TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) is thought of as an atypical type of idiopathic multicentric Castleman's disease. Interleukin-6, vascular endothelial growth factor (VEGF), and other cytokines are considered etiological factors. A 45-year-old woman was admitted to hospital with unknown fever and abdominal pain. She had thrombocytopenia, anasarca, proteinuria/hematuria, and slight hepatosplenomegaly. Based on her clinical course and laboratory data, she was diagnosed as having TAFRO syndrome. Kidney biopsy showed a membranoproliferative glomerulonephritis (MPGN)-like lesion containing lobulations of glomeruli, endothelial cell swelling, double contours of the glomerular basement membrane, and mesangiolysis. She was treated with methylprednisolone pulse (500 mg/day) and oral prednisolone (60 mg/day) therapy. The pleural effusion and ascites disappeared, and renal function normalized. Cyclosporine was added to prevent relapse. She went home, with no relapse 8 months after hospitalization. MPGN-like lesions were found frequently in patients with TAFRO syndrome in recent reports. However, there are few reports of pathologically confirmed cases of progressive renal involvement in TAFRO syndrome. The relationship between VEGF expression in renal tissue and the pathogenesis of renal injury in TAFRO syndrome was investigated in the present case.

Background Responsiveness to erythropoiesis-stimulating agents (ESAs) is thought to be related to prognosis in patients on hemodialysis. A multi-center, prospective cohort study was conducted to investigate the effects of hyporesponsiveness to long-acting ESAs on cardiovascular events and mortality in Japanese patients on chronic hemodialysis. Methods A total of 127 chronic hemodialysis patients treated with long-acting ESAs were followed-up prospectively. Responsiveness to ESA was evaluated using an erythropoietin resistance index (ERI) calculated by dividing the weekly body-weight-adjusted ESA dose by the hemoglobin concentration. The primary endpoint of this survey was defined as a combination of cardiovascular events and all-cause deaths. The association between hyporesponsiveness to ESAs evaluated by the highest quartile of the ERI and the primary endpoint was investigated. Results During the follow-up period (median 4.6 years), 32 patients reached the primary end point. Kaplan-Meier curve analysis showed that patients with ESA hyporesponsiveness belonging to the highest quartile of the ERI reached the primary end point more frequently than those without (P = 0.031). Cox regression analysis showed that an ERI in the highest quartile was an independent predictor of the primary end point, even after adjustment using a propensity score (hazard ratio 2.76, 95% confidence interval 1.19–6.40). Conclusions ESA hyporesponsiveness in hemodialysis patients treated with long-acting ESAs is related to cardiovascular events and death.

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Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI, daprodustat, in 10 maintenance hemodialysis patients. Plasma metabolites were measured before and three months after the switch from an ESA to an HIF-PHI. Among 106 individual markers detected in plasma, significant changes were found in four compounds (erythrulose, n-butyrylglycine, threonine, and leucine), and notable but non-significant changes were found in another five compounds (inositol, phosphoric acid, lyxose, arabinose, and hydroxylamine). Pathway analysis indicated decreased levels of plasma metabolites, particularly those involved in phosphatidylinositol signaling, ascorbate and aldarate metabolism, and inositol phosphate metabolism. Our results provide detailed insights into the systemic biological effects of HIF-PHIs in hemodialysis patients and are expected to contribute to an evaluation of the potential side effects that may result from long-term use of this class of drugs.