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FK506 is a recently-developed immunosuppressive drug. The aim of the present work was to investigate the effects of FK506 in experimental autoimmune glomerulonephritis (active Heymann nephritis) in rats. Active Heymann nephritis was induced in female Lewis rats by two immunizations with the homologous brush border vesicles (BBVs) at day 0 and day 28 (groups I, II, V, and VI). Rats of groups III and IV received the third immunization at day 56. In rats of groups I and III, FK506 was injected (1 mg/kg/day IM) from day 0 for 14 days. In rats of groups II and IV, significant proteinuria was observed (group II, 112.8 mg/16 hours; group IV, 55.4 mg/16 hours) at the time the rats were killed (day 84). Coarse subepithelial immune deposits (IDs) were found in these rats. In contrast, urinary protein excretion remained within normal range (less than 3.0 mg/16 hours) in groups I and III rats, and tiny subepithelial IDs were only occasionally seen. Circulating anti-BBV antibody levels were markedly lower in group I and III rats than in those of groups II and IV during the period between day 14 and day 56. To investigate the effects of FK506 on the proteinuric rats, FK506 (1 mg/kg/day, IM) was administered every day for 2 weeks beginning on day 56 (group V).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied four cases of Crow-Fukase syndrome with renal dysfunction. Kidney specimens obtained by needle biopsy showed glomerular lesions resembling those seen in conditions characterized by microangiopathy. Common glomerular findings by light microscopy were mesangial expansion and narrowing of the capillary lumina. An enlarged subendothelial space and mesangial area with deposition of amorphous material as well as swelling and vacuolization of endothelial cells were observed by electron microscopy. In an active phase, severe mesangial edema and segmental mesangiolysis, and in a late stage, mesangial cell interposition and sclerosis were seen. Tests by immunofluorescence microscopy for the presence of immunoglobulins A, M, G, lambda and kappa light chains, C3, and C4 were negative. Decay accelerating factor was found in glomeruli and in the vascular pole. Other findings included lymph node angiosclerosis, peripheral nerve microangiopathy and hemangioma formation with endothelial cell proliferation. These observations suggest that chronic endothelial injury constitutes the basic pathology of Crow-Fukase syndrome. Hemodialysis was required to manage anasarca in three of the patients although serum creatinine levels were below 5.0 mg/dl. Urinalysis revealed mild abnormalities and did not reflect the severity of the glomerular lesion. Corticosteroids given to three of the patients were effective in controlling fever and the lymphadenopathy; in two cases the corticosteroids induced a recovery of renal function. Thus Crow-Fukase syndrome may be due to chronic endothelial injury; the clinical symptoms and renal involvement respond to corticosteroid therapy.

A 52-year-old female had a nephrotic syndrome without neurological or dermatological manifestations. Renal biopsy revealed that glomeruli were filled with tumor cells which bore leukocyte common antigen and pan B cell marker. These cells occupied the capillary lumen and invaded into the mesangial area. Morphological alteration of endothelial cells and glomerular basement membrane were also noticed. The interstitium was well preserved. After five cycles of a combination chemotherapy, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone), the second biopsy revealed that tumor cells disappeared from glomeruli showing mild sclerosis. Proteinuria became absent. This is the first report of an angiotropic large cell lymphoma manifesting a nephrotic syndrome and treated successfully by CHOP therapy.