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.MDPIActa Medica Okayama2077-03831252023Serum sCD40L and IL-31 in Association with Early Phase of IgA Nephropathy2023ENKeikoTanakaDepartment 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 SciencesHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasashiKitagawaDepartment of Nephrology, National Hospital Organization Okayama Medical CenterYuzukiKanoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKokiMiseDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment 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 SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBackground: IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. Results: Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. Conclusions: The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1010-660X58112022The Beneficial Effect of Personalized Lifestyle Intervention in Chronic Kidney Disease Follow-Up Project for National Health Insurance Specific Health Checkup: A Five-Year Community-Based Cohort Study1529ENHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceShugoOkamotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceYukaOkuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceKodaiMiyajiDepartment of Health and Welfare, Division of Health Promotion, Mimasaka City Health CenterAkikoKaiDepartment of Health and Welfare, Division of Health Promotion, Mimasaka City Health CenterIzumiMatsumotoDepartment of Health and Welfare, Division of Health Promotion, Mimasaka City Health CenterKeikoTaniguchiDepartment of Health and Welfare, Division of Health Promotion, Mimasaka City Health CenterFukikoYamashitaDepartment of Health and Welfare, Division of Health Promotion, Mimasaka City Health CenterTsutomuEmiDepartment of Health and Welfare, Division of Health Promotion, Mimasaka City Health CenterHitoshiSugiyamaKawasaki Medical School General Medical CenterJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical ScienceBackground and Objectives: Mimasaka city is a relatively small city with a population of 28,381, and an aging rate (>= 65 years old) of 38.9%, where only one nephrology clinic is available. Since 2013, the city has conducted its own unique lifestyle intervention for the participants of the National Health Insurance specific medical health checkup, aiming to prevent the progression of chronic kidney disease (CKD) severity. Materials and Methods: The persons in National Health Insurance specific medical health checkup (40-74 years old) conducted in Mimasaka city in 2013, with eGFR less than 50 mL/min/1.73 m(2) or 50-90 mL/min/1.73 m(2) with urine dipstick protein 1+ or more, were registered for the CKD follow-up project, as high-risk subjects for advanced renal dysfunction. Municipal workers directly visited the subjects' homes to provide individual health guidance and encourage medical consultation. We aimed to examine the effect of home-visit intervention on the changes of renal function and related factors until 2017. Results: The number of the high-risk subjects who continuously received the health checkup until 2017 was 63, and only 23 (36.5%) visited a medical institution in the first year. The eGFR decreased by only 0.4 mL/min/1.73 m(2)/year, and the subjects with urinary protein 1+ or higher decreased significantly from 20 (31.7%) to 9 (14.3%) (p = 0.034) in the high-risk subjects. The changes in eGFR and urinary protein was almost in the same fashion regardless of their medical institution visits. Next, we examined the effects of various factors on Delta eGFR, the changes of eGFR from 2013 to 2017, by multivariate linear regression analysis. The effects of medical institution visit were not significant, and the degree of urinary protein (coefficient B: 4.503, beta: 0.705, p < 0.001), age (coefficient B: 4.753, beta: 0.341, p = 0.004), and smoking (coefficient B: 5.878, beta: 0.295, p = 0.031) had independent significant effects, indicating that they were the factors exacerbating the decrease in eGFR from the baseline. Conclusions: The personalized lifestyle intervention by home-visit in CKD follow-up project showed the possibility of beneficial effects on the deterioration of renal function. This may be an efficient method to change behavior in a small community with limited medical resources.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022The association between hypothyroidism and proteinuria in patients with chronic kidney disease: a cross-sectional study14999ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensakuTakahashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHypothyroidism is known to be correlated with kidney function and nephrotic range proteinuria. However, it is uncertain whether non-nephrotic proteinuria is associated with hypothyroidism. This study aimed to evaluate the association of proteinuria and hypothyroidism in chronic kidney disease (CKD) patients. We conducted a cross-sectional study composed of 421 CKD patients in a single hospital with measurements of 24-h urine protein excretion (UP) and thyroid function tests. Spearman