Background and objectivesPatients with kidney failure have a high risk of cardiovascular disease due to cardiac remodeling, left ventricular fibrosis, and hyperaldosteronism, all of which can be potentially mitigated by mineralocorticoid receptor antagonists. However, because of the fear of hyperkalemia, the use of mineralocorticoid receptor antagonists in patients with kidney failure is limited in current clinical practice, and few studies have investigated the efficacy and safety. Thus, we aimed to determine the benefits and side effects of mineralocorticoid receptor antagonists in patients with kidney failure treated with dialysis.Design, setting, participants, & measurementsThis is a systematic review and meta-analysis of randomized controlled trials published from 2005 to 2020 that compared the effect of mineralocorticoid receptor antagonists with either placebo or no treatment in patients with kidney failure. Two reviewers independently searched the PubMed, EMBASE, and Cochrane databases for all published studies, extracted data, assessed the risk of bias, and rated the quality of evidence. A meta-analysis was conducted on 14 eligible randomized controlled trials, and a total of 1309 patients were included.ResultsHigh-quality evidence suggested that mineralocorticoid receptor antagonists are associated with lower cardiovascular mortality (relative risk, 0.41; 95% confidence interval, 0.24 to 0.70; P=0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; P<0.001), and the risk of hyperkalemia was comparable with that of control group (relative risk, 1.12; 95% confidence interval, 0.91 to 1.36; P=0.29). However, no significant decrease in nonfatal cardiovascular events and stroke was observed, and there was no significant improvement in BP or cardiac performance parameters, including left ventricular ejection fraction and left ventricular mass index.ConclusionsOur meta-analysis suggests that mineralocorticoid receptor antagonists might improve clinical outcomes of patients with kidney failure without significant increase in the risk of hyperkalemia.
Predicting mortality in dialysis patients based on low intact parathyroid hormone levels is difficult, because aluminum intoxication, malnutrition, older age, race, diabetes, or peritoneal dialysis may influence these levels. We investigated the clinical implications of low parathyroid hormone levels in relation to the mortality of dialysis patients using sensitive, stratified, and adjusted models and a nationwide dialysis database. We analyzed data from 2005 to 2012 that were held on the Taiwan Renal Registry Data System, and 94,983 hemodialysis patients with valid data regarding their intact parathyroid levels were included in this study. The patient cohort was subdivided based on the intact parathyroid hormone and alkaline phosphatase levels. The mean hemodialysis duration within this cohort was 3.5 years. The mean (standard deviation) age was 62 (14) years. After adjusting for age, sex, diabetes, the hemodialysis duration, serum albumin levels, hematocrit levels, calcium levels, phosphate levels, and the hemodialysis treatment adequacy score, the single-pool Kt/V, the crude and adjusted all-cause mortality rates increased when alkaline phosphatase levels were higher or intact parathyroid hormone levels were lower. In general, at any given level of serum calcium or phosphate, patients with low intact parathyroid hormone levels had higher mortality rates than those with normal or high iPTH levels. At a given alkaline phosphatase level, the hazard ratio for all-cause mortality was 1.33 (p < 0.01, 95% confidence interval 1.27–1.39) in the group with intact parathyroid hormone levels < 150 pg/mL and serum calcium levels > 9.5 mg/dL, but in the group with intact parathyroid hormone levels > 300 pg/mL and serum calcium levels > 9.5 mg/dL, the hazard ratio was 0.92 (95% confidence interval 0.85–1.01). Hence, maintaining albumin-corrected high serum calcium levels at > 9.5 mg/dL may correlate with poor prognoses for patients with low intact parathyroid hormone levels.
The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.
Background Lower gastrointestinal bleeding (LGIB) is very common in the hospital setting. Most bleedings stop spontaneously, but rare infectious causes of LGIB may lead to rapid and serious complications if left untreated and are sometimes very difficult to diagnose preoperatively. Case presentation We described a young man with poorly controlled Type I diabetes mellitus and chronic alcohol abuse who presented with acute altered mental status. During his hospitalization for treatment of diabetic ketoacidosis, acute renal failure, and sepsis, he suddenly developed massive hematochezia of 1500 mL. Colonoscopy was performed and a deep ulcer covered with mucus with peripheral elevation was noted at the transverse colon. Biopsy of the ulcer later revealed nonpigmented, wide (5–20 µm in diameter), thin-walled, ribbon-like hyphae with few septations and right-angle branching suggestive of mucormycosis demonstrated by Periodic acid–Schiff stain. He received 2 months of antifungal treatment. Follow up colonoscopy post-treatment was normal with no ulcer visualized. Conclusions Early diagnosis and treatment of gastrointestinal (GI) mucormycosis infection is critical but can be challenging, especially in the setting of massive hematochezia. Therefore, clinical awareness for immunocompromised patients and prompt antifungal prophylaxis in cases with high suspicion of infection are essential.
