Effects of echinacoside on renal injury in uremia rats and its mechanism / 中国药房

OBJECTIVE To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats. RESULTS Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM- 1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （P＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （P＜0.05）. CONCLUSIONS ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

Progress in clinical application of external treatment of TCM in uremic pruritus / 国际中医中药杂志

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.

Mioclonías positivas y negativas en paciente con enfermedad renal crónica / Positive and negative myoclonus in a patient with end stage renal disease

Introducción: Las mioclonías son contracciones musculares paroxísticas de corta duración o pérdida abrupta del tono muscular, denominadas mioclonías positivas y negativas, respectivamente. Se presenta un caso clínico de mioclonías positivas y negativas generalizadas y se pretende describir los múltiples mecanismos fisiopatológicos y etiologías que lo desencadenan. Presentación del caso: Hombre de 35 años, con diabetes mellitus tipo 1 complicada con enfermedad renal diabética en hemodiálisis, desarrolló una bacteriemia asociada a catéter por Staphylococcus aureus y presentó mioclonías positivas y negativas. Se identificaron como posibles desencadenantes la uremia, la infección y los fármacos con potencial promioclónico; el hallazgo incidental de una lesión isquémica en núcleo caudado no explicaba la semiología encontrada en el paciente. Se hizo el control y retiro de todos los factores promioclónicos enunciados, junto a manejo farmacológico con levetiracetam, y con ello se logró el control de los síntomas. Discusión: Los pacientes con enfermedad renal crónica son susceptibles a la acumulación de productos tóxicos de tipo guanidinas, que tienen potencial para producir mioclonías. Además, las infecciones, el uso de fármacos con potencial promioclónico y lesiones estructurales como las isquemias corticales son etiologías que deben considerarse en el diagnóstico diferencial. El mayor impacto en los síntomas se observa con el control del factor desencadenante, y, en caso de persistir, la terapia farmacológica proporciona buenos resultados. Conclusión: Las mioclonías son trastornos del movimiento relativamente comunes en la enfermedad renal crónica. La identificación del desencadenante es crucial para su manejo junto al uso de fármacos con actividad antimioclónica.

Introduction: Myoclonus are paroxysmal muscle contractions of short duration or abrupt loss of muscle tone, called positive and negative myoclonus respectively. A clinical case of generalized positive and negative myoclonus is presented and the aim is to describe the multiple pathophysiological mechanisms and etiologies that trigger it. Case presentation: A 35-year-old man with type 1 diabetes mellitus complicated by diabetic kidney disease on hemodialysis developed catheter-associated bacteremia due to Staphylococcus aureus and presented positive and negative myoclonus. Uremia, infection, and drugs with pro-myoclonic potential were identified as possible triggers; The incidental finding of an ischemic lesion in the caudate nucleus did not explain the semiology found in the patient. The control and removal of all the pro-myoclonic factors mentioned was carried out, along with pharmacological management with levetiracetam, thus achieving control of the symptoms. Discussion: Patients with chronic kidney disease are susceptible to the accumulation of guanidine-type toxic products, which have the potential to produce myoclonus. Furthermore, infections, the use of drugs with pro-myoclonic potential and structural lesions such as cortical ischemia are etiologies that should be considered in the differential diagnosis. The greatest impact on symptoms is observed with the control of the triggering factor and if it persists, pharmacological therapy provides good results. Conclusion: Myoclonus are relatively common movement disorders in chronic kidney disease. Identification of the trigger is crucial for its management along with the use of drugs with anti-myoclonic activity.

The mechanism of macrophage-inducible C-type lectin involved in uremic microinflammatory state / 西安交通大学学报(医学版)

【Objective】 To explore the mechanism of macrophage-inducible C-type lectin (Mincle) and microinflammatory state in uremia. 【Methods】 SD rats were randomly divided into uremia group and sham operation group. The morphology and permeability of intestinal tissue, the morphology of intestinal tissue and macrophages were observed by transmission electron microscope, the expression of Mincle was detected in intestinal tissue sections, and the expressions of Toll-like receptor 4 (TLR-4) and NF-kappa B (NF-κB) protein on the surface of macrophages were detected by Western blotting. After the plasma was separated, the levels of endotoxin, C-reactive protein (CRP), interleulin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by Limulus lysate dynamic turbidimetric assay, and enzyme-linked immunosorbent assay (ELISA). The data were analyzed with IBM SPSS19.0 software. 【Results】 The expression of Mincle in the jejunum, ileum, and colon in uremia group was higher than that in sham-operation group (P<0.05). The expressions of TLR4 and NF-κB protein significantly differed in the ileum, jejunum and colon in uremia group (P<0.001). The levels of endotoxin, CRP, IL-6, and TNF-α were significantly increased in uremia group compared with sham-operation group (P<0.05). 【Conclusion】 In uremia, Mincle on the surface of intestinal macrophages increases and further through TLR4/NF-κB pathway mediates the transformation of intestinal macrophages to M1 type, releasing inflammatory products and causing systemic microinflammation.

