Chronic Kidney Disease Flashcards
How should CKD be diagnosed?
Over a long time - at least 1m, possibly 3
Creatinine in a fasted patient at least 12 hours at least a month apart
BP readings
Proetinuria on at least 2-3 readings
Imaging studies
What are the recommendations for feeding a kidney diet?
dogs with IRIS CKD Stages 3 and 4 and cats with IRIS CKD Stages 2–4
how are kidney diets different to normal diets?
reduced protein, phosphorus, and sodium content, increased B‐vitamin and soluble fiber content, increased caloric density, a neutral effect on acid‐base balance, supplementation of omega‐3‐polyunsaturated fatty acids and the addition of antioxidants. Feline kidney diets are supplemented with potassium.
What drugs can be used to stimulate appetite?
antiemetic drugs (eg, maropitant, ondansetron), H2‐receptor blockers or hydrogen pump antagonists (eg, famotidine, ranitidine, omeprazole), and appetite stimulants (eg, mirtazapine, cyproheptadine) Consider feeding tube if cannot get BCS to near 5
How can the signs of uraemia be managed?
Management of anorexia, nausea and vomiting typically includes:
(1) limiting gastric acidity using H2 blockers,
(2) suppressing nausea and vomiting using antiemetics,
(3) providing mucosal protection using sucralfate.
Of these treatments, H2 blockers are most commonly employed and few adverse effects have been attributed to their use. The most commonly used H2 blockers include famotidine and ranitidine. However, since their efficacy remains unproven, there is only weak evidence to support a recommendation to use them
Outline the use of SC fluids
Only patients that show clinically apparent benefits to chronic fluid therapy should receive chronic supplementation with subcutaneous fluids.
Administer balanced fluid e.g. Hartmanns every 1-3 days
75-150ml per cat
Why avoid hyperphosphataemia?
hyper phosphataemia can promote renal secondary hyperparathyroidism, mineralization of tissues and progression of CKD
Do for stages 2-4
Each IRIS stage has its own upper limit of phosphate recommendation. Often this is lower than lab level
How should you manage phosphate levels
Start with kidney diet
After 6 weeks rc phosphate. If not within the ideal range then add a phosphate binder (normally an aluminum salt)
Start at low end of dose and measure/ change to effect every 4-6 weeks
How do you manage acidosis (mostly only in pets with uraemia - 50%)
Ensure renal diet
Consider use of alkanising agent ini within 4 weeks
Sodium bicarbonate or potassium citrate
Only weak evidence for use of these
It is not fully known why cats becomen hypokalaemic - many stage 2 and 3 are, very few in stage 4 are.
What are the suggested reasons for this?
inadequate potassium intake, increased urinary loss, and enhanced activation of the renin‐angiotensin‐aldosterone system due to dietary salt restriction may play a role. In addition, amlodipine may promote hypokalemia in some cats with CKD
In stage for GFR may be so low as to promote retention
How do you treat hypokalaemia?
Potassium gluconate or potassium citrate ideally oral
Measure every 7-14 days and assess need for dose change
How can anaemia be managed?
Darbopoeitin - long acting erythropoietin. Has an induction phase and a maintenance phase
Give if PCV < 20%
Check iron concentrations prior to use
Typically see an increase in PCV in 2-3 weeks
Consider a one off injection of iron at the first one. Can rarely get anaphylactic shock with this so monitor closely after
PCV should be measured weekly during the induction phase (to avoid overdosage), every other week during transition to the maintenance phase, and monthly once a stable PCV in the target range has been achieved in the maintenance phase.
Dogs may require b12 supplementation at the same time - consider testing if poor response seen
Pets often have low calcitriol levels in CKD - outline management of this
Evidence to suggest supplementation in dogs stage 3-4 increases lifespan
Before giving, ensure phosphate levels are in target levels and check i Ca
Outline management of proteinuria
Initiate therapy with a kidney diet and administer an angiotensin converting enzyme inhibitor (ACEI) with the therapeutic goal of reducing the UPC at least in half or, ideally, into the normal range
ACEi dilate the efferent arteriole, decreasing filtration pressure - a small number cannot cope with this leading to azotaemia
Benazepril has been advocated preferentially over enalapril because it is cleared largely by hepatic rather than renal excretion.
