Proteinuria Flashcards
How can proteinuria be quantified?
- dip stick
- sulphosalicylic acid test
- 24hr protin loss
- UPC
- protein electrophoresis
- albumin quantification methods
Is dipstick measurement reliable? Pros and cons
\+ cheap \+ convenient \+ qualitative - trace 1+ usually normal - must consider with USG - only useful in identifying severe proteinuria
What is UPC?
- urine protein creatinine ratio adjust level of protein for concetnratino of urine (^ conc = ^ creatinine)
- practice for routine clinical use
- high day-today variability so ideally measure several times OR pool samples (cheaper)
How is UPC used for IRIS staging?
0.4 (caats) or 0.5 (dogs) = proteinuric
Where can protein be lost within the kidney?
> pre-glomerular - ^ amount low molecular weight proteins presented to filter - cannot all be reabsorbed > renal - glomerular - tubular > post-glomerular/renal - addition of protein to urine after formation in the kidney
Which proteins specifically are commonlyl lost in the urine d/t pre-renal causes?
> bencejones proteins : IG light chains
- plasma cell tuymours (or serious inflam?? maybes)
Causes of post-renal proteinuria
> LUT
- haemorrhage
- inflam/infection
- neoplasia
* importance of blood contamination over-emphasised - urine must be grossly contaminated before this casues proteinuria)
UTI
- effect highly variable and difficult to predict
- should be r/o before proceding with work up for glomerular causes of proteinuria
Is any protein usually excreted by the kidney?
YES small amount always
- mild increases may be d/t glomerular hypertension or tubular dysfunction
- serious pathological increases likely d/t 1* glomerular dz
How id gross proteinuria defined?
UPC >3 (by hattie, no actual definition)
What is PLN
> Protein losign nephropathy
- clinical syndrome of severe gross proteinuria
- may -> hypoproteinaemia
- caused by glomerular disease
What is the glomerular barrier made up of?
- fenestrated endothelial cells
- basement membrane
- epithelial cell foot processes/slit pores (modified adherent junction)
When should you suspect PLN?
- routine screening UA
- hypoalbumenaemia (specifically disopproportionate albumen v cf. pan hypoproteinaemia)
- breeds at risk
- associated diseases
- r enal failre
- clinical signs of PLN
Ddx for panhypoproteinamiea and hypoalbumenaemia
> v albumen - PLN - hypoadenocorticism (?) - liver failure > v protein in general - PLE - haemorrhage
What is nephrotic syndrome?
- proteinuria
- hypoalbumenaemia
- hyperlipidaemia
- oedema/fluid accumulation in body cavities
> NOT necessarily always azotaemic
> may occour in 1/3 glomerular disease dogs
Clinical signs of PLN
- nephrotic syndrome e
- muscle wasting/weight loss/malaise
- azotaemix CKD (sometimes)
- Azotaemic AKI (rarely)
- signs of underlying dz
- hypertension
- thromboembolism
Why do PLN pateitns get thromboemboli?
- loss of anti-thrombin (same size as albumen)
- frequently fatal
- only part of the explanation
Diagnostic plan for PLN patietns
> in all proteinuric patients - urea/creatinine/USG - albumin/cholesterol - urine culture - blood pressur - fundic exam > to ID a underlying cause - CBC/chemistry - imaging - serology - CSF/joint taps - FeLV fiv - specific tests
What needs to be attempted in PLN cases?
> identify underlying cause
- NIN (neoplastic, infectious or non, inflammatory)
- many patients cannot identify underlying cause
What are the different causes of glomerular disease and how can these be dx?
> amyloidosis > immune-complex glomerulonephritis - ICGN - many different types > minimal change dz - lesions only visible with electron microscopy > glomerulosclerosis - scarring of glomeruli - many types > familial glomerulopathy - check pure breeds - consider in young dogs - look up PDF - no specifics Tx - breeding programmes *can only be distinguished on biopsy*
How may travel history assist with dx of PLN
- leishmania
- heartworm (dirofilaria)
- Lyme dz (borrelia burgderfori)
How may drug Hx assist with dx of PLN?
