small animal med- nephrology/urology objectives

what are biomarkers of glomerular filtration rate (GFR)?

urea (BUN), creatinine, symmetric dimethylarginine (SDMA), urine specific gravity (USG)

is BUN a good marker of GFR?

BUN is a poor marker of GFR (and thus kidney disease- it is nonspecific)

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

how sensitive is creatinine as a marker of GFR?

creatinine is an insensitive marker of GFR

need 60-75% reduction in functional kidney mass before creatinine is elevated on some biochemistry panels in cats with kidney disease

what is urea?

digestion of proteins makes ammonia

-->ammonia synthesized to urea by the liver

--->urea excreted by the kidneys and intestines

what are causes of elevated BUN?

1. increased protein catabolism

2. high protein intake

3. pre-renal azotemia

4. kidney dysfunction

how does kidney dysfunction elevate BUN?

reduced GFR

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

fever, infection, starvation, hyperthyroidism

how does pre-renal azotemia increase BUN?

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

causes: dehydration, hypovolemia, hypotension

what are non-renal factors affecting creatinine?

1. muscle mass

2. age and breed

3. may vary with timing of blood collection to meal

how does muscle mass affect creatinine levels?

muscle atrophy falsely decreases creatinine

which ages/breeds of animals may have different creatinine concentrations?

-birman cat and greyhound higher creatinine in health

-small breed dogs have lower creatinine than large breed dogs

-high in younger pets (creatinine declines with age due to age-related sarcopenia)

what is SDMA? where is it excreted?

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

90% excreted by kidneys

how is SDMA used as a biomarker for GFR?

1. marker of GFR and not specific to kidney disease (rule out pre- and post- renal azotemia)

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

3. less influenced by muscle mass than creatinine

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

what is the reference range for SDMA

normal: 0-14 ug/dL

gray zone: 14-18ug/dL (may have kidney dz, look at creat and USG trend, recheck in 2-3 months)

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

what is azotemia?

elevated BUN, creatinine, and/or SDMA in blood

what are 3 categories of proteinuria?

pre, renal, and post-renal proteinuria

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

what is included in a urinalysis (UA)?

USG, dipstick, and microscopic sedimentation evaluation

what does the urinalysis assess?

1. assesses tubular function (USG)

2. glomerular and tubular function (protein, casts)

3. urine pH

4. detection of bacteria

what are markers of tubular injury on UA?

1. urine casts (sloughing of tubular epithelium)

2. glucosuria in absence of hyperglycemia

what is cystatin B?

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

what is an elevation in cystatin B a biomarker of?

biomarker of tubular injury--> if elevated, signifies active/acute kidney injury:

what should elevations in cystatin B be evaluated with?

1. need to look at clinical picture and other lab testing to support kidney injury (SDMA, creatinine, USG)

2. urine sediment on UA: glucosuria (w/o hyperglycemia), casts

3. determine: is patient sick?

what is elevated fibroblast growth factor 23 (FGF23) a biomarker of?

biomarker of phosphorus overload

when does FGF23 increase?

increases before overt hyperphosphatemia:

-phosphatonin hormone secreted by bone in response to phosphorus overload

-promotes phosphorus excretion in urine

what is the clinical significance of elevated FGF23?

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

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

how is colorimetric biochemical reagent urine dipstick used to assess proteinuria?

first-line screening test (good sensitivity, poor specificity)

highest sensitivity for albuminuria

how is the urine protein-to-creatinine (UPC) ratio used to assess proteinuria?

normal: <0.2

used when you suspect renal proteinuria (preferably performed on sample w/o gross hematuria and pyuria)

what are limitations of the UPC ratio?

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)

what are hyaline casts?

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

what is the significance of hyaline casts?

clinically insignificant- least important

can be normal in small amounts in healthy patient (<2/HPF)

what are granular casts suggestive of?

suggests stasis in tubules or associated tubulointerstitial disease

what are epithelial casts suggestive of?

serious pathologic finding associated with acute tubular necrosis

only occurs when epithelium is sloughing

what is the significance of RBC casts?

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

what do waxy casts suggest?

suggests renal stasis or tubular obstruction

what is minimum inhibitory concentration (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 of one antibiotic be compared the to MIC of another?

no

what is MIC based on? what are the 3 classifications?

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

3 classifications: sensitive, intermediate, resistant

what is a sensitive MIC?

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

what is an intermediate MIC?

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

what is a resistant MIC?

 bug is resistant to the usually achievable serum level

when provided a urine culture with susceptibility profile, what is choosing the appropriate antibiotic based on?

