Glomerulopathies Flashcards by Sophie Robinson

The filtration barrier of the glomeruli has 3 different layers, what are they?

Fenestrated endothelial cells
Glomerular basement membrane
Podocytes

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What is the function of the filtration barrier in the glomerulus?

Together they create a size and charge selective barrier
Prevents most of proteins from leaking into the urine

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How is filtration different in renal tubules?

Renal tubules excrete or reabsorb
Because they have active and passive transporters

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What is the hallmark signs of a glomerulopathy?

Proteinuria

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Are glomerulopathies more common in dogs or cats?

Dogs
Tubulointerstitial lesions more common in cats

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Describe protein loss in tubulointerstitial disease

A tubulointerstitial disease has an inability to reabsorb what’s gone into the interstitium so only a small amount of protein is lost into urine

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Describe the pathogenesis of glomerulopathies

Can be immune-mediated (a.k.a. acquired) and non-immune mediated (e.g. amyloidosis)
- Immune mediated mechanism = type 3 hypersensitivity

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Describe the pathogenesis of immune mediate glomerulopathies

Circulating immune complex may become trapped in the glomerulus or may be formed in situ
Their presence will lead to inflammation (activation complement, recruitment inflammatory cells) -> further damage to the kidney
Any severe, chronic inflammatory responses can result in a glomerulopathy so when these occur you need to think about the underlying pathological cause

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List some infective causes of glomerulopathies

Leptospira spp
Leishmania spp
Borrelial burgdorferi
Babesia spp
Erlichia spp
Anaplasma spp
Toxoplasma
FIP
FeLV/FIV
Sepsis
Pyometra

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List some inflammatory causes of glomerulopathies

Severe pancreatitis
SIRS
Chronic inflammation
Hyperglobulinemia - multiple myeloma, B cell lymphoma
Hyperadrenocorticism

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What are hereditary glomerulopathies?

Breeds that are predisposed to glomerular diseases
These breeds tend to present at a young age, then progress rapidly

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Which breed is predisposed to Familial Glomerulopathy - Amyloidosis

Shar-pei

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Describe familial glomerulopathy amyloidosis in Shar-peis

Shar-pei’s commonly preceded by episodes of “shar-pei’s fever”: self-limiting hyperthermia, swollen joints
Formation and deposit of amyloid plaques in the glomeruli
Usually very high UPC (average 9)
Usually rapidly progressive
Treatment: colchicine and/or DMSO but no evidence that either bring benefit

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What factors may lead to the suspicion of a glomerulopathy?

Unexpected proteinuria on urinalysis
Investigating renal disease
Hypertension of unknow origin
Hypoalbuminemia and/or hypercholesterolemia
Thromboembolic events
Breed at risk

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How can you confirm the proteinuria?

Can be easily detect with a dipstick
- Not 100% sensitive because the result can be affected by urine pH and the concentration
- But these are quick and cheap
If positive, the value should be quantified by Urine Protein Creatinine Ratio (UPCR)

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What feature of proteinuria should be assessed?

Important to evaluate the persistence: proteinuria should be repeatable on at least three urine samples obtained at least 2 weeks apart

List 4 causes of a pre-renal proteinuria

Fever
Systemic inflammation
Haemoglobinuria
Myoglobinuria

List 3 causes of a post-renal proteinuria

UTI
Nephrolithiasis
Tumours of the urinary tract

What is the gold standard for diagnosis of glomerulopathies?

Renal biopsy

Describe renal biopsies for glomerulopathies

When performed, samples have to be manage in a specific way and sent to specialist renal pathologist centres
Samples have to be examined by: light microscopy, immunofluorescence and electron-microscopy
In absence of biopsy, proteinuria can be used as marker

What must be done before glomerulopathies are treated?

Quantify by UPCR
Confirm persistent proteinuria
Renal origin (Rule out Pre /Post Proteinuria)

How can the magnitude of the proteinuria suggest its origin?

If >2 = glomerulopathy
If <2 = tubulointerstitial

What is the standard treatment for proteinuria?

RAAS blockade: ACE-inhibitors OR angiotensin receptor blockers
Telmisartan licensed only for cat: benazepril should be used as first line, following the cascade

How does a RAAS blockade treat proteinuria? Side effects?

Decrease the pressure in the efferent arteriole more than the afferent so glomerular pressure is reduced
Side effect: when glomerular pressure is reduced, this also decreased the GFR
Can worsen how they are in the short term as azotaemia is worsened

Is immunosuppressive treatment indicated for glomerulopathies?

- About 50% of glomerulopathies are the results of deposition of immunocomplex - A proportion of these will respond to immunosuppressive medication When to consider the use of immunosuppressive medication: Use if biopsy suggests an immune-mediated disease (rarely done though). If biopsies are not possible (costs, lack of personal trained, contraindicated), you can immunosuppress if the animal is doing badly on standard treatment.

What must you be aware of when using steroids?

Be aware that as most of the diseases, use of steroids will impact the possibility to have a diagnosis in the future!!!!

Name the 5 major complications of glomerulopathy treatment

- Thromboembolism - Azotaemia - Systemic hypertension - Diet - Oedema

Describe thromboembolisms as a complication of glomerulopathy treatment

Patients with glomerulopathies are classified as HIGH RISK of thromboembolism, and it is the main cause of death

How can you treat thromboembolisms as a complication of glomerulopathy treatment

Recommendation is to start thromboprophylaxis treatment Antiplatelets: Clopidogrel (especially in cats) Anti-coagulant: Apixaban or Rivaroxaban (monitor for signs of bleeding)

Describe systemic hypertension as a complication of glomerulopathy treatment

- Common consequence in glomerulopathy - Patients can be non-azotaemic but hypertensive - Hypertension lead to progression kidney disease, glomerulopathy and end-organ damage (eye, heart, CNS, kidney) - To be treated if BP > 170mmHg or evidence of target organ damage (TOD)

How can you treat hypertension as a complication of glomerulopathy treatment

Dog: benazepril, then amlodipine Cat: amlodipine or telmisartan

Describe azotaemia as a complication of glomerulopathy treatment

- 60% of the patients are azotaemic on presentation - Once established the patient is azotaemic, treat as per IRIS recommendation (classed as CKD) - Need to make sure the azotaemia is persistent and not a one off measurement

Describe a suitable diet for a dog with glomerulopathy/being treated

- Renal food recommended as containing highly digestible protein source which reduce proteinuria and progression azotaemia (IRIS guidelines) - Omega-3 supplementation reduce glomerular inflammation - The animal must eat!! If not eating renal diet, use other diets: starvation increase catabolism of body protein --> increase protein processed by kidney

Describe oedema as a complication of glomerulopathy treatment

- Glomerulopathies predispose to nephrotic syndrome - Usually associated with renal sodium retention - Dogs resistant to formation of oedema (incomplete nephrotic syndrome)

What are the signs of nephrotic syndrome?

Hypoalbuminemia Proteinuria Hypercholesterolemia Oedema

How can you treat oedema as a complication of glomerulopathy treatment

Treatment is with diuretics: - Furosemide: pulmonary oedema/hyperK - Spironolactone: pleural or abdominal effusion Presence of nephrotic syndrome carriers a very bad prognosis