Acute and Chronic Renal Failure Flashcards
What is the difference between acute and chronic kidney disease?
Acute:
- Recovery is possible: can take months for tissue to heal and renal function to come back
Chronic:
- Permanent loss of kidney function
- Requires 2-3 months duration in order to be referred to as chronic kidney disease
You notice an animal has azotemia, what are the 3 main divisions of Azotemia?
- Pre-renal
- Renal
- Post-renal
Therefore, just because azotemia is present, this does NOT mean renal injury is present
You have a patient that is azotemic, how can you tell if it is pre-renal Azotemia?
- Urinalysis is a MUST
- SG: >1.030 (dogs) or >1.035 (cats) then azotaemia pre-renal
- Dehydrated
- Rule out other diseases that can affect urine concentration: e.g. tubular disease, Cushing’s disease and diuretics
You have a patient that is azotemic, how can you tell if it is Post-renal Azotemia?
- Urinalysis
- U/S the bladder to ensure it is still intact and not ruptured
- X-ray to rule out urethral obstructions from urolithiasis
Why are the kidneys at high risk of ischemic and nephrotoxic insults?
- High cardiac output
- High metabolic demand and thus oxygen demand
- Can concentrate certain toxins in the urine and thus end up damaging itself
What is the definition of acute kidney injury?
A creatinine elevation >26.4µmol/L or >25% baseline within 48h
But there is no perfect definition as there are always individuals who don’t have azotemia but are experiencing sudden renal issues
What are the 4 stages of Acute Kidney Injury?
1) Ischemic or Nephrotoxic Insult
2) Structural damages and altered function
3) Maintenance Phase
4) Recovery phase
Describe the 1st stage of Acute Kidney Injury
Ischemic or Nephrotoxic Insult
- No clinical signs, non-azotemic
- Intrinsic parenchymal injury leading to dysfunction
- Rapid changes in hemodynamics, or filtration, or tubulointerstitial or outflow injury, which leads to the accumulation of metabolic toxins, dysregulation of acid-base, electrolytes and extracellular fluid balance
note: duration of this stage is dependent on the nature of the primary insult
Describe the 2nd stage of Acute Kidney Injury
Structural damages and altered function
- Continued hypoxia and inflammation, propagates renal damage
- Cortical structures (loop of Henle and collecting tubules) are predisposed to damage first due to their high metabolism and high blood requirements
- Intervention at this stage may not be successful in repairing 100% of kidney function
Describe the 3rd stage of Acute Kidney Injury
Maintenance Phase
- Critical amount of damage has occurred
- Lasts 1-3 weeks
- Urine output will increase or decrease: owners usually notice a change now
- There is a loss of tubular function
Describe the 4th stage of Acute Kidney Injury
Recovery Phase
- Injury has subsided and the renal tissue is beginning to repair
- Increased urine output
- Volume depletion can lead to the progression of kidney disease
- Repair can take months, and may not go back to 100% functionality. Damage to the basal membrane will mean irreversible loss
What are the Pre-renal causes of Acute Kidney Injury?
Hemodynamic Changes
- Absolute decrease in effective blood volume: blood loss, severe dehydration
- Relative decrease in blood volume: Hypotension
- Arterial occlusion or stenosis of renal artery: aortic thrombus
- Decrease in afferent artery pressure: NSAIDs and ACE inhibitors
What are the Renal causes of Acute Kidney Injury?
1) Ischemia
- Shock (hypovolemic, hemorrhagic, hypotensive, septic)
- Decreased cardiac output (CHF, arrhythmias, tamponade
- Hyperthermia
- Vessel occlusion
2) Nephrotoxin exposure
3) Infectious: pyelonephritis, leptospirosis, borreliosis, FIP, Leishmaniasis
4) Immune-mediated
5) Systemic Inflammation
6) Hypertension
7) Neoplasia (lymphoma)
What are the common Nephrotoxins to be aware of ?
- Ethylene glycol
- Lillies (cats)
- Grapes/ Raisins (dogs)
- Heavy metals
- Myoglobinemia/ Hemoglobinemia
- Hypercalcemia: cholecalciferol (rodenticide)
- Drugs: NSAIDs Aminoglycosides Amphotericin B Radiocontrast media ACE inhibitor Vasodilators
What are the Post-renal causes of Acute Kidney Injury?
