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Decreased Kidney Function Associated With Fever and Aseptic Meningitis
Article Outline
Clinical Presentation
A 32-year-old man from Montreal presented with frontal headache, photophobia, nausea, and vomiting. He had not traveled outside Canada, did not use any medication, and felt perfectly fine until a few days before admission. Two weeks before, his dog had been sick with fever, vomiting, and urinary incontinence.
On presentation, the patient's temperature was 38.2°C, heart rate was 70 beats/min, and blood pressure was 120/60 mm Hg. Physical examination showed a diffuse maculopapular rash, multiple indurated erythema nodosum–like macules on his legs, and neck stiffness. Laboratory tests showed a white blood cell count of 5.6 × 103/μL (5.6 × 109/L), hemoglobin level of 14.6 g/dL (146 g/L), and platelet count of 156 × 103/μL (156 × 109/L). Chemistry test results included the following values: sodium, 128 mEq/L (128 mmol/L); chloride, 97 mEq/L (97 mmol/L); potassium, 3.8 mEq/L (3.8 mmol/L); and serum creatinine, 4.34 mg/dL (384 μmol/L), with estimated glomerular filtration rate of 17.8 mL/min/1.73 m2 (0.3 mL/s/1.73 m2). Initial urinary sodium level was <20 mEq/L (<20 mmol/L). Serum creatinine level remained increased despite aggressive fluid replacement.
Urinalysis showed protein, few leukocytes, and granular casts, but no erythrocytes. A 24-hour urine collection showed mild proteinuria (protein excretion, 590 mg/d). Liver enzyme levels were increased (aspartate aminotransferase, 115 U/L; alanine aminotransferase, 132 U/L), but bilirubin and alkaline phosphatase levels were normal. Kidney and liver ultrasound was normal. Lumbar puncture showed pleocytosis (91 leukocytes/μL) with 89% lymphocytes, mildly increased protein level at 0.09 g/dL (0.91 g/L), and slightly decreased glucose level, compatible with aseptic meningitis. A kidney biopsy was obtained (Fig 1), and intravenous methylprednisolone, 1 g/d, for 3 days was initiated for a presumptive diagnosis of sarcoidosis, followed by prednisone, 60 mg/d. Meningismus resolved in 48 hours, and kidney function recovered progressively and completely. Cultures of cerebrospinal fluid and urine were negative.
Figure 1.
Kidney biopsy specimen from the patient.
■ What does the kidney biopsy show?
■ What is the differential diagnosis?
■ What tests are needed to reach a definitive diagnosis?
■ What is the recommended treatment?
Discussion
What does the kidney biopsy show?
The kidney biopsy specimen shows tubulointerstitial inflammation with lymphocytic infiltration and rare eosinophils. Glomeruli appear normal, and no interstitial granulomas were found.
What is the differential diagnosis?
Causes of interstitial nephritis include drugs, infections, and inflammatory diseases. Drugs were excluded in this patient. Several infectious diseases of viral or bacterial origin have been associated with interstitial nephritis (Box 1). However, concomitant meningitis limits the number of possibilities. Cytomegalovirus meningitis has been described in immunocompromised patients. Hantavirus infection was excluded because the patient had not traveled abroad. Bacterial infections causing interstitial nephritis and meningitis include tuberculosis, legionella, and leptospirosis. Tuberculous interstitial nephritis usually causes a granulomatous infiltration, and legionella has rarely been associated with meningitis. Leptospirosis frequently is associated with fever, headache, myalgia, gastrointestinal symptoms, and jaundice. Skin rash is present in 10% of patients. Aseptic meningitis is characteristic of the immune phase that follows the acute septicemic phase, occurring in up to 80% of cases. Humans contract the disease through direct contact with urine of infected mammals or indirectly through contaminated water. In developed countries, most cases are associated with recreational aquatic activities, occupational exposure (ie, farming and veterinary medicine), or contacts with rats in urban settings. A dog from an urban area is an unusual culprit. Sarcoidosis could present with multisystemic involvement, although the absence of pulmonary manifestations would be atypical, as well as the absence of granulomas in the kidney biopsy specimen. Systemic lupus erythematosus without other clinical criteria in a young man also would be very unusual.
