Chronic renal failure Flashcards
Differentiate CRF and CKD
- CHRONIC RENAL FAILURE: chronci azotaemia d/t intrisnic renal dz, >3/4 nephrons have to be lost
- CHRONIC KIDNEY DISEASE: patients with chroncic disease +/- azotaemia
What is the IRIS staging system for kidney dz?
- based on plasma [creatinine], proteinuria and BP
- only applicable to patients with CKD (different system AKI)
- without pre/post-renal causes of azotaemia
- if not azotaemic, then some other abnormality myst be present to ID that the patient has CKD (e.g. ultrasound changes or marked proteinuria).
- stages 1-4 (4 = most severe)
- azotaemia must be stable for this staging
What is renal insufficiency?
avoid this term!
Features stage 1 IRIS kidney dz
- some other renal abnormality present (renal structure, proteinuria)
- non-azotaemic, normal or near-normal GR
Features stage 2 IRIS kidney dz
- CS usually limited to PU/PD or may be absent
- non-azotaemic to mildly-azotaemic
Features stage 3 IRIS kidney dz
- PU/PD usually
- extrarenal CS (V, dehydration, wt loss) MAY be present
- mild-moderately azotaemic
Features stage 4 IRIS kidney dz
- PU/PD usually
- extrarenal CS (V, dehydration, wt loss) ARE LIKELY
What are the cut off values for UPC determining if animal is proteinuric or not?
NON-PROTEINURIC: 0.4 cats, >0.5 dogs
At what IRIS stage do you give renoprotective vs symptomatic tx?
- RENOPROCTECTIVE: stage 2 and 3
- SYMPTOMATIC: stage 4
Causes - CKD in cats
- lymphoma
- polycystic kidney disease *
- FIP
- amyloidosis
- primary glomerular disease
- pyelonephritis
- toxins
- recovery from ARF/ AKI
- obstructive nephropathy *
- chronic tubulointerstitial nephritis*
Inheritance - polycystic kidney disease
- persian and related breeds
- autosomal dominant
- DNA test
CS - polycystic kidney disease
- palpably enlarged in azotaemic cats
- azotaemia often doesn’t develop until middle-age
- detected ultrasonographically before azotaemia (from 8m)
Another name - obstructive nephropathy
‘big kidney little kidney syndrome’
Outline obstructive nephropathy
- calcium oxalate ureteroliths
- obstruction of 1st kidney typically asymptomatic
- CS when 2nd kidney obstructs
What is the most common diagnosis in cats with CKD?
tubulointerstitial nephritis
- FREQUENCY: cats > dogs/humans
- it is the end-stage of CKD, regardless of inciting cause
Causes - CKD in dogs
- more mixed than cats
- tubulointerstitial nephritis
- familial/breed-related syndromes
- primary glomerular dz
- Others (pyelonephritis, post-ARF/AKI)
Indications - diagnostic imaging
- young animals
- dogs > cats
- asymmetric kidneys
- large kidneys
- severe proteinuria
- uncertain chronicity
- ‘do everything’ owners
3 main management principles - CKD
- determine underlying cause
- control factors important in dz progression
- reduce patient morbidity
Progression - renal dz - dogs vs cats
- many patients diagnosed with mild azotaemia eventially die of renal failure
- more rapid in dogs vs cats
- most dogs die within 1 year of diagnosis, cats live 2-3 years and may die of other things
Name putative mechanisms for renal dz progression
- CKD-MBD (Mineral bone disorder, secondary renal hyperparathyroidism) (dietary therapy)
- glomerular hypertension
- direct proteinuria induced renal injury (ACEIs/ ARBs)
- other mechanisms (acidosis/increased renal ammoniagenesis, hypokalaemia)
Describe CKD-MBD
- abnormalities of Ca, phosphorous, PTH or vitamin D metabolism
- abnormalities in bone turnover mineralisation, volume, linear growth or strength
- vascular/other soft tissue calcification
What causes increased PTH release?
- decreased ionised Ca2+
- calcitriol
PTH -effects
- KIDNEY: increase Ca retention, decrease NaPi transporter insertion, increase phosphorous excretion
- BONE: increase osteoclastic/osteoblastic activity, release Ca2+ and phosphorous
What happens to phosphate clearance in mild CKD?
decreased nephron mass –> decreased phosphate clearance –> increase FGF-23 –> increase phosphate clearance
What happens to phosphate clearance in severe CKD?
decreased nephron mass –> decreased phosphate clearance –> increase phosphate –> 3 things:
- decreased active vitamin D3
- increased PTH
- decreased ionised Ca –> increased PTH
Does CKD-MBD cause progressive renal injury?
- dietary phosphate restriction effectively reduces PTH and FGF-23
- phosphate restriction reduce histological evidence of injury (experiments)
How does dietary management help kidney dz?
- decreased protein = decreased signs of uraemia
- decreased phosphorous = decreased secondary renal hyper-PTH
- decreased Na = decreased arterial hypertension
- increased vitamin B = water-soluble vitamins lost
- increased caloric density = counteract decreased appetite
- less acidifying = risk of acidosis
- increased K = cats predisposed to hypokalaemia
- increased ration omega 3:omega6 PUFA = decreased glomerular pressure
- increased soluble fibre = binds urea
Define PUFA
Polyunsaturated fatty acids
What are the targets for phosphorous management?
- stage 2 CKD: keep [phosphate] in lower half of reference range
- more advanced dz = have to compromise
- staged approach: initially diet, addition of phosphate binders if required.
