This is the first Australian report of confirmed minimal change disease with nephrotic syndrome, which occurred in a 62-year-old man who inhaled mercury vapour in his home. This case highlights the immediate and delayed effects of such poisoning on multiple organs. Prompt and sometimes prolonged treatment may prevent long-term damage.

A 62-year-old man first presented to his general practitioner complaining of a cough, dyspnoea and lethargy for which he was prescribed oseltamivir phosphate, as his symptoms were presumed to indicate influenza. He re-presented 2 days later with worsening dyspnoea, at which point he revealed a history of mercury exposure. He had attempted to extract gold from an amalgam containing mercury by heating the amalgam in an aluminium pan inside his home. He was exposed for 3 hours — initially, to fumes, and subsequently, through direct skin contact as he attempted to clean up some spilt liquid amalgam. The windows were open and he used a tea towel covering his nose as protection from the fumes. A chest x-ray showed extensive alveolar shadowing consistent with pneumonitis. He was admitted to a regional hospital, and was given supplemental oxygen and antibiotics. His blood mercury level was 5933 nmol/L (level of concern, > 70 nmol/L). On the advice of a toxicologist, he was transferred to a tertiary hospital for chelation therapy.

On arrival at the tertiary hospital, his oxygen saturation on room air was 92% and signs on examination and repeat chest x-ray results were consistent with severe pneumonitis. His other vital signs were stable. Findings of other clinical examinations, including neurological examination, were unremarkable. Laboratory investigations showed he had an increased white cell count of 16.3 × 109/L (reference interval [RI], 4.0–11.0 × 109/L), a platelet count of 617 × 109/L (RI, 150–400 × 109/L), a serum albumin level of 21 g/L (RI, 34–48 g/L), and mild abnormalities in liver function test results (total protein, 60 g/L [RI, 65–85 g/L]; globulin, 39 g/L [RI, 21–41 g/L]; total bilirubin, 15 µmol/L [RI, 2–24 µmol/L); γ-glutamyl transpeptidase, 274 U/L [RI, < 60 U/L]; alkaline phosphatase, 228 U/L [RI, 30–110 U/L]; alanine aminotransaminase, 92 U/L [RI, < 55 U/L]; aspartate aminotransferase, 102 U/L [RI, < 45 U/L]; and lactate dehydrogenase, 294 U/L [RI, 110–230 U/L]). In a spot urine sample, the mercury concentration was 7556 nmol/L and the mercury : creatinine ratio was 2519 nmol/mmol (level of concern, > 5.8 nmol/mmol). Pulmonary function testing was suboptimal owing to the patient’s inability to suppress coughing on inspiration, but the results suggested a restrictive deficit. Analysis of a spot urine sample showed a protein concentration of 60 mg/L (RI, < 150 mg/L) and a protein : creatinine ratio of 18 mg/mmol (RI, < 12 mg/mmol). The patient’s serum creatinine level was 82 µmol/L (RI, 50–120 µmol/L) and his estimated glomerular filtration rate was > 60 mL/min/1.73 m2.

The patient was treated with dimercaptosuccinic acid (DMSA) chelation therapy, 800 mg three times a day for 7 days, after which the dose was reduced to 800 mg twice daily for a further 14 days. He was also treated with prednisolone 50 mg daily, gradually tapering the dose to zero over 3 weeks. Box 1 shows the 24-hour urinary mercury excretion in relation to exposure to mercury vapour, serum albumin concentrations and treatment with chelation therapy.

During this initial hospital stay, the patient’s dyspnoea decreased markedly, and subsequent chest x-rays showed resolution of interstitial shadowing. His liver function test results also normalised, and his serum albumin level rose to 33 g/L. The mild vertigo he had reported, with no other neurological symptoms or deficits, resolved spontaneously.

He was discharged on DMSA 800 mg twice daily and prednisolone 15 mg daily (tapering dose), and it was planned to repeat the assessment of his mercury levels after completion of the initial 3-week course of DMSA. This reassessment showed ongoing elevated levels (blood mercury, 418 nmol/L; urinary mercury, 1019 nmol/24 h), so the patient was rechallenged with DMSA at 800 mg three times a day for 34 days, commencing on Day 66 after exposure. Improved clearance resulted, as evidenced by a subsequent increase in urinary mercury excretion (from 1762 nmol/24 h on Day 62 to a maximum of 5790 nmol/24 h on Day 67). Consequently, treatment with DMSA at 800 mg twice daily was resumed, with the intention of giving a prolonged course, and his blood mercury levels and renal mercury clearance were assessed periodically. His serum albumin level had normalised by this point, and his prednisolone course had been completed.

