PATHOLOGY - Proteinuria and Protein Losing Nephropathy (PLN) Flashcards
What is the function of the glomerular filtration barrier?
The glomerular filtration barrier acts to filter the blood based on particle size and charge to produce ultrafiltrate
How do proteins usually move through the kidneys?
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
What are the four classifications of proteinuria?
Physiological proteinuria
Pre-renal proteinuria
Renal proteinuria
Post-renal proteinuria
What are the four causes of physiological proteinuria?
Strenuous exercise
Seizures
Pyrexia
Stress
What causes pre-renal proteinuria?
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
What causes renal proteinuria?
Renal proteinuria is caused by renal dysfunction or renal inflammation
What is a key feature of renal proteinuria?
Renal proteinuria is persistent whereas physiological, pre-renal and post-renal should resolve when the underlying cause is resolved
What causes post-renal proteinuria?
Post-renal proteinuria is caused by inflammation of the ureter, bladder, urethra or prostate
How do you diagnose proteinuria?
Proteinuria can be diagnosed on a urine dipstick
Which protein are urine dipsticks most sensitive to?
Albuminn
What can cause false positives for proteinuria on a urine dipstick?
Alkaline urine
Sample contamination
What can cause false negatives for proteinuria on a urine dipstick?
Acidic urine
Bence Jones proteinuria
How does Bence Jones proteinuria cause a false negative on a urine dipstick?
Urine dipsticks are most sensitive to albumin but not Bence Jones proteins which are produced in excess in conditions such as multiple myeloma
How do you approach investigating the cause of proteinuria?
- History and clinical examination to rule out physiological proteinuria
- Haematology and biochemistry to rule out pre-renal causes of proteinuria
- History, clinical examination, urinalysis, culture and sensitivity and diagnostic imaging to rule out causes of post-renal proteinuria
- If all other causes ruled out, consider renal proteinuria and do a urinalysis and urine culture and sensitivity
What are the purposes of quanitifying proteinuria?
Evaluates the severity of the lesions
Assess disease progression
Assess response to treatment
What can be used to quantify proteinuria?
Urine protein:creatinine ratio (UP:C)
How do you carry out a urine protein:creatinine ratio (UP:C)?
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
What are the four main causes of renal proteinuria?
Renal inflammation
Glomerular disease
Tubular disease
Chronic kidney disease (CKD)
How does renal inflammation cause proteinuria?
Renal inflammation will increase glomerular vascular permeability resulting in the leakage of serum proteins into the ultrafiltrate
What are the key indicators of proteinuria secondary to renal inflammation?
Renal pain on palpation
Haematuria
Leukocytosis on haematology
Leukocytes in the urine
Bacteria in the urine
Changes on diagnostic imaging indicative of renal inflammation
How does glomerular disease cause proteinuria?
Glomerular disease causes glomerular damage and increases glomerular permeability which results in the leakage of serum proteins into the ultrafiltrate
How does the urine protein:creatinine (UP:C) ratio typically present in patients with proteinuria secondary to glomerular disease?
The urine protein:creatinine (UP:C) ratio tends to be high (more than 2) in patients with glomerular disease
Which species are more prone to glomerular disease?
Dogs are more prone to glomerular disease
How do tubular diseases cause proteinuria?
Tubular diseases are relatively rare
Tubular diseases cause reduced reabsorption of filtered proteins at the proximal convoluted tubules
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
Give two examples of tubular diseases
Fanconi syndrome
Leptospirosis
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
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
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
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
What are three of the main causes of protein-losing nephropathies (PLNs)?
Developmental abnormalities of the basement membrane
Glomerular amyloidosis
Glomerulonephritis (main cause)
Which dog breeds are predisposed to developmental abnormalities of the basement membrane of the glomerular filtration barrier?
Springer spaniels
Bull terriers
Which dog breeds are predisposed to glomerular amyloidosis?
Shar pei
Beagle
Which cat breeds are predisposed to glomerular amyloidosis?
Abyssinian
Siamese
What is glomerulonephritis?
Glomerulonephritis is a group of conditions in which antigen-antibody complexes are deposited in the glomeruli
What are the two main causes of glomerulonephritis?
Persistent antigenic stimulation
Idiopathic
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)
What are some of the main causes of persistent antigenic stimulation?
Chronic inflammation
Chronic infection
Chronic neoplasia
What are the early clinical signs of a protein-losing nephropathy (PLN)?
Asymptomatic
Weight loss
Lethargy
Anorexia
What are the later clinical signs of a protein-losing nephropathy (PLN)?
Ascites
Pleural effusion
Subcutaneous oedema
Hypertension
Thromboembolisms
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)
What is the prognosis for nephrotic syndrome?
Very poor prognosis
What are key signs of a protein losing nephropathy (PLN) on haematology and biochemistry?
Hypoalbuminaemia
Normal or mildly increased globulins
Hypercholesterolaemia
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
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
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)
How do you rule out hepatopathies as a cause of hypoalbuminaemia?
Bile acid stimulation test to assess hepatic function
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
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
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
How should you assess systemic hypertension in patients with protein losing nephropathy?
Blood pressure measurements
Assess for target organ damage (i.e. fundus examination)
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
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
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
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
How do you manage systemic hypertension?
ACE inhibitors
Angiotensin receptor blockers
Amlodipine
How do you manage proteinuria?
Renal diet
ACE inhibitors
Angiotensin receptors blockers
How do you manage hypercoagulability?
Low dose aspirin
Clopidogrel
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 or treat with diuretics unless the patients is having difficulty breathing, as the ascites will recur and can lead to dehydration
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