Infections
Systemic diseases
Drugs
Neoplastic
What tests are needed to reach a definitive diagnosis?
Serologic test results for hepatitis A, B, and C; cytomegalovirus; mononucleosis; and human immunodeficiency virus (HIV) were negative in our patient. A few weeks later, leptospira serologic tests came back positive. A confirmatory microscopic agglutination test at the Canadian National Center of Microbiology in Winnipeg showed titers of 1:50 for Leptospira grippotyphosa. The dog's serum also tested positive for leptospira. Leptospirosis thus was diagnosed retrospectively, probably transmitted from the patient's dog. Many reports published in the last decade show an increase in the prevalence of leptospirosis in domestic dogs in the United States and Canada.1 Leptospirosis also can be diagnosed using polymerase chain reaction in urine, but results were negative in our patient. It also is possible to visualize leptospira directly on kidney biopsy specimens with special staining. Post hoc Warthin-Sarry staining showed intracellular structures compatible with leptospire (Fig 2).
Figure 2.
Warthin-Sarry staining shows intracellular structures compatible with leptospirosis.
Leptospirosis is a zoonosis caused by spirochetes of the genus Leptospira. It has a worldwide distribution, but its incidence is higher in tropical areas. Leptospirosis can present with many nonspecific manifestations and may be misdiagnosed easily. Occasionally, it can evolve into a severe form of the disease, Weil disease, with a high fatality rate. It is characterized by jaundice, decreased kidney function, hemorrhagic diathesis, and, in many cases, pulmonary hemorrhages, which can progress to acute respiratory distress syndrome. Leptospirosis should be considered in febrile patients with acute renal failure of tubulointerstitial presentation, aseptic meningitis, skin rash, digestive manifestations, or lung infiltrates.
What is the recommended treatment?
Recommended treatment of patients with leptospirosis is antibiotics and supportive treatment. However, there is some rationale to the use of corticosteroids in patients with severe leptospirosis. The pathophysiologic state of leptospirosis associated with multiple organ dysfunction is not fully understood. Decreased kidney function and pulmonary complications occur during the immune phase of the disease, with the development of specific antibodies.2 It is difficult to differentiate between direct infectious lesions and indirect immune-mediated organ damage. Direct infectious tissue damage usually benefits from antibiotics, whereas immune reaction–associated organ damage may respond favorably to steroid therapy. The severity of clinical manifestations of leptospirosis usually correlates with the intensity of the immune response. There are several reports of severe pulmonary leptospirosis successfully treated using high-dose steroids.3 Recently, Meaudre et al4 reported a patient with severe leptospirosis with multiorgan failure and oliguric acute renal failure who was treated using intravenous corticosteroids. They observed a rapid clinical and biological improvement, but they also used immunoglobulins and antibiotics.
Final Diagnosis
Severe leptospirosis with multiple organ involvement.
References
- . Prevalence of and risk factors for leptospirosis among dogs in the United States and Canada: 677 cases (1970-1998). J Am Vet Med Assoc. 2002;220(1):53–58
- Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis. 2003;3(12):757–771
- . Pulmonary leptospirosis: an excellent response to bolus methylprednisolone. Postgrad Med J. 2006;82(971):602–606
- [Immunomodulation in severe leptospirosis with multiple organ failure: plasma exchange, intravenous immunoglobulin or corticosteroids?]. Ann Fr Anesth Reanim. 2008;27(2):172–176
Case provided and authored by Jasmin Levallois, MD,1 Annie-Claude Labbé, MD,2 Denis Ouimet, MD,1 and Michel Vallée, MD, PhD,1 Maisonneuve-Rosemont Hospital, 1Division of Nephrology, and 2Division of Infectious Disease, Department of Medicine, Montreal University, Montreal, Quebec, Canada.Address correspondence to Michel Vallée, MD, PhD, Maisonneuve-Rosemont Hospital, Nephrology Division, University of Montreal, 5415 blv de l'Assomption, Montréal, H1T2M4, Quebec, Canada. E-mail: mvallee.hmr@ssss.gouv.qc.ca
Support: None.
Financial Disclosure: None.
PII: S0272-6386(09)01317-1
doi:10.1053/j.ajkd.2009.09.029
© 2010 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved.
