Acute renal failure: leptospirosis is more common than you think (Proceedings)

In dogs, leptospirosis most commonly results in acute renal failure (ARF) with or without concurrent (or subsequent) hepatic disease. Although leptospirosis can cause ARF along with acute liver disease (or liver failure), ARF without liver disease has become the most common clinical presentation of the predominant serovars of leptospirosis affecting dogs in the US. Failure to recognize leptospirosis as the cause of ARF may result in exposure of veterinarians, technicians and other hospital personnel to this zoonotic disease.

Major causes of acute renal failure in dogs include ischemic, infectious (leptospirosis, Lyme disease) and toxic causes. Leptospirosis has re-emerged as a clinical disease in North America and has become a common cause of acute renal failure in most areas of the US. Ischemic causes include hypotensive events such as anesthesia/surgery, hypovolemic shock, and severe dehydration. Common toxins causing ARF include ethylene glycol, arsenic, zinc, and lead. Two recently reported toxic causes or ARF are raisin ingestion in dogs and lily ingestion in cats. Pet food contamination with melamine and cyanuric acid resulted large numbers of cases of ARF in dogs and cats in 2007. Antibiotics that may cause ARF include aminoglycosides, amphotericin B, cephaloridine, and oxytetracycline. Miscellaneous drugs that may cause ARF include thiacetarsamide, cis-platinum, methoxyflurane, and rarely radiographic contrast agents. Pigment nephropathy from hemoglobinuria or myoglobinuria is uncommon in dogs and cats. In areas where leptospirosis is endemic, any dog with ARF should be assumed to have leptospirosis unless another cause is known.

Overview of leptospirosis

Leptospirosis is one of the most common causes of ARF at Purdue VTH and the most commonly implicated serovars include grippotyphosa, bratislava, pomona, and autumnalis. Unlike traditional leptospirosis infection with canicola and icterohaemorrhagiae, hepatic involvement with these serovars may be absent, minimal or delayed compared to the onset of ARF. Leptospirosis is important to recognize because it is potentially reversible and because of the potential for zoonosis to owners and veterinary personnel. Clinical presentations may include acute renal failure, acute hepatic disease, fever, uveitis and acute pulmonary hemorrhage. Common laboratory findings in dogs with leptospirosis include azotemia (with isosthenuria), elevated liver enzymes, hyperbilirubinemia, neutrophilic leukocytosis, thrombocytopenia and renal glucosuria with normoglycemia.

The re-emergence of leptospirosis has been linked to exposure to wildlife species that act as reservoirs for the organism. The reservoir or maintenance hosts develop low antibody titers to leptospirosis and can carry the organism for longer periods of time than incidental hosts like dogs and humans. Not all maintenance hosts are well understood for all the serovars.

Pathogenesis

Leptospira spp are motile spirochetes that are able to penetrate mucus membranes or through breaks in the skin. During the spirochetemia, the organism spreads throughout the blood including brain, lung, blood vessels, liver and kidney. Next there is localization of the organism to the liver and kidneys (renal tubules) predominantly. In incidental hosts (humans and dogs), high antibody titers develop and there is a brief period of urine shedding of the organism. Infections can be subclinical, clinical or even fatal. In maintenance hosts (raccoons), there are low antibody titers and may be low term urine shedding of leptospires in the urine.

All dogs are susceptible to leptospirosis. Young adult large breed dogs have higher risk of leptospirosis in epidemiological studies because they are more likely to be exposed to infected ground water than other dogs; however, this does not represent an increased susceptibility. Likewise, male dogs are at greater risk than female dogs. One study showed that dogs that lived in areas that were formerly considered farm or woodland that had become developed into urban areas had greater risk for leptospirosis.

Diagnosis of leptospirosis

Veterinarians should consider leptospirosis as a differential diagnoses especially for ARF with or without serum biochemical evidence of hepatocellular disease, fever, acute pulmonary hemorrhage, or uveitis. Diagnosis is usually made by demonstrating MAT antibody response to non-vaccine serovars along with appropriate clinical findings. Baseline titers can be difficult to interpret especially in dogs that have been recently vaccinated. A single titer of ≥1:800 to non-vaccine serovars should raise suspicion of a diagnosis of leptospirosis, whereas a 4-fold increase in convalescent titers (> 2-4 weeks later) are considered diagnostic. Antigen detection may also be attempted by immunofluorescence of tissues or PCR of urine or tissues. The precise role of PCR based diagnostic tests for leptospirosis is yet ot be determined. PCR results have a substantial number of false positive results in dogs without confirmed clinical leptospirosis and false negative results also may occur once antibiotic therapy has been initiated. Therefore, serologic testing is still considered the diagnostic test of choice. An alternative explanation for the apparent false positives is that positive PCR results may actually be the most sensitive test method and apparent false positive PCR results could represent detection of dogs with subclinical, transient infections. Dark field microscopy for detection of spirochetes is insensitive and is not recommended as a screening test.

The prognosis of leptospirosis depends on the severity of renal and liver dysfunction, how quickly antibiotic therapy is initiated and may be affected by serovar. The mortality of leptospirosis in dogs has been reported from 11-27%. Surviving dogs may return to normal renal function or may have residual chronic kidney disease (reportedly in approximately 33-40% of surviving dogs).

Treatment of leptospirosis

Treatment of leptospirosis should include routine supportive treatment for acute renal failure plus antiobiotic therapy. For dogs that are anorexic and unable to take oral medications, ampicillin (22 mg/kg IV q8h for 2 weeks) should be started. Once the dog is able to take oral medications, doxycycline (5 mg/kg PO q12h) should be administered for 2 weeks. Because the diagnosis if often made retrospectively, all dogs with ARF should be considered Lepto suspects unless another cause is known for the ARF and treated with ampicillin and/or doxycycline.

Hemodialysis may be required for treatment of ARF caused by Leptospirosis. Adin and Cowgill reported successful hemodialysis treatment in dogs that did not respond to conservative medical management. Indications for dialysis are refractory hyperkalemia, acidosis, overhydration with oliguria, and failure to respond to conservative management (severe uremia).

Zoonotic concerns

Prevention of spread of leptospirosis to other animals and humans is an essential component of management of dogs that are 'leptospirosis suspects". The patient should be isolated from other animals and all personnel handling the dog or urine or blood samples should wear gloves. All urine should be collected and disposed of properly to prevent transmission to people or other animals. Urine samples submitted to outside clinical pathology laboratories should be labeled as Leptospirosis suspects to notify the laboratory personnel that gloves should be worn when processing the urine sample. Indwelling urinary catheters connected to a closed collection system is recommended to prevent potential exposure to personnel by infected urine. Infectious disease waste and laundry should be handled appropriately. Infectious disease laundry such as soiled cage towels should be bleached to ensure disinfection. Organic material such as urine and feces should be removed followed by disinfection with bleach or other disinfectants.

Vaccination against leptospirosis

Vaccination for leptospirosis is a complicated decision that is influenced by the prevalence of leptospirosis serovars in the geographic practice area. Available vaccines include 2 types of vaccines with serovars canicola andicterohaemorrhagiae, or serovars canicola,icterohaemorrhagiae, grippotyphosa, and pomona. Because infection with the serovars grippotyphosa and pomona are so common, vaccination with a 4-way vaccine is recommended. Duration of immunity is not definitively known for all leptospira bacterins, but protection from vaccines is likely for at least 12 months. Annual re-vaccination for leptospirosis is recommended. Vaccination with leptospirosis does not appear to increase the risk of adverse vaccine reactions. Cross protection does not occur to other non-vaccine serovars, thus vaccines do not protect against all serovars affecting dogs in North America.

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