Publications (53) View all
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Article: Fluctuation of serum C3 levels reflects disease activity and metabolic background in patients with IgA nephropathy.
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ABSTRACT: Background: We focused on the fluctuations of serum C3 levels throughout the clinical course of patients and investigated the relationship between these fluctuations and clinical findings. Methods: IgA nephropathy patients (n = 122) were enrolled in the present study. Serum C3 and other clinical markers were compared at the time of renal biopsy and at last follow-up (6.67 ± 2.07 years). Patients were divided into 3 groups based on serum C3 levels: Group I with first C3 levels below the mean -1 SD, which turned into an increase at last observation; group II with first C3 levels more than the mean +1 SD, which turned into a decrease at last observation; and group III, with first C3 levels more than the mean +1 SD, which turned into an increase at last observation. First and last levels of clinical markers were compared among the 3 groups. Results: Serum C3 levels of the patients whose renal symptoms, including hematuria, proteinuria and estimated glomerular filtration rate (eGFR), were improved, were significantly increased at last observation (p<0.05, p<0.01, p<0.01, respectively). Age, total cholesterol and triglyceride levels in group III were significantly higher than those in group I. Group II showed a significant reduction of urinary protein. Groups I and II maintained renal function, but group III showed a significant deterioration of renal function. Conclusions: The levels and fluctuations of serum C3 might reflect the disease activity and metabolic alteration in patients with IgA nephropathy.Journal of nephrology 05/2013; · 1.65 Impact Factor -
Article: Nationwide survey on current treatments for IgA nephropathy in Japan.
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ABSTRACT: BACKGROUND: A wide variety of treatments, including tonsillectomy and steroid pulse therapy (TSP), are performed for the various stages of IgA nephropathy (IgAN) in Japan. However, the current status of treatments for IgAN patients in Japan is still unclear. The objective of the present study was to investigate the current status of treatments for IgAN patients. METHODS: A nationwide survey was conducted in 2008 by sending questionnaires to the 1,194 teaching hospitals of the Japanese Society of Nephrology (JSN) via Progressive Renal Diseases Research, Research on intractable disease, from the Ministry of Health, Labour and Welfare of Japan. RESULTS: Among the total 376 hospitals (31.4 %) that responded, 188 hospitals (66.2 % in the internal medicine departments) performed TSP, out of which 137 hospitals (61.4 %) had begun to perform TSP in the period from 2004 to 2008. The following two major steroid pulse protocols in TSP were used: (1) three cycles over 3 consecutive weeks and (2) three cycles every 2 months. Approximately 68 % of pediatric hospitals (68 hospitals) performed combination therapy with prednisolone, azathioprine, heparin-warfarin and dipyridamole. The clinical remission rates for hematuria and proteinuria after TSP tended to be higher than those following other corticosteroid therapies. Almost all hospitals prescribed antiplatelet agents and renin angiotensin system inhibitor (RAS-I). CONCLUSION: In addition to popular treatments such as antiplatelet agents and RAS-I, TSP is becoming a standard treatment for adult IgAN patients in Japan.Clinical and Experimental Nephrology 03/2013; · 1.37 Impact Factor -
Article: Experimental evidence of cell dissemination playing a role in pathogenesis of IgA nephropathy in multiple lymphoid organs.
