Poisoned at Work: A Detective Story for Nephrologists

A young man with a mysterious case of kidney disease of unknown origin had physicians from Bielefeld, Germany, scratching their heads for months. Only when the patient reported occasionally seeing a white powder coating his lunch, which he brought from home, could they come closer to a diagnosis.

The following article is based on a presentation by Mariam Abu-Tair, MD, a nephrologist at the Evangelical Hospital Bethel in Bielefeld, at the 2022 congress of the German Society of Internal Medicine.

Acute Kidney Disease

A male patient born in 1991 was referred by his primary care provider to Abu-Tair for acute kidney disease of unknown origin, which had been diagnosed as an incidental finding. The man, who was 25 years old at the time, reported feeling generally unwell. "He was really very pale," said Abu-Tair. However, he did not have many symptoms at first, she added.

His vital signs on admission included slightly elevated blood pressure (156/95 mm Hg) and normal temperature, heart rate, respiratory rate, and oxygen saturation. The physical examination was completely normal. "There really seemed to be nothing wrong with him," said Abu-Tair.

Laboratory test results were as follows:

• mild leukocytosis (white blood cells 13/nL)

• hemoglobin level that was normal for a young man (Hb 14.4 g/dL)

• normal platelet count (365/nL)

• slightly elevated creatinine level (2.45 mg/dL)

• normal urea level (77 mg/dL)

• normal acid–base balance on blood gas analysis (BGA), meaning that he did not have metabolic acidosis, which Abu-Tair said can generally be expected with acute kidney disease

• normal serum potassium level (3.69 mmol/L)

Indication for a Biopsy

Owing to the slightly elevated creatinine value, Abu-Tair's team promptly decided to perform a renal biopsy. This procedure started a discussion in the interactive chat at the German Society for Internal Medicine auditorium as to whether one should "always jump straight into stabbing into the kidneys" on finding a single slightly increased creatinine value or whether physicians should wait to see how creatinine levels progress.

Abu-Tair strongly emphasized that the creatinine level does not change linearly in parallel with kidney function (eg, the higher the creatinine, the worse the kidney function). She added that a slightly increased creatinine level of 2.45 mg/dL in fact corresponds to severe impairment of kidney function, especially for such a young man. "Therefore, the patient had an absolute indication for stabbing at his kidneys," she added.

Abu-Tair stated that the general indications for a kidney biopsy are the following:

• kidney disease of unknown origin

• glomerular hematuria and proteinuria

• proteinuria >1 g despite optimized antiproteinuria therapy

• to identify renal manifestations of systemic diseases

In addition to the kidney biopsy, the medical history and imaging (abdominal MRI) were expanded, and a urinalysis was performed.

History of Stomach Ailments

"There really was nothing in the urinalysis," said Abu-Tair. The patient's urinalysis was completely unremarkable with no proteinuria. "In this case, interstitial nephritis must always be considered, for example, and thus also an expanded history of medications."

When asked again about his medical history, the patient reported repeatedly taking pantoprazole because of stomach complaints as well as taking bodybuilding supplements for several weeks.

Pheochromocytoma Screening

The kidney biopsy showed moderate nephrosclerosis with multifocal, chronic, and soon-to-be chronic tubulointerstitial damage.

An abdominal ultrasound revealed slight thickening of the parenchyma of both kidneys, with pronounced renal medullae — corresponding to acute kidney disease — as well as a space-occupying mass measuring 2.3 cm × 1.7 cm in the paraaortic region, dorsal to the pancreas.

Abu-Tair added that clarification of secondary hypertension was urgently necessary, owing to the elevated blood pressure in such a young man. She explained further that pheochromocytoma screening must be conducted for young hypertensive patients (age <30 years), which represents a corresponding diagnostic path. The space-occupying mass of unknown origin could also suggest a pheochromocytoma. The main symptoms of a pheochromocytoma, aside from high blood pressure (hypertensive crisis or continuous increase), are palpitations and tachycardia, profuse sweating and agitation, sleep disorders, and a general feeling of being unwell.

Paraganglioma Discovered

Corresponding diagnostics showed a significant increase in normetanephrine in the plasma and urine. According to Abu-Tair, urinalysis is no longer necessary for this; plasma testing is generally sufficient.

A subsequent meta-iodobenzylguanidine scan (a nuclear medicine examination that depicts noradrenergic tissue) showed a chest abnormality. In contrast, the region where the space-occupying mass was located was unremarkable.

Both the thoracic and the abdominal mass were surgically removed in stages. In both cases, histologic examination revealed a paraganglioma. The ostensibly definitive diagnosis was a hereditary pheochromocytoma/paraganglioma syndrome with SDHD mutation (paternal transmission).

