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MODULE 17 - Urinary, Endocrine and Oncological Disease > PATHOLOGY - Proteinuria and Protein Losing Nephropathy (PLN) > Flashcards

PATHOLOGY - Proteinuria and Protein Losing Nephropathy (PLN) Flashcards

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1
Q

What is the function of the glomerular filtration barrier?

A

The glomerular filtration barrier acts to filter the blood based on particle size and charge to produce ultrafiltrate

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2
Q

How do proteins usually move through the kidneys?

A

Usually, very few proteins filter through the glomerular filtration barrier and the majority remain in the circulation. Any proteins that do filter into the ultrafiltrate are usually reabsorbed into the circulation at the proximal convoluted tubule via endocytosis

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3
Q

What are the four classifications of proteinuria?

A

Physiological proteinuria
Pre-renal proteinuria
Renal proteinuria
Post-renal proteinuria

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4
Q

What are the four causes of physiological proteinuria?

A

Strenuous exercise
Seizures
Pyrexia
Stress

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5
Q

What causes pre-renal proteinuria?

A

Pre-renal proteinuria is caused by excessive concentrations of proteins reaching the kidneys resulting in reabsorption of the proteins at the proximal convoluted tubule becoming overwhelmed

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6
Q

What causes renal proteinuria?

A

Renal inflammation
Glomerular disease
Tubular disease
Chronic kidney disease (CKD)

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7
Q

What is a key feature of renal proteinuria?

A

Renal proteinuria is persistent whereas physiological, pre-renal and post-renal should resolve when the underlying cause is resolved

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8
Q

What causes post-renal proteinuria?

A

Post-renal proteinuria is caused by inflammation of the ureter, bladder, urethra or prostate

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9
Q

How do you diagnose proteinuria?

A

Proteinuria can be diagnosed on a urine dipstick

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10
Q

Which protein are urine dipsticks most sensitive to?

A

Albumin

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11
Q

What can cause false positives for proteinuria on a urine dipstick?

A

Alkaline urine
Sample contamination

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12
Q

What can cause false negatives for proteinuria on a urine dipstick?

A

Acidic urine
Bence Jones proteinuria

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13
Q

How does Bence Jones proteinuria cause a false negative on a urine dipstick?

A

Urine dipsticks are most sensitive to albumin but not Bence Jones proteins which are produced in excess in conditions such as multiple myeloma

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14
Q

How do you approach investigating the cause of proteinuria?

A
  1. History and clinical examination to rule out physiological proteinuria
  2. Haematology and biochemistry to rule out pre-renal causes of proteinuria
  3. History, clinical examination, urinalysis, culture and sensitivity and diagnostic imaging to rule out causes of post-renal proteinuria
  4. If all other causes ruled out, consider renal proteinuria and do a urinalysis and urine culture and sensitivity
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15
Q

What are the purposes of quanitifying proteinuria?

A

Evaluates the severity of the lesions
Assess disease progression
Assess response to treatment

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16
Q

What can be used to quantify proteinuria?

A

Urine protein:creatinine ratio (UP:C)

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17
Q

How do you carry out a urine protein:creatinine ratio (UP:C)?

A

Take three urine samples over two weeks and check that the proteinuria is persistent. If it is persistent, pool these samples together and send it to the laboratory. Be aware that only when urine sediment results are negative can you interpret the urine protein:creatinine (UP:C) ratio as the protein content can be altered by inflammation and gross haematuria. If either of these are present, manage these conditions and re-evaluate the urine protein:creatinine (UP:C) ratio

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18
Q

What are the four main causes of renal proteinuria?

A

Renal inflammation
Glomerular disease
Tubular disease
Chronic kidney disease (CKD)

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19
Q

How does renal inflammation cause proteinuria?

A

Renal inflammation will increase glomerular vascular permeability resulting in the leakage of serum proteins into the ultrafiltrate

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20
Q

What are the key indicators of proteinuria secondary to renal inflammation?

A

Renal pain on palpation
Haematuria
Leukocytosis on haematology
Leukocytes in the urine
Bacteria in the urine
Changes on diagnostic imaging indicative of renal inflammation

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21
Q

How does glomerular disease cause proteinuria?