> steroids - ^ proteinuria - glomerulosclerosis > sulphonamides - esp dobermans > tyrosine kinase inhibitors (MCT chemo) - freq -> proteinuria - minimal change dz
Outline non-specific Tx options for PLN
> glomerular haemodynamics
- v glomerular pressure hence GFR -> v proteinuria
- slows dz progression
- v inflam response
diet
- mild protein restriction (counterintuitive)
- reduce proteinuria
- protein high biological value
- omega 3 fatty acid (DHA/EPA)supplements
- sodium restriction
ACEI
- proven benefit (idiopathic and familial glomerular disease)
- indicated in all patients with GROSS proteinuria
- angiotensin receptor blockers (ARBs) reasonable alternative
anti-thrombotic Tx
- aspirin (low dose 0.5-1mg/kg)
- reduced thromboembolism
- clopidogrel an alternative
- delay starting this if potential renal biopsy
antihypertensive Tx
- guided by BP measurement
- ACEI or ARB
- combo with amlodipine if BP remains high
Tx oedema /ascites
- sodium restriction
- thoracocentesis
- abdomenocentesis (only if significant abdo discomfort)
- diuretics (avoid if poss)
- colloids if necessary prior to biopsy
Pros and cons of renal biopsy
*PROS* > specific Tx - immunosuppression - aim to induce remission > breed management > prognostication *CONS* > risks - haemorrhage - renal injury > complications 10% dogs 20% cats > expensive
Outline practical technique of renal biopsy
> US guided or surgical wedge biopsy > cortical tissue > specialist fixative - formalin (H&E, Congo red, PAS) - Michels (IHC) - gluteraldehyde (electron microscopy)
Why are specialist nephropathy labs needed to analyse renal tissue ?
- amyloidosis can be reliably distinguished on light microscopy
- requires very thin sections, multiple stains and interpretation by a specialist
- definitive ID of immunoglobulin deposits often only poss with ELECTRON microscopy
Which species and PDF most commonly get immune complex glomerulonephritis?
> dogs - more common - broad age range - M=F > cats - uncommon - young adults - M>F
Tx immune complex nephritis?
> remove inciting cause
-eliminate antigenic source
- often no cause can be identified
- removal may not be possible (eg, hard to remove tumour)
immunosuppression
- uncertain benefit
- proteinuria may worsen with steroids
- ONLY INDICATED IF BIOPSY SHOWS IMMUNE-COMPLEXES
- consult with specialist first
- many drug protocols
amyloidosis
- extra-cellular deposition insoluble fibrillar proteins in tissue
- compromise organ function
- if deposited in medulla will not be proteinuric
Pathophysiology of reactive systemic amyloidosis
- inflam tissue unhurt -> SAA protein -> insoluble AA amyloid and soluble peptides
- chronic inflammation and familial disease decreases soluble peptide fraction
Specific Tx of amyloidosis
- no identified Tx to solubilise amyloid fibrils once formed
> colchicine - consider in high risk animals (esp. sharpeis with recurrent hock swelling)
- unproven benefit
- may cause GI upset
- not advised once patient azotaemic
Monitoring Tx of proteinuria
- sequential evaluation UPC
- in combination with serum creatinine conc
- as no functioning nephrons declines UPC may decline
Px proteinuria
- variable
- often progressive
- remission and recovery occasionally reported
- worse if azotaemic
- poor if have nephrotic syndrome
What usually maintians low urine protein conc?
- glomerular filtration barrier sorts by charge and prticle size (-ve charge barrier facilitates passage of ctions, impedes anions - most proteins are anions)
- reabsoprtion in PCT of low molecular weight proteins
What is the protein normally present in urine made from?
- low molecular wt proteins freely filtered and not reabosorbed
- 25-70% urine protein larger (
Why may quantification of urinary proteini loss be undertaken?
- abnormal protein on urine dipstick
- isolated hypoalbumenaemia (globulins much bigger so rarely lost in urine, PLN should not cause panhypoproteinaemia)
- high suspicion familial renal dz
- paraproteinuria or bence-jones proteinuria d/t hyperglobulinaemia
How does iris staging scheme relate to proteinuria in 1* glomerular dz?
- useful for deescribing severity of proteinuria in patients with CKD BUT
> severity of proteinuria in 1* glomerulardz ORDERS OF MAGNITUDE GREATER than this - UPCs 5, 10 , 20 with 1* glomerular dz
- only at this sort of level systemic hypoalbumenaemia occours (and even then inconsistent in severity)
> fluctuations naturally occour so small changes in UPC should not be over-interpretted - also if renal function severely imparied UPC may fall d/t v no. functioning nephrons
Caues of med/severe UPC >2
> glomerular origin
- glomerulonephritis (deposition AgAb complexes)
- amyloidosis (insoluble depositioon of fibrillar protein, not limited to renal tissue but clinical signs usually d/t renal failure or nephrotic syndrome)
- familial glomerulopathies
What is amyloid
fragmment of an acute phase protein only produced in response to CHRONIC INFLAM or NEOPLASIA
Which breeds have a familial orm of amyloidosis?
- sharpei
- abyssinian cat
Do all dogs with PLN develop nephorotic syndrome?
NOT NECESSARILY
- may not be azotaemic but may develop as dz progresses
