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Uremic pruritus (UP) is a common complication in patients with end-stage renal disease, which seriously reduces the quality of life of patients. Compared with the internal treatment of TCM, the external treatment of TCM for UP is simpler and more effective, and can avoid the first pass effect caused by oral drugs and may cause liver and kidney damage. The treatment methods mainly include external washing of TCM, medicated bath, fumigation, wet compress, enema, scraping, acupuncture, auricular point sticking, acupoint application, acupoint iontophoresis, autologous blood acupoint injection and so on. At present, most studies are based on the conventional treatment of Western medicine, and the addition of external treatment of TCM can improve the efficacy, and has certain advantages in improving itching symptoms, inflammatory indicators, sleep quality, anxiety and depression. Some studies have selected parathyroid hormone, blood phosphorus, CRP, IL-6, histamine, SCr, BUN, β2-microglobulin and other indicators to evaluate the efficacy. The results suggest that external treatment of TCM can improve the micro-inflammatory state of patients and protect renal function, but further mechanism research is needed. The existing research has the following problems: the clinical efficacy evaluation scale is not uniform, and it is difficult to compare and summarize horizontally; the relief of pruritus symptoms is based on the scale evaluation, which is subjective; the course of treatment is short, and the long-term efficacy and safety can not be evaluated; some studies do not specify the patients' syndrome type, which is difficult to reflect the advantages of TCM syndrome differentiation and treatment, and needed to be improved in the future.
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Objective:To construct a mindfulness-based stress reduction (MBSR) intervention program suitable for uremic hemodialysis patients, and analyze the impact of the program on renal function and quality of life in uremic hemodialysis patients.Methods:This was a randomized controlled trial. The convenience sampling method was used to select 92 uremic patients who underwent hemodialysis in the First People's Hospital of Lianyungang City from March 2018 to March 2019. They were divided into routine group (46 cases, routine care) and MBSR group (46 cases, MBSR of face-to-face guidance combined with WeChat platform supervision) by random number table method. Both groups were intervened for 8 weeks. The Chinese version of the European Five-Dimensional Scale (EQ-5D-3L) was used to evaluate the quality of life of the patients, and the quality of life of the two groups before and after the intervention was compared; and the blood creatinine (Scr) and estimated glomerular filtration rate (eGFR), urea nitrogen (BUN), cystatin C (CysC) levels of the two groups before and after the intervention were analyzed.Results:Before the intervention, there was no significant difference in the levels of Scr, eGFR, BUN, and CysC between the two groups ( P>0.05); after 8 weeks of intervention, the levels of Scr, eGFR, BUN, and CysC were (201.81±14.77) μmol/L, (35.30 ± 2.02) ml/min and (11.47 ± 2.66) mmol/L, (2.41 ± 0.28) mg/L in the MBSR group, (218.37 ± 14.90) μmol/L, (33.99 ± 1.95) ml/min, (12.50 ± 0.76) mmol/L, (2.76 ± 0.30) mg/L in the routine group, the differences were statistically significant between the two groups ( t values were 2.53-5.79, all P<0.05). Before the intervention, there was no significant difference in EQ-5D-3L scores between the two groups ( P>0.05); after 8 weeks of intervention, the pain (discomfort), anxiety (depression), Vasual Analogue Scale (VAS) scores were (1.17 ± 0.34), (1.02 ± 0.35), (88.57 ± 20.28) points in the MBSR group, and (1.46 ± 0.63), (1.30 ± 0.32), (62.69 ± 18.79) points in the routine group, the differences were statistically significant between the two groups ( t=2.75, 4.00, 6.35, all P<0.05). Scr level was negatively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were -0.481 - -0.214, all P<0.05); eGFR level was positively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were 0.199-0.492, all P<0.05). But BUN and CysC levels were not correlated with EQ-5D-3L score (all P>0.05). Conclusions:MBSR can effectively improve the renal function and quality of life of uremic hemodialysis patients, and it is worthy of clinical application.
