Betsy, a 5-year-old spayed boxer, was presented for a 2-day history of vomiting, anorexia, and azotemia.
History & Examination
Betsy appeared dull and depressed but responsive. Mucous membranes were hyperemic, and capillary refill time was <1 second. Clinical dehydration was not detected. BCS was 5/9 with mild abdominal distension. Mild hypothermia (98.6°F [37°C]) was present, but heart and respiratory rates were normal. Severe generalized abdominal pain and ptyalism were noted.
Betsy was up-to-date on core vaccinations. More than a year before presentation, leptospirosis vaccination with serovars Canicola, Icterohaemorrhagiae, Pomona, and Grippotyphosa had been administered. Betsy received monthly heartworm and topical flea preventives but no other medications. She had access to several acres of wooded property and had suffered superficial skin wounds from a raccoon a week before presentation. Although a rabies booster was indicated, it was not administered. Betsy was hospitalized and treated with IV fluids and maropitant (1 mg/kg SC once a day), as well as enrofloxacin (5 mg/kg IV once a day) and ampicillin (20 mg/kg IM 3 times a day) for presumptive infection, but no improvement was seen. Abdominal distention developed, and Betsy was referred for specialty care. The referring veterinarian observed that Betsy did not urinate overnight despite receiving fluid therapy.
CBC was unremarkable, but serum chemistry profile identified several abnormalities (Table 1). Urinalysis revealed trace glucosuria, 1+ proteinuria, and a urine specific gravity of 1.026. A urine culture yielded no bacterial growth. Baseline ammonia was significantly elevated. Severe hypertension was present (240 mm Hg systolic Doppler) despite administration of hydromorphone. Fundic examination was normal, and no evidence of uveitis was noted. Thoracic radiography revealed a diffuse, unstructured intersitial pattern, generalized mild bronchial pattern, and mild pleural effusion.
|Diagnostic Test||Result||Reference Range|
|Alanine aminotransferase (U/L)||116||10-90|
|Alkaline phosphatase (U/L)||727||11-140|
|Urine specific gravity||1.026||1.001-1.070|
|Abdominal fluid protein (g/dL)||1||Pure transudate (<2.5)|
|Abdominal fluid cells (/µL)||<1000||Pure transudate (<1500)|
|Abdominal fluid creatinine (mg/dL)||6.0||Abdominal fluid creatinine:serum creatinine <2.0|
|Abdominal fluid potassium (mEq/L)||4.16||Abdominal fluid potassium:serum potassium <1.4|
Abdominal ultrasonography revealed a small urinary bladder, bilateral hyperechoic renal cortices, ascites, and a hyperechoic pancreas.
Abdominal ultrasonography revealed a small urinary bladder, bilateral hyperechoic renal cortices, ascites, and a hyperechoic pancreas. A SNAP (idexx.com) cPL (canine pancreas-specific lipase) was abnormal. Abdominocentesis yielded a pure transudate with fluid potassium (4.16 mEq/L) and creatinine (6.0 mg/dL) values equal to serum chemistry values. A urinary catheter was placed, but no urine was obtained despite administration of 5 L of IV fluids over the previous 24 hours. Leptospirosis titers were submitted.
What are the treatment options to improve urine output in oliguric or anuric renal failure?
What are the most common diagnostic differentials for hypertension in dogs?
Which diagnostic test(s) is(are) recommended for canine leptospirosis?
How long after recovery from leptospirosis should vaccination occur?
Acute renal failure and liver failure due to presumptive leptospirosis
Treatment & Outcome
Betsy was hospitalized for 14 days with IV fluid therapy to match intake and output and to resolve azotemia. Fluid overload, anuria, and hypertension resolved 6 hours after the start of treatment. A furosemide constant rate infusion (CRI; 1 mg/kg/hr) was necessary for the first 24 hours to maintain normal urine output. Treatment for leptospirosis was initiated with ampicillin–sulbactam, although ampicillin alone is the recommended leptospirosis treatment. IV antibiotics were continued until the patient ate well, at which time doxycycline (5 mg/kg PO twice a day) was administered for 3 weeks. Supportive care was also provided (Table 2). Betsy was discharged after 14 days of hospitalization with oral doxycycline, S-adenosylmethionine (SAMe) + silybin (20 mg/kg PO once a day), famotidine (0.5 mg/kg PO twice a day), and aluminum hydroxide (100 mg/kg PO divided daily with meals). Mild azotemia and mild hyperphosphatemia persisted at discharge. Initial leptospirosis titers were Leptospira interrogans serovar Grippotyphosa (1:100), L interrogans serovar Bratislava (1:400), and L interrogans serovar Autumnalis (1:100). Three weeks later, convalescent titers revealed an 8-fold rise in L interrogans serovar Grippotyphosa titers (1:800). Recheck bloodwork at 1 and 3 months was normal.
