Renal Biochemistry Profile Flashcards
What are the main 3 functions of the kidney?
- regulate and filter blood volume - acid-base, water, electrolyte balance
- excrete metabolic waste via urine
- conserve nutrients, like amino acids and glucose
What 3 hormones are produced by the kindey?
- RENIN - regulates blood pressure
- ERYTHROPOIETIN - RBC production
- CALCITRIOL (vitamin D) - calcium homeostasis
What dictates renal excretion of water and solutes? How do we evaluate renal function?
glomerular filtration, tubular resorption, tubular secretion
evaluating what is going into the kidney (blood) and what is coming out (urine)
What needs to be present to accurately evaluate renal function? What 2 tests are uncommonly done in veterinary medicine, but can be other options?
- history and physical exam
- presence of anemia
- biochemistry profile (urea, creatinine, phosphorus, potassium, albumin)
- urinalysis (gross appearance, dipstick, microscopic evaluation)
- bacterial culture and antimicrobial sensitivity
- urine protein (creatinine ratio)
renal function test by fractional excretion studies and renal biopsies (morphological problems)
What is required in the kidney for health?
functional renal tissue
- large functional reserve capacity if BM is intact
What 2 things happen with the loss of nephrons? How is this compensated?
1st - lose the ability to concentrate urine
2nd - become azotemic
unaffected nephrons become hypertrophic and take over function
What 2 lab tests are used to diagnose kidney disease? What analytes are measured in each?
- SERUM - urea, creatinine, phosphorus, SUN, BUN, albumin
- URINE - USG, urinalysis, urine protein (urea:creatinine ratio)
What is the glomerular filtration rate? What is it the best predictor for?
volume of plasma filtered at the glomerular capillaries into Bowman’s space per unit of time (the rate that fluid moves from plasma to glomerular filtrate)
renal function —> directly relates to the number of functioning nephrons
What is the most common way in veterinary medicine to evaluate glomerular filtration rate?
INDIRECT —> BUN and creatinine
What is urea? What are the 3 steps of its metabolism in the body?
waste product of protein catabolism
- produced in the liver
- reabsorbed passively by kidney tubules
- excreted mostly by the kidneys
What is unique about urea metabolism in ruminants?
- can be reabsorbed in the GI tract following synthesis
- excreted by GI tract, sweat, and saliva
What non-renal functions cause increases and decreases and BUN?
INCREASE - proximal GI hemorrhage
DECREASE - liver insufficiency or portosystemic shunts
What is creatinine? What can cause decreases and increases in its value?
byproduct of muscle metabolism from creatine
DECREASE - muscle wasting (cachexia), normal in small breed dogs
INCREASE - high meat diets, increased muscle catabolism (exercise), naturally heavy muscle mass (Greyhounds)
How is creatinine filtered by the kidney?
freely filtered and undergoes little modification within the renal tubules (no resorption, minimal excretion) fairly constantly
Is BUN or creatinine considered a more accurate measure of GFR? Why?
creatinine - less influenced by non-renal factors than BUN (especially in large animals)
What are 2 implications of high creatinine levels in the blood? What can cause falsely increased values?
- decreased GFR
- altered nephron function
non-creatinine chromogens (Jaffe reactions, automated analyzers) - ketones, glucose, vitamin A, pyruvate, ascorbic acid, uric acid
What new test may be considered a more sensitive (early) indicator of decreased GFR in dogs and cats? How is this product typically produced and excreted?
symmetric dimethylarginine (SDMA)
- produced by nucleated cells at a constant rate
- excreted by the kidneys without being reabsorbed by the tubules and unaffected by extra-renal functions or lean body mass (like creatinine)
What 4 factors are used by IRIS to categorize and stage chronic kidney disease?
- serum creatinine
- proteinuria
- blood pressure
- SDMA
What is urine specific gravity used to evaluate? What does it measure? How is it measured?
renal concentration or diluting ability
density of urine compared to water to approximate urine osmolality (water USG = 1.000)
refractometry
What is the normal range of urine specific gravity in healthy animals? Cats?
1.001 - 1.065
1.001 - 1.080
How should urine specific gravity be interpreted with? What does it mean when its elevated?
in light of patient’s BUN and creatinine concentrations and hydration status
more concentrated urine
What are the 3 steps to classifying azotemia? What additional diagnostics are commonly included?
