NEPHROLOGY ROUNDS

Atypical Renal Presentation in Severe

Leptospirosis
Michał Małecki1, Edyta Gołembiewska1, Anna Maria Muraszko1, Beata Fiecek2,
 ska3, Joanna Ste˛ pniewska1, Maciej Fijałkowski1 and
Magda Lewandowska3, Elz_ bieta Urasin
1
Kazimierz Ciechanowski
1
Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland;
2
Laboratory of Rickettsiae, Chlamydiae and Spirochetes, National Institute of Public Health, Warsaw, Poland; and 3Department
of Pathology, Pomeranian Medical University, Szczecin, Poland

Correspondence: Michał Małecki, Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical
 ców Wielkopolskich 72; 70-111 Szczecin, Poland. E-mail: [email protected]
University, al. Powstan
Kidney Int Rep (2019) 4, 168–170; https://doi.org/10.1016/j.ekir.2018.08.007
ª 2018 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-
NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

INTRODUCTION (Hgb level 9.2 g/dl). A chest X-ray and abdominal

computed tomography scan were normal. Serological
eil disease is a rare autoimmune complication of
W leptospirosis. It develops following a phase of
bacteremia, after the pathogens have been eliminated
tests for hepatitis B virus and hepatitis C virus infection
were negative.
Initial treatment involved continuous renal replace-
from the bloodstream, but antibody-mediated processes ment therapy and empirical antibiotic therapy with
continue to affect the patient’s internal organs. In most cephalosporin (cefotaxime).
cases, symptoms appear around 3 weeks after exposure, The patient was transferred to our hospital for
presenting as acute kidney injury and high-grade further investigation and treatment. At the time of
hyperbilirubinemia. transfer, the patient exhibited cognitive impairment,
disorientation, hiccups, and Cheyne
Stokes breathing.
CASE PRESENTATION Physical examination revealed normal vital signs,
A 72-year old Caucasian man with no prior medical jaundice, bilateral conjunctivitis, generalized edema,
history was admitted with acute renal failure and and signs of thrombocytopenic purpura. There were no
hyperbilirubinemia. Three weeks prior to hospitaliza- signs of circulatory or respiratory failure, and no focal
tion, he experienced an episode of fever, accompanied neurological signs. Urinalysis showed severe protein-
by chills. The initial symptoms were followed by uria (urinary protein 475 mg/dl) accompanied by
muscle pain and decreased exercise tolerance. Visible erythrocyturia (erythrocytes were covering the whole
jaundice and steadily decreasing urinary output field of vision, and the number of leukocytes were 2
appeared soon thereafter. Three days later he was and 5 in the field of vision). The creatinine level was 7.5
admitted to a provincial hospital. mg/dl. The serum level of creatinine phosphokinase
Initial tests revealed high total bilirubin levels in the (CPK) was CK ¼ 31 U/l (normal), and the serum level of
serum, exceeding 20 mg/dl, predominantly conjugated, potassium was 5.0 mmol/l.
increased serum inflammatory factors (C-reactive pro- As jaundice and oliguria requiring renal replacement
tein levels >90 mg/l), and an elevation of both creati- therapy persisted and a review of the patient’s history
nine and urea serum levels (8 mg/dl and 300 mg/dl, revealed that he lived close to a river bank and a lake,
respectively). Serum concentrations of other markers of the suspicion of a Leptospira infection was raised.
hepatic damage, such as alanine- and glutamate- Blood and urine samples were collected for polymerase
pyruvate transaminase, prothrombin time, and alka- chain reaction evaluation of Leptospira pathogen
line phosphatase, were all within normal ranges. A presence and a microscopic agglutination test. In the
decrease in both total serum protein (44 g/l) and presence of the severe encephalopathy observed, the
albumin (24 g/l) was noted. Urinalysis revealed eryth- decision was made to perform albumin plasmapheresis.
rocyturia and proteinuria exceeding the nephrotic- After 2 sessions, the mental status of the patient
range threshold. Full blood count analysis showed a markedly improved. After that point, the patient
decreased platelet count (30,000/ml) and mild anemia continued only treatment with hemodialysis, and his
168 Kidney International Reports (2019) 4, 168–170
M Małecki et al.: Atypical Renal Involvement—Severe Leptospirosis NEPHROLOGY ROUNDS

