Lecture 19 - Exam 2 Renal Part 1

Question 1

What are the functions of the kidney?

Answer 1

1. Regulate blood volume
2. Filter the blood
   * Produce urine
   * Acid-base, water, and electrolyte balance
3. Excrete metabolic waste via the urine
4. Conserve nutrients such as amino acids and glucose
5. Produce hormones:
   * Renin –> regulates blood pressure
   * Erythropoietin (EPO) –> RBC production
   * Calcitriol (vitamin D) –> calcium homeostasis

Question 2

What dictates renal excretion of water and solutes?

Answer 2

Glomerular filtration + tubular resorption + tubular secretion dictate renal excretion of WATER and SOLUTES

Question 3

What goes into the kidney? What comes out of the kidney? How do these parameters help us?

Answer 3

Blood, urine
By looking at blood and urine, we can get a pretty good idea as to how the kidney is functioning.

Question 4

How do we evaluate renal function?

Answer 4

1. History and physical exam
2. Is there anemia?
3. Look at biochemical profile
   - Urea, creatinine, phosphorus, K+, albumin
4. Urinalysis
   - Gross appearance, dipstick, microscopic examination
5. Bacterial culture and antimicrobial sensitivity
6. Urine protein
   - Look at urine creatinine ratio
7. Renal function tests
   - Done by Fractional excretion studies –not common b/c very convoluted-
8. 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.

Question 5

Functional renal tissue is required for ?

Answer 5

health –> renal insufficiency

Question 6

In order for the kidneys to function appropriately, they need to have a functional and intact

Answer 6

Kidneys have large functional reserve capacity if the basement membrane is intact

Question 7

What happens as a result of nephron loss?

Answer 7

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)

Question 8

Unaffected nephrons compensate for renal damage by ?

Answer 8

hypertrophy of function

Question 9

What lab tests are used to diagnose kidney disease?

Answer 9

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

Question 10

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 _______.

Answer 10

plasma, Bowman’s, time, plasma, filtrate

Question 11

GFR is the best predictor of?

Answer 11

renal function –related to the number of functioning nephrons

Question 12

DIRECT GFR Difficult to directly measure in veterinary medicine. Why?

Answer 12

B/c it is more convoluted.

Question 13

How do you measure direct GFR?

Answer 13

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

Question 14

How do you measure the IGFR?

Answer 14

Most common used in Vet. Med

• BUN and creatinine

Question 15

1. What is Blood urea nitrogen (BUN) ?
2. What is it produced by?
3. Is it reabsorbed? If so, how?
4. How is it excreted?
5. Concentration can be affected by?

Answer 15

1. Waste product of protein catabolism
2. Produced by liver
3. Reabsorbed passively by kidney tubules in all species (~40-70%)
   - Also in GI tract by ruminants
4. Excreted mostly by the kidneys
   - In ruminants: excretion is by the GI tract, sweat, and saliva
5. Concentration can be affected by non-renal factors
   - Proximal GI hemorrhage BUN will increase
   - Liver insufficiency or portosystemic shunts –> BUN will decrease

Question 16

1. What is Creatinine?
2. Creatinine value can be affected by?
3. How is Creatinine filtered?
4. Describe the rate of production and excretion?
5. What is it influenced by?

Answer 16

1. Byproduct of muscle metabolism from creatine
2. 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
3. Freely filtered and undergoes little modification within the renal tubule (no resorption and minimal excretion)
4. Rate of production and excretion are fairly constant
5. 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

Question 17

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

Answer 17

glomerulus
resorbed
unchanged
GFR
decrease
nephron

Question 18

What is Symmetric dimethylarginine (SDMA)?

Answer 18

1. Relatively new test considered to be a more sensitive (early) indicator of decreased GFR in dogs and cats
2. 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).
3. 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

Question 19

What is the IRIS kidney staging?

Answer 19

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

Question 20

What values are used for IRIS staging?

Answer 20

Serum creatine and proteinuria are used in IRIS staging

Question 21

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?

Answer 21

1. Used to determine renal concentrating or diluting ability
2. Measures the density of urine in comparison to water
   - water USG = 1.000
   – Approximates urine osmolality
3. Measured by refractometry
4. USG can range from 1.001-1.065 in most healthy animals
   
   • can be even higher in cats
5. Always interpret the USG in light of the patient’s BUN and creatinine concentrations, and hydration status

Question 22

1. Most refractometers measure from ?
2. 0.000 = ?
3. The higher the urine specific gravity, the more _________ the urine
4. Range of USG varies by species:
   - Cat ?
   - Dog ?
   - Horse & Bovine ?

Answer 22

1. 0.000-1.040
2. deionized water
3. concentrated
4. 1.001 – 1.080, 1.001 – 1.060, 1.001 – 1.055

Question 23

How do we classify azotemia?

