ObjectiveTo evaluate the effectiveness of a lower initial glucocorticoid (GC) dose (0.4-0.6 mg/kg/day) compared to the conventional dose (0.8-1.2 mg/kg/day) in achieving complete renal response (CRR) at 12 months in Japanese patients with proliferative lupus nephritis (LN).MethodsThis multicentre, retrospective observational study analyzed data from 344 Japanese patients diagnosed with LN (class III or IV ± V) via renal biopsy. Patients were divided into two groups based on their initial dose of GC. 1:1 propensity score matching (PSM) based on key baseline variables, 23 patients were included in each group. The primary endpoint was CRR at 12 months, defined according to the BLISS-LN trial criteria. A non-inferiority margin of -10% was prespecified.ResultsAfter PSM, the CRR rate at 12 months was 87.0% in the low-dose group and 73.9% in the conventional-dose group (risk difference: 13.1%; 95% confidence interval [CI]: -9.4% to 35.6%), confirming statistical non-inferiority. While GC doses differed significantly during the initial 3 months, they became comparable between the groups after 6 months.ConclusionA reduced initial GC dose of 0.4-0.6 mg/kg/day achieved renal outcomes comparable to conventional dosing in Japanese patients with LN. Given the risks of GC toxicity, these findings may support the potential for lower-dose GC strategies in LN treatment.

Atonal BHLH transcription factor 8 (ATOH8) is a basic helix-loop-helix (bHLH) transcription factor; however, its role in glomerular epithelial cells (podocytes) remains unclear. This study aimed to elucidate the function of ATOH8 in podocytes. First, ATOH8 expression in the mouse kidney was confirmed in podocytes by immunofluorescence staining and in situ hybridization. In cultured human podocytes, transforming growth factor-beta (TGF-β) treatment significantly reduced ATOH8 mRNA expression. To examine the functional consequences of ATOH8 downregulation, ATOH8 expression was knocked down with shRNA. Subsequent RNA sequencing analysis of ATOH8-knockdown podocytes revealed increased extracellular matrix gene expression and activation of TGF-β signaling. ATOH8-knockdown podocytes also showed SMAD2/3 nuclear translocation, increased SMAD transcriptional activity, as determined by a luciferase assay, and upregulated TGFB1 mRNA even without TGF-β stimulation, consistent with TGF-β signaling activation. In vivo, C57BL/6 Atoh8-deficient mice showed no renal abnormalities at baseline. However, in an adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) model, Atoh8-deficient mice developed significantly more severe glomerulosclerosis than wild-type mice, with higher renal cortical Tgfb1 and Col4a1 mRNA levels. Reduced ATOH8 expression was also observed in ADR-induced nephropathy in mice and rats and in various human glomerular diseases. These findings suggest that ATOH8 downregulation enhances TGF-β signaling and glomerulosclerosis progression, indicating a protective role for ATOH8 in maintaining podocyte integrity and preventing kidney injury.NEW & NOTEWORTHY This study identifies atonal transcription factor 8 (ATOH8) as a previously unexplored regulator of podocyte function. We demonstrate that ATOH8 knockdown activates TGF-β signaling and increases extracellular matrix gene expression. Notably, ATOH8 deficiency alone does not cause renal injury but exacerbates glomerulosclerosis in an adriamycin-induced nephropathy model, accompanied by increased Tgfb1 mRNA expression in the renal cortex. These findings indicate that ATOH8 plays a protective role in podocyte function and limits glomerulosclerosis during kidney injury.

To estimate the prevalence of active kidney involvement and its associations with comorbidities and treatment patterns among patients with systemic lupus erythematosus (SLE) at renewal application for the Designated Intractable Diseases of Japan. We analyzed Medical Certificates of Designated Intractable Diseases that were submitted in 2016 for the renewal of SLE designation. Among 35,207 digitized patients (mean age, 51.1 ± 15.7 years), active kidney involvement was defined as proteinuria (≥ 0.5 g/day) and/or urinary casts (granular casts or red blood cell casts) recorded as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) items during the 6 months preceding the renewal application. Active kidney involvement was identified in 8273 patients (23.5

