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1
Q

Examination of kidney function are based on changes of?

A
  • body weight
  • body condition
  • general status, behaviour
  • fur quality, skin turgor
  • shape of the body
  • Water intake
  • Urine output
2
Q

What can changes is body weight show us?

A

In case of edema or ascites formation body weight can be increased, in case of chronic kidney disease, animals usually loose weight, (because of decreased appetite, gastritis, vomiting, polyuria, dehydration)

3
Q

What can changes is body condition show us?

A

patients with chronic kidney failure are generally in poor condition

4
Q

What can changes is general status, behaviour show us?

A

in case of severe kidney disease, patients are usually depressed, in case of slowly progressive chronic renal diseases owners have time to get used to the slowly
decreasing activity and worsening condition of their pets. (Sometimes chronic kidney disease finally leads to acute renal failure, with sudden obvious worsening of the general status of the animal!)

5
Q

What can changes is fur quality, skin turgor show us?

A

unkempt haircoat because of bad nutritional status (vitamin and other nutrient deficiencies) and behavioural changes (animals with severe diseases usually do not
groom), decreased skin turgor due to dehydration (usually in case of chronic renal failure)

6
Q

What can changes is shape of the body show us?

A

swelling of limbs and ventral parts of the thoracic or abdominal region: edema formation under the skin, sometimes abdominal distension due to ascites formation

7
Q

What can changes is water intake show us?

A

acute: decreased, chronic: increased, in general

8
Q

What can changes is urine output show us?

A

(quantity, posture, frequency)

  • oliguria, anuria in case of acute kidney failure
  • polyuria in case of chronic renal failure.
9
Q

Values of water intake:

  1. generally
  2. maximum in dog and cat
  3. calculating: in general dog and small dog (10 kg bw)
  4. general cat (3 kg)
  5. Horse
  6. Cattle
  7. Sheep, goat
  8. Swine
A
  1. generally: 20-40 ml/kg body weight/day
  2. maximum: 80 ml/kgBW/day-dog, 40 ml/kgBW/day-cat
  3. calculating: general dog (30 ml/kg bw): 1 l/day, small dog: 3 dl/day
  4. general cat: 1 dl/day (100 ml/day)
  5. Horse: 20-30l/day
  6. Cattle: 20-40 l/day (in milking cows water intake can exceed 100l - for the prod of 1l of milk, approx. 4 l of water intake is necessary)
  7. Sheep, goat: 1-2 l/day
  8. Swine: 3-8 l/day
10
Q
General normal urine output:
dog
cat
horse
cattle
sheep, goat
swine
A

dog: 20-40 ml/kg body weight/day
cat: 10-20 ml/kg body weight/day
horse: 5-15 l/day
cattle: 20-40 l/day
sheep, goat: 1-2 l/day
swine: 3-8 l/day

11
Q

What is the diagnosis of kidney failure based upon?

A

Anamnesis, physical examination of the patient and laboratory examination of blood and urine

12
Q

When does the general blood parameters of kidney function show increased conc.?

A

General blood parameters of kidney function (plasma or serum urea and creatinine level show increased conc, if 75% of nephrons are inactive

13
Q

Examination of the glomerular function

A
  • Blood urea (BUN=blood urea nitrogen) conc in blood plasma
  • Creatinine concentration in blood plasma
  • Plasma urea (mmol/l) / plasma creatinine (µmol/l)
  • Changes in plasma urea and creatinine conc not due to renal disease:
    1. Creatinine clearance
    2. Urinary TP conc and Urinary TP / urinary creatinine ratio
    3. Other laboratory parameters:
  • Radioisotopic methods
  • C-inulin clearance
  • H-tetraaethyl-ammonium-chloride clearance
14
Q

UREA:

  1. End product of?
  2. What is needed in the process of urea formation?
  3. Is it toxic?
  4. Can it penetrate through membranes?
  5. How is it excreted?
A
  1. Urea is an end product of the Ornitine-cycle (in liver) in order to detoxify NH3 absorbed from the intestines (NH3 is a breakdown product of proteins).
  2. Energy of three ATP molecules is needed for the whole cycle.
  3. Urea is a non toxic, but osmotically active
    molecule, which is a member of the formula expressing serum or urine osmolality.
  4. It is a small molecule hence it can penetrate through membranes.
  5. Urea is filtered through the glomeruli and reabsorbed from the tubules.
15
Q

What is azotaemia

A

Can be prerenal, renal or postrenal.

