Chronic Kidney Disease Flashcards
What does it mean if there is an elevation in creatinine?
it means at least 75% of the renal function have been injured/ lost
What type of CKD is associated with dogs? cats?
Dogs: tubulointerstitial nephritis
Cats: tubulointerstitial nephritis
What are the 6 factors that should be considered to establish a diagnosis of CKD in pets?
- nature of the primary disease
- severity/ duration of clinical signs, uremia?
- probability of improving renal function
- severity of intrinsic renal function impairment
- rate of progression
- age
Who survives longer with CKD - cats or dogs?
cats
What’s the prognosis of cats with CKD?
varies with stage
- baseline PO4 and IRIS staging
- hypertension is not primary determinant of survival bust does affect severity of proteinuria
- amlodipine can also decrease proteinuria
What’s the prognosis for dogs with CKD?
MST from diagnosis = 8m (226 days)
- IRIS stage and BUN = prognostic
- proteinuria = risk factor for developing uremia and death
- arterial hypertension = risk factor for death
- higher body condition score lived longer
- CKD less progressive in familiar or congenital cases that are not associated with proteinuria
- a slower progression also noted for young dogs with acquired CKD (ex. toxins)
Define uremic syndrome.
The clinical syndrome associated with loss of kidney function
What are some clinical signs associated with uremia?
- PU/PD
- GI derangement: anorexia, nausea/ vomiting, diarrhea/ melena
- weight loss, muscle loss
- lethargy, depression
What are the 3 major mechanisms involved in the pathogenesis of uremia?
- disturbed excretion of electrolytes and water
- reduced excretion of organic solutes (ex. uremic toxins)
- impaired renal hormone production
What are some signs associated with disturbed excretion of electrolytes and water?
As GFR decreases, the remaining functional nephrons will have to work harder to maintain the balance. Some electrolytes have better compensatory mechanisms than other (ex. Na vs PO4). Clinical signs include:
- edema
- hypertension
- hyponatremia
- hyperkalemia
- metabolic acidosis
- hyper-PO4
What’s a major difference in excretion of electrolytes vs organic solutes in the kidneys?
excretion of organic solutes is generally not actively regulated - so as it begins to rise with a decline in GFR, it will progressive increase as renal functions declines
What are some abnormalities associated with uremic toxins?
- inhibition of ATPase
- inhibition of platelet function
- leukocyte dysfunction
- loss of RBC membrane lipid asymmetry
- insulin resistance
Does lowering the urea concentration = lowering the uremic toxin level?
thought it’s a good reflection, it isn’t conclusive evidence for reducing uremic toxin
What happens to cytokines and growth factors in uremia?
there is an accumulation due to decreased catabolism by the kidneys
- some peptide hormones (ex. PTH, insulin, glucagon) increased in CKD patients due to lack to catabolism and increased glandular secretion
What are some essential hormones produced by the kidneys?
- erythropoietin
- calcitriol
- prostaglandins
- kinins, renin
What’s the sequalae of decrease calcitriol?
- renal secondary hyperparathyroidism
- renal osteodystrophy
What are some GI consequences of
- nausea, vomiting, loss of appetite (can be waxing/ waning)
- stomatitis
- GI ulcers
- diarrhea, colitis
Define uremic gastropathy.
- edema
- mucosal and submucosal blood vessel mineralization
- glandular atrophy
- more common in cats than dogs
- increased gastrin and reduced renal clearance may lead to GI ulceration
How common is uremic gastropathy?
- gastric mineralization is increased with increased CKD III and IV in cats
- increased Ca-PO4 product = increase severity
How frequent is dysphagia in CKD?
dysphagia/ oral discomfort in 8% of uremic cats and 38% of end stage CKD
- halitosis
- stomatitis
- periodontal disease
How common in uremic enterocolitis?
- less common and less dramatic than uremic gastritis
- likely due to the irritation effect of increased ammonia product in the colon associated with high urea
What’s the pathophysiology for dilute urine in CKD patients?
- loss of functional nephron = the remaining nephrons will have an increased solute load
- impaired genesis of a hypertonic gradient in the renal medulla (ex. impaired countercurrent multiplier system)
- impaired responsiveness to ADH
What’s the major mechanism thought to contribute to hypertension in CKD patients?