A

Glomerular disease causes glomerular damage and increases glomerular permeability which results in the leakage of serum proteins into the ultrafiltrate

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22
Q

How does the urine protein:creatinine (UP:C) ratio typically present in patients with proteinuria secondary to glomerular disease?

A

The urine protein:creatinine (UP:C) ratio tends to be high (more than 2) in patients with glomerular disease

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23
Q

Which species are more prone to glomerular disease?

A

Dogs are more prone to glomerular disease

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24
Q

How do tubular diseases cause proteinuria?

Tubular diseases are relatively rare

A

Tubular diseases cause reduced reabsorption of filtered proteins at the proximal convoluted tubules

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25
How does the urine protein:creatinine (UP:C) ratio typically present in patients with proteinuria secondary to tubular disease?
The urine protein:creatinine ratio (UP:C) tends to be low (less than 2) as the glomerulus will prevent filtration of most proteins
26
Give two examples of tubular diseases
Fanconi syndrome Leptospirosis
27
How does chronic kidney disease (CKD) cause proteinuria?
Nephrons are damaged and lost due to chronic kidney disease (CKD) and in the early stages of disease the remaining functional nephrons will hypertrophy to compensate. As a result, this will increase the glomerular filtration rate (GFR) and hyperfiltration secondary to glomerular hypertension *(remember GFR is driven by hydrostatic pressure)* which will result in increased excretion of proteins into the ultrafiltrate. CKD also results in tubular damage which results in decreased reabsorption of filtered proteins at the proximal convoluted tubule
28
How does the urine protein:creatinine (UP:C) ratio typically present in patients with proteinuria secondary to chronic kidney disease (CKD)?
The urine protein:creatinine ratio (UP:C) tends to be low (less than 2) unless the CKD was triggered by glomerular disease
29
How does proteinuria increase the risk of going into end-stage chronic kidney failure?
Proteinuria increases the risk of developing end-stage chronic kidney failure as excess protein in the urine can cause renal inflammation which will cause further renal damage and further increase vascular permeability and protein loss into the ultrafiltrate
30
What is a protein losing nephropathy (PLN)?
Protein losing nephropathy (PLN) is the severe loss of serum proteins into the urine as a result of glomerular disease, resulting in decreased serum protein levels
31
What are three of the main causes of protein-losing nephropathies (PLNs)?
Developmental abnormalities of the basement membrane Glomerular amyloidosis Glomerulonephritis *(main cause)*
32
Which dog breeds are predisposed to developmental abnormalities of the basement membrane of the glomerular filtration barrier?
Springer spaniels Bull terriers
33
Which dog breeds are predisposed to glomerular amyloidosis?
Shar pei Beagle
34
Which cat breeds are predisposed to glomerular amyloidosis?
Abyssinian Siamese
35
What is glomerulonephritis?
Glomerulonephritis is a group of conditions in which antigen-antibody complexes are deposited in the glomeruli
36
What are the two main causes of glomerulonephritis?
Persistent antigenic stimulation Idiopathic
37
How does persistent antigenic stimulation cause glomerulonephritis?
Persistent antigenic stimulation leads to the production of large quantities of antibodies against these antigens. They form antigen-antibody complexes which are depositied in the glomeruli where they will cause inflammation and glomerular disease resulting in a protein-losing nephropathy (PLN)
38
What are some of the main causes of persistent antigenic stimulation?
Chronic inflammation Chronic infection Neoplasia
39
What are the early clinical signs of a protein-losing nephropathy (PLN)?
Asymptomatic Weight loss Lethargy Anorexia
40
What are the later clinical signs of a protein-losing nephropathy (PLN)?
Ascites Pleural effusion Subcutaneous oedema Hypertension Thromboembolisms
41
What are the components of nephrotic syndrome? | Nephrotic syndrome is very rare
Proteinuria Hypoalbuminaemia Ascites/subcutaneous oedema Hypercholesterolaemia Hypertension *(often but not always)* Hypercoagulability *(often but not always)*
