金井 孝裕

Glucocorticoids (GCs) are commonly used to treat kidney problems in children and usually work well, but they can sometimes cause bone thinning, which may lead to fractures in the spine. Despite this, there is currently no established clinical approach for managing GC-induced osteoporosis (GIOP) in pediatric patients, highlighting the need for more data. Bone strength reflects both bone mineral density (BMD) and bone quality, with BMD assessed by X-ray and bone quality evaluated through serum or urine bone turnover markers (BTMs). In this case, a seven-year-old girl diagnosed with Henoch-Schönlein purpura nephritis was monitored over a two-year period during steroid treatment. Her BMD and serum BTMs, including alkaline phosphatase (ALP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and undercarboxylated osteocalcin (ucOC), were tracked throughout the course. One month after initiating steroid therapy, her serum ALP (S-ALP) level decreased by 27.1% from baseline, while serum TRACP-5b (S-TRACP-5b) and serum ucOC increased by 34.4% and 52.3%, respectively, although BMD remained unchanged. Two months into treatment, she developed thoracic vertebral fractures (VFs) and was diagnosed with GIOP, prompting the initiation of oral alendronate sodium hydrate. Following the introduction of antiresorptive therapy and a reduction in GC dosage, both S-ALP and S-TRACP-5b levels returned to baseline by six months, accompanied by an 8.8% increase in BMD compared to the one-month level. No further fractures were observed after the cessation of antiresorptive treatment, which was guided by serial monitoring of BMD and BTMs. This case underscores the association of VFs with a decline in bone formation markers and elevations in bone resorption and matrix-related markers and demonstrates how BTMs reflecting bone quality can aid in determining the optimal duration of antiresorptive treatment in pediatric patients with GIOP.

Kidney transplant (KT) requires long-term glucocorticoid (GC) treatment against acute and/or chronic rejection. Glucocorticoid-induced osteoporosis (GIOP) is one of the major concerns in kidney transplant recipients (KTRs). Therefore, it is essential to accumulate GIOP data from paediatric KTRs to aid in their healthy growth. A serial observational study of bone strength was carried out in an 8-year-old girl with bilateral hypoplastic kidney who underwent ABO-compatible living-donor KT and GC treatment over 2 years. Bone strength was evaluated by bone mineral density (BMD) and serum bone turnover markers (BTMs), including serum alkaline phosphatase (S-ALP), serum tartrate-resistant acid phosphatase 5b (S-TRACP-5b), and serum undercarboxylated osteocalcin (S-ucOC). All the levels of BTMs and BMD from 1 M to 4 M remained lower than the levels at 0 months (0 M: baseline). After gradual reduction of GC dose (4 M-24 M), S-ALP levels increased from baseline and S-TRACP-5b levels remained lower than the baseline level, but BMD recovered to baseline and increased. The S-ucOC levels did not increase from baseline. The patient's height growth velocity SDS was +3.99 for 23 months, and no fracture occurred during this observation period. A consistent, predominantly formative state of bone, which maintained higher S-ALP levels and lower S-TRACP-5b levels compared to baseline, could contribute to increased BMD. In addition, no increase in S-ucOC levels from baseline could be associated with no deterioration of bone strength. This case suggests that measurement of BMD and, S-ALP, TRACP-5b and ucOC could be useful for evaluating the trend on bone strength in a paediatric KTR.

In kidney transplant recipients (KTRs), viral infection can lead to antibody and/or T-cell mediated rejection, resulting in kidney transplant dysfunction. Therefore, it is critical to prevent infections. However, KTRs exhibit suboptimal responses to SARS-CoV-2 and/or influenza vaccines, partly due to immunosuppressant therapy. Inter- and intra-individual differences in the biological responses to vaccines may also affect patients' antibody production ability. This study included KTRs who received an messenger RNA SARS-CoV-2 vaccine (3 doses), and an inactivated quadrivalent influenza vaccine (1 or 2 doses). We measured the patients' total antibody titers against SARS-CoV-2 spike antigen, and hemagglutination inhibition (HI) titers against influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. Five patients were eligible for this study. Of these 5 KTRs, two produced anti-SARS-CoV-2 spike antibody titers to a seroprotective level, and also produced HI titers against A/H1N1 to a seroprotective level. Another 2 KTRs did not produce seroprotective anti-SARS-CoV-2 antibody titers, but produced seroprotective HI titers against A/H1N1. The remaining KTR produced a seroprotective anti-SARS-CoV-2 antibody titer, but did not produce a seroprotective HI titer against A/H1N1. The 2 KTRs who did not produce seroprotective anti-SARS-CoV-2 antibody titers following vaccination, later developed COVID-19, and this infection increased their titers over the seroprotective level. This study demonstrated that inter- and intra-individual differences in biological responses to vaccines should be considered in pediatric KTRs, in addition to immunosuppressant effects. Personalized regimens, such as augmented or booster doses of vaccines, could potentially improve the vaccination efficacy against SARS-CoV-2 and influenza.

Plasma exchange is an effective treatment for Kawasaki disease (KD), suggesting that plasma from patients with KD bears its causative agents. The aim of this study was to use mass spectrometry to identify candidate agents in patient sera. Serum samples were obtained from 17 KD patients. In six patients, samples were collected in each of three phases: the acute phase prior to acetylsalicylic acid (ASA) and intravenous immunoglobulin administration (Phase A1), the remission phase with ASA (Phase A2), and the remission phase without any medication (Phase A3). Sera from the remaining 11 patients were collected during Phases A1 and A2. The study also included two age- and gender-matched control groups, one with eight afebrile children and one with eight febrile children diagnosed with infectious disease. Patients in Phase A1 and febrile controls did not differ in body temperature, white blood cell counts, or C-reactive protein levels. Mass spectrometry analysis revealed that the intensity levels of m/z 9416, identified as apolipoprotein CIII (Apo CIII), were lower in Phase A1 samples compared with samples from patients in Phases A2 and A3, and from febrile controls (all comparisons, p < 0.01). Serum Apo CIII levels were also lower in Phase A1 samples compared with samples from Phase A2 patients and afebrile controls (both p < 0.01), but samples from patients in Phase A2 did not differ significantly from those of the afebrile controls (p = 0.55). This study demonstrated that serum Apo CIII level was decreased in the acute phase of KD.