lab Evaluation of the Renal System

Question 1

Approach to Assessing Kidney Function

Answer 1

1. History and physical exam
2. Anemia – yes or no?
   > possible for chronic kidney disease (normocytic, normochronic, non-regenerative due to decreased erythropoietin)
3. Biochemical profile – urea, creatinine, phosphorus, K+, albumin
   > indicators of reduced GFR
   > high K with evidence of kidney injury = acute
   > with chronic, electrolytes tend to balance out
4. Urinalysis – gross appearance, dipstick, and microscopic examination
5. Bacterial culture and antimicrobial sensitivity
6. Urine protein:Urine creatinine ratio
   > creatinine lost at a steady state, so we can compare things to it

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7. Renal function tests – fractional excretion studies – not terribly common
8. Renal biopsy – not terribly common

Question 2

Laboratory Tests – Diagnosis of Kidney Disease
- on serum

Answer 2

1. Urea, creatinine & phosphorus
   * Serum urea nitrogen, blood urea nitrogen (SUN, BUN)
2. Albumin
   > high = dehydrated
   > low while globulin normal = protein losing nephropathy

Question 3

Laboratory Tests – Diagnosis of Kidney Disease
- on urine

Answer 3

4. USG
5. Urinalysis
6. Urine protein: urine creatinine ratio

Question 4

Azotemia

Answer 4

Increased nitrogenous waste in blood
- Urea, Creatinine, SDMA

Question 5

Urea, Creatinine, SDMA - assess what?

Answer 5

Assess the glomerulus
- Urea, Creatinine, SDMA = GFR
> increase with decreased GFR

Question 6

Proteinuria + decreased albumin (and normal globulins)

Answer 6

PLN

Question 7

what happens to urea in the kidney? is it a good indicator of glomerular function?

Answer 7

40% filtered back in, 60% out
- not the best indicator of glomerular function but we still use it
> non-kidney conditions can affect levels too

Question 8

Increased Urea – Prerenal reasons

Answer 8

• increased Protein in diet
• increased Endogenous protein catabolism
  > GI bleeding, fever, infection, necrosis, hyperadrenocorticism (steroid hepatopathy)

Question 9

Increased Urea – Prerenal – Ruminant specific reasons, what this means

Answer 9

• Ruminants – salivary & blood urea go to rumen
• Rumen microflora create amino acids from urea
  > Increased urea can be caused by:
  1. Rumen stasis
  2. Decreased GFR
• Urea not as useful an indicator of GFR in ruminants as in other species

Question 10

Decreased Urea reasons

Answer 10

1. Hepatic insufficiency (>80% loss)
2. Portosystemic shunt (PSS)
3. Decreased water resorption in tubules
   * e.g., Osmotic diuresis
   * Water resorption creates concentration gradient for urea resorption

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(4. Loss caudal GIT – horse)
(5. protein malnutrition)

Question 11

creatinine - what happens to it as it enters the kidney?
- what is it?

Answer 11

creatinine > 100% goes into ultrafiltrate (as with everything else) and 1005 goes out into urine
- made from muscle creatine phosphate which is an energy storage molecule (produced by breakdown of muscle at steady state)

Question 12

Increased Creatinine – Prerenal reasons

Answer 12

1. increased Crt well-muscled individuals, particularly males
   * Greyhounds, Belgian blue cattle

Question 13

Decreased Creatinine reasons

Answer 13

• Young animals
• Muscle atrophy
  > e.g., hyperthyroid cat, older animal, cachexia

Question 14

SDMA - what happens to it in the kidney

Answer 14

• produced at steady state in the body, not influenced by muscle mass
• 100% comes out in urine

Question 15

Symmetric Dimethylarginine – Interpretation
- what do we need?
- use?
- gold standard?

Answer 15

• Still need a full UA
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  Early CKD – Increased SDMA, creatinine WNL
• More sensitive than creatinine
• Muscle mass decreased? No problems!
• Feline CKD 17 mo before creatinine increased
• Canine CKD ~10 mo before creatinine increased
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  Gold standard: use both creatinine and SDMA to stage stable CKD patients

Question 16

Interpreting Azotemia and USG

Answer 16

1. Azotemia + isosthenuria (USG 1.007 – 1.012)
   * KIDNEY FAILURE
   * Especially if dehydrated
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2. Isosthenuric but NOT azotemic
   * Further assessment required
   > What is hydration status? Might be appropriate?
   > Interference w. concentrating capacity
   >If it’s not repeatable, it’s not significant
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Question 17

Postrenal Azotemia
- when do we see this?