- BUN and creatinine concentrations
- urine specific gravity
- urinary status - patient ability to urinate; anuria, oligura, polyuria
- full urinalysis including microscopic sediment exam
- radiographs and ultrasound for lower urinary tract disorders, like UTIs, obstructions, or ruptured bladder
What is azotemia? When does it occur?
increase in one or both: BUN, creatinine, indicating increased nitrogen waste products in the blood
minimum of 75% of nephrons are not adequately functioning, making it a late indicator or renal disease
What are the major measures of glomerular filtration rate and protein loss in nephrons?
GFR - urea, creatinine, SDMA
PLN - protein in urine, decreased albumin
What 3 things indicate diminished renal reserve?
- GFR ~50% of normal
- no biochemical abnormalities
- animal is clinically healthy
What is the difference between renal insufficiency and renal failure?
INSUFFICIENCY - GFR ~20-50% or normal, biochemical abnormalities, polyuric due to decreased concentrating ability
FAILURE - GFR <20-25% of normal; edema, hypocalcemia, and metabolic acidosis developed
What is indicative of end-stage renal disease? Renal disease?
END-STAGE - GFR <5% of normal with oliguria and anuria
RENAL DISEASE - morphological renal lesions of any size or severity with biochemical abnormalities related to renal function
What is isothenuria? Hyposthenuria?
ISO = urine specific gravity between 1.008 - 1.012
HYPO = dilute urine < 1.007, indicative of active dilution
What is oliguria? Anuria? Stranguria? Pollakiuria?
OLIG = markedly decreased urine production
AN = no urine production
STRANG = straining to urinate
POLLAKI = increased frequency of urination
What is the difference between azotemia and uremia?
increased urea nitrogen with/without increased creatinine
excessive urea in blood with clinical signs of renal failure, like vomiting, diarrhea, and ammoniacal breath odor
How are urea and creatinine filtered and excreted?
UREA - 40% back in blood, 60% excreted in urine
CREATININE - completely filtered, 100% excreted in urine
What are the 2 most common causes of pre-renal urea increase?
- increased protein diet
- increased endogenous protein catabolism - GI bleeding, fever, infection, necrosis, hyperadrenocorticism, prolonged exercise
How is increased BUN production observed?
increased serum BUN —> protein drives BUN synthesis by the liver, and blood is protein-rich
What are 3 common causes of pre-renal urea increase in ruminants?
- urea from saliva and blood go to rumen and microflora creates amino acids from urea
- rumen stasis
- decreased GFR
- urea not as a useful indicator of GFR in ruminants, since it is also processed in the rumen
What are 2 common causes of pre-renal decreased urea due to the liver?
- decreased urea production by hepatic insufficiency (>80% loss) or decreased protein in diet
- portosystemic shunt
What are the most common causes of pre-renal decreased urea due to the intestine?
intestinal loss of proteins
- MONOGASTRIC: protein-losing enteropathies
- CATTLE: microflora allow for GI excretion of BUN
What are 2 causes of renal decreased urea?
- osmotic diuresis: increased tubular flow
- increased GFR: IV fluid diuresis
What is the most common cause of pre-renal increased creatinine?
muscled individuals, especially males
- Greyhounds
- Belgian blue cattle
What are the 2 most common causes of decreased creatinine? Is this clinically significant?
- young animals
- muscle atrophy common in hyperthyroid cats, older animals, and cachexia
not particularly significant to kidney function - represents poor muscle mass
What does an increase in SDMA suggest?
renal tubular disease —> MUST interpret with history, clinical signs, PE, and other markers of renal injury
What should be evaluated if SDMA is increased and creatinine is normal? What must be ruled out?
does history, clinical signs, and/or PE findings support renal disease
other causes of decreased GFR besides renal failure - additional diagnostics (UPCR), urine culture and sensitivity, blood pressure measurement, infectious disease (Lyme, Lepto, Erhlichiosis), uroliths, structural changes
What is the main cause of pre-renal azotemia? How does this work? How can it be resolved?
dehydration (also shock, cardiovascular disease)
hypovolemia leads to decreased renal perfusion due to a reduced GFR
hydration/fluid therapy —> can lead to kidney damage if not corrected
What is commonly seen on biochemistry with pre-renal azotemia? Urine specific gravity?
increased BUN and creatinine
hypersthenuric —> hypovolemia increases ADH
What are the hypersthenuric values (adequately concentrated) for dogs, cats, cattle/horses/pigs, and birds?
