Successful management of germanium poisoning-induced multiple organ dysfunctions by combined blood purification therapy.

Background: Blood purification therapy has not been applied in the detoxification of germanium compounds. This report described a case of germanium poisoning with renal failure, liver dysfunction, and acute pancreatitis which was successfully treated by continuous venovenous hemodiafiltration (CVVHDF) combined with plasmapheresis.Case report: A 58-year-old male was admitted to a local hospital due to polydipsia, polyuria, and weight loss for 2 months. The patient was definitely diagnosed with germanium poisoning and was treated with blood purification therapy, CVVHDF combined with plasmapheresis. The blood and urinary germanium concentrations decreased rapidly during the first week after the combined blood purification therapy. The blood germanium concentration gradually reduced to within the normal range within the next three weeks and fluctuated at a normal level. However, the urinary germanium concentration exceeded the normal level after three months, indicating an accumulation of germanium in the organs and tissues. The patient's clinical symptoms ameliorated and the functions of kidney, liver and pancreatitis gradually recovered.Conclusion: Combined CVVHDF with plasmapheresis is an effective treatment for germanium poisoning and the associated multiple organ dysfunctions.

Cochlear damage due to germanium-induced mitochondrial dysfunction in guinea pigs.

This investigation addressed the effect of germanium dioxide (GeO(2))-induced mitochondrial dysfunction on hearing acuity. Guinea pigs were fed chow that contained 0%, 0.15%, or 0.5% GeO(2). The animals that were fed 0.5% GeO(2) for 2 months developed hearing impairment chiefly due to degeneration of stria vascularis and cochlear supporting cells, which exhibited electron-dense mitochondrial inclusions. Cytochrome c oxidase activity was decreased in the skeletal muscles and kidney, which also exhibited electron-dense mitochondrial inclusions. No apparent pathological changes were observed in the utricle, semicircular canal, or among the vestibular nerve fibers, or in the liver or heart. The untreated animals and those treated with 0.15% GeO(2) did not exhibit hearing impairment or pathological changes in any organs. These findings suggest that administration of 0.5% GeO(2) induces mitochondrial dysfunction in the stria vascularis and supporting cells in the cochlea, as in the skeletal muscles and kidney, thereby causing hearing impairment in the guinea pigs.

[Fatal multiple organ system dysfunction associated with germanium metal used in complementary therapy].

The element germanium is widely distributed in nature. It is used in industry as a semiconductor and there have been a few attempts to use it in medicine. In the past few years 20 patients have been described in the literature as suffering from germanium overdosage. Like laboratory animals affected by the element, they suffer from renal failure and injury to other organs. We describe a 52-year old man given germanium to prevent recurrence of a brain tumor. He developed multiple organ dysfunction syndrome and died of intractable hyperdynamic shock. We call for caution regarding morbidity resulting from treatments believed safe.

[Tubulointerstitial injuries in heavy metal intoxications].

The kidney is one of the organs susceptible to heavy metal intoxication. The total body burden and "saturation" level in renal tissue are important limiting factors to the onset of renal injuries. Acute or chronic exposure to many of heavy metals can induce renal tubulointerstitial injuries, including acute tubular necrosis, chronic tubulointerstitial nephritis, Fanconi syndrome, renal tubular acidosis, and renal tubular dysfunction without morphological changes. Chronic cadmium intoxication can cause irreversible Fanconi syndrome with chronic tubulointerstitial nephritis. Both urinary low-molecular weight protein excretion and urinary cadmium excretion (greater than 200-400 ppm) are the most reliable earlier markers of tubulointerstitial injury in chronic cadmium intoxication. The role of metallothionein is central to an understanding of cadmium-induced nephropathy. Acute lead intoxication in children can cause reversible Fanconi syndrome. Hypertension, hyperuricemia, and elevated serum creatinine, without Fanconi syndrome, are clinical manifestations of chronic lead exposure in adults. Nuclear inclusion body in proximal tubular cell is characteristic. Chronic exposure to inorganic germanium can cause chronic renal failure without urinary abnormalities, due to tubular degeneration and interstitial fibrosis, mainly in the thick ascending limb of Henle and distal tubulus.

Germanium intoxication with sensory ataxia.

Sensory ataxia in inorganic germanium intoxication is rare. A 63-year-old housewife had taken inorganic germanium preparations at a dosage of 36 mg a day for about 6 years (total dose about 80 g). She subsequently developed difficulty in writing and gait disturbance with peripheral neuropathy and renal involvement. Germanium, which is not usually detected in the non-germanium user, was accumulated in her hair and nails, permitting a diagnosis of inorganic germanium intoxication. The peripheral neuropathy and renal injury were not reversible after discontinuing the preparation. Pneumonia and sepsis then supervened and the patient died. Autopsy findings showed degeneration and loss of the dorsal root ganglion cells and degeneration of the dorsal column of the spinal cord. Two previously reported cases presented with ataxia. These patients took germanium for long periods and/or large quantities like our case. It was supposed that sensory ataxia was induced by chronic and dose dependent toxicity of inorganic germanium.

