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Roxadustat is one of the oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) that stimulates erythropoiesis and regulates the genes related to iron metabolism. The treatment of HIF-PHIs is useful compared with that of erythropoietin stimulating agent (ESA) using various instruments and procedures. Few clinical researchers have examined the efficacy and safety of switching treatment from Darbepoetin to Roxadustat in Japanese hemodialysis (HD) patients. However, HIF-PHIs have severe adverse drug reactions, such as thrombotic events. In the present study, we evaluated the lower dose of roxadustat in HD patients receiving high dose of ESA therapy. Eighteen anemic HD patients receiving an ESA, that is,, darbepoetin over 40 μg per week, were enrolled in this study. The treatment of these patients was changed to 20 mg of roxadustat three times weekly for 6 months, after which doses were adjusted to achieve a hemoglobin (Hb) target of 10.0-12.0 g/dL. An increase of 58.1 ± 32.5 mg roxadustat three times weekly increased Hb. It also achieved and then maintained levels within the target range at month 6. Ferritin levels of more than 100 ng/mL or TSAT levels of more than 20% were maintained during the 6-month treatment periods with oral or intravenous iron supplementation. It seems unnecessary to increase the initial dose of roxadustat for patients using high doses of ESA. It is suggested that a reconsideration of the starting dose of roxadustat in Japanese HD patients is needed. (Ikegami General Hospital, Medical Corporation SHOWAKAI、Approval number: 2020-4).

It has been reported matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), play important roles in the decomposition of the extracellular matrices of the glomerulus during the pathological processes in various glomerular diseases. Although the activity of these enzymes in cases of experimental glomerulonephritis has been described, the expression sites in the glomeruli of human renal diseases have been identified in only a few articles and remain controversial. The expression of the gelatinase group of MMPs (MMP-2 and MMP-9) and their inhibitors (TIMP-2 and TIMP-1) were evaluated in 19 renal biopsies of several types of glomerular diseases by immunofluorescence (IF) labeling. In addition, several samples of immunoglobulin A nephropathy (IgAN) were also investigated by in situ hybridization (ISH) and immunoelectron microscopy (IEM). The expression of MMP-2 was observed in all the cases examined by IF and ISH. TIMP-2 expression varied from negative to positive among 11 cases of IgAN, but was negative in the cases with lupus nephritis (LN) (n = 3), membranoproliferative glomerulonephritis (MPGN) (n = 2), and post-streptococcal glomerulonephritis (n = 1). However, it was weakly positive in the cases of diabetic nephropathy (DMN) (n = 2). MMP-2 was mainly observed along glomerular capillary loops (GCLs) and Bowman’s capsules, whereas TIMP-2 was found in the mesangial area. The expression of MMP-9 in cases of IgAN varied, and was local, not diffuse, if it was present. MMP-9 expression in cases of LN, MPGN, and DMN was diffuse, but the intensity of staining varied. MMP-9 was primarily expressed in the mesangium. TIMP-1 expression was negative in all cases except for those with IgAN. The localization of MMP-2 in patients with IgAN, which was investigated by IEM, was revealed to be mainly on the endothelial cell membranes of GCLs, podocyte membranes, the parietal cell membranes of Bowman’s capsules, and some on the membranes of mesangial cells. The study results suggest that the expression levels and patterns of MMPs and TIMPs are generally similar in several types of glomerular diseases, even though each case has a somewhat different distribution and intensity of expression. When these enzymes were present, their main sites were as follows: MMP-2 was found along glomerular basement membrane, TIMP-2 was located in the acellular mesangial area, MMP-9 was seen in the mesangium, and TIMP-1 was hardly detected. MMP-2 expression is clearly demonstrated to exist at the above-described sites by IEM in patients with IgAN.

Various glomerular diseases progress to end-stage renal failure due to an accumulation of the mesangial matrix (MM) and a thickening of the glomerular basement membrane (GBM). Both the MM and GBM are consistently metabolized through the synthesis and destruction of the matrix. Such synthesis is influenced by transforming growth factor-beta (TGF-beta) and other factors, whereas the destruction is presumed to be mediated by both matrix metalloproteinases (MMPs) and inhibitors of matrix metalloproteinases (TIMPs). Based on such evidence, we tried to detect MMP-2, MMP-9, and TIMP-1 in the peripheral blood of patients with various glomerular diseases.Serum was used to detect MMP-2 and TIMP-1, while plasma was used to detect MMP-9. These enzymes were detected using an enzyme-linked assay.The findings showed an increased level of MMP-2 in patients with a alteration of GBM, typically membranous nephropathy (MN), regardless of the differences in their etiological processes. In contrast, MMP-9 did not show a strong association with any specific glomerular abnormalities. However, it mainly tended to increase in patients with MM accumulation. In addition, the localization of MMP-2, MMP-9, and TGF-beta1 was studied using immunohistochemical staining. MMP-2 was demonstrated to exist in the glomerular capillary loop (GCL) as well as in the mesangial cells and the mesangial matrix. MMP-9 was found to exist in mesangial cells and the matrix, GCL, infiltrated neutrophils, and some tubular epithelial cells. Positive staining for TGF-beta1 in GCL was found to be associated with an increased level of MMP-2 in patients with MN, whereas in MM such positive staining was not necessarily associated with an increased level of MMP-9.These results therefore suggest that MMP-2 plays an important role in the degradation of GBM, while MMP-9 only moderately affects the degradation of MM.

Allergic granulomatous angiitis (AGA) is a disease entity that was first distinguished from classical polyarteritis nodosa by Churg and Strauss in 1951, and is characterized by the clinical features of allergic rhinitis or bronchial asthma, eosinophilia, and vasculitis. Allergic granulomatous angiitis has been described to mainly involve small vessels. We herein describe a case of Churg–Strauss syndrome which demonstrated the clinical and laboratory findings supporting a diagnosis of AGA and was also associated with the clinical and pathological findings for temporal arteritis, which was characterized by eosinophil infiltration and granuloma formation of the temporal artery (middle-sized vessel).

A 65-year old female, who had been suffered from rheumatoid arthritis, was admitted to our hospital because of fever, oral ulcers, perianal skin ulcers, petechiae in the both legs, hepatosplenomegaly and cervical lymphadenopathy. Her laboratory data showed severe anemia, leukocytopenia, and thrombocytopenia as well as low PT activity, prolonged APTT, decreased fibrinegen and elevated FDP. In addition to raised values of liver enzymes and triglyceride, marked elevation of several cytokines were found. IgM and IgG class antibodies to cytomegalovirus were demonstrated positive and their titers were 2.60 and 938.0, respectively. The study for the aspiration of bone marrow revealed hemophagocytosis of erythrocytes, leukocytes and thrombocytes. Based upon these findings, she was diagnosed as having hemophagocytic syndrome associated with cytomegalovirus infection. Steroid treatment inducing mini-pulse therapy was introduced to her and bought full recovery from the illness. The association of hemophagocytic syndrome to rheumatoid arthritis was reviewed in the literature and five cases were documented to have good prognosis with steroid treatment.