- fluid retention
- activation of renin-angiotensin-aldosterone system
- sympathetic stimulation
- retention of salt in cats may be a major driver in hypertension and ACEi don’t always work
Is the hypertension in CKD patients primary or secondary?
dogs/cats = hypertension commonly secondary
- primary hypertension = uncommon
What’s the IRIS staging system?
What’s the role of hypoxia-inducible factor in CKD?
HIF-2 is a transcription factor that regulars EPO production
- also regulates intestinal iron uptake
What are the 6 main reasons for anemia in CKD patients?
- insufficient renal EPO production –> relative decrease of EPO
- shorted RBC lifespan
- nutritional abnormalities (iron, B12, folate)
- EPO inhibitors in uremic plasma
- blood loss
- myelofibrosis
How does renal secondary hyperparathyroidism occur in CKD patients?
- reduced GFR = increased PO4 retention –> direct stimulation of PTH
- PTH can lead to increased fibroblast-growth-factor 23 (FGF23)
- FGF23 mitigate PO4 retention but also decrease calcitriol activity by inhibiting renal 1-alpha-hydroxylase activity
- decline in calcitriol stimulates PTH secretion
- PTH –> stimulates 1-alpha-hydroxylase activity –> increases calcitriol level
- calcitriol then inhibits PTH (negative feedback)
- to normalize calcitriol, there is an increased PTH secretion
- ultimately, there aren’t enough functional nephrons to produce enough calcitriol –> decreases PTH inhibition
- but deficiency in calcitriol lead to skeletal resistance to PTH (helps with stimulation of osteoclast bone resorption), and elevates the set-point for calcitriol induced PTH suppression
- uremic toxins also inhibits suppression of PTH induced by calcitriol
- low GI calcium absorption also happens due to impaired calcitriol
- persistent hyperparathyroidism even with normal or elevated Ca2+
How common is renal osteodystrophy?
uncommon
- maybe seen in young, growing animal
- mostly bones of the skull
- may also see parathyroid hyperplasia
How does CKD contribute of metabolic acidosis?
- though there is increased H+ excretion per nephron, the decreased # of functional nephrons cannot keep up to the H+ excretion
- there is usually no lack of reabsorption of bicarbonate in dogs/ cats (may be selective tubular disorder)
What’s the sequelae of chronic metabolic acidosis?
- anorexia, nausea, malnutrition
- lead to negative Ca balance, hypokalemia, renal dysfunction, and taurine depletion
- promote protein catabolism
- also blocks the adaptive response to protect degradation of skeletal muscles
How is BUN elevation promoted in CKD patients?
- decreased protein synthesis from uremia
- accelerated proteolysis due to metabolic acidosis
- the combination increases BUN
How urea is synthesized?
nitrogen derived from amino acid catabolism
- BUN is typically related to dietary protein content
How does hyperphosphatemia develop for CKD?
- at first, there is compensatory decrease in reabsorption of PO4 (FGF23 and PTH)
- as disease progresses, the adaptive mechanism reaches limits –> increase in PO4
What’s the consequence of hyperphophatemia?
it contributes to CKD progression
How reliable is tCa level for cats with CKD?
total calcium can be elevated but only a small proportion will have increased ionized calcium
- could be due to calcium bound to other organic or inorganic anions (ex. citrate, PO4, sulfate).
How common is hypokalemia?
uncommon in dogs, more seen in cats
- sodium restricted diet promotes kaliuresis
- hypokalemia worsens the CKD
What’s another endocrine disorder that can be responsible for CKD in cats?
hyperaldosteronism
What’s the relationship between GFR and creatinine?
Every time the GFR decreases by 1/2, the creatinine level 2x
Why not just make the range for creatinine narrower?
then creatinine becomes less specific to GFR
What factors other than GFR can influence BUN level?
Increase BUN can be seen with:
- decreased renal perfusion
- upper GI bleed
- increased protein catabolism/ intake
- corticosteroids use
Decrease in BUN can be seen with:
- liver dysfunction
serum BUN = glomerular filtration + tubular reabsorption
What’s the relationship between uremia, azotemia, and kidney disease?
