[Three cases of severe hyponatremia under taking selective serotonin reuptake inhibitor (SSRI)].

The association between selective serotonin reuptake inhibitors(SSRIs) and hyponatremia has been documented throughout the world. In Japan, since SSRIs have recently come into use for patients with depression, there are only a few reports of hyponatremia associated with SSRIs. We present here three cases of the syndrome of inappropriate secretion of antidiuretic hormone(SIADH) associated with the administration of fluvoxamine for depression. They were admitted to our hospital because of deep coma, and revealed severe hyponatremia. Their serum sodium levels were 103-112 mEq/l, serum osmolalities were 227-241 mmol/kg, urine sodium levels were 38-107 mEq/l, and urine osmolalities were 352-781 mmol/kg. These patients were started on fluvoxamine 3 days-3 months previously. The diagnosis of SIADH in these patients was made based on hyponatremia, and low serum and high urine osmolalities. The fluvoxamine treatment was discontinued, and hypertonic saline was infused. Their serum sodium levels and osmolalities were subsequently normalized. None of the other known causes of hyponatremia, including diuretic therapy, tumors, and respiratory and central nervous system diseases, were present. High plasma AVP levels observed in the two cases suggest that SSRIs stimulate AVP secretion, thereby causing SIADH. Many reports have shown that people older than 70 years were at a particularly high risk of developing hyponatremia when SSRIs were used. In the future, since the use of SSRIs will be increasing, the water and electrolyte balance of elderly patients should be monitored carefully during SSRIs therapy.

[A case of non-Hodgkin's lymphoma presenting with acute renal failure diagnosed by renal biopsy].

We report a case of non-Hodgkin's lymphoma (NHL) presenting with acute renal failure. A-56-year-old male was admitted to our hospital on October, 1997 with fever and renal dysfunction. Physical examination showed no abnormality except for hepatomegaly. Body surface lymphadenopathy was not observed. Computed tomography (CT) of the abdomen showed markedly enlarged kidneys bilaterally and a mass of soft tissue density, which was considered as a swelling lymph node, around the aortic artery. The renal biopsy revealed parenchymal involvement of the NHL cells without normal tubulo-interstitial structure, but the glomeruli were almost intact. Our case rapidly fell into oliguria and acute renal failure, hence needed hemodialysis. After chemotherapy was performed, his renal function gradually improved and the kidney became smaller on subsequent CT. Unfortunately, the patient happened to suffer from methicillin-resistant staphylococcus aureus (MRSA) infection in a neutropenic state and died. Necropsy revealed recovery of the renal interstitium without residual NHL cells. Renal lymphoma without any other organ or nodal involvement is a rare type of NHL, which considered primary renal lymphoma (PRL). However, we believe this case to have been a result of lymphomatous infiltration of the kidneys in disseminated lymphoma.

[A case of MPO-ANCA-related vasculitis that recurred as gastrointestinal bleeding and presented difficulty in treatment].

A 54-year-old man, who had been diagnosed as having MPO-ANCA-related glomerulonephritis in 1993, developed severe anemia and was admitted to our hospital on October, 1997. Endoscopic examination of the upper gastrointestinal tract revealed melena due to duodenal ulcer (Dieulafoy type). The level of ANCA titer was elevated considerably (640 EU), but otherwise there was no evidence of systemic vasculitis activation such as fever, arthralgia, skin eruption, renal insufficiency, and rise in C reactive protein. A renal biopsy showed neither crescentic formation nor necrosis of glomerulus. Subsequently he developed hematochezia and renal dysfunction rapidly progressed thereafter. Angiographical examination of superior mesenteric artery revealed that the bleeding was responsible for the lesion of the small intestine, probably the ileum. In spite of TAE (transarterial embolization) he had recurrence of severe hematochezia three days later. Partial ileotomy was performed and progression of the anemia was stopped. Multiple ulcer was found in the resected ileum. The small arteries in the submucosa at the ulceration showed fibrinoid necrosis of the vessel walls. These findings suggested that ANCA-related vasculitis had relapsed. The patient received methylprednisolone pulse therapy, followed by oral administration of prednisolone after the operation. Both serum levels of creatinine and MPO-ANCA gradually decreased after the initiation of treatment. However, 24 days later, he suddenly manifested severe abdominal pain, and was diagnosed as having perforation of the stomach or duodenum. Due to supportive therapy and reduction of the steroid dose, peritonitis subsided, but symptoms caused by systemic vasculitis developed. Later raised the dose of steroid suppressed the activity of systemic vasculitis. In this case, elevation of the ANCA titer demonstrated recurrence of MPO-ANCA-related vasculitis as gastrointestinal bleeding.

Evaluation of glomerular lesion and abnormal urinary findings in OLETF rats resulting from a long-term diabetic state.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats have been established as an animal model in which non-insulin-dependent diabetes mellitus develops spontaneously. We examined the renal histopathology and the urinary findings serially in OLETF rats and compared these findings with findings in age-matched Long-Evans Tokushima Otsuka (LETO) rats as a control strain. OLETF rats showed higher blood glucose levels than did LETO rats from 18 weeks of age, and hemoglobin A1c levels became higher in OLETF rats than in LETO rats from 22 weeks of age. Accompanying the development of hyperglycemia was an increase in the amount of albuminuria in OLETF rats from 18 weeks of age. The initial histopathologic change found in OLETF rats was an increase in glomerular area, and mesangial expansion started to develop from 22 weeks of age. Mesangial lesions progressed to mesangial sclerosis, and exudative lesions were found in OLETF rats from 36 weeks of age. The anionic charge of glomerular basement membrane (GBM), measured by polyethyleneimine grain density, demonstrated that the lower grain density in OLETF rats when compared with that in LETO rats became more evident with an increase in the amount of albuminuria. Therefore, the defect in the charge-selective property found in OLETF rats might be one of the causes of albuminuria. The GBM became thickened in elderly OLETF rats as compared with that in age-matched LETO rats. Disturbances in the selectivity of urinary protein, as determined by the clearance ratio of immunoglobulin G to transferrin, were found to accompany the thickening of GBM in OLETF rats. We consider that both the loss of the charge-selective property and massive albuminuria might be the causes of GBM thickening, through a clogging mechanism, and that GBM thickening might in turn produce the loss of size selectivity. Given these findings, we consider the OLETF strain of rats to be an interesting animal model for studying the relationship between diabetes and renal involvement, because the glomerular abnormalities and massive albuminuria found in OLETF rats were results of a long-term diabetic state.