SA Hypertension, Proteinuria, Glomerular and Tubular Diseases Flashcards
Why is systemic hypertension so important?
It is common - in many common renal and metabolic diseases.
High morbidity - causes clinical signs in its own right – blindness, neuro, cardiac, renal, epistaxis).
There are easy and effective treatment options:
- typically oral – liquid or tabs.
- usually required lifelong (depending on cause).
- Basic cause of systemic hypertension?
- Blood pressure regulation.
- What happens in these regulations to cause systemic hypertension?
- Either excessive vasoconstriction or excessive volumes in the vascular space.
- Various neurohormonal mechanisms:
- baroreceptors.
- renin-angiotensin-aldosterone system (RAAS). - Increase in sympathetic NS activity and/or upregulation of RAAS causes vasoconstriction.
Stimulation of RAAS causes sodium retention and so water conservation at level of kidney and volume expansion.
Causes of systemic hypertension.
Primary (idiopathic) hypertension is rare in cats and dogs.
Secondary hypertension:
- kidney disease.
- endocrinopathies.
- situational hypertension.
– previously ‘white-coat effect’ i.e. stress associated.
- increased intracranial pressure (with bradycardia = Cushing’s reflex) – to achieve brain perfusion.
Consequences of hypertension.
Target organ damage:
Ocular (hypertensive retinopathy).
- may cause acute blindness.
- retinal detachments due to fluid accumulation.
- haemorrhage.
- vessels are thicker and more tortuous.
Renal (cause vs consequence).
- causes increased progression of CKD.
Cardiac - causes pressure overload which causes left ventricular concentric hypertrophy.
- the heart is pumping blood through a more constricted vascular space.
Neurological.
- vascular lesions, bleeds etc.
Epistaxis - less common but possible.
- Normal BP.
- Systolic blood pressure levels and risk of target organ damage.
- Systolic 120-140mmHg.
Acknowledge that sight/deerhounds sit about 10-20mmHg higher.
- at home and higher in the hospital. - <140mmmHg is normotensive and risk is minimal.
140-159 is pre-hypertensive and risk is low.
160-179 is hypertensive and risk is moderate.
>180 is severely hypertensive and risk is high.
Measuring BP.
Invasive (direct) requires arterial catheterisation = gold standard.
Non-invasive w/ inflatable cuff:
- doppler.
- oscillometric.
Environmental considerations.
- well acclimatised to hospital.
- consult room w/ owner.
- most relaxed state.
5-7 consistent readings; exclude first or any before plateau.
Ideally repeat second set of reading >2hrs apart.
- to ensure repeatability.
Diagnosing SHT.
Use headphones - reduce patient stress.
Place cuff (deflated).
- right atrial height (within 10cm acceptable).
- cuff width should be 30-40% circumference of limb/tail.
Doppler contact; clip/gel.
Inflate cuff.
Deflate and listen for when arterial flow restored = systolic blood pressure.
Fully deflate cuff between readings.
Treatment principles for hypertension.
Treat any BP >180mmHg.
Treat any BP >160 with evidence of target organ damage.
Treat any BP that is sustained at >160mmHg (>1 visit).
Screen for/treat any underlying disease - e.g. kidney disease, hormonal disorders.
Aim for SBP <140mmHg (at very least <160mmHg).
Owners should monitor for signs of hypotension.
- lethargy, weakness, ataxia/syncope.
– reassess BP immediately if found.
Re-evaluate BP every 1-2 weeks and adjust dose accordingly.
When stable, monitor every 1-3m.
Medical treatment options for hypertension.
Amlodipine - 1st choice for cats.
- calcium channel blocker.
– causes vasodilation (peripheral arteriolar dilation).
Benazepril = 1st choice in dogs.
- ACE-inhibitor.
Telmisartan.
- angiotensin receptor blocker.
- acceptable first choice in dogs.
- renin converts angiotensinogen to angiotensin I which is converted by ACE to angiotensin II which causes aldosterone release which causes sodium and water retention AND vasoconstriction.
– blocking this pathway prevents volume expansion and vasoconstriction.
Why is proteinuria important?
Proteinuria = protein in the urine.
Proteinuria may affect up to 20% of geriatric patients.
Proteinuric kidney disease is most common type of CKD in dogs.
- proteinuria rare in feline renal disease.
Proteinuria accelerates progression of renal disease.
- affects health of tubules.
Diagnosing proteinuria.
Qualitative vs quantitative.
- Dipstix (qualitative).
- UPC (quantitative).
– needed clinically for accuracy and guided management.
–> normal = <0.2, borderline = up to 0.4 in cats and 0.5 in dogs, proteinuric = >0.4 in cats and 0.5 in dogs, severe = >2.
– quantifies protein ‘lost’ relative to creatinine excretion.
– creatinine excretion relatively stable in a given patient.
Pre-renal proteinuria.
Increased blood protein:
- hyperglobulinaemia.
- haemo/myoglobinaemia.
Functional:
- pyrexia.
- post-exercise.
- seizure.
All are fairly easy to rule in or out.
Post-renal proteinuria.
Anything after the kidney.
Increased protein into the lower urinary tract.
E.g. stone in bladder.
E.g. tumour.
E.g. infection causing inflammatory process in the bladder.
E.g. repro tract disease.
Ideally investigate with imaging of the urinary tracts and get cystocentesis sample.
Identifying the origin of proteinuria.
Home-caught urine sample.
Ideally pooled/average sample.