Accumulation of nitrogen containing protein breakdown products in the blood (for example: urea).

16
Q

What is ureamia?

A

Can be prerenal, renal or postrenal.
Severe increase in the level of nitrogen containing protein breakdown products and toxins in the blood, leading to obvious clinical signs (anorexia, depression, vomiting, diarrhea, lethargy, stomatitis, gastritis, etc.)

17
Q

Determination of BUN conc in blood plasma

  • Background of tests
  • Methods
  • Normal value
A

-Each test starts with urease enzyme splitting urea into two NH3 molecules
- Method 1) Urea-colour test:
NH3 in water forms NH4+. NH4+ forms green colour in alkalytic pH with Na-hypochloride and salycilic acid.
- Method 2) Enzymatic urea method: Change of NADH + H+ -> 2 NAD+ causing light emission change.
- Normal value: 8-10 mmol/l

18
Q

Causes of increased blood urea concentration

A
  1. ) Prerenal factors:
    - Increased Nitrogen (protein) intake
    - In ruminants: poor Energy status in the rumen.
    - Increased Intestinal protein catabolism
    - Intestinal or gastric bleeding
    - Haemolysis
    - Decreased blood perfusion of the kidneys
  2. ) Renal factors:
    - Kidney function, decreased amount of functionally active nephrons, decreased tubular function
  3. ) Postrenal factors:
    - Inhibition of urine flow through the lower urinary tract
    - Rupture of the kidneys, urether, urinary bladder, or urethra: “uroperitoneum”
19
Q

What happens with the proteins in ruminants?

A

90% of the protein intake is catabolysed then resynsthesised by the ruminal microorganisms.
10% of the protein intake is “by-pass” protein, which is passed to the intestines then digested and absorbed.

20
Q

What happens with the urea during energy deficiency in ruminants?

A

The ruminal micro-organisms can not produce enough protein so the catabolysed protein is passed to the bowels and absorbed from there or absorbed directly from the ruminal wall, and transported to the liver via the portal vessels. Increased NH3 load forces the liver to produce increased amount of urea, which is measurable in the blood and milk.

21
Q

Milk urea concentration

A

2-3 mmol/l

22
Q

Energy deficiency (without liver function disorder) in ruminants causes?

A
  • Increased urea concentration in blood and in milk
  • increased ketone concentration in blood, urine and milk
  • decreased glucose concentration in blood
  • increased total lipid concentration in the blood.
23
Q

Creatinine:

  1. Function
  2. Utilised to form?
  3. How much creatinine is formed from creatin every day?
  4. Excretion
A
  1. Important constituent of muscle energy stores.
  2. Creatinine is utilised to form creatin. From creatin sarcosin is formed in the muscles.
  3. 2% of total creatin is broken down to creatinine every day
  4. Creatinine is generally filtered through the glomeruli and is not reabs. from tubules (in some instances when plasma creatinine level is high and there is an increased filtration of it in the glomeruli, tubular fluid contains a great amount of conc. creatinine, and quite a few amount is secreted in the tubules). –> good indicator for GFR
24
Q

Determination of Creatinine concentration in blood plasma

A
  • Method 1) Jaffe method:
    (commonly used, colorimetric, kinetic)
    Creatinine forms yellow-orange complex with picric acid on alkalytic pH. Ion bounds. After 10 seconds preincubation the change of colour formation is measured by spectrophotometer within 2 minutes on 492 nm wavelength. Kinetic reaction and linear till 442 µmol/l.
  • Method 2) Enzymatic method:
    Reagent 1 and sample should be preincubated for 5 minutes together and measured (E1) then Reagent 2 (4-aminoantipyrine, creatininase, peroxydase) should be added and measured (E2) on 555 nm wave length. The change should be measured for standard and sample. Conc. can be calculated by the formula:
    [sample(E2 -E1) / standard (E2 -E1)] x Standard conc = Sample conc
    Kinetic reaction and linear till 1770 µmol/l.
25
Q

What is the result of Jaffe method influenced by?