correlation analysis revealed that 24-h Cr clearance (24hrCcr) was positively (r = 0.273, p < 0.001) and UP was negatively (r = - 0.207, p < 0.001) correlated with free triiodothyronine. Frequency distribution analysis stratified by CKD stage and UP for hypothyroidism revealed that the prevalence of hypothyroidism was higher among participants with higher CKD stage and nephrotic range proteinuria. Multivariate logistic regression analysis revealed that 24hrCcr and UP were significantly correlated with hypothyroidism (24hrCcr/10 mL/min decrease: odds ratio [OR], 1.29; 95% confidence interval [CI], 1.18-1.41; UP/1 g increase: OR, 1.10; 95% CI, 1.03-1.17). In addition, nephrotic range proteinuria, but not moderate UP (UP: 1.5-3.49 g/day), was significantly correlated with hypothyroidism compared to UP < 0.5 g/day. In summary, decreased kidney function and nephrotic range proteinuria, not non-nephrotic proteinuria, are independently associated with the hypothyroidism.No potential conflict of interest relevant to this article was reported.Lippincott Williams & WilkinsActa Medica Okayama0025-797410172022Silica-associated systemic lupus erythematosus with lupus nephritis and lupus pneumonitis A case report and a systematic review of the literaturee28872ENKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukoFuchimotoDepartment of Respiratory Medicine, Okayama Rosai HospitalTomoyoMifuneDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMayuWatanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaruKinomuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeMiyamotoDepartment of Respiratory Medicine, Okayama Rosai HospitalSaeWadaDepartment of Respiratory Medicine, Okayama Rosai HospitalTaisakuKoyanagiDepartment of Respiratory Medicine, Okayama Rosai HospitalHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakumiKishimotoDepartment of Respiratory Medicine, Okayama Rosai HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction Several epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of silica-associated SLE have not been well studied. Patient concerns A 67-year-old man with silicosis visited a primary hospital because of a fever and cough. His respiratory condition worsened, regardless of antibiotic medication, and he was referred to our hospital. Diagnosis The patient showed leukopenia, lymphopenia, serum creatinine elevation with proteinuria and hematuria, decreased serum C3 level, and was positive for anti-double stranded DNA antibody, anti-nuclear antibody, and direct Coombs test. He was diagnosed with SLE. Renal biopsy was performed, and the patient was diagnosed with lupus nephritis (class IV-G(A/C) + V defined by the International Society of Nephrology/Renal Pathology Society classification). Computed tomography revealed acute interstitial pneumonitis, bronchoalveolar lavage fluid showed elevation of the lymphocyte fraction, and he was diagnosed with lupus pneumonitis. Interventions Prednisolone (50 mg/day) with intravenous cyclophosphamide (500 mg/body) were initiated. Outcomes The patient showed a favorable response to these therapies. He was discharged from our hospital and received outpatient care with prednisolone slowly tapered off. He had cytomegalovirus and herpes zoster virus infections during treatment, which healed with antiviral therapy. Review: We searched for the literature on sSLE, and selected 11 case reports and 2 population-based studies. The prevalence of SLE manifestations in sSLE patients were comparative to that of general SLE, particularly that of elderly-onset SLE. Our renal biopsy report and previous reports indicate that lupus nephritis of sSLE patients show as various histological patterns as those of general SLE patients. Among the twenty sSLE patients reported in the case articles, three patients developed lupus pneumonitis and two of them died of it. Moreover, two patients died of bacterial pneumonia, one developed aspergillus abscesses, one got pulmonary tuberculosis, and one developed lung cancer. Conclusion Close attention is needed, particularly for respiratory system events and infectious diseases, when treating patients with silica-associated SLE using immunosuppressive therapies.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44261212022Prevalence of Chronic Kidney Disease and Variation of Its Risk Factors by the Regions in Okayama Prefecture97ENRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHaruhito AdamUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjective: The prevention of chronic kidney disease (CKD) progression is an important issue from health and financial perspectives. We conducted a single-year cross-sectional study to clarify the prevalence of CKD and its risk factors along with variations in these factors among five medical regions in Okayama Prefecture, Japan. Methods and Results: Data concerning the renal function and proteinuria as well as other CKD risk factors were obtained from the database of the Japanese National Health Insurance. The proportion of CKD patients at an increased risk of progression to end-stage renal disease (ESRD), classified