germanium and Acute-Kidney-Injury

A 55-year-old woman was admitted to our hospital, complaining of general malaise, muscular weakness, anorexia and weight loss. She had a history of ingesting of a certain germanium (Ge) compound over the preceding 19 months, with a total dose of 47 g as Ge element. She was found to have renal failure (blood urea nitrogen, 44 mg/dl; serum creatinine, 2.6 mg/dl) without abnormal findings in urinalysis, and muscular and nervous damage. Initially, polymyositis was diagnosed and prednisolone administered. However, no improvement was seen, and neuromuscular symptoms and signs steadily worsened, ending in death. Microscopic study of the kidney showed that lipofuscin granules increased in the cells of the thick ascending limb of Henle's loop to the distal convoluted tubule accompanying mild tubular atrophy and that some of the tubules of these segments had vacuolar degeneration or desquamation. No apparent glomerular and vascular changes were observed. High Ge content was found in serum, urine and various tissues, e.g., spleen, liver, kidney, adrenal gland and myocardium, while in controls Ge could not be detected in sera, urine or tissues. We also review case reports about Ge toxicity, and discuss the pathogenesis of renal failure induced by Ge compounds.

Topics: Acute Kidney Injury; Female; Germanium; Humans; Kidney; Middle Aged; Muscles; Nervous System

Acute renal failure (ARF) or renal dysfunction (RD) associated with germanium-induced nephrotoxicity has been reported in 18 patients since 1982. In 2 of these cases the patients died of acute renal and cardiogenic failure. In 17 of 18 cases biopsies showed vacuolar degeneration in renal tubular epithelial cells in the absence of glomerular changes, without proteinuria or hematuria. Accumulated elemental Ge intake in 17 patients over a period of 4 to 36 months ranged between 16 and 328 g, or more than 100 to 2000 times the average estimated dietary intake of Ge for man (1.5 mg/d; range 0.40 to 3.40 mg/d). The biological half-life of Ge is 4.5 days for kidneys, the highest retention level of any organ. The mean concentration of Ge in healthy adult kidneys is 9.0 mg/kg wet weight. In 3 patients studied with Ge-induced RD or ARF, urinary Ge excretion was 9, 15, and 60 ng/mL, compared to greater than 5 ng/mL in healthy controls, and remained elevated even 12 months after discontinuing supplemental Ge intake. The mechanism for Ge-induced nephrotoxicity remains unknown, although the suspected cause is the inorganic Ge salts, such as germanium dioxide. Sufficient evidence for a role of organogermanium compounds, such as carboxyethyl germanium sesquioxide or citrate-lactate germanate, in Ge-induced nephrotoxicity remains lacking. The recent introduction of over-the-counter Ge "nutritional" supplements in some countries increases the risk of additional cases of Ge-induced nephrotoxicity, especially if appreciable levels of inorganic Ge salts are present and consumed for long periods (greater than 3 months) at levels above the average daily estimated dietary intake for Ge.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Animals; Diet; Dose-Response Relationship, Drug; Germanium; Half-Life; Humans; Kidney

We report two cases of renal failure following long-term ingestion of germanium dioxide (GeO2) and comment on eight other cases reported in Japan. Ge-induced nephropathy is characterized by insidious onset of renal failure without proteinuria or hematuria after oral intake of Ge-containing compounds for more than several months, and by degeneration of renal tubular cells with minor glomerular abnormality in histology. When patients ceased to ingest Ge compounds, renal function gradually recovered but never returned to the normal range. Serious extrarenal complication can contribute to an unfavorable prognosis.

Topics: Acute Kidney Injury; Adult; Cardiomegaly; Female; Germanium; Humans; Kidney; Male; Middle Aged; Myocardium; Time Factors; Tissue Distribution

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.

Topics: Acidosis; Acute Kidney Injury; Adult; Chemical and Drug Induced Liver Injury; Female; Germanium; Humans; Lactates; Lactic Acid; Pancreatitis

Reports mainly from Japan, recommend germanium (Ge)-containing compounds as "anti-cancer" and "immunostimulatory" remedies. We report on a 25-tear-old woman with stage II HIV disease who consumed a total of 47 g Ge as Ge-lactate-citrate 18%. She developed severe renal insufficiency (creatinine clearance 7 ml/min/1.73 m2, proteinuria 0.28 g/d) and hepatomegaly. Biopsies revealed tubulointerstitial nephropathy with vacuolar degeneration, mainly of distal tubular epithelia, and severe liver steatosis. Tissue Ge content in kidney and liver biopsy specimens was increased 68-and 140 fold respectively. In agreement with previous reports, renal dysfunction persisted 9 months later (creatinine clearance 11 ml/min/1.73 m2).

Topics: Acute Kidney Injury; Adult; Citrates; Fatty Liver; Female; Germanium; Hepatomegaly; HIV Infections; Humans; Lactates; Organometallic Compounds

Germanium (Ge; atomic number 32, atomic weight 72.6) belongs to IVb group of the Periodic Table and is found as a trace metal in soil, rocks, plants, and animals. It is widely used in industry because of its semiconductive nature. Some biological activities have been shown in Ge derivatives. Recently, patients with persistent renal damage after chronic ingestion of germanium dioxide (GeO2)-containing compounds have been reported in Japan. This study aimed to investigate subacute nephrotoxicity of GeO2 in Lewis male rats. The rats were treated orally with GeO2 for 13 weeks (GeO2 group) and were compared with those treated with GeO2 for only the first 4 weeks (GeO2-4-week group) and with untreated controls. Renal dysfunction was demonstrated by the increased serum creatinine, BUN, and serum phosphate and decreased creatinine clearance. Liver dysfunction was observed as demonstrated by the increased GOT and GPT, and hypoproteinemia by the decreased total protein and albumin in the GeO2 group. However, daily urinary protein excretion or urinalysis did not differ among the groups. Kidney weight and Ge content of tissues were significantly elevated in the GeO2 group. With the light microscope, vacuoles and the depositions of PAS-stained particles, which correspond to electron-microscopic dense granules in the swollen mitochondria, were predominantly observed in distal tubular epithelium in the GeO2 group. Even in the GeO2-4-week group of rats, serum creatinine was increased and the above-mentioned histological abnormalities were observed, but were less intense.

Topics: Acute Kidney Injury; Animals; Body Weight; Eating; Germanium; Kidney Tubular Necrosis, Acute; Kidney Tubules, Distal; Male; Metabolic Clearance Rate; Microscopy, Electron; Mitochondrial Swelling; Organ Size; Rats

Acute renal failure developed in a patient accompanied by systemic manifestations such as myopathy and skin rash. The patient, a middle aged house wife, had been taking 600 mg of germanium (Ge) preparation daily for 18 months as an elixir. The main component of the preparation was GeO2 and some organic compound was also present. Histological study of the kidney post mortem showed foamy cell transformation of glomerular epithelia, degeneration of tubular epithelia with red blood cell casts and urate crystals, and a mild proliferation of mesangial matrix. Analysis of the tissue content of Ge, prompted by her history, revealed an increased accumulation of the metal. As compared to a non-user died of liver cirrhosis, the concentration of the metal was higher particularly in the spleen (183X), thyroid gland (175X), psoas muscle (93X), jejunum (76X), and renal cortex (69X). So far, neither accumulation of Ge in humal tissue nor systemic toxicity of the Ge in human has been reported. The relevance of massive accumulation of Ge to the renal failure as well as to other systemic manifestations the patient presented remains to be clarified.

Topics: Acute Kidney Injury; Female; Germanium; Humans; Kidney; Tissue Distribution