South African Equine Veterinary Association Congress 2015 Protea Hotel Stellenbosch
introduced in human and, subsequently, small animal medicine. AKI is defined as an increase in
Cr of 0.3 mg/dL (26.5 µmol/L) or a 50% increase from the baseline value, yet Cr may remain
within the reference range. Hemodynamically-induced AKI is often associated with oliguria
(urine output <0.5 ml/kg for 6 hours) while urine production with nephrotoxin-associated AKI
often remains normal (nonoliguric AKI).
Aminoglycoside antibiotics: Administration of aminoglycoside antibiotics is one of the more
common causes of acute tubular necrosis in the horse. The aminoglycoside antibiotics exert their
toxic effect by accumulating within proximal tubular epithelial cells. Once toxic amounts are
sequestered within the cell, cellular metabolism is disrupted, and tubular cell swelling, death, and
sloughing into the tubular lumen occur. Most cases of aminoglycoside nephrotoxicity are not the
result of overdosing or administration of the drug to an azotemic patient. The healthy kidney can
usually tolerate a single major overdose (10 times the normal amount) without detrimental effects.
Toxicity is a result of the cumulative effect of repeated administration of aminoglycosides.
Consequently, nephrotoxicity typically develops after several days of aminoglycoside
administration to horses with diarrhoea or septicaemia that are not adequately hydrated or because
of other factors that may exacerbate a decrease in renal perfusion (concurrent treatment with
NSAIDs).
When aminoglycosides are administered to high-risk patients (those with concurrent dehydration
or neonates), volume deficits should be replaced and serum creatinine concentration (Cr) should
be monitored closely. Because nephrotoxicity is a cumulative effect of repeated dosing, delay of
administration of the initial dose of an aminoglycoside pending rehydration of a critical patient
(e.g, a septic neonate or a markedly dehydrated horse) is unwarranted. It is rare for
aminoglycoside nephrotoxicity to develop in horses receiving appropriate fluid therapy. The shift
to once daily administration of the total aminoglycoside dose, as compared to dividing the total
dose into two to three aliquots administered at 8-12 hour intervals in the past, has become a
standard practice that likely reduces the potential for nephrotoxicity. Because aminoglycosides
exert a concentration-dependent action against bacteria, once daily dosing both ensures a high
peak serum concentration while also allowing for a longer period at which the drug concentration
is below the trough value. Since renal tubular damage is usually sustained only when the drug is
above the trough concentration, once-daily dosing can be considered “renoprotective” as it
ensures a longer period of the day with low serum aminoglycoside concentrations.
Nonsteroidal anti-inflammatory drugs: Most horses do not experience appreciable adverse
effects from NSAID use as long as they are administered at the proper dose and animals are not
dehydrated. However, NSAIDs may contribute to development of ARF/AKI in an occasional
horse when excessive doses are administered or when dehydration is not corrected promptly.
When renal blood flow decreases as a consequence of dehydration, vasodilatory mediators are
produced and released within the kidney to attenuate the decrease in renal blood flow. The best
studied of these vasodilatory mediators include renal prostaglandins (PGI2 and PGE2) and
dopamine. Renal prostaglandins are important mediators of vasodilation during periods of renal
hypoperfusion. Further, production of renal prostaglandins is several-fold greater in medullary
tissue such that action of these mediators leads to a greater increase in medullary blood flow,
regions of the kidney that normally function in a relatively hypoxic environment. Thus, it should
not be surprising that the lesion associated with NSAID toxicity is medullary necrosis that can be
manifested by microscopic or gross haematuria. Unless severe, however, this lesion rarely causes
overt clinical signs and Cr may actually decrease with fluid therapy in the face of medullary
necrosis. Recently, use of COX-2 selective NSAIDs has received considerable attention in both
the scientific literature as well as the lay press. With the introduction of firocoxib paste
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