Week 3- Large Animal Renal Disease Flashcards
What is Acute Kidney Injury defined as?
Sustained decrease in GFR leading
to azotaemia and fluid and acid-base disturbances.
What does Renal Injury usually accompany?
Sudden drop in RBF, GFR and OU
What is Acute Kidney Injury characterised by?
- Rapid & sustained increase in blood urea and creatinine concentrations.
- Disturbances to fluid, electrolyte & acid-base homeostasis
What are the main clinical signs of Acute Kidney Injury?
- Anorexia
- Abdominal Discomfort
- Dehydration
- Depression/ Dullness
- Pigmenturia
What should you think of when you see severe conjunctival oedema in horses?
Acute Kidney Injury
How would you do a Urinary fractional electrolyte excretion?
- Collect simultaneous serum and urine samples.
- Separate serum from the cellular fraction promptly.
- Comparison of electrolyte clearance compared to creatinine.
- Elevated values are indicative of renal tubular failure.
- Affected by fluid therapy.
How would you do a Urinary GGT:creatinine ratio?
- Secretion of GGT into urine is specific to the proximal tubular cells.
- Indicative of glomerular damage
What nephrotoxins might cause acute renal tubular necrosis?
- Antibiotics
- Aminoglycosides
- Tetracyclines
- NSAIDs
- Pigments (myoglobin/haemoglobin)
- Bisphosphonates
- Vitamin D toxicosis
- Heavy metals * Lead, mercury, arsenic
- Plants * Oak/acorns, red maple, onions…
What does vasomotor nephropathy go on to cause?
**Acute Tubular Necrosis **
* Severe enteritis/colitis
* Haemorrhagic shock
* Septic Shock
What two Aminoglycosides/ Nephrotoxins are commonly used in Equine Practice?
- Gentamicin in adults
- Amikacin in foals (& local perfusions & intra
-articular injections in adults)
How do aminoglycosides cause nephrotoxicity?
- Filtered into the renal filtrate, then absorbed by the
epithelial cells of the proximal tubules - Cumulative toxicity occurs once the cells are
saturated with the drug (3
-5 days after
administration) - Disrupts cell metabolism
→ tubular cell swelling
→
cell death
→ sloughing into lumen - Acute tubular necrosis
When is aminoglycoside nephrotoxicity more likely?
- Incorrect dosing (↑ frequency)
- Hypovolaemia
- Co-administration with other nephrotoxic drugs or furosemide
- Bisphosphonates, NSAIDs, polymyxin B
- Concurrent pigmenturia
What aminoglycosides can a normal kidney tolerate?
» Normal kidney can tolerate single high doses of Aminoglycosides and can clear the
drug from the tubular cells
» Impaired organelle function → proximal tubular epithelial cell damage
How would you diagnose nephrotoxicity/ aminoglycosides?
Diagnosis is based on development of clinical signs
of AKI during (or in the few days after) treatment with
aminoglycosides
* Prognosis is generally very good if recognised early
What is Amikacin considered to be?
is considered less toxic than gentamicin,
but costs usually restricts its use to foals or local
infusion/joint administration
When does NSAID toxicty occur?
Toxicity usually only occurs when NSAIDs given at very high doses
* Usually with direct IV administration
* Or when frequent therapeutic doses are given to
dehydrated/hypovolaemic patients
* Often concurrent GI ulceration
What is common with daily oral administration of phenylbutazone?
Clinical renal toxicity is not common with daily administration of oral
phenylbutazone at normal doses
* Although chronic interstitial nephritis has been reported
* Worth periodic assessment of patients on long-term NSAIDs
What is the effect of renal prostaglandins on the kidneys?
Renal prostaglandins (PGs) are important mediators of renal vascular control during
periods of renal hypoperfusion (dehydration/hypovolaemia).
* PGs are potent vasodilators of the afferent renal arteriole
* Inhibition of PG synthesis can lead to prolonged renal arteriole vasoconstriction;
→ Renal medullary crest necrosis
What is the treatment for NSAID nephrotoxicty
Stop NSAIDs
* Fluid therapy
* Monitor renal parameters!
What two bisphosphonates are considered to be nephrotoxins?
*Tiludronate
*Clodronate
What is myoglobin toxicity?
more toxic than haemoglobin (but renal disease
also reported in marked haemolytic anaemia)
What happens when pigment accumulates in proximal tubules?
Tubular obstruction
→ Necrosis to epithelial cells
→& further increasing accumulation of debris
How would you diagnose pigment nephropathy?
Diagnosis based on documenting the presence of rhabdomyolysis in the face of marked
azotaemia/clinical signs of AKI
* Clinical history
* CK & AST
» Gross pigmenturia will not always be noted
* Presence of red/brown urine is indicative of pigmenturia (or haematuria), but is not always
present at the time of the horse developing signs of renal disease
» Care with NSAIDs in myopathy cases
* Fluid bolus/ongoing fluid therapy alongside NSAIDs if needed
* Monitoring bloodwork and USG
How would you treat pigment nephropathy?
