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Two Japanese female adolescents with systemic lupus erythematosus (SLE), known cases of urinary tract involvements: one with biopsy-proven class II lupus nephritis and the other one with lupus cystitis without overt glomerulonephritis (silent lupus), who after more than 4 years' observation presented with subsequent progression to membranous glomerulonephritis (MGN) following exacerbation of urticarial rash. Although it is well known that lupus nephritis shows histological transformation with time, the late progression to MGN from another World Health Organization histologic pattern has been reported to be less common in pediatric-onset SLE. Although pathogenesis of their MGN remains speculative, these clinical observation might suggest that a possible association between exacerbation of urticarial rash and subsequent progression to MGN in the selected patients with SLE.

Two Japanese sisters with persistent uveitis showed significant increased levels of urinary beta-2 microglobulin. A percutaneous renal biopsy performed in the younger sister revealed tubulointerstitial nephritis (TIN) with helper/inducer T cell infiltrates. Also, abnormal 67-gallium accumulation in the kidneys, suggesting TIN, was observed in the other one at the same time. Although patients with the syndrome of tubulointerstitial nephritis and uveitis (TINU) have been reported to date, its occurrence in siblings has rarely been seen. Both of them shared same human leukocyte antigen (HLA) DR6, suggesting the potential association between HLA-DR6 and TINU.

A boy aged 3.5 years with post-diarrheal hemolytic-uremic syndrome (HUS) was referred to our hospital because of convulsion and stupor. He had been admitted to a regional hospital with a 3-day history of bloody diarrhea, colic abdominal pain and fever. Two days later, he had complained of generalized seizures and oliguria. On admission, he developed anuria, and serum blood nitrogen and creatinine increased to 56 mg/100 ml and 2.8 mg/100 ml, respectively. Platelets decreased to 42,000/microl. Under the diagnosis of HUS, a continuous hemodiafiltration treatment had to be instituted. Computed tomography of his head at hospital day 5 revealed abnormal low density area of infarction with edema in both the basal ganglia involving with the posterior limb of internal capsule. Serum titer of IgM antibody to Escherichia coli O157 showed positive value. Although his anuria and stupor persisted over 10 days, he recovered without serious complications. These clinical observations may indicate that patients with similar lesions do not necessarily have serious morbidity.

A Japanese boy aged 9 years referred to our hospital because of steroid-resistant proteinuria. He had a 6-year history of unremitting proteinuria and was diagnosed as having minimal-change disease (MCD) by the repeated renal biopsies performed at the age of 3.5 years and 8.5 years, respectively. His proteinuria fluctuated ranging from 115 mg/100 ml to 645 mg/100 ml, and serum total protein ranged from 59 g/liter to 63 g/liter. The third renal biopsy at the presentation also revealed MCD. Thereafter he was treated with an anti-thrombocyte agent combined with an angiotensin converting enzyme inhibitor. Despite unremitting proteinuria of long duration, he did not have any complaints. At the age of 11.5 years, severe tubulointerstitial lesion was observed in the fourth renal biopsy. The fifth renal biopsy 6 months after the fourth finally revealed the lesion of focal segmental glomerulosclerosis (FSGS). Although the interpretation of his repeated renal biopsies were considered to be limited, these clinical observation suggested that his unremitting proteinuria of long duration might have been attributed to subsequent progression FSGS.

A 9-year-old boy was referred to our hospital because of significant hematuria and proteinuria associated with hypocomplementemia. Although he had had a 3-year history of asymptomatic persistent proteinuria detected by urine screening of school children, he did not visit a physician. Finally, he visited a regional hospital, and hypocomplementemia was noted there. A percutaneous renal biopsy performed hospital day 4 revealed diffuse endocapillary proliferative glomerulonephritis with severe tubulointerstitial changes. Although his hematuria and hypocomplementemia spontaneously subsided within a month, proteinuria remained. A renal biopsy performed 4 months after the first renal biopsy revealed the lesion suggesting advanced focal segmental glomerulosclerosis (FSGS). Despite corticosteroid treatment, his proteinuria persisted, and he developed end stage renal failure. These clinical observation indicated that he had acute glomerulonephritis (AGN) superimposed on non-nephrotic FSGS, and that the episode of AGN might cause exacerbation of the FSGS.