Start with once daily but often need twice daily
Occasionally ACE inhibitor therapy is associated with a marked decline in kidney function; therefore, serum creatinine should be measured before and 1–2 weeks after initiating therapy. If creatinine is more than 20% high, discontinue
May also lead to hyperkalaemia so monitor for this too
RC UPCR 1-3 after starting treatment
If an ACEi is not working, start ARB
Outline management of hypertension
ACEIs (eg, enalapril and benazepril) and calcium channel blockers (CCB; eg, amlodipine) are the preferred drugs
ACEI generally produce relatively small reductions in blood pressure, but have a beneficial role in altering intraglomerular hemodynamics, proteinuria, and the profibrotic effects of the intrarenal renin‐angiotensin system, ACEI may have renoprotective effects even when adequate arterial blood pressure control is not achieved.
When these aren’t effective, can try spironolactone, ARBs, atenolol, prazosin,
How is proteinuria related to prognosis?
Poorer if present
What is the typical disease found with CKD?
tubulointerstitial nephritis
Why does proteinuria cause disease progression
Not fully understood, could be
direct toxicity to tubular cells, inciting inflammatory responses or the formation of proteinaceous casts resulting in tubular obstruction.
Alternatively, may be the presence of other solutes that are filtered through a damaged glomerulus alongside protein that are damaging to the tubules.
How many cats with CKD will be proteinuric?
Approx 20%
Dogs likely more as glomerular dz more common
What is the structure of the glomerulus?
The glomerulus is a network of capillaries interposed between the afferent and efferent arterioles enclosed within an epithelial capsule (Bowman’s capsule) and separated by the Bowman’s space.
Glomerular filtration is a pressure-driven process governed by hydrostatic and oncotic pressures in the glomerular capillaries and Bowman’s capsule, and by glomerular conductivity and the capillary surface area.
It is charge and size selective
What makes up the filtration membrane?
fenestrated endothelial cells, basement membrane and podocytes
How does tubulointerstitial proteinuria occur
Tubulointerstitial proteinuria can develop as a result of defects in protein reabsorption in damaged renal tubular cells or a tubulopathy (eg, Fanconi syndrome) and is also likely to be exacerbated by accelerated tubular flow rates
How can you differentiate glomerula and tubular proteinuria
Mostly all just used in research and not fully confirmed
urine electrophoresis - small molecular weight in tubular, large in glomerular
Can guess a little with severity of UPC reading
How does high BP cause proteinuria
high systemic arterial pressure to the glomerulus. This in turn will increase hydrostatic pressure at the glomerular filtration barrier, resulting in the development of, or worsening of, pre-existing proteinuria. In addition, hypertension can contribute to renal injury.
What is the goal of treatment for BP
The goal of treatment should be a SBP between 120-150 mmHg in dogs and 120-160 mmHg in cats
What blood pressure drugs should be used in dogs?
Start with ACE inhibitor, if over 200 add in amlodipine to start with, otherwise add in if not a good enough response is seen
Where are the locations of possible proteinuria?
Prerenal proteinuria results from the inability of the tubules to reabsorb the high plasma content of small proteins that can freely pass across the glomerular barrier. Examples include immunoglobulin light chains in multiple myeloma, myoglobin in rhabdomyolysis and haemoglobin in intravascular haemolysis. Serum protein electrophoresis or other diagnostics are useful in excluding prerenal proteinuria.
Renal proteinuria results from glomerular or tubulointerstitial pathology. Functional proteinuria as a result of fever, seizure activity or strenuous exercise is possible, although it is rarely recognised in clinical patients.
Postrenal proteinuria results from the entry of proteins into the urine derived from exudative or haemorrhagic processes in the lower urinary tract or genital tract. Urine sediment examination should be performed to exclude postrenal proteinuria.
Aside from dispstick, what is another qualitative method of assessing proteinuria?
sulfosalicylic acid turbidimetric method - has to be sent to lab, assess with knowledge of SG and sediment, Finds albumin and globulin
A normal animal would be expected to have a UPC of <0.2 excpet in who?
intact male cat, the UPC may be less than 0.6,
What should you doo in animals with glomerular proteinuria?
should be evaluated to determine if there are any potential infectious, inflammatory or neoplastic diseases that may serve as a trigger for glomerulonephritis or amyloidosis
What happens when the RAAS is activated in CKD?
Within the glomerulus, the effect of this is vasoconstriction of the efferent arteriole with an increase in glomerular capillary hydrostatic pressure. This results in an initial improvement in GFR.
In the long term, RAAS activation is a mediator of progressive renal injury via increasing glomerular capillary pressure and associated filtration of plasma proteins. RAAS activation and in particular aldosterone are also considered to be important mediators of proinflammatory and profibrotic pathway
Which drugs target the RAAS system?
