Acute kidney injury Flashcards
Give a definition of acute kidney injury (AKI)
AKI refers to a sudden collapse in renal function with a rapid decline in the glomerular filtration rate
This sudden renal compromise results in severe electrolytes, acid-base and fluid baalance derangements and dramatic clinical signs
AKI is accompanied by rapid onset azotemia which is usually progressive
AKI is an event that normally occurs over a matter of hours to days
It is common for AKI to progress to CKD
Name and explain the different phases of AKI course
Initiation phase
- Occurs immediately after the insult
- Clinical and/or laboratory changes may not be observed at this stage making diagnosis difficult
Extension phase
- Significant cellular injury occurs due to ischemia, hypoxia and progressive cell apoptosis and necrosis
Maintenance phase
- Severe azotemia, uremia or both occurs
- Affected animals may be hyperkalemic, acidotic and oliguric/anuric
- This phase can last for days to weeks and is when the majority of cases will present
Recovery phase
- This is a time of repair, when the tubules can recover function
- This phase is often marked by an improvement in azotemia and development of polyuria
- This phase may result in return of normal renal function or the start of CKD
Explain why kidneys are particularly vulnerable to injury
Kidneys are particularly vulnerable to injury because:
- The kidneys receive a large volume of blood (20% cardiac output) so will be compromised by conditions affecting their blood supply and affected by toxins in the blood
- They also have a high metabolic rate and depend on a constant supply of oxygen and energy
Give examples of pre-renal, renal and post-renal AKI
Pre-reanl AKI
- Reduced renal perfusion (e.g., hypovolemia, dehydration, shock, hypotension)
- Reduced renal arterial blood flow (e.g., thrombosis, hyperviscosity
- Drugs (e.g., NSAIDs, ACEi, Angiotensin Receptor Antagonist)
Renal AKI
- Toxins (e.g., Lily, EG)
- Pyelonephritis
Post-renal AKI
- Obstructive uropathy
- Uroperitoneum
- Bilateral ureteral obstruction
Lily plants are toxic in cats. Explain which parts of the plant are toxic and why is it toxic
Lilies are exceptionally nephrotoxic in cats
Ingestion of tiny quantities of leaf or flower material (all parts of the plant) is associated with the development of acute tubular necrosis and sudden AKI
Indoor cats are much more commonly affected as they are exposed to lily containing floral arrangements
What are the typical clinical signs of Lily intoxication
Typical signs of AKI develop rapidly following lily ingestion
Initially there may be gastrointestinal signs (vomiting and diarrhea) accompanied by lethargy, and these may temporarily improve as the AKI subsequently develops over 24-72 hours
Acute pancreatitis has been reported to be an additional complicating factor in some cats with lily intoxication
How a diagnosis of lily intoxication is made
Diagnosis of lily intoxication relies on the diagnosis of AKI combined with a known history of exposure to lily plants
What is the prognosis for lily intoxication in cats
The prognosis depends on the quantity of plant material ingested and the rapidity of diagnosis and therapy
As cats appear to be exquiditely sensitive to lilies, prognosis is frequently guarded unless fluid therapy is commenced before the onset of azotemia
Explain the toxicity of ethylene glycol
Ethylene glycol is commonly used as anti-freeze in vehicles
It is sweet tasting
EG itself is rapidly absorbed following ingestion, but is relatively non-toxic (although it does cause hyperosmolality)
As a result of liver metabolism via alcohol- and aldehyde-dehydrogenase enzymes, toxic metabolites (glycoaldehyde, glycolic acid and oxalic acid) are produced, which are directly toxic to renal tubular cells and result in acute tubular necrosis
The production of glycolic acid results in a profound metabolic acidosis and glycolic acid is also transformed to glyoxylate and then to oxalate, which may be deposited as calcium oxalate crystals in the kidney (causing further damage) and other tissues
What are the clinical signs associated with EG toxicity
Initial signs (1-12 hours following ingestion) are due to CNS toxic effects with depression, nausea, vomiting, nystagmus, ataxia and seizures
These can be followed by cardiopulmonary signs before the nephrotoxic effects are seen, which typically occur within 24-72 hours
What are the laboratory findings associated with EG toxicity
Metabolic acidosis
Increased anion gap
Hypocalcemia
Calcium oxalate crystalluria
Azotemia with isosthenuria
Hyperphosphatemia
EG detectable in the blood
