270 research outputs found
Dialysis-Related Amyloidosis: Pathogenesis and Clinical Features in Patients Undergoing Dialysis Treatment
Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients
Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.BackgroundThe predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.MethodsDialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.ResultsSixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium × phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 ≤9860 ng/L and iPTH ≤591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 >9860 ng/L and iPTH >591 pg/mL.ConclusionPretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism
Association of liver enzyme levels and alveolar bone loss : a cross-sectional clinical study in Sado Island
The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults
Clinical features and pathogenesis of membranoproliferative glomerulonephritis: a nationwide analysis of the Japan renal biopsy registry from 2007 to 2015
BackgroundThe incidence and age distribution of membranoproliferative glomerulonephritis (MPGN) vary throughout the world by race and ethnicity. We sought to evaluate the clinical features, pathogenesis, and age distribution of MPGN among a large nationwide data from the Japan Renal Biopsy Registry (J-RBR).MethodsA cross-sectional survey of 593 patients with MPGN (types I and III) registered in the J-RBR between 2007 and 2015 was conducted. Clinical parameters, and laboratory findings at diagnosis were compared between children (< 20 years), adults (20–64 years), and elderly patients (≥ 65 years).ResultsThe median age of the patients was 59.0 years and mean proteinuria was 3.7 g/day. The rate of nephrotic syndrome was significantly higher in adults (40.4%) and elderly patients (54.0%) than in children (14.9%), whereas the rate of chronic glomerulonephritis was significantly higher in children (66.2%) than in adults (34.4%) and elderly patients (31.2%). According to the CGA risk classification, high-risk (red zone) cases accounted for 3.4% of children, 52.5% of adults and 84.1% of elderly patients with MPGN. As for pathogenesis, primary MPGN was most frequent (56.0%). Lupus nephritis was the most common disease among adult patients with secondary MPGN, whereas infectious disease was more common in elderly patients. Multiple regression analysis revealed that high systolic blood pressure and high proteinuria were independent factors associated with decreased estimated glomerular filtration rate (eGFR) in adults and elderly patients with MPGN.ConclusionsIn Japan, adults and elderly patients with MPGN had a lower eGFR and severer proteinuria than children
Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study
It 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 to130 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 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)
Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis
Nakajima K., Yamaguchi K., Noji M., et al. Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis. Nature Communications 13, 5689 (2022); https://doi.org/10.1038/s41467-022-33247-3.Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu
Prescription of reninâ angiotensinâ aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care
Reninâ angiotensinâ aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66â 72Â years; congestive heart failure [CHF] in 11%â 19%; diabetes in 43%â 54%; serum potassium â ¥5 in 20%â 35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong classâ specific recommendations. Although the reasons for this variation could not be fully identified in this crossâ sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150590/1/jch13563.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150590/2/jch13563_am.pd
Type I Angiotensin II Receptor Blockade Reduces Uremia-Induced Deterioration of Bone Material Properties
Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type 1 angiotensin II receptor blockade (AT-1RB) on preventing CKD-related fragility fractures and elucidate its pharmacological mechanisms. AT-1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation, and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass was unchanged. Olmesartan suppressed angiotensin II-dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II-dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT-1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Wakamatsu T., Iwasaki Y., Yamamoto S., et al. Type I Angiotensin II Receptor Blockade Reduces Uremia-Induced Deterioration of Bone Material Properties. Journal of Bone and Mineral Research, 36, 1, 67. https://doi.org/10.1002/jbmr.4159
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