ACEi (eg, benazepril, enalapril), angiotensin receptor blockers (ARBs) (eg, telmisartan, losartan) and aldosterone receptor antagonists (eg, spironolactone)
How do ACE inhibitors reduce proteinuria?
most important mechanism by which ACEi reduce proteinuria is through preferential dilation of the efferent arteriole in the glomerulus to decrease glomerular capillary hydrostatic pressure. ACEi inhibit the conversion of angiotensin I (AT-I) to angiotensin II (AT-II)
Outline the use of ACE inhibitors
Enalapril slowed onset of azotaemia in CKD dogs
No studies to show improvement in lifespan in cats with CKD, is in dogs
Benzapril licensed for management of CKD in cats
Benazapril likely better than enalapril as less renal excretion
Mixed recommendation of use in cats with UPC <0.4, useful in dogs
What are possible adverse reactions of ACE inhibitors?
Administration of ACEi can result in hypotension, hyper-kalaemia or a decrease in GFR that can worsen pre-existing azotaemia. Therefore, patients should be stable, adequately hydrated and normotensive before initiating ACEi therapy
What do angiotensin receptor blockers do?
ARBs selectively inhibit ATII binding to AT1 receptor.
AT1 causes vasoconstriction and this can exacerbate systemic hypertension and proteinuria
Outline the benefits of Telmisartan
May be the drug of choice for concurrent hypertension and proteinuria in cats
Not licensed in dogs, some results suggest efficacy
Outline the use of concurrent therapy for proteinuria
Study is elderly humans showed increased risk of death so not a good choice
Outline the use of spirololactone in CKD
may be considered in a patient with high serum aldosterone concentration and persistent proteinuria despite treatment with an ACEi and/or ARB; however, its use would be off licence.
When should renal biopsy be considered?
patients with suspected glomerular proteinuria of high magnitude (UPC ≥3.5 in dogs) that have not responded to standard therapy, such as RAAS inhibition, and that do not have any contraindications to a renal biopsy being performed. Such contraindications include moderate or marked azotaemia, uncontrolled hypertension, renal cystic disease, hydronephrosis, pyelonephritis, coagulopathy or severe anaemia.
What are the IRIS recommendations for starting immunosuppressives in dogs with glomerular disease without biopsy?
when a patient is markedly azotaemic (IRIS stage 3 or 4 CKD), has rapidly progressive azotaemia or severe hypoalbuminaemia (<20 g/dl).
What is the most common glomerular disease in cats?
membranous nephropathy
What omega fatty acids may help to reduce proteinuria?
n3 PUFA and specifically docosahexaenoic acid and eicosapentaenoic acid
What else should be given to highly proteinuric dogs?
Anti-thrombotic. No evidence to prefer clopidogrel over asprin and asprin is cheaper
What can happen in late stage proteinuria
UPC goes down due to lack of nephrons
What is nephrotic syndrome?
hypoalbuminaemia, proteinuria, hypercholesterolaemia and fluid accumulation in interstitial spaces and/or body cavities.
How can you treat nephrotic syndrome
diuretics in dogs with oedema should be limited to situations where organ function is critically impaired, such as in patients with dyspnoea due to pleural effusion. Another indication would be for transient reduction in oedema and/or ascites to facilitate renal biopsy. Furosemide is the agent of choice in dogs with hyperkalaemia and spironolactone for dogs with pleural or abdominal effusion
Only give colloids for haemodynamic stabilistation, not to increase protein
How do you diagnose CKD in cats?
An increased serum creatinine concentration >140 µmol/l together with
An inappropriately low USG (<1.035); and
Evidence that these changes are sustained (over several weeks or months) or with a history suggesting sustained clinical signs consistent with CKd.
Sometimes these are not met. Can also consider a sustained 15% increase in creatinine baseline
Renal origin proteinuria
Sometimes usg can be over 1.035
What are negative prognostic indicators for CKD in cats?
< The level of proteinuria < The level of hyperphosphataemia < The FGF-23 concentration < The presence of progression of CKD < A lower PCV
Why may cats not respond to EPO therapy?
< Concurrent illnesses (present in most cats that fail to respond to ESA);
< Infections or inflammation;
< Gastrointestinal bleeding;
< Iron deficiency;
< Pure red cell aplasia (PRCA) from production of anti-EPO antibodies
Also approx 50% of cats will get hypertension from EPO
How do you treat a UTI inCKD cats
controversial to treat subclinical disease
2-4 weeks therapy, culture 7 days after cessation of treatment
What are some congential causes of CKD?