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"Uremic sarcopenia" refers to a progressive decrease in muscle mass, strength, and function despite normal skeletal muscle physiology in patients with chronic kidney disease (CKD). Sarcopenia involves multiple risk factors, comprising immunological changes, hormonal, metabolic acidosis, reduced protein intake, and physical inactivity. All these risk factors, along with complex pathophysiological mechanisms including ubiquitin, insulin/IGF-1, myostatin, and indoxyl sulfate, activate downstream pathways that ultimately increase muscle degradation while reducing muscle regeneration. Uremic sarcopenia not only affects the quality of life but also increases the risk of morbidity and mortality in patients with CKD. Of all the treatment modalities, aerobic and resistance exercise have shown prevention and reduced rate of muscle degeneration. A variety of pharmacological agents have been tried to target different steps in the known pathogenetic pathways, including the use of androgens and anabolic steroids, correction of vitamin D deficiency, use of growth hormone supplementation, and suppression of the ubiquitin pathway. Though some of these techniques have had beneficial results in animal experiments, human trials are still sparse. This review article relates to recent publications that describe the abnormalities in skeletal muscle that primarily leads to muscle wasting and its consequences in patients with CKD.
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BACKGROUND: Bleeding diatheses, common among patients with ESKD, can lead to serious complications, particularly during invasive procedures. Chronic urea overload significantly increases cyanate concentrations in patients with ESKD, leading to carbamylation, an irreversible modification of proteins and peptides. METHODS: To investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin α IIb ß 3 (a receptor required for platelet aggregation). Flow cytometry was used to study activation of isolated platelets and platelet-rich plasma. In a transient transfection system, we tested activity and fibrinogen binding of different mutated forms of the receptor. We assessed platelet adhesion and aggregation in microplate assays. RESULTS: Carbamylation inhibited platelet activation, adhesion, and aggregation. Patients on hemodialysis exhibited significantly reduced activation of α IIb ß 3 compared with healthy controls. We found significant carbamylation of both subunits of α IIb ß 3 on platelets from patients receiving hemodialysis versus only minor modification in controls. In the transient transfection system, modification of lysine 185 in the ß 3 subunit was associated with loss of receptor activity and fibrinogen binding. Supplementation of free amino acids, which was shown to protect plasma proteins from carbamylation-induced damage in patients on hemodialysis, prevented loss of α IIb ß 3 activity in vitro. CONCLUSIONS: Carbamylation of α IIb ß 3-specifically modification of the K185 residue-might represent a mechanistic link between uremia and dysfunctional primary hemostasis in patients on hemodialysis. The observation that free amino acids prevented the carbamylation-induced loss of α IIb ß 3 activity suggests amino acid administration during dialysis may help to normalize platelet function.
Subject(s)
Platelet Glycoprotein GPIIb-IIIa Complex , Uremia , Humans , Platelet Glycoprotein GPIIb-IIIa Complex/chemistry , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Protein Carbamylation , Tandem Mass Spectrometry , Blood Platelets , Uremia/complications , Uremia/metabolism , Fibrinogen/chemistry , Fibrinogen/metabolism , Amino AcidsABSTRACT
INTRODUCTION AND METHODS: Skeletal muscle mitochondrial dysfunction may cause tissue oxidative stress and consequent catabolism in chronic kidney disease (CKD), contributing to patient mortality. We investigated in 5/6-nephrectomized (Nx) rats the impact of n3-polyunsaturated fatty-acids (n3-PUFA) isocaloric partial dietary replacement on gastrocnemius muscle (Gm) mitochondrial master-regulators, ATP production, ROS generation and related muscle-catabolic derangements. RESULTS: Nx had low Gm mitochondrial nuclear respiratory factor-2 and peroxisome proliferator-activated receptor gamma coactivator-1alpha, low ATP production and higher mitochondrial fission-fusion protein ratio with ROS overproduction. n3-PUFA normalized all mitochondrial derangements and pro-oxidative tissue redox state (oxydized to total glutathione ratio). n3-PUFA also normalized Nx-induced muscle-catabolic proinflammatory cytokines, insulin resistance and low muscle weight. Human uremic serum reproduced mitochondrial derangements in C2C12 myotubes, while n3-PUFA coincubation prevented all effects. n3-PUFA also enhanced muscle mitophagy in-vivo and siRNA-mediated autophagy inhibition selectively blocked n3-PUFA-induced normalization of C2C12 mitochondrial ROS production. CONCLUSIONS: In conclusion, dietary n3-PUFA normalize mitochondrial master-regulators, ATP production and dynamics in experimental CKD. These effects occur directly in muscle cells and they normalize ROS production through enhanced mitophagy. Dietary n3-PUFA mitochondrial effects result in normalized catabolic derangements and protection from muscle wasting, with potential positive impact on patient survival.