- Restore hydration status
- Increase GFR
- Twice maintenance crystalloids +/- diuretics
- Monitor urine output and signs of fluid retention (bwt, PCV/TP, oedema)
- Alternative analgesics
What is acute pyelnephritis?
» Rare but not unheard of in horses.
» Associated with ascending urinary tract infection.
» Urolithiasis and bladder paralysis are common
causes.
» Clinical signs of systemic infection.
What is acute glomerulopathy?
» Rare.
» Acute glomerulopathy probably seen alongside other diseases.
* E.g. purpura haemorrhagica
» Histopathology resembles human haemolytic-uraemic syndrome.
» Deposition of immune complexes- renal biopsy to confirm
What is acute interstitial nephritis?
Rarely diagnosed
» Rapid increase in urea and creatinine
» Histopathology shows interstitial oedema and inflammatory infiltrate
» Unknown aetiopathogenesis
* Drug reactions?
» Corticosteroid treatment useful in humans
» Thought to be caused by delayed cell-mediated hypersensitivity or anti-tubule basement membrane antibodies
» Grave prognosis
What kind of dialysis is easiest in horses?
Peritoneal dialysis (relatively easy in horses)
* Intermittent (easier and more common)
* or continuous
What are the two potential complications of dialysis in horses?
- Peritonitis
- Ventral Oedema
What is the prognosis for acute kidney injury?
Prognosis is dependent on underlying cause and development of secondary
complications.
» If primary disease treated and the patient is producing adequate urine andreducing creatinine levels over 24-72hrs, prognosis is good!
» Oliguria/anuria indicative of a poorer prognosis.
» Therapy may be prolonged and expensive if severe AKI
What is the most likely cause for acute tubular necrosis in ruminants?
Ruminants can also suffer tubular necrosis in response to haemodynamic or nephrotoxic insults
» BUT Ingestion of nephrotoxic plants is more likely in ruminants
What are the clinical signs of acute tubular necrosis in ruminants?
often non-specific.
* Anuria/oliguria/polyuria
* Poor appetite, Diarrhoea
* Mild bloat
* Ammonia halitosis
What two conditions may you see alongside acute kidney injury in ruminants?
- Hypermagnesaemia
- Hypocalcaemia (common due to renal losses and reduced intake and ruminal stasis)
How might you treat acute kidney injury in ruminants?
Removal/binding of ingested toxin if within first 24 hours;
* Rumenotomy
* Administering activated charcoal
* IVFT to restore adequate renal perfusion and urine production
What is the prevalence of chronic kidney disease in large animals in comparison to cats?
In general, less common in large animals compared to SA (particularly cats)
What are the clinical signs of chronic kidney disease?
Chronic weight loss, anorexia
» PU/PD - Variable
» Ventral oedema (PLN)
» Lethargy
» Rough hair coat
» Uraemia
* →halitosis, excessive dental tartar formation, ?hyperammonaemia
» Azotaemia
» Mild anaemia
» Persistent isosthenuria
* 1.008 – 1.014
» Electrolyte abnormalities
* Hypercalcaemia, hypophosphataemia, hyperkaleamia, hypochloraemia,
hyponatraemia
» Hypoalbuminaemia
» Metabolic acidosis
What is the prognosis for chronic kidney disease?
guarded/ poor
What is the main aim for chronic kidney disease treatment?
Treatment aimed at prolonging life rather than resolving the condition.
» Maintain hydration
* Can try adding salt to diet…poor evidence to support this (evaluate serum electrolytes)
» Address any existing underlying causes
» Palatable diet
* Maintain adequate protein intake (but less than 10%)
* Supplement diet with CBH and fat.
» Reduce calcium intake
* E.g. avoid Alfalfa
» May require sodium bicarbonate supplementation
What are the three main causes of chronic kidney disease?
- Primary Glomerulopathies
- Primary Interstitial disease
- Neoplasia (although uncommon in horses)
What is the immune mediated cause of glomerulonephritis?
Deposition of immune complexes along glomerular basement membrane
* → thickened filtration barrier
* → haematuria and proteinuria
* Histopathology: membranous or proliferative
What does chronic interstitial nephritis look like?
Clinical signs of renal disease associated with histologic changes of tubular damage
and an interstitial inflammatory cell infiltrate
» Catchall term for extraglomerular causes of CKD in horses
» So underlying cause can vary greatly
* Group of lots of tubulointerstitial disease together
* Inciting causes may be toxic, infectious, ischaemic, etc
What is Renal Amyloidosis?
Uncommon
» Caused by extracellular deposition of insoluble, fibrillar protein
(Amyloid) in tissues.
» Subclinically affects a variety of tissues but kidneys most commonly
clinically affected.
» Chronic wasting disease of cattle characterised by:
* Chronic diarrhoea, weight loss, generalised oedema
* Sustained profound proteinuria
* Urine can form a foam due to amount of protein
* Protein losing nephropathy associated with amyloid deposition in the
glomerulus
* Systemic hypoalbuminaemia develops due to loss of protein
» No real treatment options and prognosis is very poor = EUTHANASIA
