非心臓手術において、術前・術中の利尿剤投与が術後急性腎障害と有意に関連するが、レニンーアンギオテンシン系の阻害薬は有意に関連しない。後ろ向きコホート研究

BACKGROUND AND OBJECTIVES: Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery.　DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed.　RESULTS: There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1).　CONCLUSIONS: Prescription of diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients.博士（医学）・乙第1409号・平成29年11月24日Copyright: © 2015 Tagawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial

Aim: To identify the mediators between canagliflozin and renoprotection in patients with type 2 diabetes at a high risk of end-stage kidney disease (ESKD). Methods: In this post hoc analysis of the CREDENCE trial, the effect of canagliflozin on potential mediators (42 biomarkers) at 52 weeks and the association between changes in mediators and renal outcomes were evaluated using mixed-effects and Cox models, respectively. The renal outcome was a composite of ESKD, serum creatinine doubling or renal death. The percentage of the mediating effect of each significant mediator was calculated based on changes in the hazard ratios of canagliflozin after additional adjustment of the mediator. Results: Changes in haematocrit, haemoglobin, red blood cell (RBC) count and urinary albumin-to-creatinine ratio (UACR) at 52 weeks significantly mediated 47%, 41%, 40% and 29% risk reduction with canagliflozin, respectively. Further, 85% mediation was attributed to the combined effect of haematocrit and UACR. A large variation in mediating effects by haematocrit change existed among the subgroups, ranging from 17% in those patients with a UACR of more than 3000 mg/g to 63% in patients with a UACR of 3000 mg/g or less. In the subgroups with a UACR of more than 3000 mg/g, UACR change was the highest mediating factor (37%), driven by the strong association between UACR decline and renal risk reduction. Conclusions: The renoprotective effects of canagliflozin in patients at a high risk of ESKD can be significantly explained by changes in RBC variables and UACR. The complementary mediating effects of RBC variables and UACR may support the renoprotective effect of canagliflozin in different patient groups.Doi Y., Hamano T., Yamaguchi S., et al. Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial. Diabetes, Obesity and Metabolism , (2023); https://doi.org/10.1111/dom.15191

The Utility of Serum IgG4 Concentrations as a Biomarker

IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease

International Consensus Diagnostic Criteria for Autoimmune Pancreatitis and Its Japanese Amendment Have Improved Diagnostic Ability over Existing Criteria

Objectives. The recent International Consensus Diagnostic Criteria (ICDC) for autoimmune pancreatitis (AIP) and its Japanese amendment developed by the Japanese Pancreas Society (JPS 2011) may have overcome the drawbacks of earlier criteria and achieved a higher diagnostic ability for AIP. The aim of the present study is to evaluate this possibility and identify the underlying causes of this change. Methods. We compared the diagnostic abilities of the ICDC and JPS 2011 with those of the Japanese diagnostic criteria 2006 (JPS 2006), Korean diagnostic criteria (Korean), Asian diagnostic criteria (Asian), and HISORt diagnostic criteria in 110 patients with AIP and 31 patients with malignant pancreatic cancer. Results. The ICDC achieved the highest diagnostic ability in terms of accuracy (95.0%), followed by JPS 2011 (92.9%), Korean (92.2%), HISORt (88.7%), Asian (87.2%), and JPS 2006 (85.1%). Nearly all criteria systems exhibited a high specificity of 100%, indicating that the enhanced diagnostic ability of the ICDC and JPS 2011 likely stemmed from increased sensitivity brought about by inclusion of diagnostic items requiring no endoscopic retrograde pancreatography. The diagnostic ability of JPS 2011 was nearly equivalent to that of the ICDC. Conclusions. The ICDC and JPS 2011 have improved diagnostic ability as compared with earlier criteria sets because of an increase in sensitivity.ArticleGASTROENTEROLOGY RESEARCH AND PRACTICE. 2013:456965 (2013)journal articl

C. Elegans Meets Data Sonification: Can We Hear Its Elegant Movement?

(Abstract to follow

Low erythropoietin levels predict faster renal function decline in diabetic patients with anemia: a prospective cohort study