Subject(s)
Fatty Acids, Omega-3 , Renal Insufficiency, Chronic , Adenosine Triphosphate/metabolism , Animals , Dietary Fats/pharmacology , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Mitochondria/metabolism , Mitophagy , Muscle, Skeletal/metabolism , Muscular Atrophy , Oxidative Stress , Rats , Reactive Oxygen Species/metabolism , Renal Insufficiency, Chronic/metabolismABSTRACT
BACKGROUND: Osteopenia, sarcopenia, and vascular calcification (VC) are prevalent in patients with chronic kidney disease and often coexist. In the absence of proven therapies, it is necessary to develop therapeutic or preventive nutrients supplementation for osteopenia, sarcopenia, and VC. The present study investigated the effect of omega-3 fatty acid (FA) and menaquinone-7 (MK-7) on osteopenia, sarcopenia, and VC in adenine and low-protein diet-induced uremic rats. METHODS: Thirty-two male Sprague-Dawley rats were fed diets containing 0.75% adenine and 2.5% protein for three weeks. Rats were randomly divided into four groups that were fed diets containing 2.5% protein for four weeks: adenine control (0.9% saline), omega-3 FA (300 mg/kg/day), MK-7 (50 µg/kg/day), and omega-3 FA/MK-7. Von Kossa staining for aortic calcification assessment was performed. Osteoclast surface/bone surface ratio (OcS/BS) of bone and muscle fiber were analyzed using hematoxylin and eosin staining. Osteoprotegerin (OPG) immunohistochemical staining was done in the aorta and bone. Molecules related with sarcopenia were analyzed using western blotting. RESULTS: Compared to the normal control, OcS/BS and aortic calcification, and OPG staining in the aorta and bone were significantly increased in the adenine controls. OPG staining and aortic calcification progressed the least in the group supplemented with both omega-3 FA/MK-7. In the adenine controls, the regular arrangement of muscle fiber was severely disrupted, and inflammatory cell infiltration was more prominent. These findings were reduced after combined supplementation with omega-3 FA/MK-7. Furthermore, decreased mammalian target of rapamycin and increased Forkhead box protein 1 expression was significantly restored by combined supplementation. CONCLUSIONS: Combined nutrients supplementation with omega-3 FA and MK-7 may be helpful for aortic VC prevention, reducing osteoclast activation and improving sarcopenia-related molecules in adenine and low-protein diet induced uremic rats.
Subject(s)
Aortic Diseases , Bone Diseases, Metabolic , Fatty Acids, Omega-3 , Osteoclasts , Sarcopenia , Uremia , Vascular Calcification , Vitamin K 2 , Animals , Male , Rats , Adenine/metabolism , Bone Diseases, Metabolic/ethnology , Bone Diseases, Metabolic/prevention & control , Osteoclasts/drug effects , Rats, Sprague-Dawley , Sarcopenia/etiology , Sarcopenia/prevention & control , Uremia/complications , Vascular Calcification/etiology , Vascular Calcification/prevention & control , Fatty Acids, Omega-3/therapeutic use , Vitamin K 2/therapeutic use , Aortic Diseases/etiology , Aortic Diseases/prevention & control , Drug Therapy, CombinationABSTRACT
Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.
