金井 孝裕

RATIONALE: Vacuolated podocytes are the most common form of renal damage in Fabry disease, but other types of renal damage have been reported, such as membranous nephropathy (MN) or IgM nephropathy. Enzyme replacement therapy (ERT) is effective at preventing renal damage, but the nephropathies require appropriate treatment to prevent renal damage. PATIENT CONCERNS: A 22-year-old male with Fabry disease presented with proteinuria during ERT with agalsidase-β and carbamazepine. He had received the treatment for 10 years and maintained normal plasma globotryaosylceramide levels. DIAGNOSIS: Renal biopsy revealed MN without vacuolated podocytes. Immunofluorescent staining of the IgG subclass revealed granular patterns of IgG1, G2, G4, and C3 deposition in the glomerular basement membrane. INTERVENTIONS: The carbamazepine dose was reduced from 600 mg/day to 200 mg/day (serum concentration 10.0-11.0-4.0-5.0 μg/mL). OUTCOMES: After reducing the carbamazepine dose, proteinuria was negative, and the patient has had a normal urinalysis for 17 months. Plasma globotryaosylceramide levels have also remained normal. LESSONS: This report is a reminder of the co-existence of MN without vacuolated podocytes in Fabry disease during ERT with agalsidase-β and carbamazepine.Physicians should be aware of this form of renal damage in Fabry disease, even during treatment.

AIM: Glucocorticoids (GC) are essential medicines for idiopathic steroid-sensitive nephrotic syndrome (ISSNS) and IgA nephropathy (IgAN), with good clinical results. However, they cause bone fragility. The aim of this study was to elucidate GC effects on bone strength assessed as bone mineral density (BMD) and bone quality, using bone turnover markers (BTM), in children with ISSNS or IgAN. METHODS: Eleven children with ISSNS and 13 with IgAN were included. All the patients received GC treatment according to each protocol. The BMD and BTM-serum alkaline phosphatase (S-ALP), tartrate-resistant acid phosphatase 5b (S-TRACP-5b), and undercarboxylated osteocalcin (S-ucOC)-were measured from the initiation of steroid treatment (STx) to the end of STx in both groups. RESULTS: In ISSNS, S-ALP and S-ucOC levels were decreased significantly at 1 month. BMD and S-TRACP-5b levels showed no significant change through this observation period. In IgAN, BMD and S-ALP levels were decreased significantly at 1 and 3 months, respectively, and recovered to baseline at 10 months after the initiation of GC dosage reduction. S-TRACP-5b levels were decreased significantly at 3 months and remained lower than at baseline through the observation period. In both groups, S-ucOC levels did not directly reflect bone strength. CONCLUSION: This study clarified the following three points regarding GC effects on bone strength in children with ISSNS or IgAN: first, S-ALP is a more sensitive bone quality marker than S-TRACP-5b; second, BMD loss was observed only when both S-ALP and S-TRACP-5b levels decreased, and third, S-ucOC levels do not directly reflect bone strength.

In individuals treated with immunosuppressive therapies, the varicella-zoster virus (VZV) infection can become disseminated and lead to a life-threatening condition. There is currently no established treatment strategy for this life-threatening condition. Here, we describe a case where plasma exchange (PE) with a high dose of acyclovir (ACV) ameliorated the severe effects, including VZV-hemophagocytic lymphohistiocytosis (VZV-HLH) and disseminated intravascular coagulation (DIC), in a 9-year-old girl with steroid-dependent nephrotic syndrome. This 9-year-old girl experienced frequent relapse steroid-dependent nephrotic syndrome. She had been treated with steroids, tacrolimus, mizoribine, and rituximab. She had not previously received a varicella vaccine. She was admitted with only one vesicular rash. At admission, a serum test revealed 1.6 × 106 copies/mL of VZV DNA. The patient rapidly developed VZV-HLH and DIC. A combination of a high dose of ACV, immunoglobulin, and steroid pulse therapy could not improve these severe complications. Therefore, PE was applied. PE with a high dose of ACV successfully reduced serum VZV DNA from 7.5 × 106 to 2.8 × 104 copies/mL. This reduction in the VZV DNA copy number suggested that the combination of PE and a high dose of ACV was effective in treating a disseminated VZV infection. To the best of our knowledge, this is the first report showing that PE with a high dose of ACV ameliorated the severe complications of disseminated VZV by reducing the VZV DNA copy number.

BACKGROUND: We previously reported that the top-down approach (TDA) for infants with febrile urinary tract infections (fUTI) could prevent recurrent fUTI (r-fUTI) but produced a high number of false-positives on acute-phase 99m Tc dimercaptosuccinic acid (DMSA) renal scintigraphy. Therefore we compared the ultrasonography-oriented approach (USOA) with TDA from the viewpoint of prevention of r-fUTI. METHODS: The TDA was applied between July 2010 and February 2014 and the USOA was applied between March 2014 and April 2017 in infants with first fUTI. In the USOA group, voiding cystourethrography (VCUG) was performed in the case of abnormality on acute-phase renal bladder ultrasonography (RBUS) or on chronic- phase DMSA, which were performed in all cases. The frequency of r-fUTI was compared between the TDA group and USOA group retrospectively. RESULTS: Seventy-four infants (52 male) and 79 infants (60 male) received TDA or USOA, respectively. No significant differences were found between the TDA and USOA groups in male : female ratio, age in months at initial onset of fUTI, observation period, or number of cases of r-fUTI (TDA group, n = 4; USOA group, n = 5). Seventy-four DMSA scintigraphy and 25 VCUG were carried out in the USOA group, and 111 DMSA scintigraphy and 34 VCUG in the TDA group. CONCLUSIONS: Both USOA and TDA were valid for prevention of r-fUTI, but USOA was superior to TDA with regard to the reduced number of patients undergoing VCUG and DMSA.