A case of leptospirosis presenting with end-stage renal failure

Sir,

Leptospirosis is a zoonosis caused by spirochetes. Information concerning leptospirosis-induced end-stage renal failure (ESRF) is very scarce [1]. This report describes a young male patient presenting with leptospirosis who continued as a chronic haemodialysis patient despite treatment for leptospirosis.

A 21-year-old, previously healthy man, a farmer by profession, was brought to the Emergency Room on March 20, 2004 by relatives due to high fever, headache, nausea and vomiting, and constant sleepiness. At admission, he was lethargic and clinically dehydrated. At physical examination, conjunctival congestion and petechia in the soft palate region were observed. Pupils were symmetric and reactive. No meningism was noted. Axillary temperature was 37.8°C, blood pressure was 130/90 mmHg and heart rate was 88 beats/min. Initial laboratory evaluation showed leukocyte levels of 4200/mm3 with a fraction of 86% polymorphonuclear cells, haemoglobin at 9.2 g/dl, thrombocytes at 62 000/mm3, serum urea at 474 mg/dl, creatinine at 17.8 mg/dl, albumin at 3.5 g/dl, uric acid at 10.2 mg/dl, serum sodium at 127 mmol/l, potassium at 8.8 mmol/l, calcium at 8.9 mg/dl, phosphorus at 6.1 mg/dl and proteinuria of 1750 mg/day. Liver function tests, and the levels of serum glucose, lactate dehydrogenase and creatine kinase were normal. Arterial blood gases were pH 7.25, 8.5 mmol/l, pO2 114 mmHg and pCO2 22 mmHg. Urinalysis showed microscopic haematuria, and leukocyturia. The daily urine volume was 3000–5000 ml. Blood and urine cultures were sterile. Serum antibodies for brucella, salmonella, toxoplasmosis, cytomegalovirus, Epstein–Barr virus and hantavirus were negative. At bone marrow biopsy, megakaryocytes were reduced. Haemodialysis treatment was immediately initiated. In addition, empirical antibiotic therapy was started using cefoperazone/sulbactam.

His relatives stated that he lived in the south of Turkey, which has a temperate climate, and that 20 days previously he had worked without gloves in an irrigation channel containing river water.

Leptospirosis was investigated 10 days after the patient's admission due to high fever, haematological and renal abnormalities. No leptospira were seen in the blood under dark field microscopy. Leptospira icterohaemorrhagiae and Leptospira australis were positive by macrotube agglutination (Danke-Seien) test. Leptospira immunoglobulin M (Ig M) was positive by enzyme-linked immunosorbent assay (ELISA). Blood samples were screened for anti-leptospiral IgM antibodies using a Leptospira biflexa antigen in a commercial ELISA kit (Pan Bio®, Leptospira IgM ELISA test). Microscopic agglutination test (MAT) was also positive (titre 1:200) for L. australis serotype Bratislava. Twelve days after presentation, antibiotic therapy was switched to penicillin (12x106 IU/day, intravenously).

Despite 3 weeks of haemodialysis treatment, renal function did not improve and a kidney biopsy was performed. Under light microscopy, mesangial hypercellularity, interstitial dense lymphocyte infiltration, tubular atrophy and interstitial fibrosis were determined (Figure 1). At immunofluorescent examination, C3 accumulation was observed in the glomerular capillary wall. No spirochetes were observed in the proximal tubular epithelium.



View larger version (147K):
[in this window]
[in a new window]
 
Fig. 1. Interstitial mononuclear cell infiltration and mild fibrosis in the first kidney biopsy specimen [Trichrome staining (Gomori), x10].

 
His general condition improved with regular haemodialysis and penicillin treatment. Kidney function did not improve, however. Ten weeks after beginning haemodialysis treatment, a kidney biopsy was repeated. At the second kidney biopsy, tubular atrophy and interstitial fibrosis were determined to have increased (Figure 2). In this period, MAT yielded a 1:50 titre to L. australis serotype Bratislava and leptospira IgM ELISA appeared to be negative. No icterus, respiratory insufficiency, rhabdomyolysis or multiple haemorrhage developed in the patient, who was observed and treated in our clinic between March and September 2004. The patient was admitted to a regular haemodialysis programme and discharged.



