Faculty Profiles - MAEDA Kayaho

Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy Reviewed

CiNii Research

Tanaka, A; Furuhashi, K; Fujieda, K; Horinouchi, A; Maeda, K; Saito, S; Mimura, T; Saka, Y; Naruse, T; Ishimoto, T; Kato, N; Kosugi, T; Kinoshita, F; Kuwatsuka, Y; Nakai, Y; Maruyama, S

KIDNEY360 Vol. 5 ( 11 ) page： 1692 - 1705 2024.11

Language：English Publisher：Kidney360

Background: Immunoglobulin A nephropathy often requires kidney replacement therapy because of its refractoriness and because corticosteroids pose infection risks. However, mesenchymal stem cells offer clinical benefits because of their regenerative and immunomodulatory properties. This prospective clinical trial assessed the safety and tolerability of adipose-derived mesenchymal stem cell therapy and evaluated its therapeutic efficacy. Methods: This phase 1 study included adult patients with refractory immunoglobulin A nephropathy that was difficult to treat with traditional therapies. Adipose-derived mesenchymal stem cell therapy comprising one intravenous dose of 1 × 108 cells was administered to three to six patients in cohort 1. The same intravenous dose was administered twice with a 2-week interval to six patients in cohort 2. Heparin was administered simultaneously. This study continued for 52 weeks, and the primary endpoints were safety and tolerability during the 6-week period after treatment administration. Secondary endpoints included adverse events and efficacy measures such as clinical remission, partial remission, urine protein remission, hematuria remission, time to remission, changes in the urine protein and hematuria levels, and changes in the estimated glomerular filtration rate. Results: The three patients in cohort 1 and six patients in cohort 2 who received adipose-derived mesenchymal stem cell therapy achieved the primary endpoints. No severe adverse clinical events were observed. Therefore, the safety and tolerability of adipose-derived mesenchymal stem cells were confirmed. Improvements such as significantly decreased kidney damage markers and urinary protein levels were observed immediately after adipose-derived mesenchymal stem cell administration. Conclusions: The safety and tolerability of adipose-derived mesenchymal stem cells are acceptable for patients with immunoglobulin A nephropathy. Trial registration: This trial was registered with the Japan Registry of Clinical Trials (jRCT2043200002; registration date: April 14, 2020) and ClinicalTrials.gov (NCT04342325; registration date: April 13, 2020).

DOI： 10.34067/KID.0000000000000563

MPO-ANCA-positive rapidly progressive glomerulonephritis after COVID-19 vaccination during treatment of plaque psoriasis with bimekizumab Reviewed

Sugiura, T; Doke, T; Tanaka, A; Sato, Y; Maeda, K; Furuhashi, K; Kato, N; Kosugi, T; Maruyama, S

CEN CASE REPORTS 2024.9

Language：English Publisher：CEN Case Reports

A 75-year-old man presented with MPO-ANCA-positive rapidly progressive glomerulonephritis after COVID-19 vaccination during the treatment of plaque psoriasis vulgaris with bimekizumab. Bimekizumab, an anti-IL17 monoclonal antibody, was regularly administered to control the activity of plaque psoriasis. After receiving the sixth COVID-19 vaccine, his kidney function rapidly declined over the course of weeks. Urinalysis showed microscopic hematuria and proteinuria with deformed red blood cells and granular cast. The immunology test was positive for MPO-ANCA. The patient was clinically diagnosed with MPO-ANCA-associated glomerulonephritis. As the patient lost his appetite and developed lower extremity edema with low eGFR (< 15 ml/min/1.73m2) on admission day, hemodialysis induction was initiated along with methylprednisolone pulse, followed by oral prednisolone. The kidney function and urine volume were improved in response to immunosuppressive therapy, and withdrawal from hemodialysis was considered. However, the patient developed a catheter infection due to methicillin-sensitive Staphylococcus aureus 2 weeks after the initial prednisolone treatment, causing a decline in kidney function. Antibiotics treatment for the catheter infection was effective, but kidney function remained low, resulting in dependence on regular hemodialysis. COVID-19 vaccination provides significant improvement in overall prognosis; however, there have been reports of kidney function decline and exacerbation of hematuria in patients with IgA nephropathy following vaccination. The incidence of MPO-ANCA-associated glomerulonephritis after COVID-19 vaccination was rare. Data accumulation is warranted to understand the risk factors for secondary MPO-ANCA glomerulonephritis after COVID-19 vaccination. Regular monitoring of urinalysis and kidney function after COVID-19 vaccination is recommended in patients with psoriasis vulgaris treated with IL17 monoclonal antibodies.