A

Highly influenced by haemolysis, and jaundice

26
Q

Normal value of Creatinine concentration in blood plasma

A

50-200 µmol/l

27
Q

Blood creatinine depends on

A
  • Meat content of the diet (increased or decreased) - some creatinine is formed during digestion of meat in the diet, but mostly the high protein diet has a long term indirect effect on blood creatinine conc through increasing the body’s muscle mass.
  • State of muscles: muscle necrosis causes increased creatinine level, cachexia causes decreased creatinine level
  • Kidney - glomerulus function (decreased filtration rate)
28
Q

Which determination is more reliable of serum/plasma creatinine and serum/plasma urea concentration when we want to assess the kidney function.

A

Determination of serum/plasma creatinine level

29
Q

When does creatinine concentration show a 100-150% increase?

A

When the GFR (glomerular filtration rate) is decreased to the 1/5-1/4 of the normal, creatinine
concentration shows a 100-150% increase

30
Q

Plasma urea/plasma creatinine ratio:

  1. When do we use this ratio?
  2. Normal value
  3. Causes of abnormal level
  4. Reliability
A
  1. If both parameters are increased in the blood and we are interested in the cause of the increase.
  2. Normal value: 0.1-0.06
  3. Causes of abnormal level:
    > 0.06:
    - prerenal kidney failure: decr blood supply of the kidney: shock, dehydration, hypotension, obstruction or compression of kidney arteries, vasoconstriction of kidney vessels
    - postrenal causes: ureter, urethra, urinary bladder obstruction, compression
    - extrarenal causes: not renal incr of urea conc in blood plasma
    0.06 (0.02-0.05): renal (sometimes postrenal causes)
  4. Since many factors influence the plasma urea concentration, the plasma urea:creatinine ratio has
    limited reliability and give only orientative suggestion about the cause.
31
Q

Causes for high urea, low, normal creatinine

A
High urea:
 increased protein intake
 gastrointestinal bleeding
 fever (increased protein catabolism)
 tetracycline, steroid treatment
 haemolysis
 necrotic processes
 hyperthyroidism (increased protein catabolism)
 catabolic drugs (amphetamine)
Low, normal creatinine
 cachexia
 chronic muscle atrophy
32
Q

Causes for low, normal urea, high creatinine

A
Low, normal urea:
 liver failure, portosystemic shunt
 polyuria-polydypsia
 low protein intake
 anabolic steroids
High creatinine:
 inflammation of muscles (myocarditis, rhabdomyolysis)
 rhabdomyosarcoma
 muscle trauma
 increased meat intake
33
Q

Which molecule is a good indicator of the glomerular function and why?

A

Normally creatinine is filtered by glomeruli and not reabsorbed and not secreted by tubules. Due to this character creatinine is a good indicator of the glomerular function, and knowing the filtered quantity GFR can be calculated. In some cases, when creatinine level is slightly high in plasma ( 120 µmol/l) some undergo tubular secretion, too. So, creatinine clearance can be 20-30% higher than the GFR.

34
Q

Which molecule is a good indicator of the glomerular function and why?

A

Normally creatinine is filtered by glomeruli and not reabsorbed and not secreted by tubules. Due to this character creatinine is a good indicator of the glomerular function, and knowing the filtered quantity GFR can be calculated. In some cases, when creatinine level is slightly high in plasma (> 120 µmol/l) some undergo tubular secretion, too. So, creatinine clearance can be 20-30% higher than the GFR.

35
Q

Changes in plasma urea and creatinine concentration not due to renal disease: methods

A
  1. Creatinine clearance
  2. Urinary total protein concentration and Urinary total protein / urinary creatinine ratio
  3. Other laboratory parameters:
    * Radioisotopic methods
    * C-inulin clearance
    * H-tetraaethyl-ammonium-chloride clearance
36
Q

Method: Creatine clearence

  1. normal value
  2. Calculation
  3. Generally used formula
A
  1. normal value: 2.4-5 (dog), 1.9-5 (cat)
  2. normal value
  3. Calculation: C= U x V/P
    C = clearance
    U = creatinine concentration in urine
    P = creatinine concentration in plasma
    V = urine output / minute (2-5 ml/kgbw/min.)
  4. Generally used formula:
    urine output (ml) x urinary creatinine (µmol/l) / time (minute) x plasma creatinine (µmol/l) x kgbw = creatinine clearance (ml/min/kg)
37
Q

