This study aimed to investigate the ameliorative effect of Xinyang Tablets on myocardial fibrosis in uremic cardiomyopathy(UCM) using single-cell sequencing technology. UCM mouse models were established by 5/6 nephrectomy(NPM) and randomly divided into the model group, Xinyang Tablets group, and sham-operated(sham) group as the control. The Xinyang Tablets group received postoperative interventions of Xinyang Tablets(0.34 g·kg~(-1)). After eight weeks, the hearts of the mice in each group were disassociated and subjected to 10×Genomics single-cell sequencing. The data were subjected to t-SNE dimensionality reduction, K-means clustering, and CellMarker annotation prior to analyzing differential expression and cell differentiation trajectories using the Seurat and Monocle3 tools. Additionally, the CellChat tool was used to parse intercellular signaling communication. The results showed that a total of nine types of cells including fibroblasts, endothelial cells, and immune cells were identified in this study. The single-cell expression results of fibroblasts and Gene Ontology(GO) enrichment analysis showed that Xinyang Tablets regulated myocardial fibrosis factors and related signals. Mimetic timing analysis identified three major differentiation trajectories of mouse cardiac fibroblasts and identified the expression of secreted phosphoprotein 1(Spp1) as consistent with the fibroblast differentiation trajectory. Cellular interaction network analysis showed that the communication signals between mouse cardiac fibroblasts and other cells were weakened in the Xinyang Tablets group compared with the model group. The results of ligand-receptor interaction analysis showed that the interaction between myeloid cell-derived osteopontin(OPN) and cardiac fibroblasts and between myeloid cell Spp1 ligand and cardiac fibroblast receptor of mice in the Xinyang Tablets group was weakened compared with the model group. In conclusion, Xinyang Tablets may improve myocardial fibrosis in UCM by inhibiting both endogenous and exogenous OPN at the single-cell level.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cardiomyopathies/pathology* ; Single-Cell Analysis ; Male ; Fibrosis/drug therapy* ; Myocardium/metabolism* ; Uremia/metabolism* ; Tablets ; Mice, Inbred C57BL ; Humans

uremia in chronic kidney disease (CKD) may interact with each other, further complicating the disease course. In this study, we prospectively estimated serum AHRT activity using a highly sensitive cell-based AhR-dependent luciferase activity assay in CKD patients and compared differences therein according to treatment modality.MATERIALS AND METHODS: Patients undergoing peritoneal dialysis (PD) (n=22) and hemodialysis (HD) (n=38) and patients with pre-dialysis CKD stage IV or V (n=28) were included. AHRT activity and intracellular adenosine triphosphate (ATP) levels were measured. We performed a correlation analysis for AHRT activity, ATP levels, and various clinical parameters.RESULTS: AHRT activity and intracellular ATP levels were inversely correlated and differed according to treatment modalities. AHRT activity was higher in non-dialysis CKD patients than in patients undergoing dialysis and was higher in patients undergoing HD, compared to PD. AHRT activity decreased after HD treatment in HD patients. ATP levels were higher in healthy controls than in patients with pre-dialysis CKD and PD and were further decreased in patients with HD. We noted significant correlations between multiple clinical parameters associated with cardiovascular risk factors and AHRT activity.CONCLUSION: AHRT activity was elevated in CKD patients, while dialysis treatment reduced AHRT activity. Further studies are warranted to specify AHRT activity and to evaluate the precise roles thereof in patients with CKD.]]>
Adenosine Triphosphate ; Dialysis ; Humans ; Luciferases ; Peritoneal Dialysis ; Prospective Studies ; Receptors, Aryl Hydrocarbon ; Renal Dialysis ; Renal Insufficiency, Chronic ; Risk Factors ; Uremia

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS: In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.
Anticoagulants ; Blood Platelets ; Colonoscopy ; Female ; Gastrointestinal Tract ; Glomerular Filtration Rate ; Hemorrhage ; Hemorrhoids ; Humans ; Incidence ; Logistic Models ; Lower Gastrointestinal Tract ; Renal Dialysis ; Renal Insufficiency, Chronic ; Retrospective Studies ; Ulcer ; Uremia