Answer 17

Obstruction of urinary outflow distal to nephron
* FLUTD (feline lower urinary tract disease)
* Goat urolithiasis / foal bladder rupture
> Rupture & leakage of urine into the peritoneal cavity
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* USG not helpful in determining postrenal azotemia
> USG species-appropriate… initially
* Prolonged blockage > kidney injury > kidney failure
> e.g., hydronephrosis, shock, etc.

Question 18

Proteinuria - types

Answer 18

1. Prerenal (increased protein in blood)
2. Renal (glomerular & tubular)
3. Postrenal (hemorrhagic / inflammatory)

Question 19

Prerenal Proteinuria
- what do we see?
- reasons

Answer 19

Protein normal or increased on the biochemical profile
* Physiologic – e.g., fever, exercise
* Hypertension – e.g., from endocrinopathies, heart disease > increased pressure forcing proteins out
* Multiple myeloma (Bence-Jones proteinuria)
* Hemoglobinuria
* Myoglobinuria
* Post-colostral proteinuria

Question 20

Renal Proteinuria - types, reasons
- what do we see?

Answer 20

Glomerular proteinuria
* Hypoalbuminemia noted on biochem
* Some injury to filtration barrier

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Tubular proteinuria
* Early stages, albumin normal on biochem
* Usually associated w. acute / congenital kidney diseases
> e.g., Fanconi’s syndrome, admin of gentamycin
* Proximal tubules damaged / defective – filtered proteins not resorbed
* Loss of low MW proteins and amino acids

Question 21

Postrenal Proteinuria
- causes

Answer 21

Postrenal proteinuria (hemorrhagic / inflammatory)
* Hemorrhage into genitourinary tract
> Renal or bladder calculi, impaired hemostasis, blood vessel damage from inflammation, trauma, neoplasia, etc.
* With inflammation will often see pyuria and sometimes “sub-optimal” USG

Question 22

UPCR – Interpretation
(urine protein : creatinine ratio)
- normal levels
- purpose of measurement
- what do do with results?

Answer 22

Normal ratio:
- Dog or cat: <0.2

Borderline:
- Dog: 0.2-0.5
- Cat: 0.2-0.4
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* Estimate quantity of urinary protein excreted / d
* Proteinuric: demonstrate persistence by re-evaluating in 2 to 4 weeks
* Borderline: re-evaluate within 2 months
* Most <0.2
* Proteinuria between 0.2 – 2.0 is tubular or glomerular
* Proteinuria >2.0 is considered glomerular
> UPCR >2, no need to demonstrate persistence = severe proteinuria

Question 23

Nephrotic Syndrome – Protein-losing nephropathy leading to abdominal transudation
- what do we see?

Answer 23

1. Glomerular disease
2. Hypoalbuminemia
3. Hypercholesterolemia
4. Edema / abdominal transudation
   * Loss of plasma oncotic pressure
5. Hypercoagulable state
   * Loss of antithrombin
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   * In Short:
   When there’s Protein in the Urine
   LOOK AT CHOLESTEROL & REMEMBER ANTITHROMBIN
   * Animal in hypercoagulable state!

Question 24

USG for cat dog, cow, horse?
- what does USG tell us?

Answer 24

cat: 1.035
dog: 10.30
cow, horse: 1.025
> Interpret with hydration status
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- is assessing distal collecting duct, as this is where we bring water back into the body
> if we are losing water, we have more dilute urine, if we are keeping water in the body we have more concentrated urine
> ADH receptors allow insertion of aquaporins to bring water back in

Question 25

USG Isosthenuria from Kidney Disease
- USG level
- what it means

Answer 25

USG: 1.008 – 1.012
* 2/3 of nephrons damaged
* Kidney incapable of producing concentrated urine
* Animal polyuric
> not enough places for aquaporins to bring water back into the body

Question 26

DDx Polyuria/Isosthenuria > when do we ascribe this to kidney disease?