[A patient with liver cirrhosis manifesting various symptoms including cerebellar ataxia due to germanium intoxication].

A patient with hepatitis B virus-associated cirrhosis manifested various symptoms such as anemia, renal damage and neurological signs including cerebellar ataxia due to long-term administration of germanium-containing food. The patient was a 40-year-old male who had taken germanium containing mineral cheese for 26 months after he was diagnosed as having cirrhosis. Twenty four months after beginning to take the mineral cheese, he began manifesting paresthesia of the extremities, dysarthria and gait ataxia. Laboratory findings revealed anemia and renal damage. Biopsy of the peripheral nerve revealed loss of the large sheathed nerve, a characteristic feature of germanium intoxication. A high concentration of germanium (GeO2) was detected in patient's hair and urine. Cerebellar ataxia was characteristic in this patient, which was not reported in the previous papers.

Abuse of germanium associated with fatal lactic acidosis.

Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastatic cancer disease. We observed a patient with nonmetastatic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol/l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominantly in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis. Urine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high. Lactic acidosis may have been caused by the combined, germanium-induced renal and hepatic failure (underutilization), but it remains to be seen whether germanium can affect lactate production and/or metabolism directly.

[An autopsy case of chronic germanium intoxication presenting peripheral neuropathy, spinal ataxia, and chronic renal failure].

We report here an autopsy case of chronic germanium intoxication with major pathological changes in the central and peripheral sensory nervous systems. The patient was a 4-year-old girl who had suffered from gait disturbance and generalized muscle weakness for 22 months. She had been given orally germanium compounds (containing germanium dioxide, 225-450 mg/day) for the previous 28 months. In addition to the findings of chronic renal failure and anemia, she presented characteristic neurological symptoms exemplified by diffuse muscle atrophy, tongue fasciculation, sensory impairment and truncal ataxia as well as areflexia. Median and ulnar sensory nerve conduction velocities were also reduced. On the 17th hospital day, she died of renal failure. In addition to conspicuous degeneration of renal tubular cells, pathological studies revealed marked nerve fiber loss, degeneration and gliosis in the dorsal column of the spinal cord, which were most conspicuous in the thoracic and cervical cord. Axonal degenerative changes were also conspicuous in the sural and sciatic nerves. High concentration of germanium was detected in the brain, cerebellum, spinal cord, sciatic nerve, liver and kidney. It was suggested that the neural involvement in the current case was caused by chronic toxicity of germanium.

Germanium poisoning: clinical symptoms and renal damage caused by long-term intake of germanium.

We report five patients who have taken inorganic germanium preparations over a prolonged period. In all cases, the renal function deteriorated with no proteinuria or hematuria. Histological examination of the kidneys showed widespread tubular degeneration and interstitial fibrosis with minor glomerular abnormalities. Most patients had gastrointestinal symptoms such as vomiting, anorexia and weight loss; one patient had peripheral neuropathy and myopathy. A considerable amount of germanium was detected in the hair or nails of these patients. These cases clearly show that abuse of inorganic germanium compounds can induce renal damage with various extrarenal manifestations.

[A case of inorganic germanium poisoning with peripheral and cranial neuropathy, myopathy and autonomic dysfunction].

A 51-year-old man, taking beverage containing inorganic germanium (Ge), (90-100 mg/day, total 70 g) for two years, developed body weight loss, anemia, renal dysfunction, peripheral neuropathy, myopathy, autonomic dysfunctions and multiple cranial nerve palsies. Serum CK, GOT, LDH, BUN, and creatinine levels were elevated. The cerebrospinal fluid showed albumino-cytologic dissociation. Sural nerve biopsy showed axonal degeneration, and peroneal muscle biopsy showed neurogenic changes including type 2 fiber atrophy and ragged red fibers. High level of Ge content was detected from the hair and nail by inductively coupled plasma atomic emission spectrometry. Despite discontinuation of Ge taking, the peripheral neuropathy and autonomic dysfunction progressed. The symptoms remained unchanged even in the treatment with prednisolone. These findings suggest that inorganic Ge has a serious irreversible multiple system toxicity.

Renal failure caused by long-term use of a germanium preparation as an elixir.

Two Japanese women and one Japanese man, who had been taking the same germanium preparation, mainly containing inorganic germanium, as an elixir for health almost every day at 90 mg of germanium per day for 6 to 20 months, suffered from chronic renal failure. Histological examination of the kidney in one patient showed marked interstitial changes with vacuolar degeneration of the renal tubules. High germanium concentrations were found in hair and nails of the three patients, but no germanium was detected in hair or nails of normal persons. These results suggest that long-term use of a germanium preparation at high dosage can cause serious renal tubular damage and renal failure due to germanium toxicity.