We evaluated the effect of the novel immunosuppressive agent, FK506, which is known to inhibit T cell immunity, on the development of lupus nephritis in MRL/MpJ-lpr/lpr (MRL/l) mice. FK506 was administered subcutaneously (1 mg/kg body weight) from 12 to 20 weeks of age in 13 MRL/l mice with spontaneous lupus nephritis. Nine animals receiving no treatment were used as the control. FK506 significantly reduced the development of proteinuria, lowered the level of BUN, and suppressed the elevation of serum anti-dsDNA antibodies. Histopathological study showed that FK506 significantly inhibited the progression of glomerular hypercellularity and crescent formation. Glomerular deposition of C3 was significantly reduced in the FK506-treated mice compared to the nontreated controls. These findings suggest that FK506 may protect against progression of lupus nephritis in MRL/1 mice, an animal model of systemic lupus erythematosus.

The long-term inhibition of mesangial PDGFR-β prevented age-related mesangial expansion. On the other hand, the kidney glomeruli with decreased PDGFR-β showed increased vulnerability to the acute nephron loss, and showed mesangial insufficiency in the following adaptive process.

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Wistar rats rendered cirrhotic with carbon tetrachloride excreted significant proteinuria and hematuria. Serum levels of IgA and IgG were significantly elevated in cirrhotic animals. They showed mild mesangial proliferation and immunofiuorescent studies revealed deposits of IgA and IgG predominantly in mesangial areas and along capillary walls. These findings were very similar to those seen in patients with hepatic cirrhosis or IgA nephropathy. The deposits of IgA were also found in hepatic tissue from cirrhotic animals. The intensity and distribution of glomerular IgA deposits were not diminished after treatment with acid buffer. These results suggest that glomerular IgA are IgA polymers and decreased hepatic clearance of hepatic IgA polymers may be responsible for the glomerular deposition of IgA. ACTA PATHOL. JPN. 35: 561–567, 1985.

We investigated the natural killer (NK) cell activity of peripheral blood mononuclear cells (PBMC) and the suppressive factor of NK cell activity in patients on maintenance hemodialysis (HD). NK cell activity was significantly lower in patients on HD than in healthy controls (20.2 ± 16.5 vs. 31.0 ± 13.2%, p < 0.01). There was no difference in NK cell activity between patients treated with cuprophane and high-permeability membrane. NK cells from patients on HD showed a poor response to interleukin-2, and uremic sera significantly suppressed NK cell activity of normal PBMC. Although urea, creatinine, methylguanidine or guanidinosuccinic acid alone did not suppress the NK cell activity of normal PBMC, the guanidino compound did so significantly. It is suggested that defective NK cell activity in uremic patients explains in part their susceptibility to malignancy and infection. The immunosuppressive effect may be exhibited by synergism or mosaic of uremic toxins.

Platelet-derived growth factor (PDGF) is known as a potent mediator in the proliferation of mesangial cells in culture and in mesangial proliferative nephritis. The present study was undertaken to evaluate the effect of trapidil, an antagonist of PDGF, on mesangial cell proliferation in culture and in anti-Thy-1.1 nephritis in rats. Trapidil significantly inhibited ³H-thymidine incorporation in the mesangial cells stimulated by PDGF BB and suppressed mesangial cell proliferation in culture in a dose-dependent manner. In anti-Thy-1.1 nephritis, a significant reduction in the number of total glomerular cells and also proliferating (proliferating cell nuclear antigen positive) cells was demonstrated on day 7 in the rats treated with trapidil as compared with controls. Although renal function expressed as blood urea nitrogen and creatinine levels did not differ between rats with and without trapidil treatment, the present results suggest a salutary effect of trapidil on mesangial cell proliferation. PDGF, therefore, could play an important role in mediating mesangial cell proliferation.

Two adult cases of membranoproliferative glomerulonephritis (MPGN) associated with chronic hepatitis B were reported. Serum HBsAg, HBeAg and anti-HBc were positive. Glomerular changes were essentially the same in both patients and consistent with MPGN type III. Immunofluorescence microscopy revealed diffuse granular and lumpy deposits of IgG, IgA, IgM, C1q and C3 along glomerular capillary walls and in mesangial areas. Granular deposition of HBsAg was observed along capillary walls and in mesangial areas, and the staining patterns were similar to those of immunoglobulins and complements in both patients. Glomerular deposition of HBeAg, however, was negative in one case, and only slight and segmental in the other case. These findings suggest that HBsAg rather than HBeAg may play a role in the pathogenesis of MPGN associated with hepatitis B virus infection in adults.

The incidence and pathogenetic role of hepatitis B surface antigen (HBsAg) were evaluated in patients with IgA nephropathy. Among 130 consecutive patients with IgA nephropathy, HBs antigenemia was detected in 4 patients (3.1%). Serum antibody to hepatitis B core antigen was positive in these 4 patients indicating that they were persistent carriers of hepatitis B virus. Serum hepatitis B e antigen (HBeAg) was detected in 1 patient, and antibody to HBeAg was positive in the other 3 patients. The incidence of HBs antigenemia was not significantly higher than the 2.0% of the general population. An immunofluorescent study in the renal tissues from the 4 IgA-nephritic patients with HBs antigenemia did not demonstrate HBsAg or HBeAg in the glomeruli. These findings suggest that HBsAg appears to play no role in the pathogenesis of IgA nephropathy.