as orange and red on the CKD heatmap, ranged from 6-9% and did not vary significantly by the regions. However, the causes of the increased severity differed between regions where renal dysfunction was predominant and regions where there were many patients with proteinuria. CKD risk factors, such as diabetes mellitus, hypertension, hyper low-density lipoprotein-cholesterolemia, obesity, smoking and lack of exercise, also differed among these regions, suggesting that different regions need tailored interventions that suit the characteristics of the region, such as an increased health checkup ratio, dietary guidance and promotion of exercise opportunities. Conclusions: Approximately 6-9% of people are at an increased risk of developing ESRD (orange or red on a CKD heatmap) among the population with National Health Insurance in Okayama Prefecture. The underlying health problems that cause CKD may differ among the regions. Thus, it is necessary to consider intervention methods for preventing CKD progression that are tailored to each region's health problems.No potential conflict of interest relevant to this article was reported.S. Karger AGActa Medica Okayama0250-80955312021Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray1020ENYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKokiMiseDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiekoKawakitaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyosukeSugawaraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiYamaguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalMasaoYamadaGlycoTechnica Ltd.JunHirabayashiInstitute for Glyco-core Research, Nagoya UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction. The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN. <br>
Methods. We conducted the retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between Dec. 2010 and Sep. 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA was improved by adding the urinary glycan intensity.<br>
Results. Among 45 lectins, 3 lectins showed a significant improvement of the models: Amaranthus caudatus lectin (ACA) with the difference of c-statistics 0.038 [95%CI, 0.019 - 0.058, P < 0.001], Agaricus bisporus lectin (ABA) 0.035 [95%CI, 0.015 - 0.055, P < 0.001], Maackia amurensis lectin (MAH) 0.035 [95%CI, 0.015 - 0.054, P < 0.001]. In 3 lectins, each signal plus reference standard showed good reclassification (category free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to reference standard at the pre-defined threshold probability of 40%.
Conclusions. The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan analysis by ACA is useful and robust non-invasive strategy for the diagnosis of IgAN.No potential conflict of interest relevant to this article was reported.Lippincott Williams & WilkinsActa Medica Okayama0025-7974100502021Management of corticosteroid-dependent eosinophilic interstitial nephritis A case reporte28252ENKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyoMifuneDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiekoKawakitaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: Drug-induced acute interstitial nephritis (DI-AIN) is an important cause of acute kidney injury. In renal biopsy specimens, tubulitis with eosinophilic infiltration is suggestive of DI-AIN. Although corticosteroid therapy and discontinuation of the offending drug can improve renal dysfunction in most cases of DI-AIN, some patients experience AIN recurrence, leading to corticosteroid dependency. Corticosteroid-dependent eosinophilic interstitial nephritis presents a difficult dilemma in diagnosis and information regarding optimum management is limited. <br>
Patient concerns: A 25-year-old man, who received treatment with carbamazepine, zonisamide, valproate, and lacosamide for temporal lobe epilepsy, showed an increase in serum creatinine level from 0.98 to 1.29 mg/dL over a period of 6 months. Although he exhibited no symptoms, his serum creatinine level continued to increase to 1.74 mg/dL. <br>
Diagnosis: Renal biopsy revealed tubulitis and interstitial inflammatory infiltrates with eosinophils. Immunological and ophthalmological examinations showed no abnormal findings, and thus, his renal dysfunction was presumed to be caused by DI-AIN. Although oral prednisolone (PSL) administration (40 mg/d) and discontinuation of zonisamide immediately improved his renal function, AIN recurred 10 months later. The increase in PSL dose along with discontinuation of valproate and lacosamide improved renal function. However, 10 months later, recurrent AIN with eosinophilic infiltration was confirmed by further biopsy. The patient was therefore diagnosed with corticosteroid-dependent eosinophilic interstitial nephritis.<br> Interventions: To prevent life-threatening epilepsy, carbamazepine could not be discontinued; hence, he was treated with an increased dose of PSL (60 mg/d) and 1500 mg/d of mycophenolate mofetil (MMF). <br>
Outcomes: MMF was well tolerated and PSL was successfully tapered to 5 mg/d; renal function stabilized over a 20-month period. <br>