- Urinary Tract Rupture (leading to uroabdomen)
- Urinary Tract Obstruction (pelvis, ureter, urethra)
At what Systolic BP will you get damage to organs?
> 180 mmHg
- Retinal hemorrhage
- Retinal detachment
- Intracranial hemorrhage
What is the treatment for Acute Kidney Injury?
- Crystalloid Fluid therapy: maintenance + ongoing losses + dehydration status
Best to replace 1/3 of dehydration within 6 hours, and then the remaining 2/3 is replaced over 24 hours. This will allow for minimal rehydration within the first 6 hours, followed by a SLOW rehydration so not to overwhelm the kidneys
Fluid therapy should be reassessed every 2-4 hours - Norepinephrine for severe hypotension if present
- Furosemide (diuretic) can help convert an oligo-anuric patient to a non-oliguria but must be used carefully with fluid therapy
- Calcium gluconate for the protection against hyperkalemia
You have an in-hospital patient that is suffering from AKI, and showing signs of Hyperkalemia (Bradycardia) due to anuria
You perform an ECG and notice changes reflective of Hyperkalemia (small QRS complexes, prolonged P-QRS intervals, small or absent P waves and tall tented T waves)
What is the treatment of choice?
1) Calcium gluconate (10%)
Protects the myocardium by decreasing the threshold potential and normalizing the conductivity
- It does NOT address the K+ concentration directly
Dose: 0.5 - 1.0ml/kg of Calcium gluconate 10% IV slowly while patient is on an ECG monitor
2) Glucose administration (50% Dextrose)
3) +/- Insulin/Glucose protocol
4) Antibiotics if indicated
You are presented with a patient that is diagnosed with AKI, there are no ECG changes, but serum electrolytes show a hyperkalemia
How can this be managed/ treated?
1) Glucose administration (50% Dextrose)
Dose: 1-2 ml/kg diluted 1:2 in slow IV infusion (15-20mins)
This will increase the endogenous insulin release (within 1 hour) and lead to co-transport of glucose and Na+/K+ into the intracellular space, thus reducing K+ levels
2) +/- Insulin/Glucose protocol
What is the definition of Chronic Kidney Disease?
Chronic Kidney Disease is a syndrome, it is a slow, progressive, irreversible loss of structural or functional nephrons that has been ongoing for at least 3 months
Between Acute and Chronic Kidney Disease, which is more commonly recognized in cats and dogs?
Chronic Kidney Disease
What are the causes of Chronic Kidney Disease in Dogs and Cats?
Chronic Kidney Disease can be considered a Syndrome, with many causes
Dogs:
- 58% chronic tubulointerstitial nephritis
- 28% glomerulonephropathy
- 6% amyloidosis
Cats:
- 70% tubulointerstitial nephritis
- 15% glomerulonephropathy
- 11% lymphoma
- 2% amyloidosis
What are the clinical signs associated with Chronic Kidney Disease?
Clinical signs are associated with the loss of function and thus retention of toxic metabolites and body-fluid imbalance
PUPD (44%) Anorexia (40%), nausea, vomiting (50%) Oral ulceration, stomatitis, necrosis, halitosis (12%) Diarrhoea/melena (37%), haematochesia Weight loss/cachexia (29%) Lethargy/depression (22%) Urinary incontinence (20%) Anemia (4%)
One of the clinical consequences of Chronic Kidney Disease is the disturbed excretion of electrolytes and water, why does this happen and what are the clinical manifestations of this?
- Loss of functional nephrons = decline in GFR = remaining intact nephrons will have to excrete more water and electrolytes to compensate for the loss
- Up to an 80% reduction in GFR does not impair Na, K and water balance, but beyond 80% and you enter end-stage failure leading to the following clinical manifestations:
- Edema: due to water retention
- Hypertension
- HypoNa: loss of Na and unable to reabsorb, or PUPD
- HyperK: oliguric, anuric, loss of filtering capability
- HyperPO: oliguric, anuric, loss of filtering capability
- Metabolic acidosis
What are the clinical pathophysiological consequences of chronic kidney disease?