Name 4 phosphate binders
- aluminium hydroxide
- lanthanum carbonate (Renalzin)
- calcium carbonate/acetate/ citrate
- Ipakitin/ Epakitin
Outline aluminium hydroxide as a phosphate binder
- cheap, effective
- causes constipation
- poor palatability
- rare side effects at high doses
Outline lanthanum carbonate as a phosphate binder
- reasonable cost, effective
- being discontinued
Outline calcium carbonate/acetate/ citrate as a calcium bindiner
may cause hypercalcaemia
What is ipakitin/epakitin?
chitosan/calcium carbonate
Is proteinuria of prognostic signficance?
yes (proteinuria –> excessive tubular reabsorption of protein –> renal injury. Proteinuria is also a disease marker)
Does glomerular capillary hypertension cause proteinuria?
Yes
What type of drug is benazepril?
ACE-i
What is the effect of ACEI in cats with CKD?
- significant reduction in proteinuria (effect greatest in most proteinuric cats)
- no difference if survival cf. placebo tablet
Outline use of ACEi in dogs with CKD
- no ACEI/ARB licensed for tx of CKD dogs
- definite indication in management of primary glomerular disease (paradoxically more common in dogs vs cats)
Outline rational use of ACE-i in CKD
- animals with higher UPCs
- animals likely to live long enough to reap benefits
- must not expect ‘biochemical improvement’
- aim is to slow disease
Effects on blocking Ang 2 action on AT1-R
- vasoconstriction
- aldosterone secretion
- tubular Na reabsorption
- thirst
- vasopressin secretion
- cellular hypertrophy
- calcium transport
Effects on blocking Ang 2 action on AT2-R
- vasodilation
- decreased cell growth
- antioxidant actions
- apoptosis?
What is telmisartan?
= semintra (liquid formulation)
- randomised comparison to benazepril
- primary endpoint = reduced proteinuria, not increased survival
Factors contributing to CKD morbidity
- UTIs
- anaemia
- dehydration
- hypokalaemia
- acidosis
- systemic hypertensions
Describe UTIs in CKD patients
- common
- often asymptomatic
- pyelonephritis as an inciting cause of CKD is more common in the dog than in the cat: highly concentrated urine resistant to infection
- cats: stage 2-4
- dogs: all stages
Describe hypopkalaemiain CKD patients
- CAUSE: decreased appetite, increased urinary loss, hyperaldosteronism
- RESULTS IN: mm weakness, worsens renal function?
- SUPPLEMENT: palatability issue
- CATS»_space;» dogs (more common with hypertension)
Outline dehydration in CKD patients
- variable
- may result in pre-renal component to azotaemia
- anticipate in hospitalised patients
- selected patients benefit from SQ fluids at home
For a well-hydrated cat with stable, mild CKD that you place on fluids at 3x maintenance?
- increased urine output
- unchanged GFR
- decreased [creatinine]
How do fluids help in CKD?
FACT: - correct pre-renal azotaemia - treat dehydration - expand plasma volume FICTION: - improve renal function (but have temporary dilutional effect) - don't flush out kidneys
Outline SC fluids in CKD
- valuable for cats that repeatedly get dehydrated
- more advanced dz
- 60-100ml
- hartmann’s/LRS/CSL
- can teach owners
Outline constipation in CKD
- cats > dogs
- increases with stage
Tx - constipation in CKD
- hydration, mobility
- lactulose
- miralax (polyethylene glycol, 1/4 tsp/meal, titrate to effect)
What appetite stimulants are given in CKD?
- traditionally given antacids (sucralfate, H2-blockers) but actually GI ulceration is uncommon and efficacy of these tx is unknown
- MAROPITANT
- MIRTAZAPINE
- required for cats and dogs, stages 3+4
Outline maropitant in CKD
- selective NK1-R antagonist
- decreases V in cats with CKD
- didn’t improve appetite, no wt gain
Outline mirtazapine in CKD
- appetite stimulant (unlicensed)
- increases appetite
- decreases vomiting
- wt gain
Describe anaemia in CKD
- cats and dogs, stage 4 (usually)
- multifactorial cause but lack of EPO most important
- recombinant human EPO (moderate/severe anaemia, tupocally when PCV
What is darbopoeitin?
- modified EPO molecule
- increase half-life and greater in vitro potency
- decreased immunogenicity
- initial dose tapered
- very expensive
Describe acidosis in CKD
- cats and dogs, stage 4 usually
- not usually until advanced dz or patient is dehydrated/ hypovolaemic
- correct with IVFT usually
- renal diets tend to be more alkalinising than maintenance pet foods
What is the prevalence of hypertension in CKD?
- 3/4 cats presenting with hypertensive retinopathy/ choroidpathy will have azotaemic CKD
- azotaemia usually mild at diagnosis of hypertension
- about 30% cats with CKD will be hypertensive
- prevalence in dogs is probably similar, although few develop ocular changes
What neuro signs might occur with CKD?
- depression
- seizures
- head tilt
- vestibular signs
- ataxia
- death
What cardiac signs might occur with CKD?
- overt heart failure uncommon
- may exacerbate pre-existing conditions
- murmurs are common but not specific
- mild LV hypertrophy
Normal cat/dog BP
- systolic 125mmHg
- mean 100mmHg
- diastolic 90mmHg
What constitutes hypertension in terms of tx?
- systolic BP >170mmHg repeatedly
- systolic BP >160mmHg and consistent CS present
Tx - feline hypertension with CKD
GENERALLY INEFFECTIVE - beta blockers - spironolactone - diuretics - ACEI EFFECTICE: - calcium channel blocker (amlodipine) - tx saves vision but doesn't slow CKD progression
Tx - canine hypertension with CKD
ACEI generally 1st line tx, response often poor, multimodal tx often required. Then add amlodipine (response often still poor). Consider alternatives (but risk of side-effects without high risk of end-organ damage (i.e. consider risk/benefit ratio and keep low).
