金井 孝裕

Idiopathic steroid-sensitive nephrotic syndrome (ISSNS) is the most common glomerular disease in children, yet its molecular mechanisms and lipid-mediated pathophysiology remain poorly understood. In this study, we performed comprehensive non-targeted metabolomic analysis of serum samples obtained from children with ISSNS during both the nephrotic and remission phases to identify metabolic alterations associated with disease status. Using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), we profiled low-molecular-weight metabolites and identified significant alterations in several lipid classes, including sphingolipids, glycerophospholipids, and lysophospholipids. Several sphingomyelin and phosphatidylcholine species showed strong correlations with total cholesterol levels, reflecting lipid alterations consistent with the hyperlipidemic state that characterizes ISSNS. In contrast, oxidized phosphatidylcholines may more specifically reflect oxidative membrane injury and glomerular permeability changes associated with disease status. These findings highlight membrane lipid remodeling as a key feature of active disease and suggest potential lipid-based biomarkers for disease monitoring and therapeutic evaluation in pediatric ISSNS. This study provides a metabolomic framework for understanding lipid-driven mechanisms of ISSNS pathophysiology.

C1q nephropathy (C1qN) presenting with steroid-resistant nephrotic syndrome (SRNS) often demands immunosuppressants to maintain remission. Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is one of the immunosuppressants used. However, MMF increases susceptibility to infection, which can lead to severe complications in some cases. Therefore, the optimal blood concentration of MMF for C1qN remains undefined. A three-year-old boy presented with SRNS due to C1qN and was treated with prednisolone (PSL) and MMF at 720 mg/day, achieving remission. However, the patient developed BK virus viruria and experienced a relapse of nephrotic syndrome (NS) simultaneously. After the MMF dose was reduced to 600 mg/day, the patient entered sustained remission without recurrent infections. Ultimately, he was able to maintain remission with only 600 mg/day of MMF, without the need for steroids. During the second remission, the area under the MPA concentration-time curve from 0 to 12 hours (MPA-AUC0-12) was measured at 53.2 μg·h/mL, suggesting that this level may be sufficient to maintain remission while minimizing the risk of infection, and could serve as a reference point for determining the optimal blood concentration in C1qN treatment. To our knowledge, this is the first report to suggest a potentially optimal MPA-AUC0-12 for maintaining remission in C1qN without recurrent infection. Further studies of MPA-AUC0-12 for C1qN are warranted to confirm this result.

BACKGROUND: Renal fibrosis is strongly correlated with renal functional outcomes. Therefore, this is a significant finding in determining renal prognosis. There are various reports on the imaging evaluation of renal fibrosis, but these are not well established. Scanning acoustic microscopy (SAM) uses ultra-high-frequency ultrasound to visualize tissues in just over a minute. SAM can simultaneously measure acoustic data such as speed of sound (SOS). SOS indicates the elasticity (stiffness) of a material. In this study, we aimed to compare and evaluate SAM acoustic intensity images and SOS data with light microscopy images of renal lesions, especially renal fibrosis. METHODS: Renal specimens containing fibrosis were selected. The acoustic intensity images were compared to PAS-stained images. SOS data of the tubulointerstitium were compared with Masson's trichrome (MT)-stained images. The blue intensity of MT staining, which indicates fibrosis, was numerically valued using image-processing software. Furthermore, the correlations between it and the SOS values were evaluated. RESULTS: The acoustic intensity images suggested tubular atrophy and interstitial expansion in the same areas as in the PAS staining. SOS values of interstitial expansion with fibrosis were higher than normal area, interstitial expansion without fibrosis. A weak positive correlation was observed between the SOS values and the blue intensity of MT staining. CONCLUSIONS: SOS data can be used to evaluate renal fibrosis. The combination of SOS data and MT-stained images enables a more detailed evaluation of renal fibrosis. This study can contribute to the evaluation of renal fibrosis and has potential clinical applications in the future.

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.