Lecture 19 - Exam 2 Renal Part 1 Flashcards
What are the functions of the kidney?
- Regulate blood volume
- Filter the blood
* Produce urine
* Acid-base, water, and electrolyte balance - Excrete metabolic waste via the urine
- Conserve nutrients such as amino acids and glucose
- Produce hormones:
* Renin –> regulates blood pressure
* Erythropoietin (EPO) –> RBC production
* Calcitriol (vitamin D) –> calcium homeostasis
What dictates renal excretion of water and solutes?
Glomerular filtration + tubular resorption + tubular secretion dictate renal excretion of WATER and SOLUTES
What goes into the kidney? What comes out of the kidney? How do these parameters help us?
Blood, urine
By looking at blood and urine, we can get a pretty good idea as to how the kidney is functioning.
How do we evaluate renal function?
- History and physical exam
- Is there anemia?
- Look at biochemical profile
- Urea, creatinine, phosphorus, K+, albumin - Urinalysis
- Gross appearance, dipstick, microscopic examination - Bacterial culture and antimicrobial sensitivity
- Urine protein
- Look at urine creatinine ratio - Renal function tests
- Done by Fractional excretion studies –not common b/c very convoluted- - Renal biopsy –not common-
- Not done for evaluation of renal function unless there is another test that are very convoluted in their results or there is an abnormality that can not be explained via clinical signs or physical exam; if there is a change in the morphology of the kidney, then could do this.
Functional renal tissue is required for ?
health –> renal insufficiency
In order for the kidneys to function appropriately, they need to have a functional and intact
Kidneys have large functional reserve capacity if the basement membrane is intact
What happens as a result of nephron loss?
With the loss of nephrons:
1. Lose the ability to concentrate urine (1st)
2. Become azotemic (2nd) (further damage –> azotemia; this means that loss of nephrons is more advanced)
Unaffected nephrons compensate for renal damage by ?
hypertrophy of function
What lab tests are used to diagnose kidney disease?
SERUM
1. Urea, creatinine, phosphorus
- Serum urea nitrogen, blood urea nitrogen (SUN, BUN)
2. Albumin
URINE
1. USG
2. Urinalysis
3. Urine protein: urine creatinine ration
GFR is defined as the volume of ______ filtered at the glomerular capillaries into ________ space per unit of ____. It is the rate that fluid moves from ______ to glomerular _______.
plasma, Bowman’s, time, plasma, filtrate
GFR is the best predictor of?
renal function –related to the number of functioning nephrons
DIRECT GFR Difficult to directly measure in veterinary medicine. Why?
B/c it is more convoluted.
How do you measure direct GFR?
Can be measured by studies that use substances which are freely filtered by the glomerulus and that are neither secreted nor reabsorbed (inulin, iohexol, mannitol).
Can be estimated by endogenous creatinine clearance studies
- Complex and not clinically practical
How do you measure the IGFR?
Most common used in Vet. Med
- BUN and creatinine
- What is Blood urea nitrogen (BUN) ?
- What is it produced by?
- Is it reabsorbed? If so, how?
- How is it excreted?
- Concentration can be affected by?
- Waste product of protein catabolism
- Produced by liver
- Reabsorbed passively by kidney tubules in all species (~40-70%)
- Also in GI tract by ruminants - Excreted mostly by the kidneys
- In ruminants: excretion is by the GI tract, sweat, and saliva - Concentration can be affected by non-renal factors
- Proximal GI hemorrhage BUN will increase
- Liver insufficiency or portosystemic shunts –> BUN will decrease
- What is Creatinine?
- Creatinine value can be affected by?
- How is Creatinine filtered?
- Describe the rate of production and excretion?
- What is it influenced by?