DOI： 10.1007/s13730-024-00927-6

Clinical impact of proteinuria and hematuria remission criteria in IgA nephropathy patients defined by the Japanese Society of Nephrology Reviewed

Yasuda, Y; Kaihan, AB; Kaihan, AN; Tanaka, A; Imaizumi, T; Maeda, K; Kato, N; Kosugi, T; Maruyama, S

NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 39 2024.5

Clinical impact of proteinuria and hematuria remission criteria in IgA nephropathy patients defined by the Japanese Society of Nephrology

Yasuda, Y; Kaihan, AB; Kaihan, AN; Tanaka, A; Imaizumi, T; Maeda, K; Kato, N; Kosugi, T; Maruyama, S

NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 39 page： I736 - I737 2024.5

Safety and Tolerability of adipose-derived mesenchymal stem cell "ADR-001" in the treatment of immunoglobulin A nephropathy

Maruyama, S; Tanaka, A; Furuhashi, K; Fujieda, K; Maeda, K; Mimura, T; Saka, Y; Naruse, T; Ishimoto, T; Kosugi, T

NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 39 page： I740 - I740 2024.5

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits and atypical pathological findings treated with corticosteroid and rituximab Reviewed

Mori, M; Tanaka, A; Maeda, K; Saito, S; Furuhashi, K; Maruyama, S

CEN CASE REPORTS Vol. 13 ( 2 ) page： 128 - 134 2024.4

Language：English Publisher：CEN Case Reports

A 16-year-old girl with fever that appeared after taking the second COVID-19 vaccine presented to the clinic with a serum creatinine of 0.89 mg/dL and C-reactive protein of 6.9 mg/dL. She had proteinuria and microscopic hematuria, with slowly worsening kidney function. Her kidney biopsy showed fibrocellular crescents in seven of nine glomeruli that were observed under light microscopy. Another glomerulus showed endocapillary hypercellularity and mesangial cell proliferation. Electron-dense deposits were significant in the mesangial area, with monoclonal IgG1-κ and C3 deposition by immunofluorescence. The patient was diagnosed with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and atypical pathological finding of diffuse crescent formation. The treatment regimen for PGNMID has not yet been established, and the appropriate duration of treatment is unknown. In our case, considering that rituximab acts by binding to CD20 on the surface of B cells through its crystallizable fragment, it was administered in addition to prednisolone, which successfully decreased the proteinuria over time.

DOI： 10.1007/s13730-023-00813-7

Basigin is released in extracellular vesicles derived from the renal tubular epithelium in response to albuminuria Reviewed

Watanabe, T; Maeda, K; Kato, N; Seko, H; Sugimura, M; Sato, Y; Ryuge, A; Kato, S; Kadomatsu, K; Maruyama, S; Kosugi, T

NEPHROLOGY Vol. 28 ( 11 ) page： 629 - 638 2023.11

Language：English Publisher：Nephrology

Aim: Irrespective of the cause, albumin/proteinuria induces tubulointerstitial damage and accelerates the progression of kidney diseases. Our series of studies demonstrated that proteinuria, an independent prognostic factor for chronic kidney disease (CKD), is correlated with urinary basigin/CD147 (Bsg) levels. We examined the morphology and origin of Bsg in the tubular lumen through the effects of filtered glucose and protein solutes on the tubules. Methods: Diabetic kidney disease (DKD) patients (N = 50) were treated with spironolactone 25 mg for 4 weeks or by conservative treatment. The associations between urinary Bsg values and clinical indicators were examined. Primary-cultured proximal tubular epithelial cells (PTECs) from human adult kidneys were exposed to high glucose or bovine serum albumin (BSA). Results: In patients with early phase DKD, urinary Bsg levels were closely correlated with proteinuria but not HbA1c. Full-length Bsg on extracellular vesicles (EVs) was investigated primarily in urine collected from DKD patients. EVs obtained from the urine of DKD patients included Bsg and SGLT2 proteins. Notably, spironolactone treatment concomitantly suppressed the release of Bsg-bearing EVs in correlation with decreased albuminuria. Exposure of PTECs to BSA (but not high glucose) enhanced the storage of supernatant Bsg in EVs despite the absence of exposure-specific changes in Bsg transcription. Conclusion: Proteinuria induces the release of Bsg-bearing EVs derived from PTECs into the tubular lumen.

