Kaoru Onoyama

Worsening of anemia by angiotensin converting enzyme inhibitors and its prevention by antiestrogenic steroid in chronic hemodialysis patients.

The effects of angiotensin converting enzyme (ACE) inhibitors and their combined use with an antiestrogenic steroid on erythropoiesis were investigated in patients on chronic hemodialysis (CHD). Hematocrit was decreased by 10% or more in 6 of 12 patients who received either captopril or enalapril for 2–6 months. Erythropoietin (Epo) and angiotensin II (AH) were significantly reduced in these patients. When treatment with mepitiostane was combined with ACE inhibitor, anemia was significantly improved but without evidence of changes in circulating Epo concentrations or indices of renin-angiotensin activity. The reduction of AN and Epo formation by ACE inhibitors seems to play an important role in the worsening of anemia in patients on CHD; addition of an antiestrogenic steroid should be considered.

Alpha Tocopherol Improves Focal Glomerulosclerosis in Rats with Adriamycin-lnduced Progressive Renal Failure

The effect of d-alpha-tocopherol on the progression of renal dysfunction was investigated in rats injected with adriamycin (ADR), a model of progressive glomerulosclerosis associated with the nephrotic syndrome. Treatment with d-alpha-tocopherol was started 1 day before or 1 day after ADR injections (BE-TOC or AF-TOC rats). When compared to rats without d-alpha-tocopherol treatment (ADR-CON rats), the serum total cholesterol and triglyceride levels were significantly lower in the BE-TOC and AF-TOC groups. In week 16, the LDL cholesterol level and the atherogenic index were both significantly lower in BE-TOC and AF-TOC rats than in ADR-CON rats. The urinary protein, serum creatinine, blood urea nitrogen, malondialdehyde, and systolic blood pressure levels as well as the glomerulosclerosis score were high in ADR-CON rats, and reduced in BE-TOC or AF-TOC rats. There were no significant differences in body weight and serum albumin between the three groups in week 16. It is concluded that d-alpha-tocopherol can improve hyperlipidemia and ameliorate glomerulosclerosis in rats with ADR-induced progressive renal failure. Thus, d-alpha-tocopherol may have the potential for clinical application to treat focal glomerulosclerosis.

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.

Internal jugular vein thrombosis, Lemierre's syndrome; oropharyngeal infection with antibiotic and anticoagulation therapy--a case report.

The authors present a case of Lemierres syndrome that is an uncommon septic throm bophlebitis of the internal jugular vein. A 31-year-old man developed pharyngeal pain one month before hospital admission when he suffered from a severe headache and painful swelling of the left side of his neck. He was diagnosed with tonsillitis. Contrast- enhanced computed tomography and magnetic resonance imaging of the neck revealed the presence of an occlusive thrombosis of the left internal jugular vein and an inflamed mesopharynx. His symptoms and the jugular vein thrombus showed remarkable improve ment after administration of antibiotic and anticoagulation therapy. No pulmonary embolism or other metastatic infection were observed. It was suggested that accurate diagnosis during early treatment is essential to obtain a successful prognosis for Lemierres syndrome.

Cerebral hemorrhage in patients on maintenance hemodialysis. CT analysis of 25 cases

