Sumio Tateno

Steroid Therapy during the Early Stage of Progressive IgA Nephropathy

This study was undertaken to clarify the effect of corticosteroids on the long-term clinical course of the early stage of progressive IgA nephropathy. The early stage of progressive IgA nephropathy was defined as having moderate proteinuria between 1 and 2 g/day, creatinine clearance values of 70 ml/min or more, and a histological severity score of 7 or more. The number of patients who fulfilled these three conditions during 12 years from 1972 and then were continuously followed up for 10 years or more in our renal unit was 46. Twenty of them received steroid treatment for an average period of 18 months, and the remaining 26 patients had no steroid treatment. The initial data of proteinuria, creatinine clearance values, frequency of hypertensive cases, and histological scores of 7 or more were not different between the two groups: 1.4 +/- 0.4 vs. 1.3 +/- 0.3 g/day, 85 +/- 14 vs. 88 +/- 13 ml/min, 25 vs. 38%, and 10.7 +/- 2.5 vs. 11.0 +/- 3.0, respectively. During the follow-up period of 10 years, the renal survival rate was significantly different between the two groups (100 vs. 84% 5 years after starting therapy and 80 vs. 34% 10 years later; p < 0.001). The final creatinine clearance values were significantly different between the two groups (54 +/- 35 vs. 20 +/- 29 ml/min; p < 0.005). On the other hand, the patient groups with mild histological changes or decreased renal function due to moderate proteinuria showed no significant differences in the final outcome. These results indicate that corticosteroids are beneficial in stabilizing the renal function for a long time during the early stage of progressive IgA nephropathy, although this study was not a randomized one.

IgA Nephropathy: Prognostic Significance of Proteinuria and Histological Alterations

A retrospective study of 166 patients with IgA nephropathy was undertaken to clarify possible correlations between clinical and histological features, and the severity and prognosis of the disease. At the time of biopsy, impaired renal function, with creatinine clearance (Ccr) below 90 ml/min was found in 61 cases. At the final examination, after a mean follow-up period of 34 months, 82 patients had impaired renal function, 12 of these patients went into terminal renal failure requiring hemodialysis treatment. The presence of proteinuria of more than 1.0 g/day was closely correlated with impairment of renal function both at the time of biopsy and at the final observation. An unfavorable outcome was also anticipated in the presence of hypertension. In contrast, microhematuria, macrohematuria or high serum IgA levels did not appear to be related to the outcome. Histologically, sclerotic lesions such as mesangial or global sclerosis, interstitial fibrosis and tubular atrophy, and some active changes such as mesangial hypercellularity and tuft adhesion were more frequent and severe in patients with impaired renal function. Impressive localization of IgA and C3 in the mesangium as well as in capillary loops was observed more often in these patients. These results clearly indicate that IgA nephropathy may follow a slowly progressive course in about half of the patients, and that marked proteinuria and severe histological changes appear to correlate closely with an unfavorable course.

Steroid Therapy in IgA Nephropathy: A Retrospective Study in Heavy Proteinuric Cases

29 patients with IgA nephropathy whose proteinuria persisted at a level of 2.0 g/day or more and who received prednisolone treatment for 1-3 years were retrospectively evaluated on their clinical courses. 13 of 14 patients with renal dysfunction of less than 70 ml/min in initial creatinine clearance (Ccr) values subsequently entered a progressive course during a follow-up period of 47 months, leading to end-stage renal failure in 8 cases. On the other hand, only 1 of the other 15 patients with preserved renal function of 70 ml/min or more ended up with end-stage renal failure during a follow-up period of 74 months, although 7 underwent a progressive course. Three patients in the latter group experienced a prominent reduction in proteinuria to less than 1.0 g/day and maintained renal function. Meanwhile, the steroid group of moderate proteinuric patients with a creatinine clearance greater than 70 ml/min had a benign course, while the nonsteroid group had an unfavorable one. These results suggest that steroid therapy in IgA nephropathy may be able to stabilize a progressive course, especially in the early stage of the disease, although, because they come from an uncontrolled study, a definite conclusion cannot be drawn.

Strong association of HLA-DR4 with benign IgA nephropathy.

103 adult patients with biopsy-proved IgA nephropathy were typed for HLA-A and HLA-B antigens and 80 of these cases were typed for HLA-DR antigens. A significant association with HLA-DR4 was clearly noted (pc less than 0.04). The high phenotype frequency (PF) of BW35 was observed in the patients, but not statistically significant (pc less than 0.2). Two groups, the stable group and progressive group, were selected from all patients according to their clinical courses. The PF of HLA-DR4 was significantly higher in the stable group than the progressive group (pc = 0.005). The PF of BW35 was also higher in the stable group, but this difference was not statistically significant (pc = 0.6). The frequency of the combination of HLA-BW35 and DR4 increased significantly as compared to that in the control group. Further, the patients who had both of these antigens showed favorable courses. These results suggest that the HLA-DR4 antigen, especially a combination of HLA-BW35 and DR4 antigens are related to the occurrence of benign IgA nephropathy.

