Nobuaki Oochi

Germanium dioxide-induced nephropathy: a new type of renal disease.

Chronic renal failure developed in 5 patients who were taking germanium dioxide (GeO2)-containing compounds. Renal functional deterioration was slow but progressive and dialysis treatment was necessitated temporarily in 2 patients. After the discontinuation of GeO2, the impaired renal function tended to improve but remained abnormal for an observation period of 10-40 months. The lack of proteinuria and hematuria was characterized as the clinical manifestations. Renal biopsy specimens revealed the tubular epithelial cell degeneration containing hematoxylin-positive fine granules on light microscopy, and electron-dense inclusions in the swollen mitochondria on electron microscopy. These findings localized mainly in distal segment of the tubules. In the rats given GeO2 orally for 10 weeks, similar histological lesions were evident, as manifested by marked weight loss, anemia, azotemia, and negative proteinuria. In the rats given carboxyethylgermanium sesquioxide, these changes were not observed and Ge concentration of kidney was significantly lower than in the rats given GeO2. The present study indicates that chronic GeO2 intake causes progressive renal dysfunction characterized by the degeneration of distal tubules.

Subacute nephrotoxicity of germanium dioxide in the experimental animal

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.

Dose dependency of germanium-dioxide-induced nephrotoxicity in rats.

The dose dependency of germanium dioxide(GeO2)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO2, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with higher dose of GeO2. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO2. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO2. The present study demonstrates that GeO2-induced nephrotoxicity develops dose dependently.

Nodular glomerulosclerosis in patients without any manifestation of diabetes mellitus

Aim/Methods:  Diabetic nodular glomerulosclerosis is considered to be the specific renal lesion of diabetes mellitus (DM). However, some cases, in which nodular glomerulosclerosis was found without any manifestation of DM, have also occasionally been reported. We clinicopathologically examined seven cases without a prior history of DM. They consisted of six men and one woman with a mean age of 57 years, and included three cases with family history of DM and six cases with hypertension.

A case of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure.

経過中rhabdomyolysisを発症し,急性腎不全をきたした悪性症候群の1例を報告した.症例は精神分裂病に対して向精神薬にて長期治療中の48才,男性.胃潰瘍に対して,抗潰瘍薬(H2受容体阻害薬)を投与したところ3週後に下肢を中心とした筋強直と黒褐色尿が出現し,乏尿が持続したため当科に転院した.入院時, BUN, creatinine, CPK,血中ミオグロブリン,尿中ミオグロブリンの異常高値を認め, rhabdomyolysisによる急性腎不全と診断した.臨床経過からcalpipramine系の向精神薬に抗潰瘍薬のH2受容体阻害薬を併用したことが本症発症の誘因と考えられた.向精神薬で治療中の患者に対するH2受容体作動性抗潰瘍薬の使用には十分注意すべきである.