OBJECTIVE: To investigate the proportion of aspiration pneumonia cases among patients with community-acquired pneumonia in Korea. METHODS: This retrospective study included patients with community-acquired pneumonia who had been admitted to the emergency department of a university-affiliated tertiary hospital in Gyeonggi Province, Korea between January 1, 2016 and December 31, 2016. Among these patients, those with aspiration pneumonia were identified using ICD-10 codes (J69.*). Patients with recurrent pneumonia were excluded, as were those who were immunocompromised. The proportion of cases of aspiration pneumonia was calculated, and the characteristics and clinical outcomes of patients with aspiration pneumonia and non-aspiration pneumonia were compared. RESULTS: The proportion of aspiration pneumonia cases among patients with community-acquired pneumonia was 14.2%. Patients with aspiration pneumonia were significantly more likely to be older (p<0.001) and male (p<0.001), and to have a higher confusion, uremia, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score (p<0.001) as compared to patients with non-aspiration pneumonia. They were also more likely to require admission to the intensive care unit (p<0.001) and a longer hospital stay (p<0.001). CONCLUSION: Aspiration pneumonia accounts for 14.2% of all cases of community-acquired pneumonia in Korea. These data may contribute to the establishment of healthcare strategies for managing aspiration pneumonia among Korean adults.
Adult ; Blood Pressure ; Community-Acquired Infections ; Delivery of Health Care ; Emergency Service, Hospital ; Gyeonggi-do ; Humans ; Intensive Care Units ; International Classification of Diseases ; Korea ; Length of Stay ; Male ; Pneumonia ; Pneumonia, Aspiration ; Respiratory Rate ; Retrospective Studies ; Tertiary Care Centers ; Uremia

Chronic kidney disease (CKD) is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins (UTs). Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modern medicine. There is a certain relevance between toxins and "turbid toxin" in the theory of Chinese medicine (CM). CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.
Humans ; Intestinal Mucosa ; metabolism ; Medicine, Chinese Traditional ; Renal Insufficiency, Chronic ; drug therapy ; Signal Transduction ; drug effects ; Toxins, Biological ; analysis ; metabolism ; Uremia ; metabolism

Background: Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis. Gut absorption of phosphate is the major source. Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population, and phosphorus is an essential element of bacterial survival and reproduction. The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism. Methods: A prospective self-control study was performed from October 2015 to January 2016. Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients. Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks. Thus, stools were also collected before and after the treatment. The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance profiling, and taxonomic diversity, were used in microbiome data analyses. Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community, SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera. Results: Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4 (P < 0.05). We also found that 58 bacterial operational taxonomic units (OTUs) were significantly different and more decreased OTUs were identified and seven genera (P < 0.05) were obviously reduced after using the phosphate binder. Meanwhile, the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction. The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls, whereas treatment with lanthanum carbonate reduced the network complexity. Conclusions Gut flora related to phosphorus metabolism in hemodialysis patients, and improving intestinal microbiota may regulate the absorption of phosphate in the intestine. The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.
Child ; Female ; Gastrointestinal Microbiome ; drug effects ; physiology ; Humans ; Lanthanum ; therapeutic use ; Male ; Middle Aged ; Phosphorus ; metabolism ; Prospective Studies ; Renal Dialysis ; Risk Factors ; Uremia ; drug therapy ; metabolism ; microbiology