1) Disturbed excretion of electrolytes and water
2) Reduced excretion of organic solutes (urea and creatinine)
3) Impaired renal hormone synthesis
4) Arterial hypertension and cardiovascular consequences
5) Renal Secondary Hyperparathyroidism
Which organic solutes are retained in the blood system during kidney disease which we use as biomarkers of renal sufficiency?
- Urea and Creatinine
What are the consequences associated with the accumulation of urea and creatinine?
- Na/K ATPase inhibition
- Inhibition of platelet function
- Leukocyte dysfunction
- Insulin resistance
- Increased red cell fragility
What are the hormones produced by the kidney, which can be affected during Chronic Kidney Disease?
- Erythropoietin: stimulates red cell production from the bone marrow
- Calcitriol: Active form of Vitamin D, essential for Ca and skeletal metabolism
- Prostaglandins
- Renin
- Kinins
Vitamin D deficiency and excess retention of Phosphorus in a CKD patient will lead to __________
Renal secondary hyperparathyroidism, leading to the overproduction of PTH and subsequent renal osteodystrophy
Renal osteodystrophy is the result of hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia, both of which are due to decreased excretion of phosphate by the damaged kidney.
What is the most common cause of secondary hypertension in dogs and cats, and why?
Chronic Kidney Disease
With a reduction in GFR, water is retained in gradually increasing proportions leading to excess blood volume and hypertension
Hypertension subsequently causes vasodilation of the blood vessels, including the glomerular vessels, leading to leaking of proteins into the urine (proteinuria)
What is the pathophysiology of Renal Secondary Hyperparathyroidism?
- Reduced glomerular filtration → reduced phosphorus excretion → hyperphosphatemia
- Hyperphosphatemia → Calcium-phosphate products + soft tissue mineralization (especially stomach, kidneys, myocardium, lung, and liver) → lowering of [blood calcium]
- PTH secretion → release of calcitriol from remaining nephrons → Osteoclasts release FGF-23 → increase renal excretion of phosphate + decrease phosphate reabsorption
- As the disease progresses GFR reduced further with elevated hyperphosphatemia + Vitamin D metabolism becomes defective, calcitriol levels decrease → reduced intestinal absorption of calcium → hypocalcemia
- Sustained Hypocalcemia → hypertrophy of parathyroid glands → increased PTH secretion.
- Decreased active vitamin D → stimulates PTH secretion further
- PTH → increased osteoclastic activity → bone resorption (particularly in the mandible and skull)
Refer to: https://www.vin.com/apputil/content/defaultadv1.aspx?id=7054902&pid=12886
What is the effect of PTH on the kidneys?
- Stimulates calcitriol activation
- Increases Calcium retention
What is FGF-23 and what is its function/ purpose?
Released from osteoclasts in response to elevated calcitriol levels, when there is an absolute OR relative deficiency in Ca+
How can Chronic Kidney Disease be diagnosed?
- Serum creatinine concentration: but there needs to be a 75% reduction in GFR before the creatinine conc is above the reference range = somewhat insensitive = just because its not above the reference range, doesn’t mean CKD is not present
- Blood Urea Nitrogen Concentration (BUN/ Urea): less specific and less sensitive than creatinine. Can increase with GI ulcers or bleeding, enhanced protein catabolism, dehydration/ pre-renal azotemia or drugs (e.g. corticosteroids)
- SDMA (Symmetric dimethylarginine): ideal biomarker and can detect CKD much earlier than creatinine
- Urine SG: essential to differentiate pre-renal from primary renal disease. In advanced CKD, the kidneys cannot concentrate the urine more than the blood plasma, and therefore they are isosthenuric
- Hyperphosphatemia
- Metabolic Acidosis: excretion of ammonium decreases with GFR reduction = acidosis (remember ammonium is a weak acid) and retention of renal acids
- Cats may be hypocalcemic when measuring iCa, but hypercalcemia when measuring Total calcium levels (likely due to the increased Ca-PO4 complexes)
- Hypokalemia more common in cats with CKD than in dogs
- Full Hematology + Biochemistry
- Urinalysis + Urine culture
- Blood pressure
- Urine protein: creatinine ratio
- Radiographs + U/S
You are presented with a patient who has a Urine SG of <1.006, can this patient have primary renal disease?
No
In order for the kidneys to dilute the urine below the plasma concentration requires proper renal function, and therefore this patient cannot have renal disease
A cat presents with hypokalemia, however hyperaldosteronism is also a disease resulting in hypokalemia, how can the two be differentiated with diagnostics?
