Naoki Ikegaya

Morphologic Abnormalities in the Brain of Chronically Hemodialyzed Patients without Cerebrovascular Disease

In this study, the authors evaluated the cerebral atrophy in 56 chronic hemodialyzed patients, who did not have clinical episodes or radiologic findings of cerebrovascular diseases, and 42 controls. Using computed tomography (CT) images, brain atrophy index (BAI), the proportion of subarachnoidal plus ventricular space in the cranial cavity, and ventricular area index (VAI), percent area of ventricle in the brain, were calculated. CT of the brain demonstrated an age-dependent increase in BAI in both hemodialyzed patients and controls. BAI and VAI were greater in hemodialyzed patients than healthy controls and the difference was significant at ages under 60 years in BAI and at ages less than 50 years in VAI. The atrophy of the frontal parts of the brain in patients on hemodialysis for 10 years or more was significantly greater than in patients dialyzed for less than 10 years. There was a significant negative correlation between BAI or VAI and hematocrit. These findings indicate that renal failure or hemodialysis itself might cause cerebral atrophy, and that the cerebral atrophy is more prominent in patients on hemodialysis for a long duration and with low hematocrit.

Colonic dilatation due to dialysis-related amyloidosis.

A 66-year-old woman with chronic renal failure who had undergone hemodialysis for 15 years developed severe dilatation of the ascending and transverse colon. She had received right carpal tunnel release 5 years before this episode. The follow-up study of upper gastrointestinal series disclosed marked dilatation of the ascending and transverse colon with the retention of gastrografin persisted for 5 days, whereas colonic fiberscope showed no obstructive lesion. Pathologic study of biopsy specimens obtained from the colon demonstrated amyloid deposition. Avidin-biotin peroxidase complex method showed that these deposits strongly reacted with the antibody to human beta 2-microglobulin, but did not react with AA, lambda, and kappa antibodies. This case suggests that dialysis-related amyloidosis can cause intestinal pseudo-obstruction.

Transforming growth factor-β receptors in self-limited vs. chronic progressive nephritis in rats

Increases in transforming growth factor‐β (TGF‐β) expression and extracellular matrix accumulation are transient in acute self‐limited mesangial proliferative glomerulonephritis induced by a single injection of anti‐thymocyte serum (ATS), while these increases persist following repeated injections that produce chronic progressive sclerosing glomerulonephritis with tubulointerstitial lesions. However, little is known about the expression of TGF‐β receptors (TβRs) in cells involved in the proliferative and sclerosing renal lesions. A study of protein and mRNA expression for type I (TβRI), type II (TβRII), and type III (TβRIII) TβR in both forms of nephritis was therefore carried out by immunohistochemistry and in situ hybridization. Inhibition of cell proliferation and stimulation of matrix production by TGF‐β1 were assessed in isolated glomeruli using [3H]thymidine incorporation and [3H]proline metabolic labelling, respectively. In acute self‐limited nephritis, expression of TβRI, TβRII, and TβRIII increased in the glomerular and Bowmans capsular epithelial cells comprising the glomerular tuft adhesions to Bowmans capsules. However, TβRII expression was not prominent in proliferating mesangial cells. Glomeruli isolated from rats with acute self‐limited nephritis at day 7, when mesangial cell proliferation was maximal, were partially resistant to the mitoinhibitory effects of TGF‐β1. In contrast, expression of all three TβRs was elevated in glomerular and tubulointerstitial lesions in chronic progressive nephritis, and glomeruli isolated from rats with chronic progressive nephritis 7 days after the second ATS injection were sensitive to TGF‐β1. These data suggest that distinct cellular responses to TGF‐β1 resulting from differential expression of TβR underlie the difference between acute self‐limited mesangial proliferative and chronic progressive sclerosing ATS nephritis in the development of proliferative and sclerotic renal lesions. Copyright

Bucillamine (a new therapeutic agent for rheumatoid arthritis) induced nephrotic syndrome: a report of two cases and review of the literature