Fluorescein dye could be detected with a Wood’s lamp on vomita or urine
What is the treatment for EG intoxication
Treatment should be prompt and agressive
If cats are observed ingesting EG and examined within a few hours (<6 hours) then gastric decontamination with induction of emesis and activated charcoal is indicated
Metabolism of EG can be inhibited by ethanol, which acts as a preferred substrate for alcool dehydrogenase
- After 12 hours or once AKI has developed, treatment with ethanol is unlikely to be effective and may complicate management of AKI
- Prior to the development of AKI, 20% medical ethanol can be administered IV at a dose of 5 ml/kg IV over 15 minutes and repeated every 6 hours for 5 treatments then every 8 hours for 4 treatments
Fomepizole inhibit the enzyme alcohol dehydrogenase and is only effective if ingestion is observed and the cat seen within 3 hours
Other routine treatments for AKI (i.e., fluids, furosemide, electrolyte monitoring) are required
Based on blood monitoring, bicarbonate therapy to correct acidosis or calcium supplementation to correct hypocalcemia may be needed
What are the difference between AKI and CKD presentations
Most cats with AKI (especially due to toxins) are young and in good body condition
AKI:
- Healthy until episode
- History of toxin/drug exposure
- Good body condition
- Painful kidneys, possibly enlarged
- Very sick for level of azotemia
- May have very small bladder
- Hyperkalemia
- Metabolic acidosis
- Anuria or oliguria
- Cylindruria, cell debris
- Proteinuria
- Isosthenuria
CKD:
- Prior illness (PU/PD, weight loss)
- Loss of body condition (may be subtle)
- Kidneys firmm and smal
- Coping with high level of azotemia
- Urine present in bladder
- Hypo or normokalemia (unless late stage)
- Non-regenerative anemia
- Polyuria
- Isosthenuria
- Sediment usually benign but can have occult UTI
What are the typical clinical signs of AKI
- Dehydration +/- hypovolemia
- Anorexia
- Lethargy/depression
- Vomiting +/- hematemesis
- Oral ulceration
- Melena
- Hypothermia
- Bradycardia (if hyperkalemic or hypovolemic - cats can be bradycardic despite marked volume deficits)
- Dysrhythmias may be present if hyperkalemia is severe
- Anuria/oliguria (small bladder on palpation)
- Uremic halitosis
- If post-renal cause then signs of obstructive disease such as unproductive straining and hematuria may be noted
- Renal pain is sometimes present and there may also be a degree of renomegaly
- Clinical signs are generally rapidly progressive
What are the typical laboratory findings
Azotemia
- Urea may be disproportionally increased if the cat is dehydrated/hypovolemic or suffering gastrointestinal hemorrhage
Hyperkalemia
Hyperphosphatemia
Acidosis
Calcium modification
- Total and ionized hypocalcemia with EG toxicity
- Hypercalcemia in cats with AKI due to hypercalcemic nephropathy
Urine will be isosthenuric and sediment will often be active (i.e., cellular debris, tubular casts)
- Proteinuria and glycosuria can result from tubular injury
- Positive bacterial culture as pyelonephritis can cause AKI
Imaging such as radiography, ultrasound could be helpful
If renal lymphoma or FIP are suspected then a FNA biopsy of the kidney may be useful
What are the goals of AKI treatment
The incitinng factor should be removed if possible (e.g., gastric lavage, activated charcoal, withdrawal of nephrotoxic drugs)
Correction of fluid deficits and restoration of renal perfusion
Restoration of urine production
Correction of electrolyte and acid-base abnormalities
Additional specific treatment depending on the case
Intensive and aggressive therapy is warranted and important with AKI, as the disease is often potentially reversible
List signs of hypovolemia in cats
Hypotension
Hypothermia
Cold extremities
prolonged CRT
Brady- or tachycardia
How should hypovolemia be treated
Use bolus crystalloids (10-20 ml/kg over 20-30 minutes
Closely monitor the effect of the fluids and correction of the abnormalities
What are the clinical signs for dehydration
level of dehydration < 5%: not detectable
5-8%: subtle loss of skin elasticity
6-10%: definite delay in return of skin to normal position, eyes may appear sunken, mucous membranes may appear tacky
10-12%: severe skin tenting, eyes sunken, mucous membranes tacky
12-15%: severe skin tenting, sunken eyes and tacky mucous membranes, +/- signs of shock (tachycardia/bradycardia, hypotension, poor pulse quality, prolonged CRT, weakness/collapse
How would you address dehydration in cats
Work out the percentage of dehydration and aim to correct over 12-24 hours
What is often observed in urine production when urine output is restored