- Aldosterone level
- Renin level
- Aldosterone: Renin Ratio (expecting it to be elevated)
+ Imaging (radiographs + U/S)
How can you determine if the patient has Acute Kidney Injury or Chronic Kidney Disease?
- Medical history + physical examination = loss of muscle mass or history of chronic disease will suggest chronicity
- History of changes in renal values on urinalysis will support chronic kidney disease
- Presence of structural changes seen on imaging will also support chronic kidney disease
Once a patient has been diagnosed with kidney disease, it has been established either through history or U/S that the patient has chronic kidney disease, what must be done next?
Staging of the Chronic Kidney Disease, in order to guide treatment and provide a diagnosis and prognosis
How do we stage Chronic Kidney Disease?
We base the staging on the patient’s creatinine or SDMA measurements
- Two creatinine values must be obtained in a fasted, well-hydrated patient over several weeks
- Muscle-wasted patients will benefit more from an SDMA measurement as creatinine is expected to be significantly higher from the protein catabolism
Within each Stage, we can have substages, which are established by measuring proteinuria and BP levels. This sub-staging will help tailor treatment and improve outcomes
You are staging a Dogs chronic kidney disease, and the creatinine level is <125 umol/L on both samples, what stage is this?
Stage 1
An SDMA concentration should be done to try to diagnose early CKD
You are staging a Dogs chronic kidney disease, and the SDMA level is <18 ug/dL, what stage is this?
Stage 1
A persistently elevated blood SDMA conc (>14 ug/dL) may be used to diagnose early CKD
You are staging a Cats chronic kidney disease, and the creatinine level is <140 umol/L on both samples, what stage is this?
Stage 1
An SDMA concentration should be done to try to diagnose early CKD
You are staging a Cats chronic kidney disease, and the SDMA level is <18 ug/dL, what stage is this?
Stage 1
A persistently elevated blood SDMA conc (>14 ug/dL) may be used to diagnose early CKD
You are staging a Dogs chronic kidney disease, and the creatinine level is between 125-250 umol/L on both samples, what stage is this?
Stage 2
You are staging a Dogs chronic kidney disease, and the SDMA level is 18-35 ug/dL, what stage is this?
Stage 2
You are staging a Cats chronic kidney disease, and the creatinine level is between 140-250 umol/L on both samples, what stage is this?
Stage 2
You are staging a Cats chronic kidney disease, and the SDMA level is 18-25 ug/dL, what stage is this?
Stage 2
You are staging a Dogs chronic kidney disease, and the creatinine level is between 251-440 umol/L on both samples, what stage is this?
Stage 3
You are staging a Dogs chronic kidney disease, and the SDMA level is 36-54 ug/dL, what stage is this?
Stage 3
You are staging a Cats chronic kidney disease, and the creatinine level is between 251-440 umol/L on both samples, what stage is this?
Stage 3
You are staging a Cats chronic kidney disease, and the SDMA level is 26-38 ug/dL, what stage is this?
Stage 3
You are staging a Dogs chronic kidney disease, and the creatinine level is >440 umol/L on both samples, what stage is this?
Stage 4
You are staging a Cats chronic kidney disease, and the creatinine level is >440 umol/L on both samples, what stage is this?
Stage 4
You grade a dog or cat with Stage 3 CKD, however, you treat a concurrent UTI, once this infection is cleared/ treated, what has to be done?
Re-staging of the CKD is needed, as once a pathological process has been removed, it can reduce the staging and therefore treatment may alter, and prognosis may alter
note: regardless of stage, once an animal has undergone some form of treatment, re-staging must be done to establish a new stage for that patient
You have diagnosed a patient with CKD, an important change is diet, explain what type of diet is needed and why
Type of diet needed: ideally a commercial renal diet for any Stage 2+
Reason: these diets will have limited PO4 and therefore will help:
- Reduce PO4 retention and lower PO4 levels
- Decrease the progression/ onset of Renal Secondary Hyperparathyroidism
- Slow the progression of CKD and reduce mortality
- Lower Na+ to help reduce hypertension
note: IF the commercial renal diet has not already been supplemented with omega-3 fatty acids and anti-oxidants, they can be added to the diet to lower mortality, improve renal function, reduce proteinuria and improve cholesterol levels
- -> Mechanisms unknown but have been significant in helping DOGS, not as much data in cats yet
Before placing an animal on a renal diet for CKD, a plasma [PO4] should be measured, and rechecked regularly
What is the TARGET [PO4] concentration for Stage 1 - 4?