Lessons: The presence of underdetermined autoimmune processes and difficulties in discontinuing the putative offending drug discontinuation are contributing factors to corticosteroid dependency in patients with eosinophilic interstitial nephritis. MMF may be beneficial in the management of corticosteroid-dependent eosinophilic interstitial nephritis by reducing the adverse effects related to high-dose and long-term corticosteroid use.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221112021Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy3394ENChiekoKawakitaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKokiMiseDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalMasaoYamadaGlycoTechnica LtdJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIn IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (>4 mL/min/1.73 m(2)/year), or eGFR >= 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11-7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11-4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(beta 1-4)GlcNAc and high-mannose including Man(alpha 1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike's information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.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.Elsevier BVActa Medica Okayama0041-13455352021ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study14941500ENShogoWatariDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKoichiroWadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKasumiYoshinagaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYukiMaruyamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYosukeMitsuiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceRisaKubotaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceShingoNishimuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYasuyukiKobayashiDepartment of Urology, 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 ScienceKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceMasashiKitagawaDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHitoshiSugiyamaDepartment 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 ScienceMasamiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceToyohikoWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYasutomoNasuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceBackground<br>
We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function.<br>
<br>
Methods<br>
We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF.<br>
<br>
Results<br>
The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P = .02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P = .006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation.<br>
<br>
Conclusion<br>
ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-29186072021Acute Kidney Injury Caused by Evans Syndrome with Systemic Lupus Erythematosus and Systemic Sclerosis10551060ENNatsumiMatsuokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHarukiWatanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaokoKurookaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSumariKatoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesChikaHigashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiTanabeDivision of Hemodialysis and Apheresis, Okayama University HospitalMasaruKinomuraDivision of Hemodialysis and Apheresis, Okayama University HospitalNobuharuFujiiDepartment of Transfusion Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKen-EiSadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesA 65-year-old woman with systemic sclerosis and systemic lupus erythematosus developed acute kidney injury (AKI), Coombs-positive autoimmune hemolytic anemia and autoimmune thrombocytopenia; therefore, she was diagnosed with Evans syndrome (ES). Intravascular hemolysis was suggested as the cause of AKI based on the presence of acute tubular injury and trace hemosiderin deposits on the renal biopsy. The renal function, hemolytic anemia and thrombocytopenia were restored by an increased dose of glucocorticoids, hemodialysis, and plasma exchange. Although ES with severe hemolytic anemia is very rare, it is important to detect possible renal dysfunction when encountering patients with severe hemolysis.No potential conflict of interest relevant to this article was reported.NatureActa Medica Okayama2399-3642412021A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease373ENAtsukoNakatsukaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiYamaguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunEguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShigeruKakutaDepartment of Biomedical Science, Graduate School of Agricultural and Life Sciences, the University of TokyoYoichiroIwakuraResearch Institute for Biomedical Sciences, Tokyo University of ScienceHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesProximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin-/- obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24680249592020Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells15761580ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiTakahashiDepartment of Nephrology, Faculty of Medical Science, University of FukuiMasayukiIwanoDepartment of Nephrology, Faculty of Medical Science, University of FukuiJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.Lippincott, Williams & WilkinsActa Medica Okayama0025-797499212020Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case reporte20464ENKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and MetabolismHiromitsuKanzakiDepartment of Gastroenterology and HepatologyTakahiraWadaDepartment of Nephrology, Rheumatology, Endocrinology and MetabolismYuriNakashimaDepartment of Nephrology, Rheumatology, Endocrinology and MetabolismHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and MetabolismIntroduction: Immune checkpoint inhibitors including nivolumab, an antibody against programmed death-1, have been increasingly introduced in various cancer treatment regimens, and are reported to be associated with immune-related adverse events. Nivolumab-induced renal injury is generally caused by acute interstitial nephritis and is managed by drug discontinuation and steroid therapy. Although this agent can infrequently induce glomerulonephritis, the pathogenesis and therapeutic strategy remain undetermined. Patient concerns: A 78-year-old man was diagnosed with advanced gastric cancer with portal thrombosis. First- and second-line chemotherapies were ineffective; thus, nivolumab monotherapy was initiated. Although it effectively prevented tumor growth, proteinuria and microhematuria appeared 2 months later. Despite drug discontinuation, serum creatinine progressively increased from 0.72 to 1.45 mg/dL. Renal biopsy revealed mesangial IgA and C3 deposition in immunofluorescence analysis and mesangial proliferation with crescent formation in light microscopy. Diagnosis: The patient was diagnosed with IgA nephropathy. Based on the temporal relationship between the nivolumab therapy and abnormal urinalysis, IgA nephropathy was considered to have been induced by nivolumab. Interventions: A moderate dose (0.6 mg/kg/day) of prednisolone was orally administrated, with tapering biweekly. Outcomes: Steroid therapy stabilized his serum creatinine levels and markedly reduced proteinuria. However, bacterial pneumonia substantially impaired his performance status; thus, nivolumab could not be restarted despite tumor regrowth. Lessons: IgA nephropathy should be recognized as an uncommon renal adverse event during nivolumab therapy. After drug discontinuation, nivolumab-induced IgA nephropathy is likely to respond to moderate doses of steroid therapy with early tapering. However, more evidence is needed to determine whether nivolumab can be safely restarted during or after steroid therapy.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006721122020Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury4545ENHiromasaMiyakeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiTanimuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuriNakashimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyoMoriokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanaMasudaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasufumiSatoNew Industry Creation Hatchery Center, Tohoku UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAcute kidney injury (AKI) has been increasingly recognized as a risk factor for transition to chronic kidney disease. Recent evidence suggests that endothelial damage in peritubular capillaries can accelerate the progression of renal injury. Vasohibin-2 (VASH2) is a novel proangiogenic factor that promotes tumor angiogenesis. However, the pathophysiological roles of VASH2 in kidney diseases remain unknown. In the present study, we examined the effects of VASH2 deficiency on the progression of ischemia-reperfusion (I/R) injury-induced AKI. I/R injury was induced by bilaterally clamping renal pedicles for 25 min in male wild-type (WT) andVash2homozygous knockout mice. Twenty-four hours later, I/R injury-induced renal dysfunction and tubular damage were more severe in VASH2-deficient mice than in WT mice, with more prominent neutrophil infiltration and peritubular capillary loss. After induction of I/R injury, VASH2 expression was markedly increased in injured renal tubules. These results suggest that VASH2 expression in renal tubular epithelial cells might be essential for alleviating I/R injury-induced AKI, probably through protecting peritubular capillaries and preventing inflammatory infiltration.No potential conflict of interest relevant to this article was reported.Public Library of ScienceActa Medica Okayama1932-62031512020Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndromeENAyuOgawa-AkiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiKitagawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzukiKanoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKokiMiseDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNozomuOtakaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorinagaDivision of Medical Informatics,Okayama University HospitalMasaruKinomuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAutophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-2369212020Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report113ENNatsumiMatsuokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesEikiIchiharaDepartment of Hematology, Oncology, Allergy and Respiratory Medicine,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiHaraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKishioTomaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground</br>
