At MedVet, we treat dogs and cats for ingestion of kidney toxins on at least a weekly, sometimes even daily, basis. In this article we will review common toxins causing acute kidney injury in dogs and cats, how we prevent and treat the renal effects, and how we monitor for acute kidney injury.
Non-steroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and pain via the inhibition of COX enzymes, preventing the conversion of arachidonic acid to prostaglandins. In addition to their inflammatory effects, however, prostaglandins also maintain blood flow to the kidneys and gastrointestinal tract, promote intestinal epithelial cell repair and turnover, and stimulate gastric bicarbonate production.
At lower doses, gastrointestinal (GI) effects predominate. At higher doses, reduced blood flow to the kidneys results in acute kidney injury (AKI). At very high doses, central nervous system (CNS) signs can also be seen. The toxic dose in mg/kg depends on the specific NSAID.
Induction of emesis is most effective within 30 minutes of ingestion due to rapid absorption of the medication by the GI tract. Activated charcoal should be administered as soon as possible to bind any unabsorbed medication. Enterohepatic recirculation varies with the specific medication; ibuprofen, naproxen, and meloxicam undergo extensive enterohepatic recirculation, but it is limited with carprofen, and deracoxib and robenacoxib does not undergo enterohepatic recirculation. Still, there is limited evidence for repeated doses of charcoal even with extensive enterohepatic recirculation. A recent experimental study (Schildt et al, IVECCS abstract 2009) revealed no benefit of emesis and activated charcoal over activated charcoal alone on plasma carprofen levels.
A minimum database of a complete blood count, chemistry, and urinalysis is recommended at presentation, however if costs are a concern at least a renal panel (including BUN, creatinine, phosphorus) and a urine specific gravity should be obtained. Our general recommendation is to hospitalize these patients for at least 48 hours of IV fluid diuresis (72 hours for naproxen) while monitoring renal values every 24 hours. Subcutaneous fluid therapy can also be initiated if the owner declines hospitalization. Our starting IV fluid rate accounts for dehydration (if necessary) and maintenance plus 2 ml/kg/hr for diuresis, with weaning based on recheck bloodwork.
An increase in creatinine of 0.3 mg/dL or greater is considered significant; even if the creatinine remains within the reference range this is consistent with AKI. IV fluid diuresis should be continued until renal values plateau or return to within 0.3 mg/dL of baseline creatinine. Renal values should be rechecked again 24 hours after discontinuing IV fluids, with no further recheck necessary if normal at that time. If renal values have gone up at this time point, restarting IV fluids or initiating subcutaneous fluid therapy while continuing bloodwork monitoring is recommended. Ideally, all bloodwork should be performed on the same machine to control for variation in creatinine between machines.
For GI effects, gastroprotectants are recommended. We typically use a proton pump inhibitor (PPI) (either IV pantoprazole or PO omeprazole) at 1 mg/kg q12 hours.
Grapes and raisins are thought to cause an idiosyncratic toxicity in dogs. There have also been some anecdotal reports of toxicity in cats. To date, the toxic component and mechanism of toxicity has not been identified. It is also unknown whether juice, wine, or cooked grapes can be toxic. In all instances, however, the end result is acute tubular necrosis and potentially anuric renal failure.
To treat grape and/or raisin toxicity, emesis is recommended up to six hours post-ingestion. A dose of activated charcoal can be given, but its effectiveness is unknown. Baseline chemistry and urinalysis are recommended. With renal tubular necrosis, urinalysis may show isosthenuria or hyposthenuria, proteinuria, glucosuria, or cylinduria (casts).
As the toxicity is idiosyncratic and there is no known minimum toxic dose, hospitalization for a minimum 48 hours with IV fluid diuresis is always recommended, with daily recheck of renal values and recheck of renal values 24 hours after discontinuation of IV fluids.
Plants in the Liium and Hemerocallis genera are toxic to cats. Toxicity results from ingestion of any part of the plant, and although the exact toxic entity is unknown, the result is acute renal tubular necrosis.
Early signs of ingestion include vomiting, anorexia, and lethargy. Induction of emesis with dexmedetomidine or xylazine can be attempted within 1-2 hours of ingestion and the cat should be bathed to remove any pollen from the fur. Activated charcoal can be given but has unknown efficacy. Baseline chemistry and urinalysis should be performed. Urinalysis findings indicative of acute tubular necrosis included isosthenuria or hyposthenuria, proteinuria, glucosuria, and cylinduria.
Hospitalization for IV fluid diuresis and monitoring of renal values is recommended.
We have seen many patients ingesting vitamin D3 (cholecalciferol) supplements this winter. Other sources of exposure include ingestion of cholecalciferol rodenticides and calcipotriene, an analog of calcitriol used in the treatment of psoriasis. Cholecalciferol is metabolized in the liver and then in the kidneys where it is converted to its most active metabolite, calcitriol. Calitriol increases GI absorption of calcium, increases bone resorption, and increases renal calcium reabsorption.
Hypercalcemia can result in mineralization of soft tissues throughout the body due to an increase in the calcium x phosphorus product. The result is mineralization of soft tissues throughout the body. In addition to AKI caused by metastatic calcification, GI side effects are common, bradycardia and ventricular arrhythmias can occur, and CNS signs may be seen.
On presentation to the hospital, early emesis can be performed. If a topical product has been licked, the mouth should be washed. Activated charcoal can be given q8 hours for 1-2 days to decrease enterohepatic recirculation. Baseline renal chemistry, ionized calcium and urinalysis should be obtained. Renal values and ionized calcium should be monitored every 12 hours.
In addition to a minimum 48 hours of IV fluid diuresis as described above (which in this case should be done with 0.9% NaCl to maximize calciuresis), if the patient is hypercalcemic additional medications may be necessary to promote calciuresis. Furosemide (in a well hydrated patient) can be started at 1 mg/kg q8-12 hours up to 2 mg/kg q4 hours. Furosemide can also be given as a CRI at 0.5 mg/kg/hr. Prednisone (or the equivalent of dexamethasone) can be started at 1mg/kg/day and increased up to 2 mg/kg/day. If still hypercalcemic, bisphosphonates such as pamidronate or zoledronate can be given to decrease bone resorption. Calcitonin can be tried if bisphosphonate therapy is unsuccessful. Aluminum hydroxide can be given to bind phosphate in the GI tract, reducing the Ca x Phos product. GI protectants should be started.
As vitamin D is lipid soluble, its effects may last for weeks as it is released from fat stores. Therefore, it can take several weeks to wean the patient from furosemide and prednisone, with the goal of achieving normocalcemia off these medications. Renal chemistry (including phosphorus) and ionized calcium should continue to be rechecked during this time.
We hope these tips help you manage acute kidney injury induced by some of the more common toxins in dogs and cats in your practice. For questions or to consult with one of our Internal Medicine or Emergency Medicine specialists, please visit medvetforpets.com.