Stage 1 + 2 = [0.8 - 1.45]
Stage 3 = [0.8 - 1.61]
Stage 4 = [0.8 - 1.95]
When should [PO4] levels be checked in a patient with CKD?
- Before initiation of renal diet
- 4-6 weeks after initiation of renal diet
- every 3 months after that
You have been measuring the [PO4] plasma levels in a dog with CKD that is on a renal diet, however, the [PO4] has not been within the target range, what should be done?
- Add an intestinal-binding agent to the renal diet: this will trap PO4 in the intestine and prevent absorption
note: if the Owner stops the renal diet and only uses the intestinal-binding agent you will not have good control of the phosphate levels
What intestinal-binding agents are available for use in dogs and cats?
1) Aluminium hydroxide = effective + inexpensive but can make food less palatable and cause constipation. Toxicosis has been reported in advanced CKD, leading to peripheral neuropathy + microcytosis (small red cells)
2) Lanthanum = effective and NO toxicosis is reported, but more expensive. Also well accepted and tolerated in both cats and dogs
3) Calcium based chelating agent (e.g. Calcium Carbonate) = not as effective as the above two, is cheap but can cause hypercalcemia which can be damaging to the kidneys
note: Calcitriol can help reduce PTH levels, but benefits are inconclusive and an overdose can lead to hypercalcemia and further kidney issues. Not currently recommended when you have better options described above
Dehydration is also a concern in patients with CKD, what can be done in these patients?
1) Establish if the patient is dehydrated and not drinking enough water to compensate for the Polyuria
2) SQ fluids every 1 - 3 days for patients where owners are comfortable administering
- Cats: 75 - 125 mLs per dose of Lactated Ringers
3) Alternatively, water through a feeding tube can be done
Caution: Fluid overload is still possible in patients receiving SQ fluids
What can be done to manage GI signs in patients with CKD?
Antiemetic therapy:
- Antacid (ideally a proton pump inhibitor): 1mg/kg BID for 1 week, SID for 1 week, then EOD for 1 week
- Maropitant or Ondansetron to calm the CTZ which is often stimulated by uremic toxins leading to nausea and vomiting
Appetitie Stimulant:
- Mirtazapine
Dog: 3.75-30 mg/dog PO
Cat: 1.87 mg/cat/day PO
In the event where it is difficult to control body weight, administer water or medicine, an esophagostomy or gastrostomy feeding tube can be placed
Why must hypertension be addressed in a patient with CKD?
CKD is the most common cause for hypertension in pets
It can lead to: ocular, neurological, cardiac, and renal complications
Clinical signs include: lethargy, blindness, retinal hemorrhage, retinal detachment, seizures, stupor, and cardiac remodeling (ventricular hypertrophy)
When is hypertension therapy indicated in patients with CKD?
- If a BP reading between 160 - 180 mmHg is measured 3x over 2 months
OR
- If two BP readings of 180+ mmHg within 1-2 weeks = severe hypertension
If a patient follows any of the two indications above, anti-hypertensive therapy is needed
What is the goal of treating hypertension in a CKD patient?
- Reduce the BP to <160 mmHg and maintaining that
Rapid reduction in BP is needed ONLY in patients with severe acute ocular or neurological lesions, otherwise, a gradual step-wise decrease is needed
What is the general treatment/ management of CKD in dogs and cats?
1) Diet change: renal diet +/- intestinal-binding agent
2) SQ fluids
3) Antiemetics + Antacids
4) Anti-hypertensives: ONLY in stable patients, NEVER in an AKI patient because you may reduce blood flow to the kidney and worsen the AKI
5) Anemia management (Darbopoietin)
What hypertensive medicines are used in CKD Dogs?