SummaryTwo cases of nephrotic syndrome during bucillamine treatment were encountered in 1989 in our hospital; both patients had suffered from rheumatoid arthritis for 2 years. They had received 200 mg bucillamine orally per day for 3–4 months before the onset of the nephrotic syndrome. Discontinuation of bucillamine led to complete remission of the nephrotic syndrome within 1 year. Bucillamine is a new therapeutic agent for rheumatoid arthritis developed in 1982 in Japan. Since 1985, 14 cases of nephrotic syndrome, including the two cases reported here have been reported. We review these cases and discuss the pathogenesis.

Acute aortic thrombosis associated with spinal cord infarction in nephrotic syndrome.

SummaryAcute aortic thrombosis associated with spinal cord infarction in a 47-year-old man with nephrotic syndrome is described. He was admitted to our hospital presenting with the nephrotic syndrome. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. The urinary protein excretion rate transiently decreased after the start of treatment with prednisolone, but it increased again and was followed by the development of the signs and symptoms of spinal cord infarction, which was diagnosed by magnetic resonance signal abnormalities, and then symptoms of ischemia in the lower limbs. Digital subtraction angiography revealed an obstruction at the bifurcation of the abdominal aorta. Emergency thrombectomy was performed, and the arterial blood flow was reestablished. Laboratory data on the fibrinocoagulation system showed a hypercoagulable state. In this case, fibrinocoagulation abnormalities due to the nephrotic syndrome led to the hypercoagulable state, and dehydration might have triggered the thrombotic complication.

A CASE WITH ACUTE RENAL FAILURE COMPLICATED BY WALDENSTRÖM'S MACROGLOBULINEMIA AND CRYOGLOBULINEMIA

We encountered a 53-year-old man associated with acute renal failure caused by Waldenströms macroglobulinemia and type I cryoglobulinemia. Treatment with prednisolone and cyclophosphamide induced a rapid recovery from acute renal failure. Renal histology revealed endocapillary proliferation and lobular formation with scattered subendothelial, amorphous and periodic acid-Schiff (PAS)-positive materials in the glomerular capillaries which were positive for IgM on immunofluorescence study. Although the exact mechanism for pathophysiology of acute renal failure remains unknown, treatment with prednisolone and cyclophosphamide could induce a rapid recovery from acute renal failure accompanied by Waldenströms macroglobulinemia and type I cryoglobulinemia.

Impairment of Ventilatory Response to Metabolic Acidosis in Insulin-Dependent Diabetic Patients with Advanced Nephropathy

Sudden cardiopulmonary arrest due to a defective respiratory reflex is observed in diabetic patients. Impaired ventilatory response in diabetic patients to acute hypoxia or hypercapnia induced by the inhalation of an artificial gas has been reported. Little is known regarding the respiratory compensatory ability for mild to moderate metabolic acidosis due to renal failure in insulin-dependent diabetic subjects. Arterial blood pH, HCO3-, PaCO2 and PaO2 were measured in 13 insulin-dependent diabetic subjects with advanced nephropathy and in 33 non-diabetic subjects with end-stage renal failure. The diabetic group consisted of six predialysis patients and seven on regular hemodialysis (HD) and the non-diabetic group, ten predialysis patients and 23 on HD. Differences between measured partial arterial pressure of carbon dioxide (PaCO2) and predicted PaCO2 determined from HCO3- were examined. PaCO2 was significantly higher in the diabetic than in non-diabetic group (40.0 +/- 7.4 versus 31.1 +/- 5.1 mmHg, p < 0.05 in predialysis, 42.0 +/- 6.4 versus 36.0 +/- 2.6 mmHg, p < 0.05 in HD), though plasma pH was essentially the same for either. Differences in measured PaCO2 and predicted PaCO2 were significantly larger in the diabetic group than in non-diabetic group. Ventilatory response to uremic acidosis may thus be considered impaired in subjects with advanced diabetic nephropathy.