DOI： 10.1111/nep.14227

Reduced Glycolytic ATP Production Is Responsible for Irreversible Podocyte Injury in Nephrotic Syndrome Reviewed

Sugimura, M; Maeda, K; Sato, Y; Kato, N; Kosugi, T; Maruyama, S

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 34 ( 11 ) page： 298 - 298 2023.11

IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium Reviewed

Muto, R; Maeda, K; Fukui, S; Saito, S; Kato, N; Kosugi, T; Shimizu, A; Maruyama, S

CEN CASE REPORTS Vol. 12 ( 3 ) page： 323 - 328 2023.8

Language：English Publisher：CEN Case Reports

Fibrillary glomerulonephritis (FGN), a rare disease is pathologically characterized by glomerular fibril accumulation ranging from 12 to 24 nm in diameter with negative Congo red staining. Recently, the identification of DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sensitive and specific marker for FGN has revolutionized diagnosis of this disease. However, few recent studies have reported DNAJB9-negative glomerulonephritis with fibrillar deposits. As such, it remains unclear whether DNAJB9-negative cases can be considered equivalent to FGN. Here, we report the case of a 70-year-old woman who developed renal impairment and nephrotic-range proteinuria. Renal biopsy and pathological examination revealed focal glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed IgA-dominant deposition of polytypic IgG in the glomerulus. Electron microscopy revealed hump-like subepithelial electron dense deposits with fibrils of 15–25 nm in diameter. These findings were consistent with FGN; thus, Congo red and direct fast scarlet (DFS) staining, and immunohistochemistry for DNAJB9 were performed. In addition to negative Congo red/DFS/DNAJB9 staining, laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) resulted negative for DNAJB9, which is a highly sensitive and specific marker for FGN. The patient’s renal function further declined, prompting administration of rituximab weekly for 2 weeks, similar to the treatment for FGN. This is a unique case of IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium, unlike previous DNAJB9-negative cases. Thus, DNAJB9-negative cases diagnosed based on accurate electron microscopic evaluation must be gathered, and LMD and LC–MS/MS must be used to analyze the organized fibrillar deposits to reveal the disease entity.

DOI： 10.1007/s13730-022-00759-2

A Case of TAFRO Syndrome with Two Consecutive Renal Biopsies Following the Pathological Course of the Kidney

特集多臓器不全と急性腎障害(AKI) 【各論】臓器障害とAKI ネフローゼ症候群 Reviewed

前田佳哉輔, 丸山彰一

腎と透析 Vol. 93 ( 1 ) page： 85 - 89 2022.7

Kato, N; Hasegawa, T; Muto, R; Tanaka, A; Sato, Y; Maeda, K; Furuhashi, K; Saito, S; Kosugi, T; Maruyama, S

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 32 ( 10 ) page： 823 - 824 2021.10

A Case of TAFRO Syndrome with Two Consecutive Renal Biopsies Following the Pathological Course of the Kidney Reviewed

Kato, N., Hasegawa, T., Muto, R., Tanaka, A., Sato, Y., Maeda, K., Furuhashi, K., Saito, S., Kosugi, T., Maruyama, S.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 32 ( 10 ) page： 823 - 824 2021.10

特集腎疾患治療薬update (第1章)腎疾患患者への薬の使い方ループス腎炎ミコフェノール酸モフェチル Reviewed

前田佳哉輔, 丸山彰一

腎と透析 Vol. 91 ( 7 ) page： 131 - 135 2021.8

Hyaluronic Acid Synthesis Contributes to Tissue Damage in Systemic Lupus Erythematosus International journal

Suarez-Fueyo Abel, Tsokos Maria G, Kwok Seung-Ki, Maeda Kayaho, Katsuyama Eri, Lapchak Peter H, Tsokos George C

FRONTIERS IN IMMUNOLOGY Vol. 10 page： 2172 - 2172 2019.9

Language：English Publishing type：Research paper (scientific journal)

Hyaluronic acid (HA), a component of the extracellular matrix, is the ligand for CD44 and has been implicated in the pathogenesis of kidney inflammation in patients with systemic lupus erythematosus (SLE), but its direct role and mechanism of action have not been studied. Here we show that administration of hymecromone (4-Methylumbelliferone, 4-MU), an HA synthesis inhibitor, to lupus-prone mice suppressed dramatically lupus-related pathology. Interestingly, 4-MU stopped the appearance of disease when administered prior to its onset and inhibited the progression of disease when administered after its appearance. Inhibition of HA synthesis in vivo reduced tissue damage and the number of intrarenal lymphoid cell infiltrates including double negative CD3+CD4-CD8- T cells which are known to be involved in the pathogenesis of SLE. Exposure of human peripheral blood mononuclear cells to HA in vitro increased the generation of CD3+CD4-CD8- T cells through a mechanism involving Rho-associated kinase. Our results signify the importance of the HA-rich tissue microenvironment in the activation of lymphocytes to cause tissue damage in SLE and suggest the consideration of inhibition of HA synthesis to treat patients.

DOI： 10.3389/fimmu.2019.02172