Inpatient multidisciplinary care can prevent deterioration of renal function in patients with chronic kidney disease: a nationwide cohort study

BackgroundMultidisciplinary care is necessary to prevent worsening renal function and all-cause mortality in patients with chronic kidney disease (CKD) but has mostly been investigated in the outpatient setting. In this study, we evaluated the outcome of multidisciplinary care for CKD according to whether it was provided in an outpatient or inpatient setting.MethodsThis nationwide, multicenter, retrospective, observational study included 2954 Japanese patients with CKD stage 3–5 who received multidisciplinary care in 2015–2019. Patients were divided into two groups: an inpatient group and an outpatient group, according to the delivery of multidisciplinary care. The primary composite endpoint was the initiation of renal replacement therapy (RRT) and all-cause mortality, and the secondary endpoints were the annual decline in the estimated glomerular filtration rate (ΔeGFR) and the changes in proteinuria between the two groups.ResultsMultidisciplinary care was provided on an inpatient basis in 59.7% and on an outpatient basis in 40.3%. The mean number of health care professionals involved in multidisciplinary care was 4.5 in the inpatient group and 2.6 in the outpatient group (P < 0.0001). After adjustment for confounders, the hazard ratio of the primary composite endpoint was significantly lower in the inpatient group than in the outpatient group (0.71, 95% confidence interval 0.60-0.85, P = 0.0001). In both groups, the mean annual ΔeGFR was significantly improved, and proteinuria significantly decreased 24 months after the initiation of multidisciplinary care.ConclusionMultidisciplinary care may significantly slow deterioration of eGFR and reduce proteinuria in patients with CKD and be more effective in terms of reducing initiation of RRT and all-cause mortality when provided on an inpatient basis

Clinical Guides for aHUS

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS

HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype

ObjectiveAutoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.MethodsHLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.ResultsThe predisposing association of DRB1*04:01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62–5.43), DRB1*04:05 (P = 1.89×10−21, Pc = 5.86×10−20, OR 3.41, 95% CI 2.65–4.38), and DQB1*04:01 (P = 4.66×10−18, Pc = 6.99×10−17, OR 3.89, 95% CI 2.84–5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32–0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10−9, OR 3.52, 95% CI 2.34–5.29). Susceptible diplotypes were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45–424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10−6, OR 10.64, 95% CI 3.19–35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04:05 than without.ConclusionsThe important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQα-β heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes

Porphyromonas gingivalis SOD における活性中心近傍に局在するアミノ酸残基の金属特異的活性における関与：Leu ₇2 Trp およびLeu ₇6 Phe の2残基変異による検討

The role of superoxide dismutase (SOD) as a radical scavenger in Porphyromonas gingivalis is well documented. P. gingivalis SOD (Pg SOD), which is characterized by a metal–tolerant activity, can use either iron or manganese as a cofactor. Leu ₇2 and Leu ₇6, located near the active–site metal, are characteristic amino acid sequences of Pg SOD proteins, although they are substituted to Trp in the ₇2 position and Phe in the ₇6 position in most iron–containing SOD (Fe–SOD) proteins. In the present study, we constructed a mutant of the enzyme with changes from Leu ₇2 to Trp and Leu ₇6 to Phe. This mutant SOD was examined with respect to its metal–dependent activity and structural characterization. We herein conclude the integrity of Leu ₇2 and Leu ₇6 is a necessary requisite for the metal–tolerant activity of Pg SOD

Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population

Background: Previous genome-wide association studies have evaluated the impact of common genetic variants and identified several non-HLA risk loci associated with autoimmune liver diseases. More recent genome-wide association studies and replication analyses reported an association between variants of the CARD10 polymorphism rs6000782 and risk of type 1 autoimmune hepatitis (AIH). In this case-control study, we genotyped 326 Japanese AIH patients and 214 control subjects. Results: Genomic DNA from 540 individuals of Japanese origin, including 326 patients with type-1 AIH and 214 healthy controls, was analyzed for two single nucleotide polymorphisms (SNPs) in the CARD10 gene. We selected CARD10 rs6000782 SNPs and genotyped these using PCR-RFLP method and direct sequencing. The Chi square test revealed that the rs6000782 variant alle (c) was not associated with the susceptibility for AIH in a Japanese population [p = 0.376, odds ratio (OR) 1.271, 95 % confidence interval (CI) 0.747-2.161] in an allele model. Our data also showed that CARD10 rs6000782 variants were not associated with AIH or with the clinical parameters of AIH. Conclusions: In this study we examined an association between rs6000782 SNPs in the CARD10 gene and type-1 AIH. Results showed no significant association of rs62000782 with type-1 AIH in a Japanese population. This study demonstrated no association between CARD10 rs6000782 variants and AIH in a Japanese population

Autocrine secretion of transforming growth factor-β in cultured rat mesangial cells

報告番号: 乙10924 ; 学位授与年月日: 1992-10-21 ; 学位の種別: 論文博士 ; 学位の種類: 博士(医学) ; 学位記番号: 第10924号 ; 研究科・専攻: 医学系研究