|Ampicillin–sulbactam (30 mg/kg IV 3 times a day)*||Leptospiremia in anorexic patient|
|Doxycycline (5 mg/kg PO twice a day)||Leptospiremia, leptospiruria|
|Furosemide (2 mg/kg IV bolus, then 1 mg/kg/hr CRI)*||Fluid overload, anuria|
|Maropitant (1 mg/kg SC once a day)*||Nausea, vomiting|
|Ondansetron (0.2-1 mg/kg IV 3 times a day)*||Nausea, vomiting|
|Omeprazole (1 mg/kg PO twice a day)*||Antacid, uremic gastritis|
|Famotidine (0.5-1 mg/kg PO once or twice a day)||Antacid, uremic gastritis|
|Aluminum hydroxide (30-100 mg/kg/day PO, divided with meals)||Hyperphosphatemia|
|S-adenosylmethionine (SAMe) + silybin (20 mg/kg PO once a day)||Glutathione precursor|
|N-acetylcysteine (140-180 mg/kg IV [diluted to 5%] over 20 min, followed by 70 mg/kg IV or PO every 6 hours for a minimum of 7 treatments)*||Glutathione precursor|
|Vitamin E (12 units/kg PO once a day)*|
Caution: May exacerbate a vitamin K-dependent coagulopathy, especially with high doses of vitamin E
|Vitamin K (1 mg/kg SC twice a day)*||Coagulopathy associated with liver failure|
*Treatment administered in-hospital only
Leptospirosis is a worldwide zoonotic disease.1 Acute renal failure with or without acute hepatic failure commonly develops. Pancreatitis, disseminated intravascular coagulation, hepatic failure (without renal involvement), and pulmonary hemorrhage syndrome have also been documented.1
Leptospirosis is seen most commonly in late fall and after periods of heavy rainfall.2 Organisms are shed in the urine of reservoir hosts (eg, raccoons, rodents) and transmitted through contact of mucous membranes or broken skin with contaminated water or soil—where the organism can survive for extended periods—or directly through ingestion of infected tissues.2 The incubation period is ˜1 week, and leptospiremia is present for 3 to 4 days before the organisms reach the renal tubules, where they are shed in the urine.2 Doxycycline is the treatment of choice and should be initiated as soon as oral therapy is tolerated to resolve urine shedding and decrease the risk to humans.2 Penicillins are effective at clearing leptospiremia and can be used until doxycycline is tolerated; however, they do not clear the carrier state.2 Treatment with doxycycline is recommended for 2 to 3 weeks, and prognosis can be fair at 50% to 80% survival.2 Complete renal recovery may take 3 to 4 weeks, and residual renal damage may persist.2
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What are the treatment options to improve urine output in oliguric or anuric renal failure?Show Answer
Once the patient is hydrated, urine production should increase depending on IV fluid rates. However, oliguria (ie, urine production <0.5 mL/kg/hr) or anuria (ie, no urine production) may develop in acute renal failure.3 Pharmacologic therapy to increase urine output and safely continue fluid therapy includes diuretics, mannitol, fenoldopam, and diltiazem (Table 3).3 Furosemide should be attempted first at 2 mg/kg IV bolus; if it is successful, a CRI is recommended.3 If furosemide is unsuccessful, mannitol 20% (0.5-1 g/kg IV bolus every 4-6 hours then 1-2 mg/kg/min CRI) may be attempted if the patient is adequately hydrated. Doses higher than 2 to 4 g/kg/day should be avoided because of risk for acute kidney injury.3 Fenoldopam, a selective dopamine agonist, is used in humans, but its use in veterinary medicine has not been associated with improved survival or urine output.4 Diltiazem has been shown to improve urine output in dogs with leptospirosis.3 If medical therapy fails to achieve diuresis, referral for renal replacement therapy should be discussed.