- ACE inhibitor first (enalapril or benazepril)
If the maximum dose of Ace inhibitors is not enough to control hypertension then + Calcium channel blockers
If the maximum dose of Calcium channel blockers is not enough to control hypertension, then remove ACE inhibitors and + Angiotensin Receptor Blocker (Sartans)
caution: ACE inhibitors and Angiotensin Receptor Blockers will both act on the RAAS system, and therefore shouldn’t be used together unless the patients is monitored very closely for hyperkalemia, hypotension and azotemia
What hypertensive medicines are used in CKD Cats?
- Calcium channel blocker first (Amlodipine is the first choice)
Monitor every 3 months and adjust the dose
Cats unresponsive to the maximum dose of Amlodipine should be started on an Angiotensin Receptor Blocker (Losartan or Telmisartan) and monitored very closely for hyperkalemia, hypotension and azotemia
How can Anemia be managed in CKD patients?
1) Iron supplementation or blood transfusion may be necessary in the initial treatment. Make sure to blood type the animal
2) Darbopoietin: 1 ug/kg SQ weekly until the PCV reaches the low end of the target range (25% in cats, 35% in dogs), then every 2 weeks, then monthly if the patient is holding their PCV
Why is proteinuria considered a poor prognostic indicator?
Proteinuria is associated with:
- Interstitial fibrosis
- Tubular degeneration and atrophy, the proteins have a direct toxicity effect on the tubular lining
- Proteinaceous casts can cause tubular obstruction
- Decrease perfusion of the tubulo-interstitium and cellular necrosis
You notice a dipstick urine test shows positive for protein in the urine, what should be done next?
- Repeat the dipstick at least 2 more times 2 weeks apart to confirm the presence of proteinuria
- Exclude pre-renal and post-renal causes of proteinuria e.g. UTI
- Perform a Urine Protein Creatinine Ratio: this is a quantitative test for total urine protein, expressed as a ratio to urine creatinine thus eliminating urine dilution factor
You diagnosed a dog or cat with proteinuria with repeat dipstick tests, and ruled out pre-renal and post-renal causes. You now perform a Urine Creatinine Ratio, the result is <0.2, what does this mean?
This is normal, the animal is considered to be non-proteinuric
You diagnosed a dog or cat with proteinuria with repeat dipstick tests, and ruled out pre-renal and post-renal causes. You now perform a Urine Creatinine Ratio, the result is b/w 0.2 - 0.5, what does this mean?
The animal is borderline proteinuric
You diagnosed a dog or cat with proteinuria with repeat dipstick tests, and ruled out pre-renal and post-renal causes. You now perform a Urine Creatinine Ratio, the result is 0.5+, what does this mean?
The animal is proteinuric
What are some pre-renal causes of proteinuria in small animals?
- Hemoglobinuria from intravascular hemolysis
- Myoglobinuria from rhabdomyolysis
- Immunoglobulin light chains from multiple myeloma or lymphoma
These all result in an increase in delivery of low molecular weight plasma proteins to the normal glomerulus
What are some post-renal causes of proteinuria in small animals?
- UTI
- Urolithiasis
- Transitional Cell Carcinoma
- Vaginitis
These all result in protein in the urine due to exudation of blood or serum into the lower urinary or genital tracts
A dog or cat with a Urine Creatinine Ratio of >2.0 is considered to have ________
Glomerular disease
Note: the presence of hypoalbuminemia provides further evidence of glomerular lesions
A dog with a Urine Creatinine Ratio of <2.0 is considered to have ________
Glomerular or tubular disease
Note: the presence of hypoalbuminemia provides further evidence of glomerular lesions
What 2 drug classes are available to us to control proteinuria in a patient?
- Angiotensin-Converting Enzyme Inhibitors (ACEi)
- Angiotensin Receptor Blockers (ARB)
Benazapril, Enalapril, Lisinopril, Ramipril, Imidapril are all examples of ________
Angiotensin-Converting Enzyme Inhibitors (ACEi)
Telmisartan and Losartan are both examples of ___________
Angiotensin Receptor Blockers (ARB)
What is the effect of the Angiotensin-Converting Enzyme Inhibitors (ACEi) on the Glomerulus?
- Decrease glomerular capillary hydrostatic pressure
- Decrease the size of the glomerular endothelial pores, thus more difficult for proteins to pass through
When starting Angiotensin-Converting Enzyme Inhibitors (ACEi) in a patient, the patient should be ___________
Stable/ euvolemic prior to administration
The presence of Proteinuria is not important until the clinical signs of CKD have been addressed
A hypertensive and proteinuric cat should be treated with an ACEi or an ARB?
