Nephrol Dial Transplant (2004) 19: 486-490
© ERA–EDTA 2004; all rights reserved
Case Report
Granulomatous interstitial nephritis of the allograft kidney associated with rhodococcal pulmonary infection
Kai Chung Tse1,
Tak Mao Chan1,
Samson Sai-Yin Wong2,
Kwok Wah Chan3,
Man Fai Lam1,
Kingsley Hau-Ngai Chan1,
Fu Keung Li1,
Bo Ying Choy1 and
Kar Neng Lai1
Nephrology Division, 1Department of Medicine, 2Department of Microbiology and 3Department of Pathology, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
Correspondence and offprint reequests to: Prof. Kar Neng Lai, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. Email: knlai{at}hku.hk
Keywords: granulomatous interstitial nephritis; lung abscess; renal transplantation; Rhodococcus equi
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Introduction
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Rhodococcus is an aerobic mycobacterium-like coccobacillus that
is an usual pathogen in animals, but may also cause opportunistic
infection in immunocompromised hosts. Among renal transplant
patients, pulmonary infection in the form of cavitating lung
abscesses and empyema is most frequently seen, but osteomyelitis,
pericarditis, lymphadenitis and recurrent skin infections have
also been reported [
1–
3]. We recently have encountered
a renal allograft recipient presenting with an unusual renal
complication of rhodococcal pulmonary infection.
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Case
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A 52-year-old woman had end-stage renal failure with an unknown
aetiology. Although the exact cause could not be identified
at presentation, there were no elements suggesting interstitial
nephritis as the primary cause of renal failure. Continuous
ambulatory peritoneal dialysis was started in 1987, but it was
complicated by repeated bacterial peritonitis resulting in ultrafiltration
failure which eventually required conversion to long-term haemodialysis
in July 1998. Past health was unremarkable apart from an episode
of ischaemic stroke in 1997 with good recovery. She underwent
cadaveric renal transplant on 14 April 2002. The donor was a
66-year-old woman who died of cerebral infarct. Cyclosporin
A, prednisolone, azathioprine and basiliximab were given as
primary immunosuppressive therapy. There was immediate graft
function and the best serum creatinine was 165 µmol/l
on day 14. The early post-transplant course, however, was complicated
by recurrent ischaemic strokes on day 14 and in the sixth month,
from which the patient made a full recovery. Computed tomograms
(CT) of the brain performed at the respective time points confirmed
lacunar infarcts without evidence of brain abscesses. Thrombophilic
screens were negative and the patient was maintained on aspirin
for stroke prophylaxis. The early post-transplant course was
otherwise stable.
At the ninth month post-transplant, she presented with an abrupt increase in serum creatinine, with doubling of serum creatinine from baseline within 2 weeks on repeat checking. Her maintenance immunosuppressive drugs consisted of prednisolone (7.5 mg qd), cyclosporin A (100 mg/75 mg bd) and azathioprine (50 mg qd), with a pre-dose cyclosporin level of 237 µg/l. She was called back for further work-up for the acute renal impairment. There was general malaise in the previous few weeks, but without fever, chills, urinary or chest symptoms. Physical examination showed a clear chest, normal heart sounds and blood pressure, and the graft was non-tender. Doppler and sonogram of the graft kidney revealed no obstruction or vascular abnormalities. Initial urine sample on microscopy showed occasional normomorphic red blood cells, but white blood cells were not identified and no casts were seen. Renal biopsy was therefore performed, which showed no significant features of acute rejection. However, multiple non-caseating granuloma with aggregates of epithelioid cells associated with giant cells were noted in the interstitium, with overall features compatible with granulomatous interstitial nephritis with acute tubular injury (Figure 1). Acid-fast bacilli (AFB) or fungal organisms were not demonstrated using Ziehl–Neelsen (ZN), silver, Periodic Acid–Schiff (PAS), Wade–Fite and long ZN stain, and no viral inclusions were seen. An underlying infective aetiology for the acute allograft failure, potentially with atypical organisms, was suggested. The total white cell count was 9.3 x 109/l on admission (neutrophils 8.0, lymphocytes 0.4, monocytes 0.9, eosinophils 0.0), but C-reactive protein (CRP) was grossly elevated to 32.7 mg/dl. Urine microscopy and cultures, however, were negative for bacteria, AFB and fungi.
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Fig. 1. One of the several granulomas identified in the renal biopsy. It is composed of epithelioid cells (H&E, original magnification x360). Scale bar = 10 µm per gradation.
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Empirical treatment with intravenous cefuroxime was started,
but intermittent spikes of fever developed after admission.