The advent of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with advanced malignancies. On the other hand, these drugs might cause immune-related adverse events (irAEs) including endocrinopathies and nephropathies. Thyroid dysfunction is one of the most common irAEs. For ICIs-induced nephropathies, most cases are due to tubulointerstitial nephritis, which might require steroid treatment. Here, we report a patient with non-small cell lung cancer treated with ICI who developed increased serum creatinine (s-Cr) levels due to ICIs-induced hypothyroidism.</br>
Case presentation</br>
A 57-year-old Asian man with refractory non-small cell lung cancer under ICIs therapy (pembrolizumab, an anti-programmed cell death-1 monoclonal antibody) developed increased s-Cr levels 5 months after the pembrolizumab initiation. His laboratory data, renal biopsy, and Gallium-67 scintigraphy findings denied pembrolizumab-induced tubulointerstitial nephritis. His renal function was correlated with thyroid function. Despite the increase of s-Cr levels, serum cystatin C levels were normal, which could be explained by the hypothyroidism. Levothyroxine treatment improved renal function as well as thyroid function. Then pembrolizumab was resumed, and both his thyroid and renal function remained normal level. Ultimately, we concluded that the increased s-Cr levels were caused by pembrolizumab-induced hypothyroidism.</br>
Conclusion</br>
All clinicians involved in ICI treatment need to recognize the possible increase in s-Cr levels caused by ICIs-induced hypothyroidism, and we propose monitoring serum cystatin C levels to differentiate ICIs-induced hypothyroidism from tubulointerstitial nephritis before invasive renal biopsies or steroid treatment, which are recommended by the prescribing information for pembrolizumab, are performed.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7412020Robotic Renal Autotransplantation: A Feasibility Study in a Porcine Model5358ENRisaKubotaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroWadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKasumiKawamuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiMaruyamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeMitsuiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiAriyoshiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroIwataDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShingoNishimuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsushiTakamotoDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoSakoDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiEdamuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuyukiKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzukiKanoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiKitagawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasamiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToyohikoWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasutomoNasuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/57953 We investigated the feasibility of robotic renal autotransplantation (RAT) in a porcine model to reduce invasiveness of RAT. Five pigs underwent robotic RAT using the da Vinci® robotic system. A robotic left nephrectomy was performed in all cases. Robotic RAT was performed on the left side in all but one case. Four ports were used. In 3 cases, the kidney was taken out through the GelPort® and irrigated on ice with Ringer’s solution. In 2 cases, a complete intracorporeal robotic RAT was performed. An end-to-side anastomosis was performed between the renal vein and the external iliac vein and between the renal artery and the external iliac artery. Ureteroneocystostomy was also performed in 2 cases. All cases were performed robotically without open conversion. The median (IQR) console time was 3.1 (0.7) h, and the operative time was 3.8 (1.1) h. The estimated blood loss was 30 (0) ml. The warm ischemia time was 4.0 (0.2) min, and the cold ischemia time was 97 (17) min. Intracorporeal transarterial hypothermic renal perfusion was feasible in the 2 complete intracorporeal robotic RAT cases by using a perfusion catheter through a laparoscopic port. Robotic RAT has the potential to be a new minimally invasive substitute for conventional open surgery.