Role of gut microbiota in the pathogenesis and treatment of chronic kidney disease / 中华肾脏病杂志

Chronic kidney disease (CKD) is a serious health problem worldwide, whereas there is still no efficient cure. The gut microbiota plays a crucial role in maintaining human health and disease resistance, and multiple studies have confirmed that the gut microbiota is closely related to the occurrence and development of CKD. Starting from the "gut-kidney axis" theory, this article provides a systematic review of the changes in gut microbiota composition and function in patients with CKD, such as a decrease in the abundance of butyrate-producing bacteria Roseburia and Faecalibacterium prausnitzii. Besides that, the article explores the mechanisms by which the gut microbiota affects CKD progression, such as inflammation and immunity, and also describes the application methods of using the gut microbiota as a therapeutic target for CKD, such as fecal microbiota transplantation, microecologics, and dietary therapy, in order to provide microbial- based targets for the clinical diagnosis and treatment of CKD.

Construction and Evaluation of End-to-side Anastomosis Model of Autologous Arteriovenous Fistula in Mice / 实验动物与比较医学

ObjectiveTo establish an animal model of autologous arteriovenous fistula in mice and evaluate its effect. MethodsThe left external jugular vein and common carotid artery of 10 8-week-old male C57BL/6 mice were separated by end-to-side anastomosis of external jugular vein and common carotid artery after anesthesia, and the right jugular vein was exposed without suture as a control, so as to establish an animal model of internal arteriovenous fistula. Doppler ultrasound, HE and Masson staining and immunohistochemical staining were used to observe the hemodynamics, intimal hyperplasia and protein expression of smooth muscle cell proliferation in the outflow vein of the internal arteriovenous fistula and the contralateral control vein, and to evaluate the effect of model construction. ResultsA total of 10 mice were selected for this study, and 9 mice were successfully modeled, with a success rate of 90%. Ultrasound examinations were performed on the day of surgery, 7 and 14 days after surgery, respectively. The results showed that the flow velocity near the anastomosis was linearly correlated with the diameter of the tube. The higher the flow velocity, the larger the diameter of the tube. There was a positive correlation between peak velocity and lumen diameter (P=0.000 6, R2=0.831 7). After surgery 14 days, HE staining results showed that after autologous arteriovenous fistula molding, the average lumen area of outflow segment vein was significantly decreased (P < 0.000 1), the intima area was significantly increased (P < 0.000 1), the intimal area was significantly increased (P < 0.000 1). On the surgical side of arteriovenous fistula, collagen deposition was significantly increased, and the proportion of Masson-positive regions was significantly increased (P < 0.000 1). Immunohistochemical staining showed that the proportion of collagen 1 positive areas on the surgical side of arteriovenous fistula was significantly upregulated (P < 0.000 1), and α-smooth muscle actin (α-SMA) , proliferating cell nuclear antigen (PCNA) positive cells increased significantly (P < 0.000 1), indicating an increase in local cell proliferation level. ConclusionThe established mouse autologous arteriovenous fistula model has the advantages of high success rate, good stability and low cost. The model provides a good carrier for exploring the biological mechanism of intimal hyperplasia in arteriovenous fistulas.

Dual-phase 18F-fluorocholine PET/CT imaging in uremic hyperparathyroidism / 中华核医学与分子影像杂志

Objective:To investigate the application value of dual-phase 18F-fluorocholine (FCH) PET/CT imaging in uremic hyperparathyroidism (uHPT). Methods:Twenty patients (10 males, 10 females, age: (46.8±12.3) years) who were diagnosed with uHPT and underwent neck ultrasound and dual-phase (5, 45 min) 18F-FCH PET/CT imaging at Affiliated Hospital of Southwest Medical University between December 2019 and March 2022 were retrospectively analyzed. Patients underwent parathyroidectomy within 1 month after PET/CT imaging. The sensitivity of neck ultrasound and dual-phase 18F-FCH PET/CT imaging for the diagnosis of hyperfunctioning parathyroid glands were compared based on the surgical results. The early- and late-phase 18F-FCH PET/CT images were compared visually and quantitatively, and the difference of SUV max between parathyroid hyperplasia and parathyroid adenoma was compared. The correlations between SUV max and important laboratory parameters and the volume of lesions measured on CT were tested. Fisher exact test, paired t test, independent-sample t test and Spearman rank correlation analysis were used for statistical analysis. Results:A total of 69 masses were removed in 20 patients with uHPT, and 55 parathyroid hyperplasia and 10 parathyroid adenomas were identified by pathology. Dual-phase 18F-FCH PET/CT imaging (87.69%, 57/65) was more sensitive than neck ultrasound (56.92%, 37/65) for the diagnosis of hyperfunction of the parathyroid gland ( P=0.001). The early imaging detected more lesions than late imaging (57 vs 49) respectively, which showing higher sensitivity (87.69%(57/65) vs 75.38%(49/65); P<0.001). The SUV max(5.75±2.21 vs 4.08±1.51) and the corresponding parathyroid-to-thyroid ratio (2.99±0.99 vs 3.57±1.30) were both significantly different between early and late imaging ( t values: 8.28, 4.33, both P<0.001). There were no significant differences between parathyroid hyperplasia and parathyroid adenoma in SUV max(early imaging: 5.08±2.27 vs 6.58±2.24; t=-1.90, P=0.063; late imaging: 3.89±1.54 vs 4.93±1.04; t=-1.94, P=0.059). The sum of SUV max of all lesions in early imaging was not correlated with preoperative serum parathyroid hormone (PTH) or Ca or P or lesion size ( rs values: from -0.22 to 0.06, all P>0.05). Conclusions:Dual-phase 18F-FCH PET/CT imaging has high sensitivity in the diagnosis of uHPT, and early and late imaging shows advantages in different aspects, with good preoperative localization ability. Therefore, for patients with uHPT, it is recommended to complete the dual-phase 18F-FCH PET/CT examination before surgery.