At this juncture, blood culture performed on admission was notable
for Gram-positive rods, which on further processing grew
Rhodococcus equi. Chest radiograph also revealed a suspicious mass in the
right superior mediastinal region (
Figure 2), and further assessment
by contrast CT confirmed a lung abscess in the right upper lobe
(
Figure 3). In view of the absence of other alternative causes,
it was presumed that there was secondary infection of the allograft
kidney by
Rhodococcus resulting from haematogenous spread from
the primary pulmonary focus. The antibiotic regime was therefore
changed to a combination of intravenous meropenem (500 mg q
24 h), vancomycin (1 g q 1 week) and oral rifampin (300 mg bd)
based on the
in vitro sensitivity results of rhodococcus species.
A 7 Fr pigtail catheter was also put in for drainage of the
lung abscess, and endobronchial obstruction was ruled out by
fibre-optic bronchoscopy. The same
Rhodococcus species was also
cultured from pus and bronchoalveolar lavage. Cyclosporin and
azathioprine were both stopped in view of the underlying severe
sepsis, while oral prednisolone was increased to 10 mg qd. Despite
early institution of treatment, however, renal function continued
to deteriorate, with serum creatinine creeping up to 527 µmol/l
after 1 week, and temporary haemodialysis support was started.
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Fig. 2. An abnormal superior mediastinal mass lesion from the chest radiograph performed on admission: (A) posteroanterior view; (B) lateral view.
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The initial pigtail catheter was blocked 2 days after insertion,
and repeated drainage with another 8 Fr pigtail catheter also
failed; repeated CT showed extension of the abscess with a right-sided
empyema. A 32 Fr Argyle chest drain was therefore put in for
adequate drainage (
Figure 4). This was eventually followed by
resolution of fever with an improved clinical state, coupled
with a gradual decrease in CRP. Apart from cholestatic jaundice
related to rifampin requiring reduction of dosage, treatment
was well tolerated. Combination antibiotics were continued for
a total of 7 weeks, at which point the chest drain was removed
and antibiotics were stepped down to oral ciprofloxacin (250
mg qd), minocycline (100 mg qd) and rifampin (300 mg qd). The
patient remained dialysis dependent until the eighth week, when
improved urine output and gradual decrease in serum creatinine
were noted. There was concomitant resolution of the lung abscess
seen on a serial chest radiograph (
Figure 5). She subsequently
went into a polyuric phase and temporary haemodialysis was then
stopped.
The exact source from which the patient contracted the infection
initially could not be established on detailed enquiry, although
she had always lived in rural areas and could have had contact
with animals previously. The other patient who received the
contralateral cadaveric kidney remained well, and there was
no evidence suggestive of graft-transmitted infections. A repeat
renal biopsy of the index patient at 3 months of antibiotic
therapy documented complete resolution of granulomatous inflammation
of the allograft. When last seen on 19 June 2003, the patient
was clinically well, with serum creatinine stabilized at 214
µmol/l with a CRP of 0.92 mg/dl by the fifth month of
treatment, and the duration of oral antibiotics was planned
to be 9 months in total.
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Discussion
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Infection with
R.equi is mainly a zoonosis occurring in immunocompromised
hosts. Being a facultative aerobic coccobacillus that is present
in soil, it is a usual pathogen in animals such as horses, cows
and foals. It was first identified in 1923 as
Corynebacterium equi, and the first case of human disease was described in 1967
[
4]. Among patients on renal replacement therapy, infection
with
Rhodococcus species has been described in both renal transplant
recipients and patients on dialysis [
1–
3,
5–
8]. The
exact portal of entry for rhodococcal infection in our index
patient is not known. However, her usual residence was in rural
areas and infection could have been transmitted through forgotten
animal contacts or might have occured via inhalation [
6].
Our index patient illustrates an atypical presentation of rhodococcal pulmonary infection, in whom acute allograft failure was noted in the complete absence of chest symptoms. Acute rejection was excluded initially from biopsy, and unusual findings were noted instead. Despite failure of direct demonstration of the organism, the features of granulomatous inflammation in the allograft, positive haemoculture and subsequent recovery of renal function after treatment were strong supportive clues for secondary infection of the graft kidney by Rhodococcus, occurring most probably via haematogenous spread from the primary pulmonary focus. Moreover, the evidence for underlying rhodococcal infection of the allograft was supported further by the response to treatment, as documented by serial allograft biopsy showing complete resolution of the granulomatous inflammation. While fungal or mycobacterial infection, drugs and sarcoidosis are the known causes of granulomatous interstitial nephritis, rhodococcal-associated granulomatous interstitial nephritis has not been reported previously 9–11]. However, from a microbiological point of view, Rhodococcus species have certain mycobacterial-like properties in that they are obligate intracellular aerobes and associated with granulomatous inflammation. Clinical presentations of rhodococcal infection should be similar to that of mycobacterium [11], and rhodococcal infection should therefore be considered as one of the potential infectious aetiologies of granulomatous interstitial nephritis in addition to the above-mentioned causes. Furthermore, since primary rhodococcal infection of the kidney is exceedingly rare and unreported, a primary focus should be identified particularly when haemoculture for the organism is positive, as in our case, although this may sometimes be mistaken for diptheroids and hence contaminants from initial Gram smears. A high clinical suspicion is needed for early diagnosis, and imaging of the chest is essential, since it is the most common site of involvement in human infection [12].