Answer 23

1. Pre renal azotemia
2. Renal azotemia
3. Post renal azotemia

In a case of azotemia, we will either have one or both elevations of BUN and Creatinine

Question 24

What are the steps in classifying azotemia?

Answer 24

1. BUN and creatinine concentrations
2. Urine specific gravity measurement
   3.Urinary status
   
   • Is the animal able to urinate?
     
     • Clinical signs such as anuria, oliguria or polyuria
3. Results of a full urinalysis, including microscopic sediment exam
4. +/- additional diagnostics: radiographs and ultrasound -especially for lower urinary tract disorders (e.g. UTIs, obstructions, ruptured bladder)

Question 25

The magnitude of BUN and/or Creatinine increase does NOT?

Answer 25

definitively indicate which type of Azotemia is present

Question 26

The magnitude of increase also does not differentiate between ?

Answer 26

acute and chronic renal disease for cases of renal azotemia The rate of increase from baseline is more indicative

Question 27

Define azotemia.

Answer 27

AZOTEMIA: one or both BUN/CREA is/are elevated = increased nitrogen waste products

Question 28

Azotemia does not occur until ?

Answer 28

a minimum of 75% of nephrons are not adequately functioning

Question 29

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

Answer 29

LATE, early

Question 30

______, ______, _______ provide measurement of Glomerular filtration (GFR) ______ in urine and decrease _________ are indicators of Protein loss in nephron (PLN)

Answer 30

UREA, CREATININE, SDMA Protein, Albumin

Question 31

SDMA may be a promising ______ marker for renal disease

Answer 31

early

Question 32

Renal disease - Morphologic renal lesions of any ____ or ___ - May or may not have ___________ abnormalities related to renal function

Answer 32

size, severity biochemical

Question 33

Diminished renal reserve - GFR ~____% of normal - No ___________ abnormalities - Animal is clinically _________

Answer 33

50, biochemical, healthy

Question 34

Renal insufficiency - GFR ~___-____% of normal - Biochemical abnormalities present in ________ - Animal is often _______ because of decreased concentrating ability

Answer 34

20, 50, serum, polyuric

Question 35

Renal failure - GFR is < ___-___% of normal function - (3?) develop

Answer 35

20-25 Edema, hypocalcemia, and metabolic acidosis

Question 36

End-stage renal disease - GFR is < __% of normal – Patients present with _____ or ______

Answer 36

5 Oliguria, anuria

Question 37

In a case of Isosthenuria, the urine specific gravity is ?

Answer 37

urine specific gravity between 1.008-1.012

Question 38

Hyposthenuria = _____ urine, USG = ?

Answer 38

dilute urine, USG < 1.007 (active process)

Question 39

Oliguria =

Answer 39

markedly decreased urine production

Question 40

Anuria =

Answer 40

no urine produced

Question 41

Stranguria =

Answer 41

straining to urinate

Question 42

Pollakiuria =

Answer 42

increased frequency of urination

Question 43

Azotemia =

Answer 43

increased urea nitrogen with/without increased creatinine

Question 44

Uremia =

Answer 44

excessive urea in blood with clinical signs of renal failure (vomiting, diarrhea, ammoniacal breath odor)

Question 45

Urea is filtered and then _____% goes back into the glomerulus and ___% goes into urine

Answer 45

40, 60

Question 46

What are the causes of pre-renal disease [INCREASED UREA]?

Answer 46

1. Increased protein diet 2. Increased endogenous protein catabolism. May also see this in animals with... - GI bleeding, - fever, - infection, - necrosis, - hyperadrenocorticism - Prolonged exercise

Question 47

Remember, PROTEIN drive BUN synthesis by the liver, and blood is protein-rich

Question 48

↑ production of BUN → ↑ _______ BUN

Answer 48

serum

Question 49

What are the causes of pre-renal disease [INCREASED UREA] in ruminants?

Answer 49

1. Urea from salivary and blood go to rumen - Rumen microflora creates amino acids from urea 2. CAUSES of increased UREA - Rumen stasis - Decreased GFR 3. Urea not as useful indicator of GFR in this specie as in others

Question 50

What can decrease urea?

Answer 50

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)

Question 51

Creatinine is filtered in the _________ and ___% is excreted in the urine.

Answer 51

glomerulus, 100

Question 52

Causes of PRE-renal Increased Creatinine ?

Answer 52

Associated with Muscled individuals, particularly males - Greyhounds, Belgian blue cattle

Question 53

Causes of DECREASED Creatinine ?

Answer 53

1. Young animals 2. Muscle atrophy - Hyperthyroid cat - Older animal - Cachexia Not clinically significant, but may represent poor muscle mass

Question 54

Interpreting the SDMA results: INCREASES in SDMA results --> suggest renal _____ disease - Must interpret alongside: ?

Answer 54

tubular history, clinical signs, PE findings, other markers of renal injury

Question 55

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.)