Restoration of urine output is often followed by a period of polyuria
What are the risk in the management of oliguric/anuric cats and how could you diagnose them
Oliguric/anuric animals are at risk of over-perfusion and hypervolemia
Clinical signs include:
- weight gain
- tachypnoea
- chemosis
- serous nasal discharge
- crackles on thoracic auscultation
How can you restore urine production if the cat remains oliguric despite appropriate fluid therapy
If urine production remains inadequate after appropriate fluid therapy then diuretic therapy is appropriate
Do not give diuretics until volume deficits have been corrected
- risk of further dehydration and worsening of renal blood flow
Give examples of two commonly used diuretics
Furosemide
- a loop diuretic
- will increase kaliuresis so also indicated in hyperkalemia (once re-hydrated)
- Initial dose of 2 mg/kg, IV and repeated after 30 minutes if oliguria persists
- if diuresis is induced then the dose can be repeated 6-8 hours later
Mannitol
- Osmotic diuretic
- has additional effects of free radical scavenging, increases renal blood flow and GFR
- it should be uesd cautiously (0.25-0.5 g/kg as a 25% solution over 30 minutes followed by CRI 60-120 mg/kg/h) to avoid overhydration
- should not be used in patients with pre-existing hypervolemia
- it is contraindicated in anuric patients and those with significant cardiac disease
What is of most importance when recovery begins to occur
If recovery begins to occur, it is important that adequate fluids are supplied during the recovery phase when there will be an obligatory diuresis
- do not wean the cat off fluid therapy too quickly, otherwise a relapse will occur
Why is severe hyperkalemia an emergency and how would you diagnose ir
Severe hyperkalemia will result in life-threatening cardiac arrhytmias
Typical ECG changes assoicated with severe hyperkalemia include:
- bradycardia
- flat P waves
- prolonged PR interval progressing to atrial standstill and a ventricular escape rhythm, which may progress to cardiac arrest
What are the options to treat severe hyperkalemia
Fluid therapy is the mainstay of treatment for hyperkalemia
IV calcium gluconate is cardioprotective and should be given as a slow bolus whilst the ECG is continually observed
- this treatment has no effect on the hyperkalemia which should be addressed
- it has only a limited duration of activity (15-30 minutes) and thus needs to be combined with potassium-lowering measures
- calcium gluconate acts as a cardioprotectant by stabilizing cardiac myocyte cell membranes, increasing the depolarization threshold
- dose: 0.5-1 ml/kg IV over 10-20 minutes
Glucose stimulates endogenous insulin release which will promote cellular potassium uptake
- dose: 0.5-1 g/kg IV (20% solution given as a bolus)
- soluble insulin (0.2 U/kg) can be administered along with the glucose bolus, but this is not usually necessary as the glucose itself is usually a sufficient stimulus for rapid release of endogenous insulin
Peritoneal and hemodialysis could be used in very unstable patient but availibility is limited
What are other important considerations in the management of AKI
Maintaining nutrition is important
Control of vomiting and uremic gastritis
- H2 blockers (e.g., cimetidine 5 mg/kg, IV, BID or TID
- Metoclopramide as a CRI
- Mirtazeapine as appetite stimulant and anti-nausea
Hypertension may be present in the AKI patient
- it may indicate over-hydration if urine output is inadequate
- or true systolic hypertension due to the AKI
- once the hydration/urine output has been assessed consider treatment with amlodipine
What is the prognosis for AKI
Prognosis for AKI is variable
- for intrinsic AKI it is generally poor to guarded especially if there is continued and progressive azotemia, hyperkalemia and acidosis
- successful therapy may still result in residual CKD
Factors at presentation associated with a decreased survival include:
- Hyperkalemia
- Hypoalbuminemia
- Decreased serum bicarbonate
The degree of azotemia and serum phosphate/calcium at presentation are not associated with survival
For pre- and post-renal AKI the prognosis is often much better, depending on the cause and the duration prior to appropriate therapy being insdtituted
When supportive treatments should be discontinued
Return of normal renal function (i.e., USG > 1.035, non-azotemic)
Stabilization of renal function (i.e., no change in urea/creat over 24 hours despite continued treatment) and clinical improvement
Level of azotemia worsens, or fails to improve despite treatment and the patient is not doing well clinically => consider euthanasia or dialysis