- Byproduct of muscle metabolism from creatine
- Value can be affected by:
- Muscle wasting (cachexia) or small breed dogs –> lower creatinine
- High meat diets, heavy muscle mass (e.g. Greyhounds) or muscle catabolism –> higher creatinine - Freely filtered and undergoes little modification within the renal tubule (no resorption and minimal excretion)
- Rate of production and excretion are fairly constant
- Less influenced by non-renal factors than BUN
- Considered to be amore accurate measure of GFR than BUN, especially in large animals
- Can be falsely increased by non creatinine chromogens (Jaffe reaction on automated analyzers)- Ketones, glucose, carotenes, vitamin A, pyruvate, ascorbic acid, uric acid
Creatinine
Filtered by the __________
Not ________ by the renal tubules
Excreted _________ by kidneys
Creatinine is an excellent indicator of ____.
If CREA is increased in blood, it implies:
1) A ________ in GFR
2) Possibly altered ______ function
glomerulus
resorbed
unchanged
GFR
decrease
nephron
What is Symmetric dimethylarginine (SDMA)?
- Relatively new test considered to be a more sensitive (early) indicator of decreased GFR in dogs and cats
- It is a compound produced by nucleated cells at a constant rate and excreted by the kidneys
- Not reabsorbed by the tubules and therefore not impacted by many extra-renal factors or by lean body mass (like creatinine is). - Still being investigated
- A recent study showed non-azotemic dogs with elevated SDMA had improved renal function when fed a renal diet
- Now used as part of the IRIS kidney staging guidelines for dogs and cats
What is the IRIS kidney staging?
It is the International Renal Interest Society (IRIS)
A tiered stratification system has been proposed by the International Renal Interest Society (IRIS) to help provide guidelines for clinical management of CKD. Staging is based on serum creatinine values, with substages identified for blood pressure and proteinuria
What values are used for IRIS staging?
Serum creatine and proteinuria are used in IRIS staging
Urine specific gravity (USG)
1. Used to determine?
2. Measures the?
3. Measured by?
4. USG can range from?
5. Always interpret the USG in light of?
- Used to determine renal concentrating or diluting ability
- Measures the density of urine in comparison to water
- water USG = 1.000
– Approximates urine osmolality - Measured by refractometry
- USG can range from 1.001-1.065 in most healthy animals
- can be even higher in cats
- Always interpret the USG in light of the patient’s BUN and creatinine concentrations, and hydration status
- Most refractometers measure from ?
- 0.000 = ?
- The higher the urine specific gravity, the more _________ the urine
- Range of USG varies by species:
- Cat ?
- Dog ?
- Horse & Bovine ?
- 0.000-1.040
- deionized water
- concentrated
- 1.001 – 1.080, 1.001 – 1.060, 1.001 – 1.055
How do we classify azotemia?
- Pre renal azotemia
- Renal azotemia
- Post renal azotemia
In a case of azotemia, we will either have one or both elevations of BUN and Creatinine
What are the steps in classifying azotemia?
- BUN and creatinine concentrations
- Urine specific gravity measurement
3.Urinary status- Is the animal able to urinate?
- Clinical signs such as anuria, oliguria or polyuria
- Is the animal able to urinate?
- Results of a full urinalysis, including microscopic sediment exam
- +/- additional diagnostics: radiographs and ultrasound -especially for lower urinary tract disorders (e.g. UTIs, obstructions, ruptured bladder)
The magnitude of BUN and/or Creatinine increase does NOT?
definitively indicate which type of Azotemia is present
The magnitude of increase also does not differentiate between ?
acute and chronic renal disease for cases of renal azotemia
The rate of increase from baseline is more indicative
Define azotemia.