ARB = Angiotensin Receptor Blockers
– Telmisartan specifically (Semintra)
What is the definition of an Aldosterone escape/ breakthrough?
When using drugs that target the RAAS system, the system cannot be completely inhibited/ diminished, and therefore you can get a sudden increase in Aldosterone production as a way to compensate for the reduction in the RAAS system (1/3 of dogs suspected to experience this)
This increase is termed the Aldosterone breakthrough, and can have adverse effects on the heart, systemic blood vessels and glomeruli, and even create worse proteinuria and prognosis for the dog that you are treating
You have just started a dog or cat on ARB or ACEi, when should you see the patient next for reassessment?
In 1-2 weeks
Note: when you add or change the quantity of a drug, you should also reassess after 1-2 weeks
Note: At reassessment, you will want to perform a physical exam, urinalysis, UPCR, Biochemistry Profile (at least a creatinine + potassium), and a BP
You are reassessing a patient that has been on an ARB or ACEi for the last 1-2 weeks, at the follow-up appointment you notice one of the following:
- Worsening azotemia (>30% increase in creatinine)
- Hyperkalemia
- Hypotension
What should be done?
Discontinue the drug and start a different agent
You want to perform a UPCR (urine protein creatinine ratio) on a urine sample from a dog/cat
What sample should be collected for this and why?
3x morning samples obtained over 3 consecutive days leading up to the appointment
e. g. If the appointment is on Wednesday
- Collect 1st morning urine sample on Monday, Tuesday and Wednesday, label each of them and store in the fridge
At the appointment, perform a urinalysis on the Wednesday morning sample, then take 1mL aliquot of all 3 samples, mix into a sterile container and send that mixed sample to the lab for UPCR
Reason:
A morning sample is needed as it will have the highest conc of protein in the urine
A mixed sample is needed as it will give a more accurate representation of the urine
You have started to treat a patient with either an ACEi or an ARB, what is the ideal therapeutic target for UPCR?
What is the more realistic target?
- Ideal target = a UPCR < 1.0 without worsening of renal function
However, this can be difficult to achieve
- More realistic target = a reduction in UPCR by 50% or more
You have been treating a dog with an ACEi, at your revisit appointment you notice the UPCR target has not been achieved, what do you do?
1) Assess the creatinine and [K+], if both are acceptable then the dose of ACEi can be increased every 4-6 weeks
2) If you have reached the maximum dose of the ACEi, then either add an ARB, or you can discontinue the current drug and start just the ARB alone
Hyperkalemia is a common side effect of RAAS inhibition, you notice a patient has hyperkalemia but it is <6mEq/L, what should you do?
- Perform an ECG and look for any cardiotoxic effects by looking for ECG abnormalities
If abnormalities are seen, reduce the drug dose and implement a potassium-reduced diet (this diet will have to be homemade as renal diets are often supplemented with potassium)
Hyperkalemia is a common side effect of RAAS inhibition, you notice a patient has hyperkalemia >6mEq/L, what should you do?
- Reduce the drug dose and implement a potassium-reduced diet (this diet will have to be homemade as renal diets are often supplemented with potassium)
A Schnauzer has presented with proteinuria, before starting ACEi or ARB, what can you try first?
- Low-Fat diet and supplementing with omega-3 FAs to reduce the hypertriglyceridemia that this breed is predisposed to
Proteinuria in this breed can correlate to glomerular lipid thromboemboli and therefore if the hypertriglyceridemia can be controlled it’s possible the proteinuria can be controlled too
If control of proteinuria does not occur then ACEi or ARB can be started
What are the 2 main complications associated with Proteinuria?
1) Edema: proteinuria will lead to loss of albumin into the urine –> hypoalbuminemia –> drop in oncotic pressure and loss of fluid to the extravascular space. Treatment is plasma transfusion to replace the albumin and replace some volume in the vessels
Caution: NEVER treat edema with a diuretic, it is dangerous and ineffective. These animals are in a hypovolemic space and cannot access the fluid in the extravascular space
2) Thromboembolisms: Clopidogrel is the drug of choice for preventing a thromboembolic event
Can also treat with acetylsalicylic acid (Aspirin)