Apart from early diagnosis, successful management of rhodococcal infection in our patient also relied on prolonged combination antibiotic treatment. In this context, bactericidal antibiotics with synergistic actions and high intracellular penetration are required to eradicate the infection [7]. Combinations of meropenem, vancomycin and rifampin are appropriate as the initial regime and can be stepped down to oral drugs including quinolone and tetracycline groups of antibiotics, and the course of antibiotics should be given for not less than 6 months. Adequate drainage of pus is also important to decrease the overall bacterial load; repeated drainage is frequently needed, and sometimes open surgical intervention is necessary [8]. After dialysis support for 8 weeks, and despite the discontinuation of cyclosporin and azathioprine, the allograft function in this patient recovered, although her serum creatinine did not return to her previous baseline levels. We believe that reduction of immunosuppression should form an integral part of management in similar settings, and favourable patient and graft outcomes are still possible, as illustrated in this case. It cannot be over-emphasized that serial monitoring for adequate treatment is required since some patients may suffer from relapse of rhodococcal infection on subsequent follow-up [6,8].
In conclusion, infection with R.equi should be considered as one of the potential causes of granulomatous interstitial nephritis in renal transplant patients, in whom a primary pulmonary focus should be sought since this most probably occurs as a secondary infection of the allograft via haematogenous spread. With prolonged antibiotic treatment and pleural drainage for the underlying pulmonary lesion, favourable graft and patient outcomes are possible.
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Acknowledgments
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The authors would like to thank Dr Chin Shui-Wak and his team
members (Department of Cardiothoracic Surgery, The Grantham
Hospital) for their help in the management of this patient.
Conflict of interest statement. None declared.
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References
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- Novak RM, Polisky EL, Janda WM, Libertin CR. Osteomyelitis caused by Rhodococcus equi in a renal transplant recipient. Infection 1988; 16:186–188[Medline]
- Lee-Chiong T, Sadigh M, Simms M, Buller G. Case reports: pericarditis and lymphadenitis due to Rhodococcus equi. Am J Med Sci 1995; 310:31–33[Web of Science][Medline]
- Ellis-Pegler RB, Parr DH, Orchard VA. Recurrent skin infection with Rhodococcus in an immunosuppressed patient. J Infect 1983; 6:39–41[Medline]
- Prescott JF. Rhodococcus equi: an animal and human pathogen. Clin Microbiol Rev 1991; 4:20–34[Abstract/Free Full Text]
- Tang S, Lo CY, Lo WK, Ho M, Cheng IK. Rhodococcus peritonitis in continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 1996; 11:201–202[Free Full Text]
- Barsotti M, Cupisti A, Morelli E, Meola M, Barsotti G. Sepsis from Rhodococcus equi successfully treated in a kidney transplant recipient. Nephrol Dial Transplant 1997; 12:2002–2004[Abstract/Free Full Text]
- Gonzalez-Roncero FM, Gentil MA, Rodriguez-Algarra G et al. Medical management of pneumonia caused by Rhodococcus equi in a renal transplant recipient. Am J Kidney Dis 2002; 39: E7[Medline]
- Munoz P, Burillo A, Palomo J, Rodriguez-Creixems M, Bouza E. Rhodococcus equi infection in transplant recipients: case report and review of the literature. Transplantation 1998; 65:449–453[CrossRef][Medline]
- Meehan SM, Josephson MA, Haas M. Granulomatous tubulointerstitial nephritis in renal allograft. Am J Kidney Dis 2000; 36: E27[Medline]
- Robson MG, Banerjee D, Hopster D, Carins HS. Seven cases of granulomatous interstitial nephritis in the absence of extrarenal sarcoid. Nephrol Dial Transplant 2003; 18:280–284[Abstract/Free Full Text]
- Vanhille P, Kleinknecht D, Morel-Maroger L et al. Drug-induced granulomatous interstitial nephritis. Proc Eur Dial Transplant Assoc 1983; 20:646–649[Medline]
- Scott MA, Graham BS, Verrall R, Dixon R, Schaffner W, Tham KT. Rhodococcus equi—an increasingly recognized opportunistic pathogen. Report of 12 cases and review of 65 cases in the literature. Am J Clin Pathol 1995; 103:649–655[Web of Science][Medline]
Received for publication: 30. 5.03
Accepted in revised form: 31. 8.03
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