View larger version (122K):
[in this window]
[in a new window]
 
Fig. 2. Interstitial dense fibrosis, hyalinization and tubular atrophy in the second kidney biopsy specimen [Trichrome staining (Gomori), x10].

 
Katz et al. reported that serum creatinine levels were >1.5 mg/dl in 54% of patients with leptospirosis [2]. Covic et al. determined that renal functions normalized in 64% of leptospirosis patients presenting with acute renal failure (ARF) and followed-up for 90 days, and that there was persisting mild renal insufficiency in 10% [3].

Acute tubulointerstitial nephritis/post-infectious nephritis is reported to be the most characteristic renal lesion observed in leptospirosis [4,5]. In our patient, there was a gap of ~6 weeks between likely onset of illness and the first kidney biopsy being performed, showing mild interstitial fibrosis. Moreover, in a second kidney biopsy 7 weeks later, these lesions were shown to be still progressive, and it was thought that irreversible histopathological findings of interstitial fibrosis with tubular atrophy could develop (tubular atrophy, interstitial fibrosis).

Thrombocytopenia linked to increased peripheral platelet consumption frequently occurs in severe leptospirosis. In addition to an increase in megakaryocyte series in bone marrow being expected in this case, Nicodemo et al. reported that the static microscopic examination of a bone marrow aspirate cannot accurately depict the dynamic mechanisms of platelet production when these cells are being consumed in peripheral blood [6].

As well as a leukocyte count of 4200/mm3 being remarkably low for a severe case of leptospirosis, the size of the neutrophil fraction is noteworthy. Furthermore, leptospirosis patients with a low or normal leukocyte count together with ARF have been reported [4,7].

A case of leptospirosis resulting in irreversible dialysis-dependent ESRF is a very rare condition.

Enes Murat Atasoyu1, Vedat Turhan2, Suat Unver1, T. Rifki Evrenkaya1 and Sukru Yildirim3

Departments of 1 Nephrology2 Infectious Diseases3 Pathology Gulhane Military Academy of Medicine Haydarpasa Training Hospital Istanbul Turkey Email: ematasoyu{at}superonline.com

Acknowledgments

We are grateful to our colleagues Vildan Ozdemir, PhD from the Etlik Veterinary Central Searching Institute for the reference and research on leptospirosis and other zoonoses in Ankara, and Erdal Polat, PhD from the Clinical Microbiology Laboratory of Cerrahpasa University in Istanbul, Turkey for his great individual effort and dedication in the diagnosis of our case.

Conflict of interest statement. None declared.

References

  1. Peces R. Acute renal failure in severe leptospirosis [letter]. Nephrol Dial Transplant 2003; 18: 1235[Free Full Text]
  2. Katz RA, Ansdell VE, Effer PV, Middleton CR, Sasaki DM. Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974–1998. Clin Infect Dis 2001; 33: 1834–1841[CrossRef][ISI][Medline]
  3. Covic A, Goldsmith DJA, Gusbeth-Tatomir P, Seica A, Covic M. A retrospective 5-year study in Moldova of acute renal failure due to leptospirosis: 58 cases and review of the literature. Nephrol Dial Transplant 2003; 18: 1128–1134[Abstract/Free Full Text]
  4. Yang CW, Wu MS, Pan MJ. Leptospirosis renal disease. Nephrol Dial Transplant 2001; 16 [Suppl 5]: 73–77
  5. Sitprija V, Pipatanagul V, Mertowidjojo K, Boonpucknavig V, Boonpucknavig S. Pathogenesis of renal disease in leptospirosis: clinical and experimental studies. Kidney Int 1980; 17: 827–836[ISI][Medline]
  6. Nicodemo AC, Del Negro G, Amato Neto V. Thrombocytopenia and leptospirosis. Rev Inst Med Trop Sao Paulo 1990; 32: 252–259[ISI][Medline]
  7. Meites E, Jay MT, Deresinski S et al. Reemerging leptospirosis, California. Emerg Infect Dis 2004; 10: 406–412[ISI][Medline]




This Article
Extract
Full Text (PDF)
All Versions of this Article:
20/10/2290    most recent
gfi014v1
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Atasoyu, E. M.
Articles by Yildirim, S.
PubMed
PubMed Citation
Articles by Atasoyu, E. M.
Articles by Yildirim, S.