- ensure same quantity from each sample.
Rule out pre-renal causes with Hx and serum biochemistry.
Rule out post-renal causes with cystocentesis and genito-urinary tract imaging.
Renal proteinuria.
Is a protein losing nephropathy (PLN).
Marked renal proteinuria (UPC >2) due to glomerular disease.
- increased permeability to albumin causing proteinuria.
Tubular disease may cause mild proteinuria.
Proteinuria >2 or persistent proteinuria of any magnitude warrant investigation.
Proteinuria comes from the glomerulus.
<2 = earlier glomerular disease or tubular disease.
Consequences of glomerular disease?
NOT necessarily azotemic and may retain urine concentrating ability.
- glomerular, NOT tubular disease.
Only become azotemic when tubular damage ensues as left glomerular disease allowing protein in for so long.
Protein loss into the urine can cause hypoalbuminemia which causes effusions/oedema.
Loss of some natural anticoagulants can lead to hypercoagulability of the blood.
Hypertension exacerbates/accelerates glomerular pathology.
Hypercholesterolaemia
- compensatory mechanism for the low albumin.
= nephrotic syndrome.
Primary glomerular disease.
Inherited / familial glomerular disease e.g. developmental collagen defects.
Idiosyncratic disease.
- random event.
Autoimmunity.
- attach of the glomerulus.
Secondary glomerular disease.
Inflammatory (sterile, infectious).
Neoplastic disease - elsewhere in the body – immune complexes of big proteins get stuck in glomeruli and damage them.
– amyloid produced and deposited in the kidney.
Drug/toxin exposure.
Secondary much more common than primary.
Amyloidosis.
Chronic inflammatory disease (elsewhere in the body) causes production of serum amyloid A (SAA).
AA deposited in tissue:
- kidneys.
- liver.
- other organs.
Polymerises and forms beta-pleated sheet.
- insoluble.
– deposit damages glomerulus and other parts of kidney.
Chinese sharpeis susceptible.
On histopathology, apple green birefringence when stained with Congo Red and examined with polarising microscopy.
Renal amyloidosis in chinese sharpeis.
Marked proteinuria.
Typically glomerular deposition.
Medullary deposition predominates.
Familial Shar-pei Fever (FSF) believed to be inflammatory trigger.
- treat FSF episodes with NSAIDs.
Present with renal amyloidosis ay young-middle (4-6yrs) aged adults.
- disease often advanced at diagnosis.
- many euthanised shortly (days) after diagnosis.
– <10% survive >1yr.
How to find out what type of glomerular disease a patient has.
Need to consider if you need to find out.
Important to evaluate for a possible underlying trigger of the glomerulonephritis/amyloidosis.
- primary vs secondary / reactive glomerular pathology.
Renal biopsy.
- specialist level (US guided tru-cut).
- NOT appropriate if secondary disease or end-stage disease.
– not helpful.
- use in primary cases (no trigger), without familial cause, NOT responding to ‘standard’ therapy.
- normal histopathology alone inadequate – need to go out of UK.
Screening for triggers.
Drug history:
- steroids.
- ABX – TMPS.
- immunomodulators – oclacitinib.
- chemotherapeutics – masitinib / toceranib.
Evaluation/exclusion of obvious exam abnormalities.
- e.g. cytology of cutaneous masses/skin lesions/ lymphadenopathy.
BP - cause vs consequence.
Haematology.
Serum biochemistry.
Further screening for triggers.
Imaging:
- urinary tract US.
– during initial investigation to exclude post-renal causes.
- thoracic/abdominal imaging.
– evaluate for systemic inflammatory/neoplastic disease.
- Echocardiography – to exclude endocarditis).
Infectious / exotic disease testing:
- FIV Ab ELISA, FeLV Ag ELISA (cats).
- travel screen.
Standard therapy for glomerular disease.
Treat underlying disease.
- e.g. periodontal disease, infection, MCT etc.
Then treat proteinuria.
Then treat complications.
Treating proteinuria.
Angiotensin receptor blocker (first line therapy).
ACEi (second line).
- Significantly reduces proteinuria and delays onset and progression of azotaemia.
- reduce pressure in glomerular to reduce proteins lost here.
Be mindful of adverse events:
- worsening azotaemia (due to reducing GFR), hypotension, hyperkalaemia (rarely clinically significant).
Monitor every 2w (every 3m once stable).
- UPC – aim UPC <0.5 or <50% from baseline.
- creatinine, albumin, Na+, K+.
- BP.
Adjunctive therapies in all glomerular patients.
Renal diet.
Omega-3 PUFA.
Anti-platelet therapy e.g. clopidogrel or aspirin).
Oedema management; light exercise.
Manage hypertension.
Monitor/manage otherwise as per IRIS guidelines (glomerular disease is a form of CKD),
Glomerular disease prognosis.
Highly variable, depending on subtype.
- poor in those presenting with azotaemia and nephrotic syndrome.
– <2m.
Typically progressive.
- may be slow with survival of a number of year.
Spontaneous resolution / remission also reported.
Proximal tubular disorders.
Glucosuria in absence of hyperglycaemia.
- tubule has failed to re-absorb glucose and so it is lost in the urine.
– osmotic diuresis so PUPD.
– exclude hyperglycaemia / DM.
Fanconi syndrome:
- hereditary – Basenjis.
- acquired.
– copper hepatopathy.
– lepto.
– Chinese Jerky treats.
–> contaminated with heavy metals or ABX.
