1 Department of Renal Medicine and 2 Clinical Infection Unit, St George's Hospital Medical School, Cranmer Terrace, London, UK
Keywords: Burkholderia pseudomallei; melioidosis; nephrotic syndrome
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() |
---|
Resistance to a wide range of antibiotics, including most aminoglycosides and first- and second-generation cephalosporins, used as blind treatment for Gram-negative sepsis, is inherent. Optimal initial treatment is with either intravenous imipenem or ceftazidime, which is continued for 2 weeks [1]. Even with this treatment the mortality is 35% in clinical disease and is over 50% with other antibiotic combinations. Following this initial treatment, oral therapy with doxycycline, cotrimoxaxole and chloramphenicol should be given for 3 months to prevent relapse [2]. Abscesses are a common complication.
Infection may follow an acute or sub-acute course, and may affect one or more of any organ system, resembling a wide range of alternative infectious diseases, from tuberculosis to mumps. Therefore, diagnosis relies on being able to identify those patients at risk, an accurate travel history, a high degree of clinical suspicion and an experienced laboratory [3].
Melioidosis is already known to interact with the kidney in three ways. Renal impairment specifically pre-disposes to acquiring infection [4]. Re-activation of infection, occasionally many years after an initial exposure, tends to follow the onset of renal failure or diabetes, although the reason for this is unclear. Melioidosis is also complicated by acute renal failure in up to 30% of cases [5]. In this series, very few patients' kidneys were examined histologically. However, acute tubular necrosis, interstitial nephritis and microabscess formation were seen.
Melioidosis therefore provides a fascinating example of an interaction between an infectious disease and the kidney, about which many issues remain unresolved. It is also a disease of practical importance to renal physicians and their patients, who may come from or visit endemic areas. They are particularly at risk of acquiring a disease which, if treated incorrectly, is usually fatal. We present the first reported case of an additional renal complication, nephrotic syndrome, complicating melioidosis in a patient with a congenitally solitary kidney.
![]() |
Case |
---|
![]() ![]() ![]() ![]() ![]() |
---|
On examination she appeared unwell and was prexial, 38.5°C. Clinically and radiographically there was consolidation in the right lower lobe. There was no peripheral oedema. She had acute renal failure with oliguria and a serum creatinine concentration of 423 µmol/l. Serum albumin concentration was low at 29 g/l. Urine microscopy revealed 150 white blood cells per high power field. Urinary protein excretion was not measured during the initial admission.
A year previously she had been admitted to this hospital with pyelonephritis. A solitary left kidney of normal appearance had been noted on ultrasound scanning. On follow up, a serum creatinine of 141 µmol/l was noted. This baseline renal impairment may have increased her risk of developing clinical disease with melioidosis.
After this acute admission she improved and her renal function recovered, with creatinine falling to 114 µmol/l with supportive measures and intravenous ceftazidime (1 g twice daily). On ultrasound scanning the solitary kidney appeared normal. She was discharged after 9 days on outpatient parenteral treatment, but was re-admitted with generalized tonic-clonic seizures the following day. Urgent CT scan of her head, thorax and abdomen excluded abscess formation.
The ceftazidime was withheld, as accumulation of cephalosporin as a result of her renal impairment was suspected as a possible aetiological factor for her seizures. An alternative explanation was relative hypertension with a blood pressure of 150/90. She was grossly nephrotic at this time, with bilateral pleural effusions and peri-orbital and ankle oedema. Serum albumin was 24 g/l with 24-h urinary protein excretion of 9.6 g. Urine microscopy showed small numbers of normal red blood cells and tubular cell casts with no white blood cells or red cell casts. After 3 days, the ceftazidime was restarted at a lower dose (750 mg twice daily), to allow for her renal impairment.
The nephrotic syndrome rapidly resolved, with resolution of her oedema and pleural effusions, despite recommencing therapy with ceftazidime, which was increased back to conventional dosage (1 g twice daily) after 5 days. There was 4 g proteinuria after a further 7 days, and a creatinine of 117 µmol/l. There were no further seizures after loading with phenytoin.
