The term nephrotoxicity simply means "toxic to the kidneys,"therefore nephrotoxicty in dogs depicts the toxic effect that some substances and medications have on the dog's kidneys. While the purpose of most medications is to heal the body, sometimes adverse reactions may occur. A dog's kidneys can be particularly vulnerable to toxicity because of their primary role in filtering and excreting drugs and therefore it's important to report to the vet as soon as possible any signs of trouble. Some drugs are more likely to be toxic to the dog's kidneys than others.
Toxic Effects on Kidneys
It's not unusual for some drugs to have toxic effects on a dog's organs. Drugs that are toxic to the dog's liver are known as "hepatoxic," drugs that are toxic to the dog's ears are known as "ototoxic," and as seen, drugs that are toxic to the dog's kidneys are known as "nephrotoxic."
It's not surprising that a dog's kidneys can be negatively impacted by the use of certain drugs. When drugs reach the bloodstream, with each heart beat, the heart sends trace amounts of the drug to the kidneys, which can reach appreciable amounts over a period of time. Just think that an estimated 20 to 25 percent of the total heart output perfuses the drug to the kidneys each minute, explains veterinarian Dr. Lloyd E. Davis in the Textbook of Veterinary Internal Medicine.
Information, about whether a drug is toxic to a dog's kidneys or not, is generally displayed on the accompanying drug information sheet. Several bottles of potentially nephrotoxic drugs also recently have placed a warning on their labels to incite dog owners to inform their vet should their dog develop any signs of digestive upset which can be a potential warning sign of kidney toxicity.
Some dogs are more predisposed to kidney toxicity than others. Dogs who have decreased blood flow to the kidneys such as dogs who are dehydrated, under shock or dogs who have underlying pre-existing kidney problems may be predisposed.
Veterinarians take preventive steps to combat potential adverse reactions by performing a thorough physical examination before prescribing any potentially nephrotoxic drugs along with blood work prior to, and periodically during use of such drugs.
Signs of Trouble
There are several different problems that can occur to the dog's kidneys when they are affected by nephrotoxic drugs.
Problems include kidney failure, interstitial nephritis, lower nephron neprohsis, and nephrotic syndrome. Recognizing early warning sign of kidney problems is important, however, in many cases, signs occur when already a significant amount of damage was done.
Warning symptoms of potential damage to the dog's kidneys include loss of appetite, vomiting, diarrhea, presence of ulcers in dog's mouth, bad breath, lethargy and increased drinking and increased urination.
These symptoms can be indicative of the kidneys not working as they should and should therefore be reported to the vet as soon as possible. When the kidneys are not working properly, they fail to excrete toxins from the body and when these toxins accumulate in the bloodstream, they can make the dog quite ill.
List of Nephrotoxic Drugs in Dogs
While these drugs are meant to heal or make dogs feel better, at times, things may not go as planned. It can be that toxic effects occur as a result of an exaggeration of the drug's pharmacological effects or there may be other predisposing factors at play (dogs with underlying renal problems, older dogs, dogs with decreased cardiac output, dogs taking other nephrotoxic drugs, dogs with low blood pressure, dog undergoing anesthesia).
This list of drugs is therefore not to label this drugs as "bad," but just to raise awareness of any potential early warning signs of potential complications.
Generally, vets suggest use of these drugs as their benefits outweigh the risks. In dogs with normal renal function, risks for the occurrence of these adverse nephrotoxic effects are generally minimal. So what drugs are considered to be nephrotoxic to dogs? There are several.
Antimicobrial Drugs (Antibiotics)
Several antibiotics are known for potentially producing toxicity to the kidneys. These include ampicillin, penicillin, amphotericin B, bacitracin, cephaloroidine, colistin, polymyxin sulfonamides, tetracyclines and several aminoglycoside antibiotics such as neomycin, tobramycin, amikacin, gentamycin, kanamycin, amikacin and streptomycin.
" The nephrotoxicity associated with aminoglycosides is often reversible, although treatment can be prolonged due to the slow elimination of the drug from the proximal tubular cells."~Dr. Jennifer L. Davis
Analgesic Drugs (Pain Relievers)
Many over-the-counter pain relievers meant for humans to combat inflammation are considered dangerous for use in dogs and are potentially nephrotoxic. These include ibuprofen, naproxen and aspirin. Prescription veterinary non-steroidal-anti-inflammatory drugs for dogs such as Deramaxx and Rimadyl, are safer to use and while they still have potentially nephrotoxic effects, usually that tends to happen at higher dose, explains veterinarian Dr. Drew.
The problem with these drugs is they block the action of the cyclooxygenase (COX 1, COX 2) which is an enzyme that plays an important role in maintaining blood flow to the kidneys.
"In particular, dogs express higher basal levels of COX-2 in the kidney than some other species and may be uniquely sensitive to the nephrotoxic effects of COX-2 selective drugs."~Dr. Gregory F. Grauer, board-certified veterinarian.
Antineoplastic Drugs (Against Cancer)
Several drugs used for cancer and drugs used for chemotherapy may have negative effects on the dog's kidneys. These drugs include cisplatin, adriamycin, cyclophosphamide, daunorobicin, methotrexate, doxrubicine and mitramycin.
Other Nephrotoxic Drugs
There are several other drugs known for their toxic effects to the dog's kidneys such as angiotensin-converting enzyme inhibitors (ACE) such as enalapril, benazepril, diuretic drugs such as furosemide, mannitol and thiazide and radiographic contrast agents. There are several other drugs that may not be listed.
At the Vet's Office
If you suspect liver damage from the use of a nephrotoxic drug in your dog, report to your vet as soon as possible. Left untreated, the damage can lead to kidney failure.
Once at the vet, the vet will take a history and discuss symptoms that were noted and type and frequency of drugs given. He or she will perform a physical examination. The vet will check the dog's heart rate, rhythm, pulse quality, blood pressure and hydration status.
Urine may be collected and the vet may look at its turbidity and check for signs of damage such ad increased white blood cells, presence of renal epithelial cells or granular casts. Detection of gamma-glutamyl transpeptidase (GGT) and N-acetyl-beta-D-glucosaminidase (NAG) in the dog's urine has been considered an indicator of renal tubular damage, explains Dr. Gregory F. Grauer.
A biochemistry profile will reveal changes that are suggestive to kidney damage. In particular, the vet will look at levels of blood urea nitrogen (BUN) and creatinine. Taking a biopsy of kidney tissue while doing an ultrasound can help the vet detect the presence of kidney failure.
Fluid therapy is essential so to keep the dog hydrated and to flush the kidneys from toxins in the bloodstream. The vet may suggest dietary changes consisting in foods that don't contain excessive protein and phosphorous for the purpose of reducing the workload of the kidneys. Dialysis can aid excretion of the drug but not all drugs are readily dialyzable.
Sadly, drug-induced damage sustained to the kidney's nephron is not always reversible; dogs that recover kidney function may require prolonged and expensive intensive care. Kidney disease in affected dogs may become chronic several months or years later.
- American Society for Microbiology: Aminoglycosides: Nephrotoxicity
- DVM360: Using NSAIDS in dogs with kidney and liver disease (Proceedings)
- DVM360: Antimicrobials in practice part 2: specific antibiotic drugs (Proceedings)
- DVM360: Early detection of acute kidney injury (Proceedings)