To analyze the clinical profile and therapeutic effect of re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism(SHPT)after parathyroidectomy with autotransplantation.Twelve persistent SHPT patients who were treated with reoperation of paramyroidectomy(PTX)were enrolled in this study during the period from Jan 2014 to Jul 2017 in our hospital.We evaluated the location of the remaining parathyroid glands by ultrasonography,dual-phase 99 Tcm-sestamibi scintigraphy,CT and MR imaging of the neck before the operation.We resected the parathyroid gland tissue in situ,and the ectopic parathyroid glands hiding in thymus,mediastinal,tracheal esophageal groove,thyroid gland and other locations in the neck.During the surgery,nanocarbon imaging was used to help identify the parathyroid gland and parathyroid hormone assay(IOPTH)was measured at the end of the surgery.We observed the changes of clinical symptoms after the surgery and collected blood parameters including serum intact aramyroidhomone(i-PTH),calcium(Ca),phosphoms(P),calcium and phosphorus product before and after surgery.Complications and failure were also analyzed.All the 12 patients underwented successful operation.The postoperative pathological results were hyperplastic parathyroid glands tissue.22 parathyroid glands were resected,among which 14 were located at the neck in situ,8 were ectopic,i.e.,located at thymus in 4 cases,superior mediastinum in 2 cases and thyroid parenchyma in 2 cases.The clinical symptoms were significantly improved including osteoarthritis,skin itching and limb weakness.The levels of serum iPTH,calcium,phosphorus and calcium and phosphorus product were significantly lower than those before operation(<0.05).Ten patients presented hypocalcemia after surgery and the level of calcium returned to normal after supplement of calcium.Temporary injury of laryngeal nerve was found in4 cases,but there was no patient with transient bucking,dyspnea or death.No recurrence was found during 1 year follow-up.It was very important to locate the residual parathyroid gland accurately with a variety of imaging methods in uremic patients complicated with persistent or recurrent SHPT when they needed re-operation.Surgeons should explorate ectopic parathyroid gland according to the concept of the superior mediastinum dissection and the central compartment neck dissection.Meanwhile,the use of nanocarbon assisted parathyroid gland negative imaging and rapid IOPTH can significantly improve the success rate of surgery and reduce surgical complications.
Humans ; Hyperparathyroidism, Secondary ; complications ; surgery ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroidectomy ; Reoperation ; Transplantation, Autologous ; Uremia ; complications

The high mortality rates associated with acute kidney injury are mainly due to extra-renal complications that occur following distant-organ involvement. Damage to these organs, which is commonly referred to as multiple organ dysfunction syndrome, has more severe and persistent effects. The brain and its sub-structures, such as the hippocampus, are vulnerable organs that can be adversely affected. Acute kidney injury may be associated with numerous brain and hippocampal complications, as it may alter the permeability of the blood-brain barrier. Although the pathogenesis of acute uremic encephalopathy is poorly understood, some of the underlying mechanisms that may contribute to hippocampal involvement include the release of multiple inflammatory mediators that coincide with hippocampus inflammation and cytotoxicity, neurotransmitter derangement, transcriptional dysregulation, and changes in the expression of apoptotic genes. Impairment of brain function, especially of a structure that has vital activity in learning and memory and is very sensitive to renal ischemic injury, can ultimately lead to cognitive and functional complications in patients with acute kidney injury. The objective of this review was to assess these complications in the brain following acute kidney injury, with a focus on the hippocampus as a critical region for learning and memory.
Acute Kidney Injury* ; Blood-Brain Barrier ; Brain Diseases ; Brain* ; Hippocampus* ; Humans ; Inflammation ; Learning ; Memory ; Mortality ; Multiple Organ Failure ; Neurotransmitter Agents ; Permeability ; Uremia

Calcific uremic arteriopathy (CUA), termed calciphylaxis, is a rare but highly fatal clinical syndrome. There is no clearly laboratory diagnostic criteria for CUA. The medium and small arterial calcification and microthrombosis discovered by skin biopsy, radiologic imaging，bone scan and the evidence of activation of the bone morphogenetic protein signal (BMPs) transduction pathway are useful for early diagnosis of this disease. The common therapies (including intravenous sodium thiosulfate (STS) and bisphosphonates, hyperbaric oxygen therapy and other symptomatic supports) are used for the management of wounds, pain, nutrition, dialysis and so on. Controlling the chronic kidney disease-mineral and bone disorder (CKD-MBD) and some complications of dialysis and drugs (such as warfarin, active vitamin D) can prevent CUA. However, CUA patients still have poor prognosis and high mortality. Since some patients progress rapidly, it is of great importance to make early diagnosis and provide effective treatments with multidisciplinary management.
Calciphylaxis ; diagnosis ; prevention & control ; therapy ; Early Diagnosis ; Humans ; Renal Dialysis ; Uremia ; Warfarin

No abstract available.
Brain Diseases ; Posterior Leukoencephalopathy Syndrome ; Uremia