DOGS: >1.030
CATS: >1.035
C/H: >1.025
BIRDS: >1.020
What are 3 additional clues that can point toward pre-renal azotemia?
- oliguria
- CBC: erythrocytosis
- CHEM: hyperalbuminemia
What biochemistry markers are elevated in renal azotemia? What causes this? How is this different in ruminants?
increased BUN and/or creatinine due to a reduced nephron function decreasing GFR
may only seen elevated creatinine, since urea is excreted in the rumen
What is the most common finding on the urine specific gravity for renal azotemia? What affects urine status?
isothenuria (1.008-1.012)
underlying disease
- CKD = polyuria
- AKD = oliguria
What is commonly concurrent with renal azotemia? How does this affect urine specific gravity?
pre-renal azotemia - patients with kidney disease are commonly dehydrated
should still be isothenuric
What is most commonly seen in the CBC with renal azotemia? Why?
non-regenerative anemia —> kidneys are damaged and will produce less erythropoietin
What are 4 characteristic findings in the chemistry panel for renal azotemia?
- hyperphosphatemia - decreased GFR
- increased amylase/lipase - decreased GFR
- hypoalbuminemia - loss through glomerulus/tubules
- titrational metabolic acidosis - uremic acids, lactic acids, ethylene glycol
How are potassium levels affected by renal azotemia?
- hypokalemia if polyuric
- hyperkalemia if anuric/oliguric
What 2 chemistry panel findings are commonly seen in horses with renal azotemia? What is seen in other species? What are 2 additional findings in cattle and horses?
hypercalcemia and calcium carbonate crystals in urine due to a lack of excretion and decreased GFR
hypocalcemia due to increased excretion and decreased calcitriol production
hyponatremia and hypochloridemia
What are 2 common findings in the urinalysis with renal azotemia?
- proteinuria due to glomerular or tubular protein loss
- microalbuminuria
- measured on dipstick (primarily detects albumin)
How are PCV, potassium, acid-base status, rate of azotemia development, albumin, urine sediment, size of kidneys, and body condition commonly affected by acute vs. chronic kidney disease?
What are 7 common causes of renal azotemia?
- inflammatory conditions - glomerulonephritis, pyelonephritis
- amyloidosis
- toxic nephrosis
- ischemia, hypoxia
- hypoplasia, aplasia
- hydronephrosis
- neoplasia
What are some common causes of toxic nephrosis?
- hypercalcemia
- ethylene glycol
- myoglobin
- gentamicin
- phenylbutazone
How does proteinuria compare in glomerular and tubular disease? What diseases should be considered with each?
GLOMERULAR = marked proteinuria 3-4+, UPC >2, edema, ascites - amyloidosis, glomerulonephritis, glomerulosclerosis
TUBULAR = mild proteinuria 1-2+ - leptospirosis, ethylene glycol toxicity
What is the most common cause of post-renal azotemia? How does it affect urine specific gravity? Urination ability?
lower urinary tract disease - outflow obstruction or rupture (urolithiasis, urethral plug, neoplasia, prostatic disease)
highly variable —> history, PE, imaging
anuric or oliguric
How can post-renal azotemia diagnosis be confirmed due to a ruptured bladder?
uroabdomen —> creatinine in peritoneal fluid should be greater than in the serum
How do BUN and creatinine levels help classify azotemia?
BUN:creatinine ratio
- increased BUN, normal creatinine = pre-renal
- normal BUN, increased creatinine = renal or post-renal
What does the urine specific gravity measure? What 2 things is it dependent on?
kidney’s ability to concentrate and dilute urine, requiring 33% of functional nephrons —> the density of urine with respect to water
- production and responsiveness to ADH (vasopressin)
- maintenance of medullary hypertonicity by producing urea (BUN) and aldosterone (Na+)
(ADH and aldosterone affect distal tubule)
What does USG need to be interpreted with?