TABLE 3TREATMENT OPTIONS FOR ANURIA & OLIGURIA
Drug Dose Furosemide
0.66 mg/kg IV bolus, then 0.66 mg/kg/hr CRI
0.5-1 mg/kg/hr CRI
2 mg/kg IV bolus, increasing to 4-6 mg/kg IV hourly until diuresis
0.5-1 g/kg IV bolus slowly every 4-6 hrs then 1-2 mg/kg/min CRI
Repeat 0.25-0.5 g/kg bolus every 4-6 hrs
Fenoldopam 0.8 µg/kg/min CRI Diltiazem 0.1-0.5 mg/kg IV slowly then 1-5 µg/kg/min CRI
What are the most common diagnostic differentials for hypertension in dogs?Show Answer
The most common diagnostic differentials for hypertension in dogs include renal disease, hyperadrenocorticism, fear and anxiety, pain, and diabetes mellitus.5 Less common causes of canine hypertension include acromegaly, primary hyperaldosteronism, pheochromocytoma, congestive heart failure, hypothyroidism, obesity, fluid overload, and side effects from medications such as phenylpropanolamine.5 Arterial hypertension is especially common in acute kidney failure and may further worsen renal function by inducing glomerular damage.5
Which diagnostic test(s) is(are) recommended for canine leptospirosis?Show Answer
The current standard for diagnosis of leptospirosis is serology using the microscopic agglutination test (MAT), in which serial dilutions of the patient’s serum are mixed with live organisms of different serovars (see Notable Leptospira Interrogans Serovars). Antibody titer is reported as the highest dilution to cause agglutination of the organisms using darkfield microscopy.2 Vaccination can cause a rise in antibody titer, which may persist for months. A 4-fold or greater rise with convalescent titers to 1 or more serovars (2-4 weeks after initial titer) is required for diagnosis.2 Significant cross reaction occurs among serovars, and titers may not accurately identify the true infecting serovar.2 Whole blood polymerase chain reaction (PCR) may be useful for early diagnosis when antibodies are not present during the 3-to-4-day leptospiremic phase.2,6 After the leptospiremic phase, urine PCR may be used.2,6 Vaccinations do not cause a false-positive PCR result.6 False negatives may occur with both MAT and PCR testing, especially if they are performed after starting antibiotics.2,6 An enzyme-linked immunosorbent assay (ELISA) was not performed on Betsy because it was not available at the time.
Notable Leptospira Interrogans Serovars
How long after recovery from leptospirosis should vaccination occur?Show Answer
It is unknown if lifelong immunity occurs after infection, and dogs that recover are likely to be continuously exposed to the organism if continuously exposed to the same environment.2 Therefore, vaccination is recommended 1 year after recovery, followed by continued annual revaccination.2
BCS = body condition score, CBC = complete blood count, CRI = constant rate infusion, MAT = microscopic agglutination test, PCR = polymerase chain reaction, SAMe = S-adenosylmethionine
- Tangeman LE, Littman MP. Clinicopathologic and atypical features of naturally occurring leptospirosis in dogs: 51 cases (2000-2010). JAVMA. 2013;243(9):1316-1322.
- Sykes JE, Hartmann K, Lunn KF, Moore GE, Stoddard RA, Goldstein RE. 2010 ACVIM small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment, and prevention. JVIM. 2011;25(1):1-13.
- Ross L. Acute kidney injury in dogs and cats. Vet Clin North Am Small Anim Pract. 2011;41(1):1-14.
- Nielsen LK, Bracker K, Price LL. Administration of fenoldopam in critically ill small animal patients with acute kidney injury: 28 dogs and 34 cats (2008-2012). JVECC. 2015;25(3):396-404.
- Brown S, Atkins R, Bagley R, et al. Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. JVIM. 2007;21(3):542-558.
- Fraune CK, Schweighauser A, Francey T. Evaluation of the diagnostic value of serologic microagglutination testing and a polymerase chain reaction assay for diagnosis of acute leptospirosis in dogs in a referral center. JAVMA. 2013;242(10):1373-1380.
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