Hirofumi Tamai

Localization of 20-kD homologous restriction factor (HRF20) in diseased human glomeruli. An immunofluorescence study.

The 20‐kD homologous restriction factor (HRF20), which is identical to CD59, is a membrane‐associated protein which inhibits the reaction of C9 to form membrane attack complex (MAC) of homologous complements. In various human glomerular diseases deposition of complement components is frequently seen and MAC is reported to associate with immune deposits. Using a specific monoclonal antibody, 1F5, against HRF20, we attempted to study the localization of HRF20 in human glomerulonephritides and to compare the localization of HRF20 with those of immune deposits and MAC. The frozen sections of kidney specimens were fixed in acetone at room temperature before staining. In normal kidneys and kidney specimens from the patients with minimal change nephrotic syndrome, membranous nephropathy. and IgA nephropathy. HRF20 was strongly localized in the peritubular capillaries and along Bowmans capsules. A weaker but well‐defined staining was obtained in the mesangial area and faint staining was seen along the glomerular capillary walls. In contrast, glomerular capillary walls were rather strongly stained in the cases with diffuse lupus nephritis which had subendothelial dense deposits. These data suggest that HRF20 (CD59) is present in the human glomeruli and its expression is enhanced under certain conditions such as lupus nephritis.

Long-Term Effects of Spironolactone in Peritoneal Dialysis Patients

ESRD treated with dialysis is associated with increased left ventricular hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure; however, the effects in patients undergoing dialysis remain uncertain. We conducted a multicenter, open-label, prospective, randomized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without (control group) spironolactone for 2 years. As a primary endpoint, rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone compared with the control group. Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment (P=0.02). The benefits of spironolactone were clear in patients with reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period. No serious adverse effects, such as hyperkalemia, occurred. In this trial, spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis, without significant adverse effects. Further studies, including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints, should confirm these data in a larger cohort.

A case of angiotropic large cell lymphoma manifesting nephrotic syndrome and treated successfully with combination chemotherapy.

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.

Formation of subepithelial dense deposits in rats induced by a monoclonal antibody against the glomerular cell surface antigen

We developed a monoclonal antibody, H5H3, of IgG1 subclass by hybridization technique using spleen cells of mice immunized with plasma membrane fraction of isolated rat glomeruli. H5H3 recognized main bands at about 220 kD by immuno‐overlay technique and bound to the glomerulus as well as brush border of proximal tubules by indirect immunofluorescenec (IF) microscopy on normal rat kidney frozen sections. By immunoelectron microscopy (IEM) it bound to the surface of mainly glomerular epithelial cell and weakly to the endothelial cell. After injection to Wistar rats it remained granularly in the glomerulus for more than 2 weeks seen by IF. When rats were pre‐immunized with murine IgG 4 days before the injection of H5H3, mouse IgG, rat IgG and C3 were strongly visible granularly in the glomerulus in 14 days by IF. Numerous dense deposits were formed at subepithelial area seen by transmission electron microscopy. Perfusion experiment of H5H3 into rat left kidney showed granular distribution of mouse IgG in 48 h. indicating that the reaction occurred in situ. H5H3 bound diffusely in tine granular pattern on the surface of cultured glomerular epithelial cells (GEC) studied by IF and IEM. Antigenic redistribution occurred on GEC after incubation of H5H3 at 37°C. These results suggested the required conditions to form subepithetial immune dense deposits, namely that H5H3 after reaction with antigen could stay for long time in the glomerulus: that H5H3 became an antigen in autologous phase to induce large immune complexes: and H5H3 could induce antigenic modulation.

NON-ALCOHOLIC SCLEROSING PANCREATITIS WITH SJOGREN'S SYNDROME AND TUBULOINTERSTITIAL NEPHRITIS

We recently encountered a 56‐year‐old Japanese man with pancreatitis who had hyperglobulinemia, was autoantibody‐positive and responded to steroid therapy. The patient had been found to have asymptomatic proteinuria at an annual medical check‐up and had experienced a dry mouth for several years. He was diagnosed as having Sjögrens syndrome indicated by the dry mouth and positive findings from a lip biopsy and a Schirmers test. Tubulointerstitial nephritis, causing proteinuria, was verified by percutaneous renal biopsy. Antinuclear antibody was positive at the 1 : 160 titer. Serum γ‐globulin and IgG values were markedly increased, whereas complement components C3 and C4 were lowered. Abdominal computed tomography and ultrasonography demonstrated a diffusely enlarged pancreas without localized pancreatic mass or para‐aortic lymphadenopathy. Neither calcification nor cysts were detected in the pancreas. Endoscopic retrograde cholangiopancreatography revealed a diffuse narrowing of the main pancreatic duct with an irregular wall. Wedged biopsy specimens of the pancreas by an exploration of the abdomen showed prominent lymphocytic infiltrates including some plasmacytes, as well as decreased exocrine parenchyma and inter‐ and intralobular fibrosis. These findings suggested a diagnosis of autoimmune‐related pancreatitis. Steroid therapy was carried out with a marked improvement of his clinical symptoms and laboratory data.