A-16-year-old male adolescent with a 4-year history of protean clinical manifestations such as fever, abdominal pain, back pain, erythema nodosum and uveitis developed complete occlusion of left renal artery. Although he had been suspicious of having an autoimmune disease and treated with prednisolone, a definite diagnosis was not made. Finally, an angiography disclosed stenosis of abdominal aorta just beneath the origin of the renal arteries as well as complete occlusion of left renal artery. It has been reported that pediatric-onset Takayasu's arteritis sometimes shows protean clinical manifestations as in ours. Takayasu's arteritis should be considered as one of the underlaying disease, when a child develops protean manifestations suggesting an autoimmune disease.

A boy aged 4 years with nephrotic syndrome (NS) was referred to our hospital because of the third relapse of NS. Hypogammaglobulinemia associated with massive proteinuria was observed at the presentation. Residual urinary tract infection required intravenous piperacillin and immunoglobulin therapy (IVIG). Soon after IVIG, he complained of high fever with chills, bilateral knee joint pain, dry cough and chest discomfort. Although he did not develop renal insufficiency, a transient increase in the urinary beta2-microglobulin and decrease in the serum complement hemolytic activity were observed. These clinical manifestations spontaneously ceased. A percutaneous renal biopsy for his NS performed 19 days after the episode of allergic reaction revealed tubulointerstitial nephritis (TIN) with marked eosinophil infiltrates. Glomeruli showed minor glomerular abnormalities. Renal complications associated with IVIG treatment have been reported to date, however, acute TIN has rarely been seen.

Long-term azathioprine therapy as an alternative treatment to cyclophosphamide was done in 2 children with steroid-dependent minimal-change nephrotic syndrome (MCNS). They had already been treated with prednisolone, intravenous methyl-prednisolone pulse therapy, cyclophosphamide and mizoribine. Although cyclophosphamide had been proved to be effective in maintaining their remission, the cumulative dose of the agent limited another course of cyclophosphamide therapy. Since ciclosporine therapy is much expensive, a trial of azathioprine (2 mg/kg per day) was started, and the therapy resulted in inducing sustained remission and reducing prednisolone. The patients were well tolerated the long-term azathioprine therapy over a year. Although the efficacy of azathioprine in the management of childhood MCNS might be restricted, we therefore suggest that this agent should be reconsidered as an alternative treatment to cyclophosphamide.

A boy with hyperimmunoglobulin E syndrome (HIE syndrome), who was successfully treated with long-term sulfamethoxazole-trimethoprim (SMX-TMP) is reported. He had been suffering from recurrent pruritic dermatitis soon after birth and had a significant high level of serum immunoglobulin E. Although an initiation of SMX-TMP therapy resulted in resolution of his clinical manifestations, cessation of the treatment exacerbated the symptoms. Chemoprophylaxis of other oral antibiotics, which were suitable for Staphylococcus aureus isolated from lesions of the patient were unsuccessful. Another trial of low-dose SMX-TMP therapy resulted in gradual subsidence of the clinical manifestations. From these observations, efficacy of SMX-TMP therapy to prevent bacterial infection in the patient is clinically apparent. Although precise mechanism of the therapy remains speculative, long-term SMX-TMP therapy might be of benefit and low clinical toxicity in HIE syndrome.

To examine whether the age of onset of clinical symptoms in childhood IgA nephropathy may affect changes of histologic alterations after receiving prednisolone therapy, an evaluation of glomerular lesions seen in biopsy specimen was done. Eighteen children with IgA nephropathy met study criteria. They received alternate-day prednisolone therapy within a month after the first renal biopsy. Renal biopsies were done at presentation and repeated at a mean interval of 23 months. The patients were grouped as follows: Group A, 8 cases which showed clinical symptoms at the age of 9 or under; Group B, 10 cases which showed the symptoms at the age of 10 or over. At the initial presentation, histologic indices including a percentage of mesangial area occupying glomeruli (the M/G ratio) in the 2 groups did not show a significant difference. The activity score and the M/G ratio in the group A decreased significantly at the second biopsies (4.6+/-0.9 vs. 1.8+/-1.0 and 25.7+/-6.1% vs. 21.4+/-2.7%, respectively), while in the group B did not. These observations may indicate the age of onset of clinical symptoms in childhood IgA nephropathy affects changes of histologic alterations after receiving prednisolone therapy.

The pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) is poorly defined. We previously demonstrated that monocytes from SSNS patients with proteinuria were activated to display exaggerated phagocytosis of opsonized particles and paradoxically reduced chemotaxis. In this study, we evaluated the capacity of hydrogen peroxide (H2O2) release from monocytes in 19 patients with SSNS and 13 healthy controls, by exposure to phorbol myristate acetate (PMA), using scopoletin method. Of 19 patients of SSNS, 7 were proteinuric and 12 in remission. The H2O2 release was significantly higher in SSNS patients with proteinuria than those in remission or normal controls [177.49 +/- 94.75 (mean +/- S.D.) vs. 60.67 +/- 58.89 (p < 0.02) or 85.02 +/- 48.62 nmol/90 min/mg cell protein (p < 0.05)]. Follow-up measurements in two SSNS patients showed that H2O2 release was reduced when proteinuric condition was improved to be in remission. Our data suggest that monocytes in SSNS with proteinuria were activated and were prepared to receive some extracellular signaling leading to protein kinase-C activation for releasing H2O2.

We studied the effect of serum from patients with renal diseases characterized by mesangial proliferation on the proliferation of rat mesangial cells (MC) in culture. Indirect immunofluorescence technique with human anti-proliferating cell nuclear antigen (PCNA) antibody was utilized to detect proliferating MC in S-phase on microscope slides. MC from serum-starved culture medium containing 0.5% fetal calf serum (FCS) showed 6 +/- 2% of PCNA-positive MC, whereas those from complete medium containing 20% FCS showed 45 +/- 7%. This was confirmed by flow cytometry for MC from both conditions, in which 10.9% and 55.2% of S-phase MC were detected, respectively. Serum from 17 patients with IgA nephropathy as a prototype of mesangial proliferative glomerulonephritis produced more PCNA-positive MC than serum from 18 healthy controls (mean +/- S.D. = 21.5 +/- 9.9% vs. 4.4 +/- 5.9%, p < 0.001). In IgA nephropathy, this effect correlated tentatively with active histologic lesion in the glomeruli, but not with severity of urinary abnormalities. Serum from membrano-proliferative glomerulonephritis (MPGN) also produced significant PCNA-positive MC (mean +/- S.D. = 15.6 +/- 9.3%), compared to controls (p < 0.01), independent of the severity of urinary abnormalities. These findings suggest that serum effect on the proliferation of cultured rat MC may reflect an active histologic lesion in the glomeruli, and that anti-PCNA antibody to detect proliferating MC is, if not quantitative, relevant methodology to enumerate proliferating MC in culture.

The monocyte function of 112 specimens from 42 children with idiopathic nephrotic syndrome (INS) aged from 2 to 17 years was studied by the methods of nitroblue tetrazolium (NBT) reduction, phagocytosis of immunobeads (IB) and yeast cells, chemotaxis and acid alpha-naphthyl acetate esterase (ANAE) staining. The dissociation between phagocytosis and chemotaxis was observed in the fresh cases of steroid sensitive INS and in the cases of steroid non-sensitive INS. In the fresh cases of steroid sensitive INS, NBT reduction and phagocytosis were increased, but chemotaxis was decreased. In the cases of steroid non-sensitive INS, the phagocytosis of IB was decreased, but chemotaxis was increased. These findings suggest a different pathogenesis between steroid sensitive and steroid non-sensitive INS. The dissociation between phagocytosis and chemotaxis may be explained by the alteration of the surface receptors of monocyte and by lymphokines.

The monocyte function in 2-15 year old patients with idiopathic nephrotic syndrome (INS) in childhood was studied in reference to the phagocytosis of sensitized red blood cells and NBT reduction. The monocyte function was found to be increased in fresh cases of INS. In the case of refractory INS not responding to steroid treatment, the monocyte function was normal or tended to be low.