MDPIActa Medica Okayama2075-44261342023The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study582ENYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoheiMaeshimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYukaOkuyamaJapanese Red Cross Society Himeji HospitalNozomuOtakaKagawa Prefectural Central HospitalHaruyoUjikeKagawa Prefectural Central HospitalKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasashiKitagawaNational Hospital Organization Okayama Medical CenterKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasaruKinomuraOkayama Saiseikai General HospitalShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKosukeOtaNational Hospital Organization Okayama Medical CenterKeisukeMaruyamaOkayama Saiseikai General HospitalMakotoHiramatsuOkayama Saiseikai General Hospital,YoshiyukiOshiroKawasaki Medical School General Medical CenterShigeruMoriokaOkayama Central HospitalKeiichiTakiueOkayama City HospitalKazuyoshiOmoriShigei Medical Research HospitalMasakiFukushimaShigei Medical Research HospitalNaoyukiGamouJapanese Red Cross Okayama HospitalHiroshiHirataAkebono ClinicRyosukeSatoSato ClinicHirofumiMakinoOkayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221112021Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study14990ENMarikoTsuchida-NishiwakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceNoriyukiNishiwakiDepartment of Gastroenterological Surgery Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYoheiMaeshimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceChieSaitoDepartment of Nephrology, Faculty of Medicine, University of TsukubaHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceIchieiNaritaDivision of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental ScienceTsuyoshiWatanabeTokyo-Kita Medical CenterSeiichiMatsuoNagoya UniversityHirofumiMakinoOkayama UniversityAkiraHishidaYaizu City HospitalKunihiroYamagataDepartment of Nephrology, Faculty of Medicine, University of TsukubaIt is well-known that hypertension exacerbates chronic kidney disease (CKD) progression, however, the optimal target blood pressure (BP) level in patients with CKD remains unclear. This study aimed to assess the optimal BP level for preventing CKD progression. The risk of renal outcome among different BP categories at baseline as well as 1 year after, were evaluated using individual CKD patient data aged between 40 and 74 years from FROM-J [Frontier of Renal Outcome Modifications in Japan] study. The renal outcome was defined as >= 40% reduction in estimated glomerular filtration rate to<60 mL/min/1.73 m(2), or a diagnosis of end stage renal disease. Regarding baseline BP, the group of systolic BP (SBP) 120-129 mmHg had the lowest risk of the renal outcome, which increased more than 60% in SBP<greater than or equal to>130 mmHg group. A significant increase in the renal outcome was found only in the group of diastolic BP >= 90 mmHg. The group of BP<130/80 mmHg had a benefit for lowering the risk regardless of the presence of proteinuria, and it significantly reduced the risk in patients with proteinuria. Achieving SBP level<130 mmHg after one year resulted in a 42% risk reduction in patients with SBP level >= 130 mmHg at baseline. Targeting SBP level<130 mmHg would be associated with the preferable renal outcome.Clinical Trial Registration-URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000001159 (16/05/2008).No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6842014Renal Distribution of Vasohibin-1 in Patients with Chronic Kidney Disease219233ENNorikazuHinamotoYoheiMaeshimaDaisukeSaitoHirokoYamasakiKatsuyukiTanabeTatsuyoNasuHiroyukiWatataniHaruyoUjikeMasaruKinomuraHitoshiSugiyamaHikaruSonodaNaokiKanomataYasufumiSatoHirofumiMakinoOriginal Article10.18926/AMO/52788Experimental studies have demonstrated the involvement of angiogenesis-related factors in the progression of chronic kidney disease (CKD). There have so far been no reports investigating the distribution and clinical roles of Vasohibin-1 (VASH-1), a negative feedback regulator of angiogenesis, in CKD. We recruited 54 Japanese CKD patients and 6 patients who had normal renal tissues excised due to localized renal cell carcinoma. We evaluated the correlations between the renal expression level of VASH-1 and the clinical/histological parameters. VASH-1 was observed in renal endothelial/mesangial cells, crescentic lesions and interstitial inflammatory cells. Significant positive correlations were observed between 1) crescent formation and the number of VASH-1+ cells in the glomerulus
(r0.48, p0.001) or cortex (r0.64, p0.0001), 2) interstitial cell infiltration and the number of VASH-1+ cells in the cortex (r0.34, p0.02), 3) the glomerular VEGFR-2+ area and the number of VASH-1+ cells in the glomerulus (r0.44, p0.01) or medulla (r0.63, p0.01). These results suggest that the renal levels of VASH-1 may be affected by local inflammation, crescentic lesions and VEGFR-2.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-6203822013A Decreased Level of Serum Soluble Klotho Is an Independent Biomarker Associated with Arterial Stiffness in Patients with Chronic Kidney DiseaseENMasashiKitagawaHitoshiSugiyamaHiroshiMorinagaTatsuyukiInoueKeiichiTakiueAyuOgawaToshioYamanariYokoKikumotoHaruhito AdamUchidaShinjiKitamuraYoheiMaeshimaKazufumiNakamuraHiroshiItoHirofumiMakinoBackground: Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD).
Methods: We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification.
Results: The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV >= 1400 cm/sec, atherosclerosis defined as maximum IMT >= 1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075).
Conclusions: Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted.No potential conflict of interest relevant to this article was reported.Biomed Central LtdActa Medica Okayama1471-236913142012Acatalasemic mice are mildly susceptible to Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosisENKeiichiTakiueHitoshiSugiyamaTatsuyukiInoueHiroshiMorinagaYokoKikumotoMasashiKitagawaShinjiKitamuraYoheiMaeshimaDahongWangNoriyoshiMasuokaKeikiOginoHirofumiMakinoBackground: Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model.
Methods: ADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) and control wild-type mice (C3H/AnLCs(a)Cs(a)). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups.
Results: The ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation.
Conclusions: These data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.No potential conflict of interest relevant to this article was reported.ͺRγwοActa Medica Okayama0030-155812312011ΗVΆnegative feedback§δφqVasohibin-1Ιζι}EXAa«tΗiW§δψΚΜ’1925ENTatsuyoNasuYoheiMaeshimaMasaruKinomuraKumikoHirokoshi-KawaharaKatsuyukiTanabeHitoshiSugiyamaHikaruSonodaYasufumiSatoHirofumiMakinoNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6362009Inflammatory Cytokine-induced Expression of Vasohibin-1 by Rheumatoid Synovial Fibroblasts349358ENKoheiMiyakeKeiichiroNishidaYasutakaKadotaHirokoYamasakiTatsuyoNasuDaisukeSaitouKatsuyukiTanabeHikaruSonodaYasufumiSatoYoheiMaeshimaHirofumiMakinoOriginal Article10.18926/AMO/31820<p>Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immunohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (p0.002, r0.842). In vitro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.</p>No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1997Antisense oligonucleotides to proliferating cell nuclear antigen and Ki-67 inhibit human mesangial cell proliferationENNo potential conflict of interest relevant to this article was reported.