Subject(s)
Renal Insufficiency , Toxins, Biological , Uremia , Humans , Uremic Toxins , Uremia/therapy , Quality of Life , Renal Dialysis/methodsABSTRACT
Preclinical animal models of chronic kidney disease (CKD) are critical to investigate the underlying mechanisms of disease and to evaluate the efficacy of novel therapeutics aimed to treat CKD-associated pathologies. The objective of the present study was to compare the adenine diet and 5/6 nephrectomy (Nx) CKD models in mice. Male and female 10-wk-old C57BL/6J mice (n = 5-9 mice/sex/group) were randomly allocated to CKD groups (0.2-0.15% adenine-supplemented diet or 5/6 Nx surgery) or the corresponding control groups (casein diet or sham surgery). Following the induction of CKD, the glomerular filtration rate was reduced to a similar level in both adenine and 5/6 Nx mice (adenine diet-fed male mice: 81.1 ± 41.9 µL/min vs. 5/6 Nx male mice: 160 ± 80.9 µL/min, P = 0.5875; adenine diet-fed female mice: 112.9 ± 32.4 µL/min vs. 5/6 Nx female mice: 107.0 ± 45.7 µL/min, P = 0.9995). Serum metabolomics analysis indicated that established uremic toxins were robustly elevated in both CKD models, although some differences were observed between CKD models (i.e., p-cresol sulfate). Dysregulated phosphate homeostasis was observed in the adenine model only, whereas Ca2+ homeostasis was disturbed in male mice with both CKD models. Compared with control mice, muscle mass and myofiber cross-sectional areas of the extensor digitorum longus and soleus muscles were â¼18-24% smaller in male CKD mice regardless of the model but were not different in female CKD mice (P > 0.05). Skeletal muscle mitochondrial respiratory function was significantly decreased (19-24%) in CKD mice in both models and sexes. These findings demonstrate that adenine diet and 5/6 Nx models of CKD have similar levels of renal dysfunction and skeletal myopathy. However, the adenine diet model demonstrated superior performance with regard to mortality (â¼20-50% mortality for 5/6 Nx vs. 0% mortality for the adenine diet, P < 0.05 for both sexes) compared with the 5/6 Nx surgical model.NEW & NOTEWORTHY Numerous preclinical models of chronic kidney disease have been used to evaluate skeletal muscle pathology; however, direct comparisons of popular models are not available. In this study, we compared adenine-induced nephropathy and 5/6 nephrectomy models. Both models produced equivalent levels of muscle atrophy and mitochondrial impairment, but the adenine model exhibited lower mortality rates, higher consistency in uremic toxin levels, and dysregulated phosphate homeostasis compared with the 5/6 nephrectomy model.
Subject(s)
Adenine/pharmacology , Glomerular Filtration Rate/genetics , Muscle, Skeletal/metabolism , Renal Insufficiency, Chronic/metabolism , Animals , Disease Models, Animal , Kidney/metabolism , Kidney/pathology , Male , Mice, Inbred C57BL , Muscle, Skeletal/pathology , Muscular Diseases/pathology , Muscular Diseases/physiopathology , Nephrectomy/methods , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/pathology , Uremia/physiopathologyABSTRACT
INTRODUCTION: Uremic pruritus (UP) is one of the most bothersome symptoms among chronic kidney disease (CKD) patients. The pathophysiology of UP remains elusive, resulting in limited treatment options. The inability of standard medical treatments to provide effective relief has piqued interest in complementary and alternative medicine (CAM). METHODOLOGY: A systematic review of randomized controlled trials (RCTs) summarizing the efficacy and safety profile of CAM used for UP in CKD patients was performed. CAM interventions were classified using categories proposed by the National Center for Complementary and Integrative Health. The efficacy of each CAM was determined from changes in UP severity and all reported adverse effects were extracted. RESULTS: Of 5242 articles screened, 34 RCTs were included, with 15 (44.1 %) studies having a sample size greater than 50. The studies considered 21 treatments including omega-3 fatty acid supplementation (n=5), acupuncture (n=5), topical capsaicin (n=4) and acupressure (n=3). Acupuncture, acupressure and topical capsaicin were shown to be effective in improving uremic pruritus. Interventions which include oral omega-3 fatty acid and zinc supplementation demonstrated mixed efficacy. Other therapies such as evening primrose oil, turmeric, vitamin B3, vitamin D and thermal therapy were not effective for treatment of UP. Common adverse effects reported with topical capsaicin included mild burning sensations (50.0-88.2 %) or erythema (6.7-22.7%) while that of acupuncture included soreness (7.5 %), bleeding (6.0-7.5%) and hematoma (1.9 %). CONCLUSIONS: Acupuncture, acupressure and topical capsaicin have the largest body of evidence for efficacy in the treatment of UP. Larger and higher quality RCTs are required to examine the efficacy and safety of promising CAM.