Objectives:While recent guidelines recommend early glucocorticoid (GC) tapering for LN, supporting evidence for pure membranous LN remains limited. The present study investigated the impact of rapid GC tapering on renal outcomes in this population. Methods:We performed a multicentre retrospective study across 16 centres in Japan, including 67 patients with biopsy-proven pure membranous LN who initiated GC therapy between 2003 and 2023. Patients were classified into rapid tapering (GC dose ≤7.5 mg/day at 6 months) and conventional tapering (>7.5 mg/day at 6 months) groups. The primary endpoint was the partial renal response (PRR) at 12 months. Secondary endpoints included the complete renal response (CRR), relapse and severe adverse events (SAEs). Adjusted risk ratios (aRRs) were estimated using modified Poisson regression models for failure to achieve PRR/CRR. Results:Fifteen patients underwent rapid tapering and 52 conventional tapering. Baseline characteristics were generally comparable. At 12 months, PRR was achieved in 85.7% of the rapid group and 84.3% of the conventional group (aRR for failure 1.04; 95% CI 0.17-6.39). CRR rates at 12 months were 64.3% and 56.9%, respectively (aRR for failure 0.90; 95% CI 0.40-2.02). At 24 months, PRR and CRR did not differ statistically between groups. Relapse occurred in 20.0% versus 7.7% (P = 0.185). No SAEs were reported in the rapid group, while three occurred in the conventional group. Conclusions:Rapid GC tapering to ≤7.5 mg/day at 6 months appeared feasible in a subset of patients with pure membranous LN, but the findings are preliminary and should be interpreted cautiously because of the small rapid-taper group and imprecise estimates.

The purpose of this study was to clarify the characteristics of newly diagnosed systemic lupus erythematosus (SLE) patients with or without kidney involvement in Japan. We used electronic data of SLE patients in the National Database of Designated Intractable Diseases of Japan who newly registered between 2015 and 2017. We analyzed patients within one year of disease onset. Kidney involvement was defined as any of the following: urinary protein ≥ 0.5 g/day, granular casts, a clinical diagnosis of nephrotic syndrome, acute or chronic renal failure, or rapidly progressive glomerulonephritis, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, lupus nephritis confirmed by renal biopsy, or hemodialysis. Among 2315 SLE patients, 1088 (47.0

Membranous lupus nephritis (MLN), a distinct subtype of lupus nephritis (LN), is generally associated with more favorable outcomes than proliferative LN (PLN). However, clinical data regarding pure MLN are limited. We investigated the prognosis of patients with pure MLN in Japan. We performed a sub-analysis of a previously reported nationwide retrospective cohort study of patients with LN in Japan. This study included patients who underwent renal biopsy between 2007 and 2012. Patients with pure MLN (Class V, n = 90) were compared to those with PLN (Class III/IV ± V, n = 362) over a median follow-up period of 5 years. The primary outcome was defined as a 50

OBJECTIVES:Recent guidelines and recommendations for LN suggest rapid glucocorticoid (GC) reduction; however, robust supporting evidence remains limited. This study aimed to evaluate the impact of rapid GC reduction on renal outcomes in patients with proliferative LN. METHODS:We conducted a multicentre retrospective chart review of patients with GC-naïve, biopsy-proven proliferative LN with available urinary protein-to-creatinine ratio (UPCR) data before and 52 weeks after GC treatment. Patients who reduced their prednisolone-equivalent dose to ≤7.5 mg/day within 6 months (rapid GC reducers) were compared with those who did not (conventional GC reducers) regarding partial renal response (PRR) at 12 months. Modified Poisson regression analysis was used to adjust for confounding factors. RESULTS:A total of 344 patients from 17 centres were included: 50 rapid GC reducers and 294 conventional GC reducers. PRR at 12 months was achieved by 43/50 (86%) in the rapid GC group and 248/294 (84.4%) in the conventional group. After adjusting for age, initial UPCR, initial estimated glomerular filtration rate, the presence of a concomitant membranous lesion in the glomerulus, initial GC dose, use of methylprednisolone pulse therapy, strong immunosuppressants (mycophenolate mofetil, cyclophosphamide or rituximab) and hydroxychloroquine, no significant difference was observed in PRR at 12 months (adjusted risk ratio: 0.92, P = 0.758). Relapse rates and serious adverse events over 2 years of follow-up were also comparable between the groups. CONCLUSION:Rapid GC reduction to ≤7.5 mg/day within 6 months did not compromise renal outcomes or increase relapse in proliferative LN.

Relapse is a major concern in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). There are several reports on predictors of AAV relapse; however, reports on Japanese patients are limited. This study aimed to identify risk factors for relapse in Japanese patients with AAV. We retrospectively analyzed 200 patients who initiated treatment at our institution and were subsequently managed across affiliated facilities. Clinical and laboratory data were analyzed. The primary outcome was relapse, and Cox proportional hazards models were used to identify associated risk factors. The median age of AAV onset was 69 years (interquartile ranges (IQR), 62–76 years). There were 103 (51