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ABSTRACT: Background Since the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) remains unclear, the rationale for current IgAN therapies is still obscure. Recent studies have shown that galactose-deficient IgA1 (GdIgA1) plays a critical role in the pathogenesis of IgAN and can be a non-invasive IgAN biomarker, although the origin of the pathogenic cells producing GdIgA1 is unknown. We examined the cell types and localization of pathogenic cells in IgAN-prone mice.Methods We transplanted bone marrow (BM) or spleen cells with or without specific cell types from IgAN-prone mice, which have many features similar to human IgAN, to identify cell types responsible for the IgAN phenotype and to determine their localization.ResultsBM transplantation and whole spleen cell transfer from IgAN-prone mice reconstituted IgAN in normal and severe combined immunodeficiency mice. Depletion of CD90(+) spleen cells had no affect on reconstitution, whereas CD19(+) B cells from the spleen were sufficient to reconstitute IgAN in both recipients.Conclusions These results indicate that CD19(+) B cells, which can regulate nephritogenic IgA production in a T-cell-independent manner, are responsible for the disease and are disseminated in peripheral lymphoid organs.Nephrology Dialysis Transplantation 11/2012; · 3.40 Impact Factor -
Article: Determination of severity of murine IgA nephropathy by glomerular complement activation by aberrantly glycosylated IgA and immune complexes.
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ABSTRACT: The pathogenic roles of glomerular deposition of components of the complement cascade in IgA nephropathy (IgAN) are not completely clarified. To investigate the pathologic role of complement pathways in IgAN, two IgAN-prone mouse models were examined. Grouped ddY (gddY) mice showed significant high proteinuria, severe glomerular lesions, and extracellular matrix expansion compared with high serum IgA (HIGA) mice but with similar intensity of glomerular IgA deposition. Glomerular activation of the classical, lectin, and alternative pathways was demonstrated by significantly stronger staining for complement (C)3, C5b-9, C1q, C4, mannose-binding lectin (MBL)-A/C, MBL-associated serine protease-2, and factor B and properdin in gddY mice than in HIGA mice. Similarly, the serum levels of IgA-IgG2a/IgM and IgA-MBL-A/C immune complexes and polymeric IgA were significantly higher in gddY mice than in HIGA mice. Moreover, the serum levels of aberrantly glycosylated IgA characterized by the binding of Sambucus nigra bark lectin and Ricinus communis agglutinin I were significantly higher in gddY mice than in HIGA mice. This aberrancy in glycosylation was confirmed by monosaccharide compositional analysis of purified IgA using gas-liquid chromatography. This study is the first to demonstrate that aberrantly glycosylated IgA may influence the formation of macromolecular IgA including IgA-IgG immune complexes and subsequent complement activation, leading to full progression of IgAN.American Journal Of Pathology 08/2012; 181(4):1338-47. · 4.89 Impact Factor -
Article: Acceleration of crescent formation by L1 retrotransposon in mouse BSA-induced nephritis.
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ABSTRACT: Background: While crescentic glomerulonephritis (GN) is frequently associated with a rapid clinical course and poor prognosis, its pathogenesis has not been elucidated. Bovine serum albumin -induced nephritis (BSA-N), an established mouse model of crescentic GN, is a favorable model for investigation of chronologic gene expression because it is characterized by synchronized progression of crescentic GN. Methods: Specific genes expressed in glomeruli of crescentic GN were screened using representational difference analysis before and after crescent formation. The obtained LINE-1 (L1) elements were suppressed and the methylation status of promoter sequences was analyzed. Results: The endogenous reverse transcriptase (RT) of L1 retrotransposon was identified from glomeruli with crescents. L1 retrotransposon was strongly expressed at sites of crescents and tubulo-interstitial areas adjacent to crescents. The marked glomerular crescent formation and renal dysfunction observed in this model significantly reduced on treatment with the non-nucleoside RT inhibitor, efavirenz (EFV) (P<.01). The L1 promoter sequences in mice with crescents were more frequently hypomethylated than those in mice without crescents. Furthermore, the sequences were not affected by EFV treatment. MAPK 13 and c-MYC were strongly expressed in mice with crescents, but their expression decreased on EFV treatment. Conclusions: This study revealed that increased L1 expression in glomeruli of crescentic GN and downregulation of RT activity in L1 decreased crescent formation. Preferential expression of L1 retrotransposon appears to be related to cell proliferative signals. Finally, our findings provide new insights into the epigenetic factors responsible for crescent formation.Journal of nephrology 04/2012; · 1.65 Impact Factor