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7152017Immunohistochemistry of Vasohibin-2 in Human Kidney Disease : Implications in Impaired Glucose Tolerance and Reduced Renal Function369380ENYukaArataDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical SciencesNorikazuHinamotoPharmaceuticals and Medical Devices AgenciesHirokoYamasakiTakahashi Central HospitalHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical SciencesYoheiMaeshimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical SciencesNaokiKanomataDepartment of Pathology 2, Kawasaki Medical SchoolYasufumiSatoDepartment of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/55434 Several angiogenesis-related factors are known to play important roles in the pathogenesis of kidney disease. Vasohibin-2 (VASH-2) was recently reported as a novel proangiogenic factor. Although VASH-2 was demonstrated to accelerate tumor angiogenesis, its roles in non-tumor processes including renal disease have not been well elucidated yet. Here, we performed a retrospective study including an immunohistochemical analysis of human kidney biopsy specimens from 82 Japanese patients with a variety of kidney diseases, and we evaluated the correlations between the immunoreactivity of VASH-2 and the patients’ clinicopathological parameters. VASH-2 immunoreactivity was detected in varying degrees in renal tubules as well as in peritubular capillaries and vasa recta. The cortical and medullary tubule VASH-2+ scores were correlated with the presence of hypertension, and the medullary tubule VASH-2+ score was significantly correlated with the blood glucose (p=0.029, r=0.35) and hemoglobin A1c levels (p=0.0066, r=0.39). Moreover, decreased VASH-2+ scores in the vasa recta were associated with reduced renal function (p=0.0003). These results suggest that VASH-2 could play an important role in the pathogenesis of renal diseases, and that VASH-2 is closely associated with hypertension and impaired glucose tolerance.No potential conflict of interest relevant to this article was reported.Taylor & FrancisActa Medica Okayama1439-75952652016Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study730737ENKen-eiSada Department of Nephrology, Rheumatology, Endocrinology and Metabolism , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayoshiHarigaiDepartment of Rheumatology, Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental UniversityKoichiAmanoDepartment of Rheumatology and Clinical Immunology , Saitama Medical Center, Saitama Medical UniversityTatsuyaAtsumiDivision of Rheumatology, Endocrinology and Nephrology at the Graduate School of Medicine , Hokkaido UniversityShouichiFujimotoDepartment of Hemovascular Medicine and Artificial Organs, Faculty of Medicine , Miyazaki UniversityYukioYuzawaDepartment of Nephrology , Fujita Health University School of MedicineYoshinariTakasakiDepartment of Internal Medicine and Rheumatology , Juntendo University School of MedicineShogoBannoDivision of Rheumatology and Nephrology, Department of Internal Medicine , Aichi Medical University School of MedicineTakahikoSugiharaTokyo Metropolitan Geriatric Hospital and Institute of GerontologyMasakiKobayashiDepartment of Nephrology , Tokyo Medical University Ibaraki Medical CenterJoichiUsuiDepartment of Nephrology, Faculty of Medicine , University of TsukubaKunihiroYamagataDepartment of Nephrology, Faculty of Medicine , University of TsukubaSakaeHommaDepartment of Respiratory Medicine , Toho University Omori Medical CenterHiroakiDobashiDivision of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine , Kagawa University NaotakeTsuboiDepartment of Nephrology, Internal Medicine , Nagoya University Graduate School of MedicineAkihiroIshizuFaculty of Health Sciences , Hokkaido UniversityHitoshiSugiyamaDepartment of Chronic Kidney Disease and Peritoneal Dialysis , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YasunoriOkadaDepartment of Pathology , Keio University School of MedicineYoshihiroArimuraNephrology and Rheumatology, First Department of Internal Medicine , Kyorin University School of MedicineSeiichiMatsuoDepartment of Nephrology, Internal Medicine , Nagoya University Graduate School of MedicineHirofumiMakinoOkayama University HospitalOBJECTIVE:
To compare disease severity classification systems for six-month outcome prediction in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
METHODS:
Patients with newly diagnosed AAV from 53 tertiary institutions were enrolled. Six-month remission, overall survival, and end-stage renal disease (ESRD)-free survival were evaluated.
RESULTS:
According to the European Vasculitis Study Group (EUVAS)-defined disease severity, the 321 enrolled patients were classified as follows: 14, localized; 71, early systemic; 170, generalized; and 66, severe disease. According to the rapidly progressive glomerulonephritis (RPGN) clinical grading system, the patients were divided as follows: 60, grade I; 178, grade II; 66, grade III; and 12, grade IV. According to the Five-Factor Score (FFS) 2009, 103, 109, and 109 patients had ≤1, 2, and ≥3 points, respectively. No significant difference in remission rates was found in any severity classification. The overall and ESRD-free survival rates significantly differed between grades I/II, III, and IV, regardless of renal involvement. Severe disease was a good predictor of six-month overall and ESRD-free survival. The FFS 2009 was useful to predict six-month ESRD-free survival but not overall survival.