Site of hematoma and clinical outcome in cerebral hemorrhage were analyzed in 25 maintenance hemodialysis (HD) patients and compared with those in 27 non-HD patients. Ganglionic-thalamic hemorrhage was found in 56% of HD and 74% of non-HD patients, lobar hemorrhage in 36% and 11%, respectively. Size of hematoma, expressed as a ratio (%) of hematoma area to entire brain on CT slice, was 6.5 +/- 4.2% (mean +/- SD) in HD, being significantly larger than that of 4.7 +/- 3.5% in non-HD patients (p less than 0.05). Mortality rate was 60% in HD patients, nearly twice as much as the 33% in non-HD patients. The hematomas were significantly larger in the death cases (8.4 +/- 3.7%) than the survivors on HD (3.6 +/- 3.1%, p less than 0.005). Likewise, the fatal cases in the non-HD group had bigger hematomas (6.9 +/- 4.3%) than the non-fatal ones (3.6 +/- 2.4%, p less than 0.05). Intraventricular hemorrhage (IVH) was found in 40% of HD and 44% of non-HD patients. Hematomas were significantly larger in HD patients with IVH (9.3 +/- 3.3%) than in those without IVH (4.6 +/- 3.7, p less than 0.005). Ninety percent of the HD patients with IVH but only 42% of non-HD patients died of hemorrhage. Hypertension was equally seen in HD (76%) and non-HD patients (74%). It is concluded that in HD patients cerebral hemorrhage is more severe in terms of hematoma size, association of IVH and clinical outcome. Chronic systemic heparinization might be responsible to the severity in HD patients.

High Incidence of Glomerular Sclerosis in Rats Subjected to Uninephrectomy at Young Age

To examine the effect of age on a compensatory renal growth, adaptive renal hemodynamics and renal histology in solitary kidney, unilateral nephrectomy was performed in young rats at 4 weeks of age (group 4-UN) or in adult rats at 10 weeks of age (group 10-UN). Urinary protein was measured every 4 weeks until the 48th week. Serial changes in kidney weight, glomerular filtration rate (GFR), renal plasma flow (RPF) and renal histology were investigated at weeks 4, 8, 24 and 48 after the uninephrectomy. Increase in proteinuria was significantly greater in group 4-Un than in group 10-UN from weeks 32-48 after uninephrectomy. The remnant kidney showed a compensatory enlargement which was more marked in group 4-UN than in group 10-UN at weeks 24 and 48. GFR or RPF in group 4-UN was significantly greater than that in group 10-UN at weeks 4, 8, and 24. Focal and segmental glomerular sclerosis was evident at week 24 or later in the uninephrectomized rats, being more severe in group 4-UN than in group 10-UN at week 48. We conclude that uninephrectomy in young rats leads to augmented compensatory renal growth and glomerular hyperperfusion, resulting in extensive glomerular sclerosis compared to that in adult rats.

Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS) — induced mesangiolysis in spontaneously hypertensive rats

The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS)-induced glomerulo-nephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Group 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation.

Idiopathic Membranous Glomerulonephritis Associated with Diabetes mellitus

The present study described 3 patients with idiopathic membranous glomerulonephritis associated with diabetes mellitus. Clinical characteristics of the 3 patients contrasted with diabetic glomeruloscl

Effect of Swimming Exercise on the Progress of Renal Dysfunction in Rat with Focal Glomerulosclerosis

The effect of exercise on the progression of experimental renal disease was studied in adriamycin (ADR)-treated rats, a model of sclerosing glomerulonephritis with nephrotic syndrome. Two hours of daily swimming exercise was carried out for 20 weeks in ADR-treated male Lewis rats fed with either an ad libitum intake of regular chow (group 1) or a restricted amount of food (group 3), which was equal to the amount of food freely ingested by ADR-treated rats not undergoing swimming exercise (group 2). Group 3 resulted in a significantly lower serum creatinine, higher inulin clearance and lower glomerular sclerosis index compared to group 2. The progress of renal dysfunction did not differ significantly between group 1 and group 2. Hyperlipidemia, especially, hypertriglyceridemia was significantly lower in the exercise groups than in the sedentary group. Among all the rats, inulin clearance was inversely correlated with either cholesterol (r = 0.560, p less than 0.01) or triglyceride (r = 0.423, p less than 0.05) and the glomerular sclerosis index correlated positively with cholesterol (r = 0.599, p less than 0.005). Systolic blood pressure was 10 mm Hg lower in group 3 than in group 2 and the difference was significant. It is concluded that swimming exercise with a relative restriction of food intake can improve hyperlipidemia and prevent progressive renal dysfunction in ADR-induced nephritic rats.

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.