Subject(s)
Complementary Therapies/methods , Pruritus/therapy , Humans , Pruritus/etiology , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/complicationsABSTRACT
Hypocalcemia is a rare, but reversible, cause of dilated cardiomyopathy. Although cardiomyopathy may cause severe heart failure, calcium supplementation can reverse heart failure. We report here a patient with uremia and secondary hyperparathyroidism, who was complicated by persistent hypocalcemia and refractory heart failure. The cardiac failure was refractory to treatment with digitalis and diuretics, but dramatically responded to calcium therapy and restoration of normocalcemia. As a result, the patient was eventually diagnosed with hypocalcemic cardiomyopathy. To the best of our knowledge, this is the first case of this disease to be reported in a patient with uremia. Findings from our case may help clinicians to better understand hypocalcemic cardiomyopathy. Our case might also provide new insight into long-term cardiac complications and prognoses of patients undergoing parathyroidectomy due to secondary hyperparathyroidism.
Subject(s)
Cardiomyopathies , Hypocalcemia , Hypoparathyroidism , Uremia , Calcium , Humans , Hypocalcemia/complications , Parathyroidectomy , Uremia/complicationsABSTRACT
BACKGROUND: Chronic kidney disease (CKD) and acute decompensation of CKD (ACKD) are common in cats. OBJECTIVES: To characterize the etiology, clinical and clinicopathologic findings, and the short- and long-term prognosis of feline ACKD. ANIMALS: One hundred cats with ACKD. METHODS: Retrospective study, search of medical records for cats with ACKD. RESULTS: Common clinical signs included anorexia (85%), lethargy (60%), weight loss (39%), and vomiting (27%). Suspected etiologies included ureteral obstruction (11%), renal ischemia (9%), pyelonephritis (8%), others (6%), or unknown (66%). Hospitalization duration was longer in survivors versus nonsurvivors (median = 7 days, range = 2-26 versus median = 3 days, range = 2-20, respectively, P < .001). The survival rate to discharge was 58%. Age, serum creatinine, urea, and phosphorous concentrations were higher and venous blood pH was lower in nonsurvivors. However, only serum phosphorus remained associated with the short-term outcome in the multivariable model (P = .02; 95% confidence interval = 1.03-1.39). Survivors had a median survival time of 66 days after discharge. Serum creatinine concentrations at presentation as well as at discharge were associated with long-term survival (P < .002 for both). CONCLUSIONS: The short-term prognosis of ACKD is comparable to acute kidney injury, while the long-term prognosis is guarded.
Subject(s)
Acute Kidney Injury/veterinary , Cat Diseases/etiology , Renal Insufficiency, Chronic/veterinary , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Animals , Cat Diseases/blood , Cat Diseases/pathology , Cats , Creatinine/blood , Female , Hospitalization/statistics & numerical data , Ischemia , Kidney/blood supply , Male , Phosphorus/blood , Prognosis , Protons , Pyelonephritis/veterinary , Renal Insufficiency, Chronic/blood , Retrospective Studies , Urea/blood , Ureteral Obstruction/veterinaryABSTRACT
BACKGROUND: This study aimed to investigate the clinical efficacy of two surgical methods on hyperparathyroidism secondary to uremia and summarize the advantages and disadvantages of both methods. METHODS: Uremic patients who received parathyroidectomy (PTX) in the last 3 years were divided into two groups according to the surgical methods used [subtotal parathyroidectomy (SPTX) group and total parathyroidectomy + autologous implantation (TPTX + AT) group]. TPTX was performed if less than 4 glands were found during surgery. The changes of various indexes after operation, and calculate the success rate and recurrence rate of patients were observed. The serum biochemical parameters were routinely monitored, the success rate, postoperative complications and recurrence were recorded. The patients were followed up. RESULTS: There were 20 patients in the SPTX group and 12 in the TPTX + AT group. The success rate of surgery was 85% and 91.7% in the SPTX group and TPTX + AT group, respectively, among 32 patients included for final analysis. The mean PTH and postoperative ALP in the TPTX + AT group were slightly lower than in the SPTX group, except for the PTH levels at 6 months after surgery (P<0.05). The incidence of postoperative hypocalcemia was 100% in both groups. The incidence of wound infection in the two groups was 0% and 16.7% in the SPTX group and TPTX + AT group, respectively. The mean calcium supplementation in the TPTX + AT group was significantly more than in the SPTX group within 1 year after surgery. The mean postoperative bone mineral density in the SPTX group was significantly higher than in the TPTX + AT group. The time to postoperative remission of bone pain and muscle weakness was markedly shorter in the SPTX group than in the TPTX + AT group. The post-operative quality of life (QOL) in the SPTX group was significantly better than in the TPTX + AT group. CONCLUSIONS: These findings suggest that SPTX achieves a better short-term efficacy, but TPTX + AT has a better long-term efficacy. Therefore, the selection of surgical method for PTX may be based on the age, estimated survival time and possibility of kidney transplantation.