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 are indications for performing a contrast cystography and urethrogram?

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)

how is a positive contrast cystography procedure performed?

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

7. immediately take radiographs

how is a double contrast cystography procedure performed?

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

6. bladder stones create filling defects

what are findings on urine culture suggesting bacterial contamination rather than bacteriuria?

1. commensals/atypical bacteria

2. low counts (don't rely on this, but especially if a commensal- should have high CFU)

3. multiple bugs (usually only 1 bug causes a UTI)

what are indications for taking abdominal radiographs for urinary disease?

1. assess renal size, asymmetry, and contour

2. absent kidney (renal aplasia)

3. visualize urethra

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

what are advantages of abdominal rads for urinary dz?

1. determine radiodensity of urinary stones

2. easily accessible for most small animal clinicians

what are disadvantages of abdominal rads for urinary dz?

1. cannot see inside architecture of organs

2. feces in colon can obstruct image of ureters

what are indications for doing an abdominal ultrasound for urinary disease?

everything except:

-partially obstructed ureter without ureteral dilation

-visualization of distal (post-prostatic) urethra

what are advantages of abdominal ultrasound for urinary dz?

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

what are disadvantages of abdominal ultrasound for urinary dz?

1. cannot visualize non-dilated (normal) ureter

2. requires additional training post-DVM

how is a CT excretory urogram performed?

ie CT with contrast: give IV contrast that is excreted by kidneys

what is CT excretory urogram the preferred diagnostic method for?

for diagnosis of ectopic ureters in male dogs

how is a antegrade pyelogram performed?

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

2. iodinated contrast material introduced into pelvis during fluoroscopic imaging

what is the gold standard diagnostic for diagnosing ureteral obstructions?

antegrade pyelogram

what is the diagnostic method of choice for diagnosing ectopic ureters in female dogs?

cystoscopy

what is cystoscopy used for?

used to evaluate the vagina, urethra, bladder, ureterovesical junctions

what is chronic kidney disease (CKD)?

progressive tubulointerstitial fibrosis

CKD is an umbrella term to describe any renal disease that leads to progressive loss of kidney function over time

what are renal diseases that can lead to CKD?

1. idiopathic or age-related degenerative disease (most common)

2. congenital (renal dysplasia, agenesis)

3. genetic (amyloidosis, polycystic kidney disease)

4. infection (pyelonephritis, retroviruses, FIP, ehrlichia, lyme nephritis)

5. immune-complex glomerulonephritis

6. chronic ureteral obstructions

what are the stages of CKD?

stage 1 (no azotemia/normal creat)

stage 2 (mild azotemia/normal or mildly elevated creat)

stage 3 (moderate azotemia)

stage 4 (severe azotemia)

what is the creatinine and SDMA of cats with stage 1 CKD?

creatinine: Less than 1.6

SDMA: Less than 18ug/dL

what is the creatinine and SDMA of dogs with stage 1 CKD?

creatinine: Less than 1.4

SDMA: Less than 18ug/dL

what is the creatinine and SDMA of cats with stage 2 CKD?

creatinine: 1.6-2.8

SDMA: 18-25ug/dL

what is the creatinine and SDMA of dogs with stage 2 CKD?

creatinine: 1.4-2.8

SDMA: 18-35ug/dL

what is the creatinine and SDMA of cats with stage 3 CKD?

creatinine: 2.9-5.0

SDMA: 26-38ug/dL

what is the creatinine and SDMA of dogs with stage 3 CKD?

creatinine: 2.9-5.0

SDMA: 36-54ug/dL

what is the creatinine and SDMA of cats with stage 4 CKD?

creatinine: greater than 5.0

SDMA: greater than 38ug/dL

what is the creatinine and SDMA of dogs with stage 4 CKD?

creatinine: greater than 5.0

SDMA: greater than 54ug/dL

what is the IRIS UPC substage for dogs with CKD?

nonproteinuric: <0.2

borderline proteinuric: 0.2-0.5

proteinuric: >0.5

what is the IRIS UPC substage for cats with CKD?

nonproteinuric: <0.2

borderline proteinuric: 0.2-0.4

proteinuric: >0.4

what is the IRIS blood pressure substage for animals with CKD?

normotensive: <140mmHg

prehypertensive: 140-159mmHg

hypertensive: 160-179mmHg

severely hypertensive: at or greater than 180mmHg

what is the minimum diagnostic database needed after diagnosing CKD to rule out treatable conditions?