- kidney disease can occur without azotemia or uremia
- azotemia doesn’t mean kidney disease
- uremia is always associated with azotemia but not the reverse
- uremia can occur without kidney disease
Does renal azotemia respond to fluid therapy?
no, the animal will never be able to regain concentration ability
How is SDMA synthesized?
from protein degradationW
Why is SDMA a good marker for GFR?
over 90% is filtered without reabsorption
itself has little physiologic activity
Which treatment for CKD has the greatest benefit and scientific evidence?
Renal diets!
What are some qualities of renal diets?
- low Na, PO4
- high quality protein
- acid/ base neutral
- added B vitamins
- calorie dense
- added soluble fiber
- added fatty acids, and omega 3
- K supplement for cats
What is actually more physiologically appropriate to give for fluid therapy at home?
Water via feeding tube
(Na containing fluid can make things worse)
What are some common complications of GI uremia?
Dogs: uremic gastritis, ulcers
- thought to be due to increased gastrin level
Cats: gastric mineralization and fibrosis
Both can have decreased appetite, nausea, and vomiting
How are the GI signs due to uremia managed?
Dogs: can use H2 blockers, proton pump inhibitors, sucralfate for the gastric ulcers
Both: anti-nausea: maropitant, ondensatron
Both: appetite stimulant- mirtazapine, cyproheptadine
- esophageal feeding tube
How is metabolic acidosis managed in CKD patients?
Usually through diet
- if very acidosis (pH <7.10) can consider oral K-citrate supplements
How common is hypokalemia in CKD patients?
Dogs- uncommon
Cats- common in IRIS stage II-III, not IV
What are 4 possible reasons for hypokalemia in cats?
- Decreased dietary intake
- Diuresis from PU
- Activation of RAAS due to dehydration
4 restricted salt intake
What are some implications of hypokalemia in cats?
- Further promotes renal damage by reducing renal blood flow and GFR (angiotensin vasoconstriction)
- Promote PU
- Muscle weakness (polymyopathy, cervical ventral flexion)
How is hypokalemia treated?
Best with oral supplementations - ex. K-citrate, can also help to alkaline / reduce risk of acidosis
- SC if can’t tolerate oral or in emergency
How common is hyperkalemia in CKD patients?
Uncommon, can be noted with feeding tube, use of ACEi or ARB
- diet modification
What are some complications associated with hypertension?
- worsens the kidney disease
- end organ injury: retinopathy, cerebral hemorrhage/ stroke, ventricular hypertrophy
- proteinuira
What’s are some indications for hypertension treatment?
If persistent systolic pressure >180mm Hg
- >200mg Hg = emergency, need to start treatment immediately
- presence of end organ injury
What are the goals for hypertensive therapy?
- slow and gradually reduction toward ~160mm Hg
- ACEi, amlodipine good for both dogs and cats
- don’t do ACEi and ARB at the same time —> risk of hyoerkalemia
- monitor every 3m, titrate to effect
What’s the cause of anemia in CKD patient?
- lack of EPO production
- decreased nutrient intake (iron, folate, protein, etc) can also contribute
- there may be GI bleeding, and altered RBC lifespan
- thrombocytosis and hypochromasia –> GI bleeding/ iron deficiency
What’s the treatment for CKD induced anemia?
Erythropoietin stimulating agent
- ex. darbepoietin
- should see improvement in PCV 2-8 weeks
- repeated dosage may lead to neutralizing anti-EPO antibody formation
What’s the likelihood of developing neutralizing antibodies to EPO?
25-30% of cats, up to 50% of dogs
- these antibodies will cross-react with all exogenous and endogenous EPO –> essentially the pet has pure red cell aplasia –> will need to be on blood trasnfusion
- darbepoetin may be less immunogenetic due to longer half-life/ less dosing
What are some side effects of EPO?
- antibody formation
- allergic reaction
- hypertension
- seizure
What’s the benefit of calcitriol therapy?
Calcitriol = most active metabolite of Vitamin D. Supplementation in dogs with CKD III and IV slows disease progression/ mortality
- involved in Ca and PO4 uptake from GI tract, suppresses PTH production and secretion, suppresses parathyroid gland growth, and activates cellular receptors
- PO4 retention and hyperphosphatemia, and increased FGF-23 reduce calcitriol
When should renal diets be recommended?
- renal diet: dogs CKD stage III-IV, cats CKD stage II-IV
- all dogs with proteinuria
What are management goals for CKD?
- renal diet (if needed)
- treatment for limiting proteinuria and hypertension