CONCLUSIONS:
The RPGN grading system was more useful to predict six-month overall and ESRD-free survival than the EUVAS-defined severity or FFS 2009.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812722015腹膜透析Update111115ENHitoshiSugiyamaNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6922015A Paraganglioma in a Hypertensive Patient with Unilateral Renal Hypoplasia119122ENTomohiroTerasakaHideharuHagiyaKosukeKimuraTakahiroNadaEriNakamuraYoshihisaHanayamaHitoshiSugiyamaYasuyukiKobayashiHiroyukiYanaiFumioOtsukaCase Report10.18926/AMO/53341We report the case of a 46-year-old hypertensive Japanese female with renal insufficiency related to unilateral renal hypoplasia. The patient was found to have developed paraganglioma in the retroperitoneal space over a 5-year period. Catecholamine-producing tumors are not usually recognized as conditions associated with renal hypoplasia. Our long-term observation of the patient eventually led us to the diagnosis of paraganglioma. In hypertensive patients with chronic kidney disease, not only the renin-angiotensin-aldosterone system but also catecholamine activity may be involved, particularly in the patients whose cases are complicated with unilateral renal hypoplasia.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6912015ONO-1301, a Sustained-Release Prostacyclin Analog, Ameliorates the Renal Alterations in a Mouse Type 2 Diabetes Model Possibly Through Its Protective Effects on Mesangial Cells115ENHiroyukiWatataniHirokoYamasakiYoheiMaeshimaTatsuyoNasuNorikazuHinamotoHaruyoUjikeHitoshiSugiyamaYoshikiSakaiKatsuyukiTanabeHirofumiMakinoOriginal Article10.18926/AMO/53117Diabetic nephropathy is the most common pathological disorder predisposing patients to end-stage renal disease. Considering the increasing prevalence of type 2 diabetes mellitus worldwide, novel therapeutic approaches are urgently needed. ONO-1301 is a novel sustained-release prostacyclin analog that inhibits thromboxane A2 synthase. Here we examined the therapeutic effects of the intermittent administration of slow-release ONO-1301 (SR-ONO) on diabetic nephropathy in obese type 2 diabetes mice, as well as its direct effects on mesangial cells. The subcutaneous injection of SR-ONO (3mg/kg) every 3 wks did not affect the obesity or hyperglycemia in the db/db obese mice used as a model of type 2 diabetes, but it significantly ameliorated their albuminuria, glomerular hypertrophy, glomerular accumulation of type IV collagen, and monocyte/macrophage infiltration, and also the increase of TGF-β1, α-smooth muscle actin (α-SMA) and MCP-1 compared to vehicle treatment. In cultured mouse mesangial cells, ONO-1301 concentration-dependently suppressed the increases in TGF-β, type IV collagen, α-SMA, MCP-1 and fibronectin induced by high ambient glucose, at least partly through prostacyclin (PGI2) receptor-mediated signaling. Taken together, these results suggest the potential therapeutic efficacy of the intermittent administration of SR-ONO against type 2 diabetic nephropathy, possibly through protective effects on mesangial cells.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
(r=0.48, p=0.001) or cortex (r=0.64, p<0.0001), 2) interstitial cell infiltration and the number of VASH-1+ cells in the cortex (r=0.34, p=0.02), 3) the glomerular VEGFR-2+ area and the number of VASH-1+ cells in the glomerulus (r=0.44, p=0.01) or medulla (r=0.63, p=0.01). 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.Okayama University Medical SchoolActa Medica Okayama0386-300X6812014Long-term Observation of Osteomalacia Caused by Adefovir-Induced Fanconi’s Syndrome5356ENTomohiroTerasakaEijiroUetaHirotakaEbaraKoichiWasedaYoshihisaHanayamaAkinobuTakakiTomokoKawabataHitoshiSugiyamaKoHidanFumioOtsukaCase Report10.18926/AMO/52145A 64-year-old man suffering polyarthralgia and bone pain was referred to our hospital. Renal dysfunction,
hypophosphatemia and increased levels of bone alkaline phosphatase were found. The patientʼs serum creatinine level had gradually increased after the initiation of adefovir dipivoxil administration for hepatitis B. In agreement with multifocal uptakes of bone scintigraphy, iliac bone biopsy revealed an abnormal increase in osteoid tissues. Reducing the dose of adefovir and initiating the administration of eldecalcitol were effective for reducing proteinuria and glucosuria, and for ameliorating bone pain with an increase in serum phosphate level. This case first showed a clinical course of hypophosphatemic osteomalacia caused by secondary Fanconiʼs syndrome for 8 years after adefovir administration. Early diagnosis is important for the reversibility of bone damage and for a better renal prognosis.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.岡山医学会Acta Medica Okayama0030-155812312011血管新生negative feedback制御因子Vasohibin-1によるマウス糖尿病性腎症進展制御効果の検討1925ENTatsuyoNasuYoheiMaeshimaMasaruKinomuraKumikoHirokoshi-KawaharaKatsuyukiTanabeHitoshiSugiyamaHikaruSonodaYasufumiSatoHirofumiMakinoNo potential conflict of interest relevant to this article was reported.