The Kidney Question

"But how do we proceed now with regard to the kidneys?" Abu-Tair asked the audience, who voted as follows:

• Research into additional causes: 58%

• Stop pantoprazole, no bodybuilding supplements: 38%

• Is kidney function impaired due to high blood pressure?: 4%

• Prednisolone therapy to treat the nephritis: 0%

• Follow-up at the primary care provider: 0%

"Yes to follow-ups, but not with the primary care provider," the physician commented on the final option. "Patients with kidney disease must absolutely be cared for by nephrologists!" She said the primary care provider must be brought on board urgently, since many additional parameters must be monitored. However, the main point of call must always be a nephrologist in this case.

The further course of action initially involved regular checks of parameters and discontinuation of pantoprazole and bodybuilding supplements.

New Symptoms and Biopsy

Half a year later, the patient returned with new symptoms. He had previously gone to the hospital several times for removal of the paraganglioma in stages and was still on sick leave. His creatinine level had fallen to 1.5 mg/dL in the meantime, but he now complained of recurrent paravertebral pain and reduced strength. He had also taken pantoprazole again because of repeated stomach complaints.

The physical examination findings were unremarkable once again. "But this time, his creatinine was over 8. And this time he also had metabolic acidosis. Plus, this time he also had proteinuria," stressed Abu-Tair.

Laboratory values were as follows:

• Hb, 13.3 g/dL

• White blood cells, 12.8/nL

• Potassium, 4.5 mmol/L

• LDH, 201 U/L

• Creatinine, 8.5 mg/dL

• BGA: pH 7.35

• Bicarbonate, 13.7 mmol/L

• BE, −10.8 mmol/L

• CO₂, 25.5 mm Hg

• Urine status: protein to creatinine ratio 947 mg/g (<200)

"But what would you do in this situation? Delve deeper into the medical history? Perform another kidney biopsy? Conduct advanced imaging once more to find any paragangliomas? It was a tricky situation," said Abu-Tair.

The team performed another kidney biopsy, which revealed a diffuse, moderately acute, potentially reversible tubule injury in the context of preexisting multifocal chronic tubulointerstitial damage.

Mysterious White Powder

In the differential diagnosis, the finding primarily seemed to be caused by a drug or toxic substance, said Abu-Tair.

She explained that pantoprazole, as a proton pump inhibitor, could cause interstitial nephropathy, but it could not have been the culprit in the young man's case. He had been taking about one tablet per week, which was too little for this to be the cause. He wasn't taking any other medications.

The patient was sent home again. He signed off work on medical leave, owing to ongoing fatigue. It was not possible for him to continue his work, which was at a water treatment facility, in his present condition. Over time, his creatinine value again fell to 2.4 mg/dL, so his place of work increasingly came under suspicion as being related to his illness. On an expanded medical history, consideration was given to whether he had been working directly with chemicals. No nephrotoxic substances were found.

Abu-Tair pressed the patient about whether he could have come into contact with something unusual. The questions struck a chord, and the patient reported occasionally finding a powder coating his lunch, which he would bring with him from home.

Akin to Chemical Weapons

A police investigation involving video recordings resulted in the conviction of a 57-year-old work colleague, who had been sprinkling something on his co-workers' packed lunches. Analysis of the powder revealed that, as later described by a judge, the substance on the packed lunch was more toxic than the chemical weapons used in World War I.

The complaint in the subsequent legal proceedings stated, "Over the years, the accused also focused in particular on the effects of lead on blood formation and of cadmium on renal function, quicksilver and its inorganic compounds, radioactive polonium […]."

The perpetrator, who was the father of two, is said to have mixed increasingly poisonous substances in a primitive laboratory in the cellar of his house in Bielefeld.

The patient's blood samples showed significantly increased — and varying — concentrations of lead (93.7 µg/L and 130 µg/L) and cadmium (1.8 µg/L).

During court proceedings, it came to light that the 57-year-old had poisoned other colleagues, whose illnesses of unknown causes were retrospectively attributed to the experiments of their co-worker. These included one patient who had worked at the same facility as an undergraduate assistant and had been diagnosed with quicksilver poisoning of unknown origin at the University Hospital Münster several months prior.

"If we had known what we were looking for, we would definitely have seen basophilic stippling in the patient's blood," said Abu-Tair. If lead poisoning had been suspected, the patient could have been examined for the corresponding lines at the oral mucosa. "But we did not know!"

"Two Illnesses at Once"

The nephrologist summed it up by saying that the young patient in Bielefeld had a "medley" of illnesses: the tubulointerstitial kidney disease due to repeated exposure to lead, and also hereditary paraganglioma/pheochromocytoma syndrome.

"So, this patient had two illnesses at once," said Abu-Tair. She emphasized how advisable it is to not limit oneself to one disease but to broaden one's view to discover what else could be present.

There is no specific therapy for lead and cadmium poisonings, according to Abu-Tair. Only supportive and nephroprotective measures could be utilized. There was also no indication for administering steroids or anything else.

Abu-Tair did not mention the patient's current condition during her presentation. According to a report from the Süddeutsche Zeitung, at least one of the poisoning victims died. It is not known whether that patient was the 25-year-old patient described in this case.

This article was translated from Coliquio.