Analysing methods for urinary total protein concentration

A
  • Objective protein measurements (i.e. Biuret reaction: sensitivity: 62-80 g/l - linearity: max. 100 g/l, ultrasensitive protein measurements sensitivity: 0.2-4 g/l)
  • Specific protein determination - electrophoresis, immune-electrophoresis, Western-blot analysis
  • Proteinuria/day: < 20 mg/kgbw/day
  • Urinary protein/creatinine ratio < 1
38
Q

What is an essential indicator for glomerular dysfunction

A

Proteinuria (mainly albuminuria)

39
Q

Urinary total protein/creatinine ratio:

  1. When is it used?
  2. How do we convert the creatinine to g/l?
  3. Physiological value of the TP:creatinine ratio?
  4. Caues for abnormal values?
  5. Normal value in dog
  6. Cause of increased value in dog?
A
  1. When equivocally high TP conc is measured in the urine, it can be useful to detect the TP (g/l) / creatinine (µmol/l) ratio, because it is not influenced by the specific gravity of the urine.
  2. By multiplying the µmol/l by 0.000113.
  3. < 1.
  4. If the value is > 1 it means that a 20 kg BW dog passes at least 30 mg/kgbw/day or 1 g/day proteins.
    - If the value is bw 1-5, the proteinuria is usually prerenal.
    - In some renal diseases (glomerulonephropathy) protein loss increases and the creatinine excretion does not show change, the value of the ratio becomes increased.
    - In case of other renal diseases (tubulonephropathy) protein loss does not show change, the creatinine excretion becomes decreased, the value of the ratio is also increased ( > 5).
  5. Normal value in dog: < 0.078
  6. If the ratio is more than 0.131, there is pathological proteinuria
40
Q

Analysis of tubular function - methods

A
  1. Basic tests
  2. Analysis of enzymuria
  3. Urinary sediment analysis
  4. Water deprivation test
  5. Tubular clearance examinations
41
Q

Specific gravity analysis of urine and water deprivation test - normal value at 5% dehydration

A

1050-1080 g/l

42
Q

Calculation of fractional electrolyte clearance %

A
i.e. for Na+:
(urinary Na+/plasma Na+ / urinary creatinine/plasma creatinine) x 100
Na+ < 1 (reabsorption!)
K+ < 24
Cl- < 1,3
inorganic phosphate < 39 dog, < 73 cat
43
Q

What happens with the electrolytes during tubular damage, generally?

A

Na+ reabsorption decreases (increased urinary sodium conc, and hyponatreamia), and usually K+ reabsorption increases (decr urinary potassium conc, hyperkalaemia).

44
Q

Which enzymes does tubular cells contain?

A

ALKP: Alkaline phosphatase
GGT: Gamma-glutamyl transferase

45
Q

Analysis of enzymuria:

  1. When is the enzymes increased?
  2. Which level must the values must be referred to and why?
  3. Calculation
  4. Normal values
A
  1. In case of acute/peracute tubular damage (for example in case of oxalatenephrosis)
  2. To the creatinine levels in order to exclude the misdiagnosis caused by the high enzyme level in concentrated urine.
    • Alkaline phosphatase (U/l) / Creatinine (µmol/l)
      normal value: 0.02
      - Gamma-glutamyl transferase (U/l) / Creatinine (µmol/l)
      normal value: 0.01
46
Q

When do we perform water deprivation test?

A

We perform this test when we want to evaluate the causes of polyuria and polydypsia

47
Q

Water deprivation test in hospitalised patients (1) - needed parameters

A

body weight, haematocrit, creatinine, urea, total protein, osmolality

48
Q

Result of Water deprivation test in hospitalised patients (1)

A

1) 1050-1080 g/l: diagnosis: psychogenous polydypsia
2) 1001-1007 g/l: diagnosis: tubular cell damage or decreased ADH function
(give ADH im. or intranasally and check specific gravity again 60 min after adm of the drug)
a) 1050-1080 g/l: diagnosis: central diabetes insipidus
b) 1001-1007 g/l: diagnosis: peripheral diabetes insipidus

49
Q

When is water deprivation test in hospitalised patients contraindicated?

A

In case of high urea conc in the blood (>25mmol/l), and in case of animals having diabetes mellitus! You must not continue water deprivation, if there is hyposthenuria at 5% dehydration.

