Serial changes in urine protein, blood chemistry, and histology of the kidney were investigated in rats for 28 weeks after injections of adriamycin (ADR). Massive proteinuria, hypoalbuminemia, and hyperlipidemia were observed at week 4 and throughout the experiment. Both BUN and serum creatinine began to increase at week 16 and reached the uremic level at week 28. Light microscopic study of the kidney demonstrated a normal appearance at week 4, vacuole formation in glomerular tuft at weeks 8 and 12, focal and segmental glomerular sclerosis at weeks 16 and 20, and extensive glomerular sclerosis with tubulointerstitial degenerations at weeks 24 and 28. Immunohistologically, IgM with a small amount of IgG and C3 appeared in the sclerosing glomeruli from week 16. Aggregated human IgG, injected intravenously at week 24, had accumulated mainly in the glomeruli. Electron microscopy revealed degenerative changes of glomerular epithelial cells with small vacuoles in the cytoplasm at week 4. Size of vacuoles increased at the later stage. In conclusion, ADR produced chronic, progressive glomerular changes in rats, which led to terminal renal failure. The segmental glomerular sclerosis and IgM-dominant glomerular deposition in these animals are similar to pathological characteristics of focal and segmental glomerular sclerosis seen clinically.
During long-term captopril administration to hypertensive patients on maintenance hemodialysis, a decrease in hemoglobin, hematocrit, and red blood cell count was observed in 9 out of 12 cases. The maximum decrease in hemoglobin, on the average, was detected after 10.9 months of captopril treatment, when the average decrease was 20.5%. The average daily dose of the drug was 27.6 mg/day throughout the observation period. Mean corpuscular constants, reticulocyte count, serum iron, and total iron-binding capacity did not change significantly. Coombs’ test was negative. Neither serum total protein nor body weight changed significantly. Fever, skin rashes, leukopenia, and eosinophilia were not observed. There was no significant correlation between the degree of decrease in hematological indices and the dose of captopril. After discontinuation of captopril administration, anemia improved to pretreatment levels. In 2 of the 3 patients who did not show worsening of anemia, an anabolic steroid was administered in association with captopril. It is suggested that captopril should be used with caution in hemodialysis patients.
Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH >10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen >7.1 mmol/l and creatinine >106 μmol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30(83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67–15591 μg/l, N=19) and a high thyroidal radioactive iodine uptake (51.5±29.3%at24h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.
SUMMARYThe incidences of cerebral hemorrhage (CH), cerebral infarction (CI) and subarachnoid hemorrhage (SAH) were examined retrospectively in patients with chronic renal failure on maintenance hemodialysis, followed for 13 years in our 26 satellite dialysis centers. During 10,364 patient-years of experience (PYE), CH developed in 66, CI in 16, SAH in 3 and unclassified stroke in 5 cases. The incidence was 637 per 105 PYE for CH and 154 for CI, the former being approximately 5 times and the latter one third of the incidence of CH or CI in the general population in Japan.Forty-six percent of fatal CH cases died within 24 hours and 73% within 3 days after the onset, while 13% of CI deaths died within 24 hours and 26% within 3 days. These data suggest that factors such as the regular use of heparin as an anticoagulant in hemodialysis patients or other inherent factors in these patients may increase vulnerability to CH and decrease the probability of CI.
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