Answer 26

• Acute kidney injury
• Chronic kidney disease
• NB: cats > even is chronic kidney disease, they may not be isothenuric, as they are super good at concentrating. Look for other signs. Anything less than 1.035 is bad for cats.

Question 27

USG Isosthenuria – when it’s not the kidneys’ fault

Answer 27

• Diuresis / Endocrine / Drugs
• Pyometra / Pyelonephritis
• Medullary washout
• Hypercalcemia
• Fanconi syndrome

Question 28

Hyposthenuria - what is this?
- causes?

Answer 28

USG <1.008 = active process
* Overhydration/Euhydration
* Central or nephrogenic diabetes insipidus
* Primary polydipsia

Question 29

Acute Kidney Injury (AKI)
- how do we identify?
- what will we see?
- causes?
- prognosis?

Answer 29

• History… acute
• Assuming no other disease – good body condition & not anemic
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  Marked decrease in GFR – oliguria / anuria
• Abrupt azotemia & hyperphosphatemia
• Hyperkalemia
• Commonly associated with: toxicants, renal ischemia, or infection
  > Reversible if primary insult resolves
  AnQfreeze
  > Death or CKD if not resolved

Question 30

Diagnosing Acute Kidney Injury

Answer 30

USG is variable
* Urine in bladder produced prior to insult?
* Consider polyuric states and ↓ concentrating capacity
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Abrupt decrease in GFR hours – days
* Animal usually oliguric or anuric
* May have hyperkalemia & acidemia
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* May have proteinuria
* May see cellular casts on urinalysis

Question 31

Chronic Kidney Disease (CKD) - signs

Answer 31

i. Poor body condition

ii. Anemia – decreased EPO production

iii. Polyuria, isosthenuria, azotemia & hyperphosphatemia

iv. Electrolytes stable and no A-B abnormalities until next insult
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- With further kidney injury – metabolic acidosis
> Kidneys cannot regulate body water or electrolyte balance
- May have uremia
> Neuro, GIT, CV signs, etc.

Question 32

AKI / End-Stage CKD (they are similar for this)
- Acid – Base & Electrolyte Imbalances

Answer 32

Metabolic acidosis is noted
* increased urinary loss of HCO3-
* decreased tubular secretion of H+ ions
* Retention of K+ with oliguric / anuric kidney injury
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Hyperkalemia:
* Life-threatening in AKI or post-renal conditions associated w. oliguria or anuria

Question 33

Summary – Kidney Function
1. Azotemia & concentrated urine =
2. Azotemia & dilute urine =
3. Decreased serum albumin + proteinuria generally indicates….
4. Coarse Granular Casts =
5. Isosthenuria ~ how nonfunctional
6. Azotemia ~ how nonfunctional
7. Ethylene glycol toxicosis

Answer 33

1. Azotemia & concentrated urine = pre-renal
2. Azotemia & dilute urine = renal unless some other reason can’t concentrate such as medullary washout
3. Decreased serum albumin + proteinuria generally indicates glomerular damage
   * Unless there’s a monoclonal gammopathy, inflammation/neoplasia/hemorrhage involving the urinary tract
4. Coarse Granular Casts = tubular damage
5. Isosthenuria ~66% nonfunctional
6. Azotemia ~75% nonfunctional
7. Ethylene glycol toxicosis – clinical signs, increased AG, increased osmol gap, ethylene glycol detection kit (NB: it only detects ethylene glycol), calcium oxalate monohydrate crystals in urine

Question 34

Summary – Chronic Kidney Disease vs. Acute Kidney Injury

Answer 34

1. Duration of signs – long-standing CKD, acute AKI
   - Electrolytes and acid-base balance generally WRI with CKD – until terminal CKD
   - Acid-base abnormalities, and particularly increased K often noted with AKI
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2. Speed of onset of azotemia – slower CKD, fast AKI
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3. Amount of urine production – high CKD, low-absent AKI
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4. Other findings: anemia CKD, no anemia with AKI, hypocalcemia end-stage CKD, hypokalemia in feline CKD patients
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5. Body condition – poor CKD, good with AKI
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6. ± Reversibility of AKI
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7. Usual causes of AKI: toxicants (EG), infection, anesthesia with insufficient fluids admin ± pain meds to dehydrated animal
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   for 4 and 5:
   - So long as the animal didn’t have a concurrent disease causing anemia or poor body condition