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We are reporting a rare case of acupuncture-related acute pericarditis in an old-aged gentleman due to Staphylococcus aureus infection who was successfully managed with drainage of pericardial fluid and broad-spectrum antibiotics. We also reviewed the literature and found cardiac tamponade as the most common acupuncture-related cardiac complication, followed by infective endocarditis, bacterial abscess, and infected myxoma. There was no available literature on post-acupuncture acute pericarditis.
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OBJECTIVE: To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. METHODS: A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. RESULTS: Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. CONCLUSIONS: In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.
Subject(s)
Bone Diseases/diagnosis , Bone and Bones/metabolism , Hyperparathyroidism, Secondary/surgery , Hypocalcemia/diagnosis , Hypophosphatemia/diagnosis , Magnesium Deficiency/diagnosis , Parathyroidectomy , Postoperative Complications/diagnosis , Renal Dialysis , Adult , Bone Diseases/metabolism , Case-Control Studies , Female , Humans , Hyperparathyroidism, Secondary/etiology , Hypocalcemia/metabolism , Hypophosphatemia/metabolism , Magnesium Deficiency/metabolism , Male , Middle Aged , Postoperative Complications/metabolism , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Retrospective Studies , SyndromeABSTRACT
BACKGROUND/AIMS: Thromboembolic episodes are a frequent problem in end stage renal failure patients. The pathomechanism of the disorder is complex, including bioincompatibility of renal replacement therapy, endothelial dysfunction, increased blood level of procoagulant factors and uremic toxins. We studied changes in the functional properties of venous endothelial cells (VEC) in the presence of uremic serum and evaluated their possible modulation by N-acetylcysteine (NAC) or sulodexide (SUL). METHODS: Serum samples from 12 uremic patients treated with hemodialysis were studied ex vivo on in vitro cultured VEC. In separate experiments, NAC 1 mmol/L or SUL 0.5 LRU/mL were added to uremic serum samples. Both changes in the gene expression and secretory activity of VEC were studied. RESULTS: Uremic serum increased the expression of the following genes: IL6 +97%, p < 0.002; VEGF +28%, p < 0.002; vWF +47%, p < 0.002; PECAM +76%, p < 0.002; ICAM-1 +275%, p < 0.002; t-PA +96%, p < 0.002. Changes in gene expression were reflected by the increased secretory activity of VEC treated with the uremic serum. Exposure of VEC to uremic serum supplemented with NAC or SUL resulted in weaker stimulation of the studied genes' expression. Also, secretion of the studied solutes, with the exception of ICAM-1, was reduced in the presence of NAC: IL6 -34%, p < 0.01; VEGF -40%, p < 0.005; vWF -25%, p < 0.001; t-PA -47%, p < 0.01, and MMP9 -37%, p < 0.001. SUL reduced the uremic serum-induced secretion of all solutes: IL6 -24%, p < 0.05; ICAM-1 -43%, p < 0.01; VEGF -38%, p < 0.01; vWF -23%, p < 0.01; t-PA -49%, p < 0.01, and MMP9 -25%, p < 0.05. CONCLUSIONS: Uremic serum induces prothrombotic changes in VEC, which may cause a predisposition to thrombotic disorders in patients with renal failure. NAC and SUL reduce the effects of the uremic serum in VEC, which suggests their potential therapeutic application in uremic patients.