Table 1. Kidney biopsy results Following the biopsy, a 3-day course of i.v. meth-
Bioptate 12 mm long (preserved in paraffin block), containing mostly renal cortex ylprednisolone infusions (250 mg/d) was prescribed,
Glomeruli (n ¼ 27) followed by a conversion to oral prednisone (20 mg per
 1 glomerulus sclerotic day). This resulted in a marked increase in the pa-
 26 glomeruli without pathological findings
tient’s urinary output, which rose up to 6000 ml per
Interstitial tissue
 Lymphoid cells, plasmocytes, and single neutrophil; infiltration of up to 10% of
day, accompanied by a continuous drop in serum
bioptate surface creatinine and bilirubin levels (Figure 2). Within 1
 Edema week, the dialysis treatment was suspended, and bili-
Tubules rubin and hematological parameters returned to normal
 Atrophy of 2 tubules
levels. Three more weeks of continued prednisone
 Some tubules presenting signs of ATN
 Some tubules containing erythrocyte rolls
therapy resulted in a serum creatinine level of 1.3 mg/
Vessels dl, with no proteinuria or other abnormal findings on
 Arteries: small-grade fibrosis of internal membrane urinalysis. The serum bilirubin and inflammatory
 Arterioles: unchanged marker concentrations all returned to normal. At the
 Inflammatory cells present in peritubular capillaries time of discharge, the patient was on 20 mg of pred-
Immunohistochemistry
nisone, with a planned weekly dose reduction of 5 mg.
Glomerular deposits
 IgA (–), IgG (–), IgM (þ in mesangium)
During a clinic visit 4 weeks later, the patient was
 C1 (þ in mesangium), C3 (–), C9 (–) asymptomatic, with normal physical examination
Conclusion: Histopathological image together with clinical data suggest changes findings.
secondary to leptospirosis.

ATN, acute tubular necrosis.

DISCUSSION
urine output started to increase significantly. Subse- Weil disease is the most severe presentation of lepto-
quently, Leptospira tests showed the microscopic spirosis, with a reported mortality rate often exceeding
agglutination test results as highly positive with an 22%.1 In most cases, kidney involvement in Weil
antibody titer of 1:3600, but the polymerase chain re- disease presents as acute renal failure involving oli-
action test was negative in both urine and blood. guria, hypokalemia, loss of urinary concentration
The patient’s physical condition continued to ability, albuminuria and hematuria.1,2 Most commonly,
improve, with most of the signs present on admission the renal involvement occurs as a result of interstitial
subsiding completely. In view of persistent renal damage (inflammation or necrosis), with the glomeruli
dysfunction, kidney biopsy was performed (Table 1). remaining unaffected. On admission, our patient suf-
Using Grocott’s methenamine silver staining protocol, fered from nephrotic-range proteinuria accompanied
cellular inclusions resembling intact Leptospira were by anasarca, with the kidney biopsy specimen
found in the tubular lumen of the kidney biopsy revealing typical interstitial inflammation without any
specimen (Figure 1). glomerular involvement on light microscopy. In the
course of the treatment, urinalysis results returned to
normal. Electron microscopic evaluation of the biopsy
specimen was not performed; however, podocytopathy
(e.g., minimal change disease) is a highly possible
explanation of nephrotic-range proteinuria in this case.
The treatment of Weil disease is not standardized.
Typically, improvement in kidney function usually can
be achieved within several days of antimicrobial and
dialysis treatment.3,4 However, in our case, the time
interval between the onset of initial symptoms (fever,
fatigue, myalgia) and the hospital admission exceeded 3
weeks, with persistence of symptoms despite antibi-
otics. Following corticosteroids, continued antibiotics,
plasmapheresis, and a hemodialysis regimen, the pa-
tient’s general condition began to improve. His mental
status improved significantly after 2 plasmapheresis
Figure 1. Kidney biopsy specimen. Grocott’s methenamine silver sessions. It is hypothesized that antibody-mediated
staining revealing inclusions (arrows) resembling Leptospira in the damage to the nervous system could lead to encepha-
lumen of renal tubules (original magnification 100). lopathy, and prompt neurological recovery following
Kidney International Reports (2019) 4, 168–170 169
NEPHROLOGY ROUNDS M Małecki et al.: Atypical Renal Involvement—Severe Leptospirosis

24 10

22
9
20
8
18
7
16

14 6

12 5

10 4
8
3
6
2
4

2 1

0 0
26-09-2016 30-09-2016 04-10-2016 08-10-2016 12-10-2016 16-10-2016 20-10-2016 24-10-2016 28-10-2016 01-11-2016 05-11-2016 09-11-2016

BILT-BILT KREA-KREA

Figure 2. Graph showing serum creatinine and total bilirubin levels during treatment. Treatment regimen: Biotaksime 2  1 g i.v. 28.09 to
21.10.2016; methylprednisolone (250 mg) i.v. 14 to 16.10.2016; Encortone 20 mg orally 17.10.2016; hemodialysis sessions (8 in total) 28.08, 30.09,
02.10, 04.10, 08.10, 12.10, 14.10, and 17.10.2016; plasmapheresis sessions (2 in total) 27.09 and 29.09.2016.

plasmapheresis5 with no recovery of the kidney CONCLUSION

function.
I.v. methylprednisolone infusions, on the other In severe persistent Weil disease, treatment with
hand, led to polyuria and a decrease in serum creati- combined therapy involving antibiotics, plasmaphe-
nine level. The improvement in kidney function was resis, hemodialysis, and glucocorticosteroid therapy
parallel to jaundice resolution. may be required to accelerate recovery (Table 2).4
Leptospira tests showed polymerase chain
DISCLOSURE
reaction
negative results and positive microscopic
agglutination test results confirming Leptospirosis All the authors declared no competing interests.
infection.6 Because Leptospira are present in the
bloodstream for about 7 to 14 days following infection, REFERENCES
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170 Kidney International Reports (2019) 4, 168–170