PKD (persians, autosomal dominant) Renal amyloidosis (abyssinians, others) Renal dysplasia (boxers, ragdolls, persians) Glomerular disease
What are the main causes of CKD?
congenital causes neoplasia drugs or diets Infectious disease consequence of AKI Renal ischaemia (infarcts, hypoperfusion, thrombosis, hypotension) Endocrine (hypo or hyperthyroidism) Metabolic (high Ca, nephro or ureteroliths
Outline the cycle of decreasing renal function
Decrease in functional nephrons = increase in compensatory GFR
Leads to glomerular hypertension, RAAS activation, tubular interstitial disease
These lead to proteinuria, glomerular sclerosis, a damage filtration barrier, activation of the RAAS, inflammatory cytokines, fibrosis, and renal hypoxia
This leads to further nephron loss and decrease in GFR
This leads to further kidney insults and the cycle beings again
Why be careful with kidney FNAs if amyloidosis is a ddx?
Can lead to significant renal h+
Which breeds are especially prone to white coat hypertension
sighthounds - use values 20mmHg higher for cut offs
/How does CKD lead to hyperparathyroidism?
Decrease in GFR Increase in phosphorous Decrease in 1 alpha hydroxylase Decrease in calcitriol Decrease in Ca (may stay wnl in bloods) Increase PTH Increase calcitriol Increase Ca
What are the 4 main treatment goals with CKD?
Alleviate signs of uraemia
Appropriate nutrition
Control fluid levels, electrolyte levels, mineral/ vitamins
Modify progression of disease
What can the main treatment goals of CKD be further broken down into? (12)
- Supportive gut protection
- Addressing/treating UTI
- Controlling hypokalemia
- Controlling metabolic acidosis
- Reducing proteinuria
- Addressing hypertension (systemic)
- Reducing intraglomerular hypertension
- Protecting the kidney from fibrosis/remodeling
- Controlling phosphate
- Preventing 2‐HPTH from developing/progressing
- Avoiding malnutrition
- Preventing anaemia
Why does K go low (mostly stage 2 and 3)
Decreased intake
increased loss
RAAS
amlodipine usage
What can low K cause?
PUPD Poor gut motility myopathy progressive CKD weakness/ lethargy
How do you treat low K
Initially trial renal diet
If this fails, give sodium bicarbonate or potassium citrate
Outline the cycle of proteinuria
An increased glomerular pressure leads to increased proteinuria which causes further kidney damage and loss of function
What phosphate binders are there?
Aluminium, Ca or lathanium based PBs
Also Sevelamer hydrocholride and Epakitine
Outline aluminium based PBs
Common, effective, inexpensive
Bind Phophorous in the intestines
Mostly excreted by the kidneys so you can get build up in the tissues in advanced disease, this can lead to nuero signs
Can also see constipation
Outline Ca based PBs
Not as good as aluminium
Higher doses needed
Ca Carbonate –> best in acidic environment (consider this is patient on antacids)
Ca acetate –> lower doses needed than carbonate and more effective. Not as affected by pH
S/e - hypercalcaemia
Outline lanthanum based PBs
Must be crushed
very little systemic absorption
Excreted by the liver
Outline Epakitine
10% Ca carbonate, the rest is chitosan and lactulose
Decreases phosphate absorption and protein digestability
How do you manage secondary renal hyperparathyroidism
Calcitriol (low dose)
Give every 3.5d (CANNOT BE 4)
Avoid giving with food
PTH levels will drop gradually, can measure after 4-6 of starting treatment
How would you generally assess the degree of glomerular disease?
UPC
How does serum aldosterone increase over time with use of ACEi and ARBs?
In people leads to increases
This can lead to adverse events in the kidneys, systemic blood vessels and heart
When may spironolactone (aldosterone blocker) be appropriate in CKD?
could be tried in animals that have high serum aldosterone concentrations and persistent proteinuria in spite of treatment with an ACEi, ARB, or both with the understanding that its efficacy in reducing proteinuria has not been established.
When is it important to do pooled UPC samples?
When borderline or >4. Lots of variation in different samples.
When looking for efficacy, ensure there has not been a marked change in creatinine at the same time as this will affect results
Why feed a low salt diet?
likely that dogs with kidney disease,33 particularly those with nephrotic syndrome (NS), are salt‐sensitive. Furthermore, salt restriction enhances the antihypertensive efficacy and renal hemodynamic effects of some antihypertensive agents in dogs34 and cats,35 particularly those that interfere with the renin angiotensin system