Subject(s)
Acetylcysteine/pharmacology , Endothelium, Vascular/cytology , Glycosaminoglycans/pharmacology , Kidney Failure, Chronic/drug therapy , Thrombosis/prevention & control , Uremia/blood , Acetylcysteine/therapeutic use , Anticoagulants , Blood Specimen Collection , Cells, Cultured , Endothelial Cells/drug effects , Endothelium, Vascular/drug effects , Female , Free Radical Scavengers , Glycosaminoglycans/therapeutic use , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Male , Uremia/drug therapyABSTRACT
BACKGROUND: Uremia is the condition generally associated with the last stage of chronic kidney disease (CKD) due to highly reduced glomerular filtration rate. Mortality of the patients diagnosed with Uremia generally occurs due to cardiovascular involvement. This occurs due to the transdifferentiation of vascular smooth muscle cells (VSMCs) into osteogenic cells in hyperphosphatemic condition that is associated with kidney failure promoting extra-osseous calcification. PURPOSE: Linalool is an essential oil that has been recently studied for its procardiovascular effects, thus the aim of the study involved to identify its potential role on vascular calcification (VC). METHODS: Uremia was induced in male wistar rats, weighing 250-350 gm by giving adenine diet for 4 weeks followed by phosphate diet for next 4 weeks. Linalool was given orally at two different doses (100â¯mg/kg bodyweight and 150â¯mg/kg bodyweight) daily for 4 weeks with phosphate diet. RESULTS: Linalool being a moderate antioxidant probably scavenged superoxide radicals (in vitro analysis). Deposition of calcium was observed by alizarin and von-kossa stains in aorta of uremic rats whereas linalool co-administration prevents calcium deposition in aorta of uremic rats. Elevated mRNA expression of calcification markers, increased lipid peroxidation levels and increased levels of catalase and superoxide dismutase (SOD) was found in aorta of uremic animals. However, with supplementation of linalool reduction in the mRNA expression of calcification markers, lipid peroxidation and antioxidant enzymes were observed. CONCLUSION: Therefore it can be concluded that linalool could be a promising therapeutic candidate for exploring its clinical application in VC.
Subject(s)
Monoterpenes/pharmacology , Uremia/complications , Vascular Calcification/drug therapy , Acyclic Monoterpenes , Animals , Antioxidants/pharmacology , Aorta/drug effects , Aorta/pathology , Calcium/metabolism , Catalase/metabolism , Cell Transdifferentiation , Lipid Peroxidation , Male , Myocytes, Smooth Muscle/drug effects , Phosphates , Rats , Rats, Wistar , Renal Insufficiency , Superoxide Dismutase/metabolism , Vascular Calcification/etiologyABSTRACT
Kidney diseases are common and the incidence rate is increasing. Gut microbiota is involved in metabolic and immune regulation of the host. Genetic, alimentary and environmental disease factors may change gut flora and increase opportunistic and pathogenic bacteria, contributing to immune or non-immune mediated kidney diseases including IgA nephropathy and diabetic nephropathy. Additionally, bacterial metabolites may be a source of uremic toxins. Thus, identification of diversity, composition, and metabolic and immunologic features of gut bacteria in chronic kidney diseases may help understand pathogenetic mechanism and develop therapy for diseases.
