Takeo Koshida

This study evaluates the dynamic clinical reasoning of 4 leading large language models in complex nephrology cases, demonstrating that while Gemini 2.5 Pro achieved the highest reasoning scores and computational efficiency, all tested models excelled at static data synthesis but shared vulnerabilities in formulating nuanced differential diagnoses and in prospective clinical planning.

Minimal change nephrotic syndrome (MCNS) has traditionally been linked to T‐cell dysfunction; however, mounting evidence suggests that B‐cell‐mediated mechanisms also play a significant role. Rituximab (RTX) is increasingly utilized as maintenance therapy for recurring MCNS, yet its extended safety profile remains uncertain. In this study, we report a rare case of MCNS complicated by classical Hodgkin lymphoma (cHL) that emerged during prolonged RTX maintenance therapy. A 23‐year‐old woman with relapsing MCNS achieved sustained remission with RTX maintenance therapy. Following 13 RTX courses, the patient developed nodular sclerosis–type cHL and attained complete remission with A + AVD chemotherapy (adriamycin, brentuximab vedotin, vinblastine, and dacarbazine). Despite successful chemotherapy for cHL, the patient relapsed with nephrotic syndrome featuring significant proteinuria (8.43 g/day) as RTX efficacy declined. This clinical progression illustrates a close temporal link between RTX effect loss and disease recurrence, supporting the contributory role of elevated peripheral CD19+ B cells in MCNS relapse. Although sustained B‐cell–targeted therapy seems effective for prolonged disease management, the exceedingly rare incidence of cHL during extended RTX maintenance in this patient highlights the importance of vigilant long‐term safety monitoring with prolonged B‐cell depletion.

Objective: The sodium–glucose cotransporter-2 inhibitor dapagliflozin reduces proteinuria and slows the decline in estimated glomerular filtration rate in patients with chronic kidney disease. Dapagliflozin is reported to be effective in patients with immunoglobulin A nephropathy; however, there have been only a few real-world clinical trials involving patients with immunoglobulin A nephropathy. Therefore, we aimed to evaluate the effect of dapagliflozin in Japanese patients with immunoglobulin A nephropathy. Method: We performed a multicenter, nonblinded, single-arm, prospective observational study involving 44 patients with immunoglobulin A nephropathy. Patients who had completed corticosteroid treatment and were currently undergoing renin–angiotensin system inhibitor therapy were primarily enrolled. Results: At baseline, the mean estimated glomerular filtration rate was 56.2 ± 29.4 mL/min/1.73 m ² , and the median urinary protein-to-creatinine ratio was 0.63 g/g (interquartile range: 0.32–1.22 g/g). The estimated glomerular filtration rate decreased significantly after 1 month and plateaued thereafter. The urinary protein-to-creatinine ratio significantly decreased in patients with higher proteinuria (>0.5 g/g), but not in those with less proteinuria (<0.5 g/g). The post-treatment estimated glomerular filtration rate slope was significantly attenuated compared with the pretreatment slope, especially in patients with a relatively rapid decline in estimated glomerular filtration rate. Conclusion: Dapagliflozin reduces residual proteinuria, even after treatment with corticosteroids and renin–angiotensin system inhibitors, in patients with biopsy-confirmed immunoglobulin A nephropathy. These findings may guide future treatment strategies for immunoglobulin A nephropathy.

The composition of the gut microbiome is altered in patients with chronic kidney disease (CKD). Dysbiosis leads to decreased levels of stool organic acids (OAs) and systemic inflammation, followed by accumulation of uremic toxins (UTs) and the development of end-stage kidney disease (ESKD). We assessed the relationship between the microbiome and UT levels or the development of ESKD by comparing patients undergoing hemodialysis (HD) and those with normal renal function (NRF). This cross-sectional study recruited 41 patients undergoing HD and 38 sex- and age-matched patients with NRF, and gut microbiome, levels of plasma UTs, inflammatory markers, and stool OAs were compared. The indices of beta-diversity differed significantly between patients with NRF and those undergoing HD, and between patients undergoing HD with and without type 2 diabetes. The levels of stool total OA, inflammatory markers, and UTs differed significantly between the patients with NRF and those undergoing HD. The combined main effects of type 2 diabetes and kidney function status were accumulation of indoxyl sulfate and p-cresyl sulfate. The relative abundances of Negativicutes and Megamonas were associated with development of ESKD and with the levels of UTs, even after adjustment for factors associated with the progression of ESKD. The present study indicates that the gut environment differs between patients with NRF and those undergoing HD and between patients undergoing HD with and without type 2 diabetes. Moreover, ESKD patients with diabetes accumulate more UTs derived from the gut microbiome, which might be associated with cardio-renal diseases and poor prognosis.

Identifying novel biomarkers of kidney function in patients with chronic kidney disease (CKD) has strong clinical value as current measures have limitations. This study aims to develop and validate a sensitive and specific ephrin type-A receptor 2 (EphA2) enzyme-linked immunosorbent assay (ELISA) for human serum, and determine whether its results correlate with traditional renal measures in patients with hypertension. The novel ELISA of the current study was validated and used to measure circulating EphA2 levels in 80 hypertensive patients with and without kidney function decline (eGFR less than 60 mL/min/1.73 m²). Validation of the EphA2 ELISA showed good recovery (87%) and linearity (103%) and no cross-reactivity with other Eph receptors. Patients with kidney function decline had lower diastolic blood pressure, and higher UPCR and EphA2 than those without kidney function decline. The association of age and eGFR with EphA2 was maintained in the stepwise multiple regression analysis. In a multivariate logistic model, EphA2 was associated with a lower eGFR (2) after adjustment for age, sex, and UPCR. High circulating EphA2 levels have potential application as a clinical biomarker for the presence of CKD in patients with hypertension.