Elevated erythropoietin (EPO) levels have been reported to predict poor survival in various populations including diabetic patients. However, data regarding its impact on renal outcomes are scarce. We conducted a single-center, prospective cohort study of 339 type 2 diabetic patients with anemia. The primary outcome was the estimated glomerular filtration rate (eGFR) slope for two years. We performed multiple linear regression and restricted cubic spline analyses to assess the association of serum EPO levels with the renal outcome. Chronic kidney disease (CKD) was defined as eGFR 30 mg/g creatinine. Median baseline EPO and eGFR level were 14.4 IU/L and 53 mL/min/1.73 m2, respectively. Inappropriately low EPO levels were observed in 73% of anemic patients and 59% of anemic patients even without CKD, suggesting that EPO deficiency precedes the onset of CKD in diabetes mellitus. Multivariable analysis revealed that iron status and hemoglobin levels were major determinants of EPO levels. Median eGFR slope was −1.3 mL/min/1.73 m2/year. We found that low EPO levels, but not low hemoglobin levels, were associated with a faster decline in eGFR, independent of clinically relevant factors. The eGFR decline was steeper, particularly when the EPO level was below the upper limit of normal. Lower EPO concentrations were associated with rapid eGFR decline, especially in patients with iron deficiency (P for interaction = 0.01). Relative EPO deficiency should be considered as a culprit in anemia of unknown etiology in diabetic patients, even those without CKD. Low EPO levels, especially when accompanied by poor iron status, are predictive of rapid loss of renal function.Fujita Y., Doi Y., Hamano T., et al. Low erythropoietin levels predict faster renal function decline in diabetic patients with anemia: a prospective cohort study. Scientific Reports 9, 14871 (2019); https://doi.org/10.1038/s41598-019-51207-8

Mechanisms of Lower Bile Duct Stricture in Autoimmune Pancreatitis

Objectives We attempted to clarify the mechanism underlying lower bile duct stricture in autoimmune pancreatitis. Methods Imaging and histologic finding of the bile duct were assessed for 73 patients with autoimmune pancreatitis to clarify whether IgG4-related biliary inflammation or pancreatic head swelling is associated with lower bile duct stricture. Results Lower bile duct stricture was found in 59 (81%) patients. Pancreatic head swelling was significantly more frequent among patients with lower bile duct stricture than those patients without lower bile duct stricture (53 [90%] vs 4 [29%]; P < 0.01). Intraductal ultrasonography findings revealed lower bile duct wall thickening in 21 (95%) of the 22 patients with lower bile duct stricture, and the lower bile duct wall of the patients with pancreatic head swelling was significantly thicker than those patients without pancreatic head swelling (P = 0.028). Among the 38 patients with lower bile duct biopsies, 14 (37%) exhibited abundant IgG4-bearing plasma cell infiltration. Among the patients with lower bile duct stricture, an IgG4-related inflammation seemed to exert a dominant effect under limited conditions, including concomitant middle bile duct stricture and neither pancreatic swelling nor pancreatic duct stricture in the head region. Conclusions Both pancreatic head swelling and IgG4-related biliary inflammation affect lower bile duct stricture, which may be included in IgG4-related sclerosing cholangitis. Pancreatic head swelling affects IgG4-related biliary wall thickening.ArticlePANCREAS. 43(2):255-260 (2014)journal articl

Recurrence of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits with a Striated Ultrastructure

This is the peer-reviewed but unedited manuscript version of the following article: Nephron 2020;144(suppl 1):43–48 (DOI: 10.1159/000512330)]. The final, published version is available at http://www.karger.com/?doi=10.1159/000512330

Lymphocyte Cell Ratios and Mortality among Incident Hemodialysis Patients.

BackgroundNeutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously suggested as oncologic prognostication markers. These are associated with malnutrition and inflammation, and hence, may provide benefit in predicting mortality among hemodialysis patients.MethodsAmong 108,548 incident hemodialysis patients in a large U.S. dialysis organization (2007-2011), we compared the mortality predictability of NLR and PLR with baseline and time-varying covariate Cox models using the receiver operating characteristic curve (AUROC), net reclassification index (NRI), and adjusted R2.ResultsDuring the median follow-up period of 1.4 years, 28,618 patients died. Median (IQR) NLR and PLR at baseline were 3.64 (2.68-5.00) and 179 (136-248) respectively. NLR was associated with higher mortality, which appeared stronger in the time-varying versus baseline model. PLR exhibited a J-shaped association with mortality in both models. NLR provided better mortality prediction in addition to demographics, comorbidities, and serum albumin; ΔAUROC and NRI for 1-year mortality (95% CI) were 0.010 (0.009-0.012) and 6.4% (5.5-7.3%) respectively. Additionally, adjusted R2 (95% CI) for the Cox model increased from 0.269 (0.262-0.276) to 0.283 (0.276-0.290) in the non-time-varying model and from 0.467 (0.461-0.472) to 0.505 (0.500-0.512) in the time-varying model. There was little to no benefit of adding PLR to predict mortality.ConclusionsHigh NLR in incident hemodialysis patients predicted mortality, especially in the short-term period. NLR, but not PLR, added modest benefit in predicting mortality along with demographics, comorbidities, and serum albumin, and should be included in prognostication approaches