Subject(s)
Gastrointestinal Microbiome , Kidney Diseases/microbiology , HumansABSTRACT
BACKGROUND: Vascular calcification is highly prevalent in end-stage renal disease (ESRD) and is a significant risk factor for future cardiovascular events and death. Warfarin use results in dysfunction of matrix Gla protein, an inhibitor of vascular calcification. However, the effect of warfarin on vascular calcification in patients with ESRD is still not well characterized. Thus we investigated whether arterial calcification can be accelerated by warfarin treatment both in vitro and in vivo using a mouse remnant kidney model. METHODS: Human aortic smooth muscle cells (HASMC) were cultured in medium supplemented with warfarin and phosphate to investigate the potential role of this drug in osteoblast transdifferentiation. For in vivo study, adult male C57BL/6 mice underwent 5/6 nephrectomy were treated with active vitamin D3 plus warfarin to determine the extent of vascular calcification and parameters of cardiovascular function. RESULTS: We found that the expressions of Runx2 and osteocalcin in HASMC were markedly enhanced in the culture medium containing warfarin and high phosphate concentration. Warfarin induced calcification of cultured HASMC in the presence of high phosphate levels, and this effect is inhibited by vitamin K2. Severe aortic calcification and reduced left ventricular ejection fractions were also noted in 5/6 nephrectomy mice treated with warfarin and active vitamin D3. CONCLUSION: Warfarin treatment contributes to the accelerated vascular calcification in animal models of advanced chronic kidney disease. Clinicians should therefore be aware of the profound risk of warfarin use on vascular calcification and cardiac dysfunction in patients with ESRD and atrial fibrillation.
Subject(s)
Anticoagulants/adverse effects , Heart Diseases/etiology , Kidney Failure, Chronic/complications , Vascular Calcification/chemically induced , Warfarin/adverse effects , Animals , Cells, Cultured , Humans , Male , Mice , Mice, Inbred C57BL , Myocytes, Smooth Muscle/drug effects , NephrectomyABSTRACT
BACKGROUND: High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets. METHODS: Wistar rats (n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rats were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the other half were maintained on basic VitE requirements (27 mg/kg). Thus, rats were allotted to four experimental groups: Nx-NF (n = 8), Nx-NF-VitE (n = 8), Nx-HF (n = 8) and Nx-HF-VitE (n = 8). At the time of sacrifice (day 66), blood and tissue samples were obtained. RESULTS: Feeding a HF diet for 45 days did not increase body weight but elicited hyperglycemia, hypertriglyceridemia, an increase in plasma fibroblast growth factor 23 and a reduction in plasma calcitriol concentrations. After Nx, rats fed HF diet showed substantial extraskeletal calcification with aortic calcium content that was higher than in rats fed NF diet. Supplementation with VitE significantly (p < 0.05) reduced aortic (from 38.4 ± 8.8 to 16.5 ± 1.4 mg/g), gastric (from 5.6 ± 2.7 to 1.2 ± 0.4 mg/g) and pulmonary (from 1.8 ± 0.3 to 0.3 ± 0.2 mg/g) calcium content in rats on HF diets. CONCLUSIONS: Uremic rats fed HF diets developed more severe extraosseous calcifications than their normocaloric-fed counterparts and dietary VitE supplementation protected against uremic calcifications in rats fed HF diets. Thus, eating energy-rich foods should be discouraged in patients with renal disease and their deleterious effect may be ameliorated with adequate antioxidant supply.
Subject(s)
Diet, High-Fat/adverse effects , Uremia/drug therapy , Vascular Calcification/prevention & control , Vitamin E/therapeutic use , Animals , Antioxidants/therapeutic use , Rats , Rats, Wistar , Uremia/etiology , Uremia/pathology , Vascular Calcification/etiology , Vascular Calcification/pathologyABSTRACT
BACKGROUND: We aimed to observe the effect of holistic nursing on patients undergoing hematodialysis for uremia who simultaneously were suffering from moderate to severe malnutrition. METHODS: Eighty patients with uremia on maintenance hematodialysis with malnutrition between June 2014 and June 2015 from Yantaishan Hospital, Yantai, Shandong, China were included and equally and randomly were divided into the control group (n=43) and observation group (n=43). Routine nursing was used in the control group while holistic nursing was used in observation group (before, during and after dialysis) and the clinical effects in the two groups were compared after 3 months. RESULTS: At follow-up visits, serum creatinine and urea nitrogen levels of the patients in the two groups were decreased, whereas hemoglobin and albumin levels were increased. In addition, these improvements were greater in the observation group and the differences were statistically significant (P<0.05). Furthermore, during follow-up visits, MQSGA and MIS scores of the two groups were lower and the scores of the observation group were lower than those in the control group were, and the differences were statistically significant (P<0.05). CONCLUSION: Holistic nursing is able to improve significantly malnutrition in patients with uremia on hematodialysis.