50
Q

When is it not necessary to continue the Water deprivation test in hospitalised patients and why?

A

If specific gravity reaches 1020-1030 g/l, as tubular functions seems to be normal.

51
Q

Water deprivation test in hospitalised patients:
What can we suspect if:
1. the urine samples are hypostenuric?
2. If specific gravity shows increase 60 minutes after drug administration (> 1030g/l)
3. If urine remains hypostenuric after drug adm.?

A
  1. We can suspect diabetes insipdus.
  2. If specific gravity shows incr. 60 min after drug adm. central diabetes insipidus seems to be proven, as substitution therapy helped.
  3. If urine remains hypostenuric after drug adm. we can suspect renal diabetes insipidus, as ADH could not bind to receptors of damaged tubular cells.
52
Q

What can be used for tubular clearance examinations

A

Para-amino-hyppuric acid (PAH), diodrast, phenolred clearance. These molecules are only secreted in the tubules, not reabsorbed.

53
Q

Analysis of postrenal kidney failure

A
  • Analysis of creatinine and urea conc in ascites fluid (uroperitoneum)
  • Urinary sediment analysis
54
Q

Laboratory diagnosis of acute kidney failure

  1. Anamnesis
  2. General considerations
  3. Blood tests
  4. Urinalysis
A
  1. Anamnesis: oliguria, anuria, recumbence, fatigueness, etc.
  2. General considerations:
    - Clinical status: Ht, ionogram, acid-base
    - Kidney function test: urea, creatinine and alpha-amylase levels in plasma and urine
    - Urinalysis
  3. Blood tests:
    - Ht: increased
    - Red blood cell damage: Burr-cells, schysocytes
    - K+: increased
    - Na+: increased or same
    - Ca2+: increased or same
    - Urea: increased
    - Creatinine: increased
    - Inorganic phosphate: increased
    - TP: increased
    - Amylase: increased
    - Lipase: increased
    - pH: decreased
    - Plasma osmolality: increased
  4. Urinalysis:
    - sediment: casts, tubular epithelial cells, neutrophils, RBCs,
    - upper layer: prot.++/+++, glucose +/-, GGT incr., ALKP incr., specific gravity incr.
55
Q

Laboratory diagnosis of chronic kidney failure

  1. Anamnesis
  2. Blood tests
  3. Urinalysis
A

Laboratory diagnosis of chronic kidney failure
1. Anamnesis: Polyuria, polydypsia, weight loss, dehydration, vomiting, anaemia etc.
2. Blood tests:
- Ht/K+/Na+/Urea/Creatinine: incr./decr.same
- Non regenerative anaemia
- Inorganic phosphate: incr.
- Ca2+/TP/Plasma osmolality: decr./same
- Amylase/Lipase: incr./same
pH: decr.
4. Urinalysis: casts, tubular epithelial cells (lipid droplets), prot..+/++, glucose?, GGT ?, ALKP ? , specific gravity decr.

56
Q

Laboratory alterations in oliguria:
osmolality in:
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: >500 (hum)

2. Acute renal or postrenal: <400 (hum)

57
Q

Laboratory alterations in oliguria:
urinary Na+ (mmol/l) in:
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: <10-20 due to hypotension, aldosterone function increases
  2. Acute renal or postrenal: >25 no effective aldosterone function
58
Q

Laboratory alterations in oliguria:
urinary creatinine / plasma creatinine in:
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: >20:1 still functioning renal tissue

2. Acute renal or postrenal: <10:1 non functioning renal tissue

59
Q

Laboratory alterations in oliguria:
plasma urea / plasma creatinine in:
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: >0,1 (>0,06)

2. Acute renal or postrenal: 0,02-0,06

60
Q

Laboratory alterations in oliguria:
specific gravity
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: >1,030 g/ml

2. Acute renal or postrenal: 1,008-10,08 g/ml

61
Q

Laboratory alterations in oliguria:
urine quantity in:
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: oliguria

2. Acute renal or postrenal: acute: oliguria, postrenal: anuria (sometimes: polyuria)

62
Q

Laboratory alterations in oliguria:
TP in urine in:
1. Prerenal
2. Acute renal or postrenal

A
  1. Prerenal: proteinuria (middle)

2. Acute renal or postrenal: proteinuria (high) (in postrenal it remains unchanged in the beginning)