BUN, CREA, hydration status
- collect blood AND urine
In what 5 situations should urine samples be obtained to measure USG?
- suspected renal disease
- geriatric wellness
- history of PU/PD
- animal is not dehydrated
- animal is not azotemic
At what levels is USG hyposthenuric and isothenuric? What does this mean?
HYPO = <1.007 - kidney is actively diluting urine (NOT renal insufficiency)
ISO = 1.008-1.012 - kidney is no adjusting urine concentation
What is the “gray zone” of the USG?
inadequately concentrated urine between isothenuric and hypersthenuric (1.013-1.029 in the dog)
What is the range of minimal concentration (ROMC) in dogs, cats, and ruminants/horses/pigs?
DOGS = 1.013-1.030
CATS = 1.013-1.034
R/H/P = 1.013-1.024
What should be done if the values of a USG does not reflect a patient’s hydration status, BUN, and/or CREA?
take another sample, is it reproducible?
- NO = original measurement is not significant
- YES = particles interfering with the refractometer, like glucose, ketones, mannitol, etc.
What measurement is affected by renal disease first?
USG
- 66% functional loss = impaired concentration
- 75% functional loss = impaired concentration + azotemia
What are 3 causes of impaired urine concentrating ability other than kidney disease?
- central diabetes insipidus
- nephrogenic diabetes insipidus
- diseases that cause PU and medullary washout
What is central diabetes insipidus?
pituitary disease causing a lack of ADH secretion, resulting in collecting ducts NOT reabsorbing water
What is nephrogenic diabetes insipidus? What are primary and secondary causes?
ADH is being secreted by the pituitary, but the kidney is unresponsive
- PRIMARY = tubular defects
- SECONDARY = hypercalcemia, hypokalemia, Cushing’s, endotoxemia (E. coli pyometra)
What is medullary washout? What does it result in? What are 4 common causes?
loss of hypertonic medullary interstitium
tubules are unable to concentrate urine, even in the presence of ADH
- psychogenic polydipsia
- fluid overload diuresis
- loop diuretics
- tubular disease
How does diabetes and hyperadrenocorticism cause medullary washout?
osmotic/chemical diuresis caused by impaired Na, Cl, and urea reabsorption due to increased tubular flow
What changes in potassium and calcium cause medullary wash out? What does this result in?
- hypokalemia
- hypercalcemia
increased blood flow in vasa recta flushes out solutes
How does diarrhea, hypoadrenocorticism, and liver disease cause medullary washout?
D, H = loss of Na and Cl
LIVER DX = decreased urea production
What is the difference between abrupt and gradual water deprivation tests? What are each used to determine?
ABRUPT = abrupt deprivation of water + USG monitoring to observe if the animal’s kidneys are able to adequately concentrate (hyperthenuric) it - determining if PU is due to PD
GRADUAL - very similar, but occurs over several days so the kidneys are able to re-establish medullary hypertonicity - determines if PU/PD is due to medullary washout
What do the ADH response test and modified water deprivation test differentiate between?
nephrogenic vs central DI —> nephrogenic DI will have no response (no concentration)
(hybrid of water deprivation and ADH test) - psychogenic PD vs. central DI vs. nephrogenic DI
USG…..
a. becomes hypersthenuric with loss of renal tubular function
b. decreases with dehydration
c. is an exact measurement
d. should always be interpreted with hydration status
D
- hyposthenuris with loss of renal tubule function
- increases with dehydration
- ESTIMATE of urinary concentration
Which of the following contribute to USG?
a. bacteria
b. creatinine
c. electrolytes
d. urea
B, C, D
- bacteria is suspended in urine (if there is a lot, it may make the line harder to read on the refractometer)
- CREA, ELECT, and UREA are all dissolved in plasma, so they are also dissolved in the ultrafiltrate (urea contributes to half of the medullary concentration gradient)
What are some non-renal reasons for isothenuric urine?
- administration of diuretics or IV fluids
- DM
- medullary washout
- hypercalcemia
- tubular damage from infection or drug toxicity
- tubular immaturity in younger animals
- hyperadrenocorticism
- hyperthyroidism
- glucocorticoids