AZOTEMIA: one or both BUN/CREA is/are elevated = increased nitrogen waste products
Azotemia does not occur until ?
a minimum of 75% of nephrons are not adequately functioning
Therefore, when we have azotemia or we detect azotemia in a patient, these are _____ indicators of renal disease
* There is a strong need for ____ indicators of renal disease in veterinary medicine
LATE, early
______, ______, _______ provide measurement of Glomerular filtration (GFR)
______ in urine and decrease _________ are indicators of Protein loss in nephron (PLN)
UREA, CREATININE, SDMA
Protein, Albumin
SDMA may be a promising ______ marker for renal disease
early
Renal disease
- Morphologic renal lesions of any ____ or ___
- May or may not have ___________ abnormalities related to renal function
size, severity
biochemical
Diminished renal reserve
- GFR ~____% of normal
- No ___________ abnormalities
- Animal is clinically _________
50, biochemical, healthy
Renal insufficiency
- GFR ~___-____% of normal
- Biochemical abnormalities present in ________
- Animal is often _______ because of decreased concentrating ability
20, 50, serum, polyuric
Renal failure
- GFR is < ___-___% of normal function
- (3?) develop
20-25
Edema, hypocalcemia, and metabolic acidosis
End-stage renal disease
- GFR is < __% of normal
– Patients present with _____ or ______
5
Oliguria, anuria
In a case of Isosthenuria, the urine specific gravity is ?
urine specific gravity between 1.008-1.012
Hyposthenuria = _____ urine, USG = ?
dilute urine, USG < 1.007 (active process)
Oliguria =
markedly decreased urine production
Anuria =
no urine produced
Stranguria =
straining to urinate
Pollakiuria =
increased frequency of urination
Azotemia =
increased urea nitrogen with/without increased creatinine
Uremia =
excessive urea in blood with clinical signs of renal failure (vomiting, diarrhea, ammoniacal breath odor)
Urea is filtered and then _____% goes back into the glomerulus and ___% goes into urine
40, 60
What are the causes of pre-renal disease [INCREASED UREA]?
- Increased protein diet
- Increased endogenous protein catabolism. May also see this in animals with…
- GI bleeding,
- fever,
- infection,
- necrosis,
- hyperadrenocorticism
- Prolonged exercise
Remember, PROTEIN drive BUN synthesis by the liver, and blood is protein-rich
↑ production of BUN → ↑ _______ BUN
serum
What are the causes of pre-renal disease [INCREASED UREA] in ruminants?
- Urea from salivary and blood go to rumen
- Rumen microflora creates amino acids from urea - CAUSES of increased UREA
- Rumen stasis
- Decreased GFR - Urea not as useful indicator of GFR in this specie as in others
What can decrease urea?
Pre renal causes for decreased urea could be due to:
1. LIVER:
- Decreased urea production
- Hepatic insufficiency
- when there is x>80% loss of function –> decreased urea
- Decreased Protein in diet –> decreased urea
- Animals with a Portosystemic shunt (PSS) –> decreased urea production
2. INTESTINAL loss of proteins
- Monogastric species: associated with Protein-losing enteropathies
Cattle: associated with microflora that allow for GI excretion of BUN
Renal causes
1. RENAL: Decreased water resorption in tubules
- Osmotic diuresis (ie.: increased tubular flow)
- Increased GFR (ie: Intravenous fluid diuresis)
Creatinine is filtered in the _________ and ___% is excreted in the urine.
glomerulus, 100
Causes of PRE-renal Increased Creatinine ?
Associated with Muscled individuals, particularly males
- Greyhounds, Belgian blue cattle
Causes of DECREASED Creatinine ?
- Young animals
- Muscle atrophy
- Hyperthyroid cat
- Older animal
- Cachexia
Not clinically significant, but may represent poor muscle mass
Interpreting the SDMA results:
INCREASES in SDMA results –> suggest renal _____ disease
- Must interpret alongside: ?
tubular
history, clinical signs, PE findings, other markers of renal injury
If SDMA is increased and CREA is normal:
1. Does your history, clinical signs, and/or physical exam findings support renal disease?
2. Rule out all other causes of ↓ GFR besides renal failure
- May need to run additional diagnostics: Urine protein: creatinine ratio (UPCR)
- Urine culture and sensitivity
- Blood pressure measurement
- r/o other infectious diseases (Lyme, leptospirosis, ehrlichiosis)
- Imaging (uroliths, structural changes, etc.)