1. abdominal imaging (rads and/or ultrasound)- urolithiasis?

2. blood pressure- hypertension?

3. UPC ratio- proteinuria?

4. if active urine sediment LUT signs on UA→ urine culture

5. if proteinuria consider infectious dz testing

when is CKD staging done?

following diagnosis of CKD

what is IRIS CKD staging based on?

based on fasting blood creatinine and/or SDMA on at least 2 occasions in a hydrated, stable patient 

stable= less than 20% variation in creat over at least 2 wk interval

what is IRIS CKD substaging based on?

based on UPC ratio and blood pressure

what can IRIS staging not be applied to?

-pre- or post-renal azotemia

-acute (AKI) or decompensated (acute on chronic) kidney disease

what are the defining nutritional characteristics of renal therapeutic diets?

1. restricted in phosphorus

2. restricted in protein

3. high caloric density

4. restricted sodium

5. alkalinizing

6. omega-3 fatty acids

7. variable potassium

what are the benefits of renal therapeutic diets having restricted phosphorus?

lowers FGF-23 and PTH (since less phosphorus absorbed)

what are the benefits of renal therapeutic diets having restricted protein?

reduces uremic toxin production (that leads to signs of uremia) and improves proteinuria

what are the benefits of renal therapeutic diets having high caloric density?

increases caloric intake and prevents weight loss

what are the benefits of renal therapeutic diets having restricted sodium?

prevents sodium loading and worsening polyuria

what are the benefits of alkalinizing renal therapeutic diets?

treats metabolic acidosis

what are the benefits of renal therapeutic diets having omega-3 fatty acids?

anti-inflammatory effects, treats proteinuria

what potassium abnormalities are seen in cats and dogs with CKD?

cats get hypokalemia, dogs get hyperkalemia

what is the only way you can compare therapeutic renal diets?

by caloric density (not byguaranteed analysis!)

guaranteed gives you minimums/maximums, not absolute values

what is the difference between early and late stage renal diets?

in general, diets for stage 1 and 2 CKD are higher in protein and phosphorus than diets formulated for stage 3 and 4

diets formulated for early stage CKD often have protein and phosphorus concentration above AAFCO minimum required for adult maintenance

diets for advanced-stage CKD can have a protein or phosphorus concentration below the AAFCO minimum for adult maintenance

what happens if you restrict phosphorus too early on in the early stages of CKD?

if you restrict phosphorus too early (feed early stage CKD an advanced-stage CKD diet), can result in hypercalcemia

what is the significance of hyperphosphatemia in patients with CKD?

-consequence of reduced GFR

-leads to renal secondary hyperparathyroidism

-associated with negative survival

what are the associated target serum phosphorus levels for each IRIS CKD stage?

stage 2: <4.6mg/dL

stage 3: <5.0mg/dL

stage 4: <6.0mg/dL

when should a renal diet be given to patients with CKD?

considered in stage 2:

-signs of uremia? (vomiting, poor appetite, weight loss, ADR)

-ff fasted blood phosphorus above IRIS target range and if serum FGF-23 is elevated (cats only)

Recommended in stage 3 and 4

what is the treatment for hyperphosphatemia in patients with CKD?

1. reduce dietary intake of phosphorus (renal diets, OTC senior diets)

2. reduce GI absorption of phosphorus (phosphate binder if persistent)

3. monitor serum phosphorus every 2-4 weeks until target is achieved 

what oral phosphate binders are available for treatment of persistent hyperphosphatemia?

1. aluminium hydroxide most common (dogs and cats)

2. lanthanum

--> inhibits dietary phosphorus absorption in GI tract (only works if given with food)

what is a normal blood pressure in healthy dogs and cats?

120-160mmHg

if CKD patient is <160, recheck in 3-6 months

what are the next steps if a patient with CKD has a blood pressure over 160mmHg with signs of target organ damage (TOD)?

look for underlying condition, recommend anti-hypertensive therapy

what are the next steps if a patient with CKD has a blood pressure 160-179mmHg with no signs of target organ damage (TOD)?

repeat BP twice within 8 weeks:

-if under 160mmHg, recheck in 3-6 months

-if over 160mmHg, look for underlying condition, recommend antihypertensive therapy

what are the next steps if a patient with CKD has a blood pressure 180mmHg with no signs of target organ damage (TOD)?

repeat BP twice within 14 days

recheck for TOD:

-if under 160mmHg: recheck in 3-6 months

-if over 160mmHg: look for underlying cause, anti-hypertensive tx