Glomerulonephritis Flashcards
How frequent is glomerulonephritis in cats
Clinically apparent glomerulonephritis is an uncommon disease of cats
Sub-clinical glomerular disease is likely to be a much more common entity
What are the two most common glomerular diseases
Immune-complex glomerulonephritis
Amyloidosis
- seen primarily in dogs
- predominantly an interstitial disease in cats
Describe the normal glomerular anatomy
Endothelial cell of glomerular capillary
- this is a fenestrated cell which is more permeable to water and crystalloids than other endothelial cells
Glomerular basement membrane (glycoprotein)
- this serves as a filtration barrier for large molecular weight protein molecules
Visceral epithelial cells (podocytes)
- these line the glomerular capillary tuft on the urinary side
- they have “foot processes” which enable glomerular filtrate to form in the nephron
- they are an important factor in the selective permeability of the glomerulus as they are coated with negatively charged glycoproteins and thus strongly repel other negatively charged proteins (e.g., albumin) preventing them passing into the filtrate
Mesangial space
- this is the space between several capillary loops that are all surrounded by one basement membrane
Describe the normal glomerular physiology
Under normal physiological conditions, the glomerulus acts as both a charge a size selective filter
- albumin has a size just above the filtrable limit
- negatively charged molecules are repelled
Immune complex damage can decrease the amount of negatively charged fixed proteins
What is the pathomechanism of glomerulonephritis
In glomerulonephritis, the damage is primarily immune-mediated
Damage most commonly results from circulating immune complexes (HS III reaction)
- intermediate size complexes form most commonly with mild to moderate antigen excess
- they bind relatively large amounts of complement but offer little stimulation for phagocytosis
- therefore, they circulate for long periods with the likelihood of eventually being trapped in endothelial structures such as the glomerular filter
- damage may then occur as a result of complement activation and neutrophils chemotaxis
- damaged endothelium may attract platelets with activation of the coagulation system and fibrin deposition
The antigens involved are not of renal origin and their source is often undetermined (idiopathic glomerulonephritis)
Damage may also result from production of antibodies against the glomerular basement membrane (true auto-immune disease)
- has not been conclusively proved to exist in cats
Glomerulonephritis can also occur where antibodies are directed against proteins that have become attached to the glomerular membrane
Damage in glomerulus is generally permanent, as healing takes place by fibrosis
What can you conclude from the pathomechanism of glomerulonephritis regarding the diagnostic investigation
The fact that most cases of glomerulonephritis are secondary immune-mediated conditions should always provoke an appropriate search for underlying inflammatory/infectious disease processes
Can you give some potential causes of feline glomerulonephritis
The vast majority of cases of glomerulonephritis remain idiopathic
Some potential causes of feline glomerulonephritis are:
- Infections
- FeLV
- FIP
- Other chronic infection (e.g., leishmania)
- Neoplasia
- Lymphoma
- Myeloproliferative disorders
- Mast cell tumors
- Inflammatory
- Associated with polyarthritis
- Associated with SLE
- Endocrine
- Possible association with diabetes and hyperadrenocorticism
- Drug-associated
- Idiopathic
What are the two clinical presentations of glomerulonephritis
Nephrotic syndrome
Asymptomatic proteinuria
What is the typical clinical presentation for nephrotic syndrome in cats
Average age at onset is 3-4 years but a wide range is reported
A male predisposition is possible
When uncomplicated by CRF, affected cats are often bright, afebrile, eating well, although mild to moderate weight loss may be a feature
Other clinical signs may include:
- anorexia
- diarrhea
- depression
- polydipsia
- vomiting
Edema usually first appears in the lower limbs and ventral abdomen/thorax
- characterized by pitting peripheral edema
Hydrothorax and/or ascites may be present but is not usually severe
Hypertension is a relatively common complication
What is the typical clinical feature of asymptomatic proteinuria and its implication for the treatment
Increased proteinuria may be associated with a wide range of feline diseases
- in many cases this may reflect low-grade glomerulonephritis
In many if not most cases, it appears that treatment of the underlying disease will result in resolution of the glomerular damage and cessation of proteinuria
How is a diagnosis of nephrotic syndrome made
The diagnosis of the nephrotic syndrome is base on a combination of:
- appropriate clinical signs (e.g., ascites, hydrothorax, pitting edema)
- persistant proteinuria
- In cases of nephrotic syndrome the UPC ratio is generally markedly elevated (> 3.0, and often much higher than this)
- hypoproteinemia and hypoalbuminemia
- typically albumin levels < 15 g/L are required before fluid transudation will occur
- hypercholesterolemia (not consistent in cats)
- hyaline casts in urine sediment analysis (due to proteinuria)
Is renal biopsy important for diagnosis glomerulonephritis in cats
Renal biopsy is important to differentiate glomerulonephritis from amyloidosis
- important in dogs
- less important in cats as amyloidosis tends to affect medulla, not glomeruli in cats
Immunofluorescence can confirm the diagnosis, and combiend with electronic microscopy analysis can identify type of glomerulonephritis
Give a differential diagnosis list for proteinuria
Pre-renal causes
- hemoglobin
- myoglobin
- Bence-Jones proteins
Post-renal causes
- lower urinary tract infection/inflammation
- genital tract infection/inflammation
Renal causes
- AKI
- CKD
- Pyelonephritis
- Fanconi syndrome
- Benign transient proteinuria
- Stress/exertion
- Pyrexia
Which laboratory test result is highly suggestive of glomerulonephritis
Persistent moderate to heavy proteinuria without urine sediment abnormalitis is highly suggestive of glomerulonephritis
What would be contra-indications to renal biopsy
Presence of renal failure
Increased clotting time
Systemic hypertension
