant to an antibiotic?

organism is resistant to the usually achievable serum level

how are antibiotics chosen when given a urine culture with a sensitivity profile?

1. MIC interpretation (knock out ones that are resistant)

2. antibiotic safety: choose weakest and safest that will clear infection

3. site of infection

what findings on urine culture suggest bacterial contamination rather than bacteriuria?

1. commensals/atypical bacteria

2. low counts (low CFU/mL, should have high CFU/mL)

3. multiple organisms present (UTIs usually only caused by one bug)

what are indications to perform abdominal radiographs for urinary disorders?

1. see renal size, asymmetry, and contour

2. if absent kidney (renal aplasia)

3. visualize urethra

4. urolithiasis (struvite and calcium oxalate stones, large radiolucent stones)

what are advantages of abdominal radiographs for urinary disorders?

-determine radiodensity of urinary stones

-easily accessible for most small animal clinicians

what are disadvantages of abdominal radiographs for urinary disorders?

-cannot see inside architecture of organs

-feces in colon can obstruct image of ureters

what are indications to perform abdominal ultrasound for urinary disorders?

everything except:

-partially obstructed ureter without ureteral dilation

-visualization of distal (post-prostatic) urethra

what are advantages of abdominal ultrasound for urinary disorders?

can get thorough look at kidneys and bladder, can see architecture of organs

what are disadvantages of abdominal ultrasound for urinary disorders?

-cannot visualize non-dilated (normal) ureter

-requires additional training post-DVM

what are indications to perform a contrast cystography/urethrography?

1. determine location of bladder (pelvic bladder)

2. bladder rupture

3. bladder tumor

4. urethral defect (stricture, stone, diverticulum, dilation, etc)

5. radiolucent bladder stones (double contrast: air and contrast)

what is the procedure for a positive contrast cystography?

1. give enemas (1+) 2-3 hours prior to procedure

2. take pre-contrast abdominal radiographs

3. place urinary catheter

4. empty bladder of urine

5. infuse soluble iodinated contrast medium (diluted 20-50% with saline) into bladder (about 5ml/kg)

6. pull out catheter while infusing, immediately take radiographs

what is the procedure for a double contrast cystography?

1. perform positive contrast cystography and urethrography first

2. replace urinary catheter

3. drain the contrast from bladder

4. re-install room air until bladder is turgid (firm) about 5-10ml/kg

5. contrast will adhere to damaged mucosa, and bladder stones create filling defects

what is the preferred imaging modality for diagnosis of ectopic ureters in male dogs?

computed tomography (CT) excretory urogram

animal is given IV contrast that is excreted by the kidneys

what is the gold standard diagnostic for ureteral obstructions?

antegrade pyelogram

what is the procedure for an antegrade pyelogram?

1. spinal needle advanced into renal pelvis with U/S guidance

2. iodinated contrast material introduced into pelvis during fluoroscopic imaging

what is the preferred imaging modality for diagnosis of ectopic ureters in female dogs?

cystoscopy

what can be evaluated with cystoscopy?

can evaluate vagina, urethra, bladder, ureterovesical junctions