Approaching 1 month into this prolonged course of DMSA, he re-presented with a history of fatigue, increasing peripheral oedema, nausea and vomiting. Physical examination revealed significant peripheral oedema with intravascular volume depletion. Biochemical analysis showed a serum albumin level of 6 mg/L (nadir, 3 g/L), urinary protein level of 13.4 g/24 h (RI, < 150 mg/24 h), serum creatinine level of 133 µmol/L (peak, 220 µmol/L) and serum cholesterol level of 13 mmol/L, indicating severe nephrotic syndrome. A renal ultrasound scan was unremarkable. In a renal biopsy specimen, light microscopy showed glomeruli of normal appearance and electron microscopy showed podocyte effacement consistent with minimal change disease (Box 2). He was treated with prednisolone, regular infusions of concentrated albumin, and diuretics, and was restricted to 1.2 L of fluids daily. Treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor and prophylactic warfarin therapy were also commenced. His nephrotic syndrome abated and renal function gradually normalised over the course of 4 months.

The patient experienced significant nausea, which necessitated cessation of chelation therapy after a total of 7 weeks. At this point, his blood mercury level was 112 nmo/L; within 1 month it fell below the level of concern. Three months after cessation of treatment with DMSA, his urinary mercury level was also normal. When last reviewed, his serum albumin level was 35 g/L and urinary protein excretion was 0.25 g/24 h. Resolution of his respiratory injury was almost complete, without evidence of developing neurotoxicity.

We present a case of prolonged exposure to mercury vapour with characteristic “fume fever” illness followed by pneumonitis and nephrotic syndrome, and an associated body mercury burden requiring prolonged chelation therapy.

Heating of mercury forms mercury vapour, which is actively absorbed in the lungs. About 80% of mercury vapour formed from amalgams is absorbed through inhalation.1 Once absorbed, metallic mercury is rapidly oxidised to mercurous and mercuric ions,2 and distributes in a variety of tissues including the brain, kidneys, liver, testes, thyroid gland and oral mucosa. A small amount of elemental mercury remains in the blood and can easily pass through the blood–brain barrier and the placental barrier.

The symptoms and signs of mercury inhalation vary according to the concentration of mercury to which the patient is exposed and the duration of exposure. Acute exposure to high levels primarily causes respiratory symptoms such as dyspnoea, chest pain, tightness, and dry cough, secondary to chemical pneumonitis. Absorption at the alveolar and bronchiolar levels causes capillary damage, pulmonary oedema, and desquamation and proliferation of airway lining cells, leading to the obliteration of air spaces.3 Airway obstruction and capillary leakage may cause alveolar dilatation, pneumothorax and, in severe cases, acute respiratory distress syndrome.4 Systemically, mercurous and mercuric ions can bind with sulfhydryl groups, leading to inactivation of sulfhydryl-containing enzyme systems and structural proteins and alteration of cell-membrane permeability.5

The evolution of clinical symptoms after mercury vapour inhalation may be described in three phases.6 The initial phase is typically an influenza-like illness occurring 1 to 3 days after exposure. The intermediate phase is dominated by severe pulmonary toxicity and may involve renal, hepatic, haematological, and dermatological dysfunction. Our patient had hypoalbuminaemia and a mild and transitory abnormality in liver enzyme levels, followed by a delayed onset of minimal change disease with severe nephrotic syndrome. It is possible that DMSA chelation may have contributed to the nephrotic syndrome by subjecting nephrons to a high load of chelated mercury. Both his initial hypoalbuminaemia and subsequent nephrotic syndrome appeared to respond to steroid therapy. The most commonly reported histological abnormality in the kidney associated with mercury exposure is membranous glomerulopathy;7 however, minimal change disease, with negative findings on light microscopy and confirmed by characteristic findings from immunofluorescence and electron microscopy, has been previously described.8 The late phase is characterised by gingivostomatitis, tremor and erethism, which we have not seen in our patient.

Aggressive supportive care including continuous cardiac monitoring and pulse oximetry, supplemental oxygen therapy and mechanical ventilation4 remains the cornerstone of therapy after acute inhalational mercury poisoning. Several chelating agents bind mercury, increasing its water solubility and augmenting its renal elimination. Historically, dimercaprol, D-penicillamine and N-acetyl-penicillamine have been used.5 Recently, DMSA has proven to be more effective and less toxic. It is unclear to what extent chelation therapy reduces mercury tissue burden or prevents long-term neurological injury.9 Awareness among clinicians of the immediate and the delayed consequences of mercury poisoning, with prompt treatment, may help to avoid long-term organ damage.

1 Twenty-four-hour urinary mercury excretion in relation to exposure to mercury vapour, serum albumin concentrations and treatment with chelation therapy

DMSA = dimercaptosuccinic acid; shading indicates periods of therapy.

2 Micrographs of the patient’s renal biopsy specimen, showing features consistent with minimal change disease

A: Light micrograph showing glomeruli of normal appearance (haematoxylin and eosin stain; original magnification, × 200). B: Electron micrograph showing flattening of podocyte foot processes (arrows).