The effectiveness and safety of direct-acting antiviral agents (DAAs) in hepatitis C virus (HCV) patients with renal insufficiency remain controversial. Therefore, this network meta-analysis aims to assess effectiveness and safety of DAAs in populations with different renal function. The pooled data were obtained from Cochrane Library, EMBASE, PubMed, and Web of Science. Thirteen studies recruited 6884 patients with hepatitis C infection and reported their outcomes in relation to different levels of renal function after treatment with DAAs. The results showed no difference in the virologic responses among patients with different renal function. Regarding safety, whereas in patients without chronic kidney disease (CKD) or with early CKD DAAs were associated with a risk ratio (RR) of 0.14 (95% confidence interval (CI), 0.04 to 0.43) for renal disorder, increased risk of renal function deterioration was found in advanced-CKD patients, though this effect may be related to the natural course of advanced CKD. Similarly, patients without CKD or with early CKD showed a lower risk of anemia (RR, 0.34; 95% CI, 0.20 to 0.57) and discontinuation (RR, 0.41; 95% CI, 0.39 to 0.56) than patients with advanced CKD. The efficacy of DAAs for HCV treatment was comparable in patients with advanced CKD and in those with early CKD or without CKD. However, the safety of DAAs should be verified in future studies.
BackgroundAnemia is common among end-stage renal disease (ESRD) patients who undergone hemodialysis. The total reduction of red blood cell (RBC) count is associated with poor prognosis in these patients. Although erythropoietin (EPO) has been used as an effective treatment for ESRD patients with anemia, a large number of patients still present poor responses to EPO treatment.MethodsWe measured T-cell receptor sequencing profiles, including length of complementarity-deteremining region 3 (CDR3), intra- and inter-group (EPO resistant vs. responsive) clonotype diversity, V(D)J usage profiles and V-J combinations from ESRD patients and to investigate the correlation between these features and EPO treatment efficacy.ResultsOur results revealed statistical significance in the top 3 ~ 15 most abundant joint distributions of Vβ/Jβ among the two groups, suggesting the importance of V or J gene utilization in the EPO response of ESRD patients.ConclusionsIn summary, we provided evidence addressing the potential correlation between the immune repertoire and EPO response in ESRD patients.Trial registration TMU-JIRB 201309026. Registered 16 October 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-017-0349-5) contains supplementary material, which is available to authorized users.
Rationale Glycosylation on immunoglobulins is important for the immune function. In this study, we developed and validated a method for the absolute quantification of IgA subclasses and relative quantification of IgA‐Fc glycopeptides by using affinity purification and ultrahigh‐performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS). Only micro‐volumes of plasma were required from each sample and we also applied the method to discover IgA and IgA‐glycopeptide profiles in patients with chronic kidney diseases and IgA nephropathy. Methods Peptide M affinity beads were used to purify IgA, and a cost‐effective peptide analogue was added as internal standard. With an efficient on‐bead digestion process, purified samples were analyzed by UHPLC/MS/MS in multiple reaction monitoring mode. Results Correlation coefficients were greater than 0.999 for the IgA1 and IgA2 calibration curves and greater than 0.994 for glycopeptide regression curves. Intraday and interday precisions for IgA1 and IgA2 were <1.6% and <5.1% RSD, respectively. Intraday and interday accuracies ranged from 102.6 to 114.9% and 103.5 to 113.5% for IgA1 and IgA2, respectively. Stabilities of IgA1 and IgA2 at −80°C for 7 to 15 days ranged from 96.0 to 109.4%, respectively. The Pearson's correlation coefficient was 0.916 when comparing the IgA quantification results of the 30 clinical samples by using ELISAs and the developed UHPLC/MS/MS method. Compared with healthy controls, IgA and IgA‐glycopeptides showed different profiles in patients with chronic kidney diseases and IgA nephropathy. Conclusions The developed method showed good validation results, and the absolute quantification results of IgA correlated with those from ELISA. The pilot application study showed that IgA and IgA‐glycopeptides can be potential biomarker candidates for kidney diseases, and more clinical sample applications are worth investigating.
Background: Chronic kidney disease (CKD) patients tend to have a reduced immune response to infection and vaccination. The efficacy of current available COVID-19 vaccines in CKD patients has not been widely evaluated. Methods: In the present study, three hundred and eight chronic dialysis patients received ChAdOx1 nCoV-19 (Oxford-AstraZeneca, AZ). Blood tests using an antibody against the receptor-binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike protein had performed at four designed time points before and after the first and second vaccine. Results: The mean age of patients was 65.5 ± 12.38 years, and the male/female ratio was 61.4%:38.6% (189/119). Two weeks after the first vaccination, only 37.66% of patients had a positive antibody response (>50 AU/mL). However, 65.58% of the participants showed a delayed antibody response ten weeks after the first vaccine. Four weeks after the second vaccine, 94.16% of participants had positive antibody levels. Age was the most significant factor associated with antibody response. Flow cytometry analysis revealed that immune-naïve patients had significantly lower early active B cells and proliferative B cells than the age- and sex-matched immune responders. Conclusion: Despite a delayed response, 94.16% of chronic dialysis patients achieved a positive antibody response after two doses of the AZ vaccine. Age is the most significant factor associated with antibody response.
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