Moderately Proteinuric IgA Nephropathy: Prognostic Prediction of Individual Clinical Courses and Steroid Therapy in Progressive Cases

Eighteen of 60 patients with persistent moderate proteinuria between 1.0 and 2.0 g/day and a long-term follow-up of more than 4 years received steroid therapy for a mean period of 18 months. Fifteen of these 18 patients maintained their initial creatinine clearance (CCr) of 70 ml/min or more. The remaining 42 received antithrombocyte drugs and/or nonsteroidal anti-inflammatory drugs, with 31 of them keeping their initial Ccr values of 70 ml/min or more. All 14 cases with initial Ccr values of less than 70 ml/min in both the steroid and nonsteroid groups followed progressive courses, with 12 ending up in hemodialysis. Of the nonsteroid, preserved group of 31 cases, 12 followed a stable course, 10 a progressive course, and the other 9 went into end-stage renal failure necessitating hemodialysis. There were no differences in initial clinical features among these three subgroups. But histological changes were milder in the stable subgroup than in the progressive and hemodialysis subgroups. Further, the total score of eight histological parameters was 6 or less in all but 1 of the cases of the stable subgroup, but 8 or higher in the other two subgroups. Therefore, in the progressive cases alone with initial Ccr values of 70 ml/min or more and high total scores of 7 or more, the long-term clinical courses were compared between steroid and nonsteroid groups (10 and 20 cases, respectively). In the steroid group proteinuria decreased significantly and renal function was preserved well as compared with that in the nonsteroid group.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural Glomerular Loop Abnormalities in IgA Nephritis

Glomerular capillary walls of 65 cases of IgA nephritis were observed electron microscopically. At least one-third of the cases showed local abnormalities including thinning and splitting. Usually suc

Effective Antibiotic Treatment of Methicillin-Resistant Staphylococcus aureus-Associated Glomerulonephritis

Background: A new type of glomerulonephritis following a methicillin-resistant Staphylococcus aureus (MRSA) infection has been reported. The purpose of this study is to elucidate the clinicopathological features and the responsiveness to treatment of the disease. Methods: We studied the treatment of 8 patients with glomerulonephritis related to MRSA infection. We observed the eight cases and analyzed clinical features, laboratory findings and histopathological data. Results: On admission, all patients had no renal abnormalities. One to four months after suffering from MRSA infection, severe proteinuria and hematuria developed. Renal biopsy specimens revealed moderate to severe mesangial proliferative glomerulonephritis with various degrees of crescent formation. Immunofluorescence studies showed IgA and C3. Antibiotic therapy was performed in six cases, resulting in successfully reducing the proteinuria in parallel with the decreased activity of MRSA infection in five cases. The other 2 cases received corticosteroid treatment after complete cessation of MRSA infection, but they had a relapse of MRSA infection and later died from sepsis. Conclusions: These results suggested that MRSA-associated glomerulonephritis might respond to antibiotic treatment in most cases. This also indicated that special care must be taken in the application of steroid therapy for the glomerulonephritis with crescents, even though the MRSA infection has gone into an inactive state.

Renal Retinal Dysplasia with Diffuse Glomerular Cysts

A 32-year-old male with renal retinal dysplasia is presented. He also showed hearing loss and growth retardation. Laboratory data showed mild proteinuria, renal dysfunction and type-1 renal tubular acidosis. Computed tomography showed multiple cysts at the corticomedullary junction of both kidneys. Ocular examinations disclosed retinitis pigmentosa. On light microscopy of renal biopsy specimens, diffuse cystic dilatation of Bowmans space as well as dilated tubules with interstitial fibrosis and cellular infiltration were noted. Electron microscopy revealed a peculiar chromatin condensation of epithelial cell nuclei in Bowmans capsules, glomeruli and tubules. The association of renal retinal dysplasia with diffuse glomerular cysts has not, to our knowledge, been previously reported.

Quantitative Analysis of Mesangial Areas in Serial Biopsied Patients with IgA Nephropathy

Clinical courses of 22 patients with IgA nephropathy, who received serial renal biopsies at a mean interval of 36 +/- 11 months, were observed until 2 years after the second biopsy. Of 22 patients, 12 showed no detectable changes in semiquantitatively analyzed mesangial sclerosis between the serial biopsies. By quantitative analysis, on the other hand, mesangial areas decreased between the serial biopsies in 12 patients (group I), and increased in 10 (group II). At the time of the first biopsy, there were no differences between the two groups in sex, age, creatinine clearance (Ccr), urine protein, hematuria, hypertension, treatment and histological parameters. Although Ccr in group I was stable during the 5-year follow-up, group II showed progressive deterioration of Ccr (p less than 0.005). Histologically, mesangial hypercellularity and crescent formation improved in group I (p less than 0.005 and (p less than 0.05, respectively), and tubular atrophy and interstitial fibrosis progressed in group II (p less than 0.05, each). These results demonstrate that changes in mesangial areas evaluated by quantitative analysis between serial renal biopsies are a valuable prognostic indicator in IgA nephropathy.

Prednisone Treatment in Non Nephrotic Patients with Idiopathic Membranous Nephropathy

18 adults with nonnephrotic proteinuria showed a milder form of idiopathic membranous nephropathy on renal biopsy. These patients were allocated to two groups, 2 years’ steroid treatment or nontreatme