Hypocomplementaemia was present, with a C3 component of 0.3 g/l (normal: 0.751.65 g/l) and a C4 component of 0.12 g/l (normal: 0.150.55 g/l). Immunoglobulin levels were normal, ANA, ANCA and rheumatoid factor were negative. Anti-hyaluronidase antibodies were not measured. A renal biopsy to establish the cause was not felt to be justified, in view of the unacceptable risks involved with a solitary kidney, and the rapid and spontaneous resolution of the nephrotic syndrome.
She completed a further 2 weeks therapy with ceftazidime, an extended course to compensate for it being withdrawn for 3 days and because of the clinical deterioration. Following this, oral therapy with doxycycline, chloramphenicol and co-trimoxazole was instituted for 3 months to prevent relapse.
At outpatient follow up after 3 months, she was well, with a creatinine of 128 µmol/l. The nephrotic syndrome had resolved with a serum albumin of 40 g/l and serum complement concentrations had returned to normal.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() |
---|
Successful initial management, and resolution of the initial acute renal failure, was complicated by the development of nephrotic syndrome that was acute and completely self-limiting. This was likely to be due to a mechanism distinct from that causing the initial oliguria.
A drug-induced mechanism was one possibility. Amoxycillin, ceftazidime and ibuprofen can all rarely cause nephrotic syndrome, with histological examination usually showing a combination of minimal change nephropathy and interstitial nephritis [68] or membranous nephropathy [9]. However, the nephrotic syndrome developed 10 days after cessation of therapy with amoxycillin and ibuprofen, and spontaneously and rapidly resolved despite continued therapy with ceftazidime. In view of this, drug-induced nephrotic syndrome seems unlikely. Moreover, antibiotic- and NSAID-induced nephrotic syndrome are not associated with hypo-complementaemia.
It is likely that the nephrotic syndrome seen in this case was directly related to infection with B. pseudomallei. Hypoalbuminaemia is usually seen in melioidosis [5] possibly due to sepsis, and may have been, in part, responsible for the hypoalbuminaemia observed here but would not explain the significant proteinuria. The hypo-complementaemia we observed suggested that immune-complex deposition in the kidney may have been involved as is classically seen in cases of bacterial endocarditis and in the presence of chronic visceral abscesses. CT scanning in our patient did exclude the formation of a large abscess. However, micro-abscesses are known to occur in melioidosis. A possible alternative explanation for the hypo-complementaemia which would explain the relatively greater reduction in C3 is the activation of complement, primarily via the alternative pathway, which has been described in vitro for B. pseudomallei [10]. C3 nephritic factor was not assayed and, in theory, could have been involved here. Typically, urine microscopy in melioidosis reveals a variable number of erythrocytes and leucocytes [5]. In this case, leucocytes were noted on urine microscopy at initial presentation and erythrocytes and tubular casts when she was found to be nephrotic with no specific indication of an underlying glomerular lesion.
A wide range of infectious diseases can cause nephrotic syndrome. Immune complex formation and deposition has been established as the aetiology in nearly all cases. In contrast to the renal impairment seen in melioidosis, specific renal lesions in several conditions have been well documented. These are varied and examples include post-infectious membranoproliferative glomerulonephritis (streptococcal infection); amyloidosis (leprosy); tubulo-interstitial nephritis (Plasmodium falciparum malaria); diffuse capillary basement membrane thickening (P. malariae); and proliferative glomerulonephritis (secondary syphilis). Hypocomplementaemia is frequently found [11].
The tubulo-interstitial nephritis of falciparum malaria and the proliferative glomerulonephritis of syphilis are relatively acute lesions and respond rapidly to treatment of underlying infection. In contrast, in those infections such as hepatitis B where the antigen is much more difficult to eliminate, the prognosis is much worse [11]. In the case we present, nephrotic syndrome was of acute onset some days into acute therapy, and the rapid resolution may have indicated clearance of the bacterial antigen load, and therefore successful anti-microbial therapy.
In summary, we present a case of melioidosis that amply demonstrates its ability to cause severe illness, often in patients with pre-existing renal problems, and its propensity to cause further severe derangement in renal function. Usually this is in the form of oliguric acute renal failure presumably caused, in the main, by acute tubular necrosis. However, the case we present indicates that, in common with certain other specific infectious diseases, nephrotic syndrome may be a significant (albeit rare) complication of infection with B. pseudomallei. We postulate that immune-complex mediated renal injury may occur in melioidosis.
![]() |
Acknowledgments |
---|
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() |
---|