42
What is the prognosis for nephrotic syndrome?
Very poor prognosis
43
What are key signs of a protein losing nephropathy (PLN) on haematology and biochemistry?
Hypoalbuminaemia Normal or mildly increased globulins Hypercholesterolaemia
44
Why can you get normal to mildly increased serum globulins with a protein losing nephropathy (PLN)?
You can have normal to mildly increased globulins in patients with protein losing nephropathy (PLN) as globulins are much larger proteins than albumin and thus are less likely to be lost into the ultrafiltrate
45
Why can you get hypercholesterolaemia with a protein losing nephropathy (PLN)?
Hypoalbuminaemia triggers the liver to produce more proteins, including lipoproteins which are rich in cholesterol
46
What are the other potential differential diagnoses for hypoalbuminaemia?
Hepatic dysfunction Protein losing enteropathy (PLE) Third space losses *(i.e. peritonitis)* Inflammation *(negative acute phase proteins)*
47
How do you rule out hepatopathies as a cause of hypoalbuminaemia?
Bile acid stimulation test to assess hepatic function
48
How do you rule out protein losing enteropathy as a cause of hypoalbuminaemia?
Evaluate the history, clinical examination and clinical pathology to differentiate betwene protein losing nephropathy and protein losing enteropathy. Furthermore, protein-losing enteropathies also typically have decreased serum globulins
49
Which further investigative tests can you do if you diagnose a protein losing nephropathy (PLN)?
- Investigate if there are any causes of persistent antigenic stimulation - Blood pressure measurement and assess for target organ damage - Renal biopsy
50
How does a protein-losing nephropathy (PLN) cause systemic hypertension?
Protein losing nephropathy (PLN) causes hypoalbuminaemia resulting in a reduction in oncotic pressure and fluid loss from the intravascular space. In response to renal hypoperfusion, the kidneys will stimulate the renin-angiotension-aldosterone system which will cause vasoconstriction and hypertension
51
How should you assess systemic hypertension in patients with protein losing nephropathy?
Blood pressure measurements Assess for target organ damage *(i.e. fundus examination)*
52
Why are renal biopsies indicated in patients with protein losing nephropathy (PLN)?
Renal biopsies are indicated in patients with protein-losing nephropathy as they can establish a definitive diagnosis as to what the underlying cause is *(i.e. glomerulonephritis, amyloidosis etc)* and establish a prognosis
53
How can you carry out a renal biopsy?
A renal biopsy can be carried out using a tru-cut needle and ultrasound guidance, laprascopically or via a laparotomy. Remember to only biopsy the renal cortex
54
How do protein losing nephropathies (PLNs) cause hypercoagulability?
Protein losing nephropathies (PLNs) cause a loss of anti-thrombin into the urine which leads to hypercoagulability and can lead to thromboembolisms
55
How do you treat protein losing nephropathies (PLNs)?
Treat underlying disease if possible Manage systemic hypertension Manage proteinuria Manage hypercoagulability Manage uraemia Consider immunosupporessive therapy | Ideally use immunosuppressive drugs based on renal biopsy results
56
How do you manage systemic hypertension?
ACE inhibitors Angiotensin receptor blockers Amlodipine
57
How do you manage proteinuria?
Renal diet ACE inhibitors Angiotensin receptors blockers
58
How do you manage hypercoagulability?
Low dose aspirin Clopidogrel
59
Why should you avoid treating ascites in patients with protein-losing nephropathy (PLN)?
Patients with protein-losing nephropathy (PLN) often present with ascites however do not do an abdominocentesis as the ascites will recur and can lead to dehydration. Furthermore, you can treat with diuretics but be aware the kidneys can't regulate volume levels as efficiently so there is an increased risk of dehydration
60
What is the prognosis for a protein losing nephropathy (PLN)?
The prognosis for a protein losing nephropathy (PLN) depends on the underlying cause, severity of renal dysfunction and response to management. Be aware protein losing nephropathies often progress to chronic renal failure

MODULE 17 - Urinary, Endocrine and Oncological Disease (31 decks)

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