Sepsis due to ureteral stones in a patient with uremia: a case report / 中华泌尿外科杂志

Urosepsis caused by upper urinary tract stone obstruction is a common critically disease in urology.However, it rarely occurs in the patient who underwent a dialysis with uremia.We report a patient who underwent an implantation of ureteral stent to control the infection, and we saved the patient with perinephric hematoma following the surgery. We removed the stones in the left ureteral through a flexible ureteroscope two month later.The hematoma was completely absorbed 6 months after the implantation of ureteral stent.

Relationship and associated mechanism of serum fibroblast growth factor 21 and sarcopenia in hemodialysis patients / 中华肾脏病杂志

Objective:To investigate the relationship between serum fibroblast growth factor 21 (FGF21) and sarcopenia in hemodialysis (HD) patients, and to explore the relationship between FGF21 and signal pathways related to skeletal muscle metabolism in uremic state at the cellular level.Methods:The data of the HD patients from the blood purification center of the Third Affiliated Hospital of Soochow University were collected in this prospective observational study between January 2018 and December 2019. Serum FGF21 concentration was detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the skeletal muscle indexes (SMI) at the fourth thoracic vertebra (T4) and the first lumbar vertebra (L1) were assessed by chest CT. According to the T4 SMI and L1 SMI, the patients were divided into sarcopenia group and non-sarcopenia group. The relationship between serum FGF21 and sarcopenia was analyzed. The C2C12 mouse myoblasts were cultured in vitro, which were intervened with healthy human serum, healthy human serum+different concentrations of FGF21, uremic serum, uremic serum+different concentrations of FGF21. The expressions of muscle ring finger protein-1 (MURF1), muscle atrophy F-box (Atrogin-1), myogenic differentiation (MyoD) and myogenin (MyoG) were detected by Western blotting. Results:A total of 118 HD patients with age of (52.64±15.29) years were enrolled in the study, including 64 males (54.2%) and 54 females (45.8%). The images at T4 and L1 level assessed by chest CT could be acquired from 118 patients and 82 patients, respectively. According to the lowest sex-specific quartile ( P25) of T4 SMI (male < 59.92 cm 2/m 2, female < 46.75 cm 2/m 2) and the lowest sex-specific quartile ( P25) of L1 SMI (male < 29.02 cm 2/m 2, female < 24.50 cm 2/m 2), patients were divided into sarcopenia group and non-sarcopenia group, and there were 29(24.58%) and 20(24.39%) patients in the sarcopenia group, respectively. When the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI, although the serum FGF21 level in the sarcopenia group was higher than that in the non-sarcopenia group, there was no statistical significance between the two groups [448.52(183.96, 1 684.08) ng/L vs. 273.65 (152.83, 535.54) ng/L, Z=-1.741, P=0.082]. When the patients were divided into two groups according to the sex-specific lowest quartile of L1 SMI, the serum FGF21 level in the sarcopenia group was significantly higher than that in the non-sarcopenia group [460.95(188.91, 1 276.38) ng/L vs. 239.10(133.25, 466.36) ng/L, Z=-2.170, P=0.030]. Binary logistic regression analysis showed that higher serum FGF21 was an independent influencing factor for sarcopenia in HD patients regardless of whether the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI or the sex-specific lowest quartile of L1 SMI (T4 SMI grouping: OR=4.085, 95% CI 1.778-9.388, P=0.001; L1 SMI grouping: OR=7.327, 95% CI 1.841-29.160, P=0.005). At T4 and L1 levels, the area under the receiver operating characteristic curve of FGF21 in predicting sarcopenia in HD patients was 0.636(95% CI 0.494-0.779, P=0.036) and 0.684(95% CI 0.535-0.833, P=0.018), respectively. Cell experiment showed that compared with the uremic serum group, the expressions of MURF1 and Atrogin-1 in myotube cells were increased, while the expressions of MyoD and MyoG were significantly decreased in uremic serum+FGF21 group (both P < 0.05). Conclusions:Higher serum FGF21 is associated with an increased risk of sarcopenia in HD patients. FGF21 may increase the expression of ubiquitin proteasome system, reduce the synthesis and differentiation of skeletal muscle protein, and promote the occurrence of muscle atrophy in uremic patients

The effect of mindfulness-based stress reduction on renal function and quality of life in uremic hemodialysis patients / 中国实用护理杂志

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.

Dialysis-related constrictive pericarditis: old enemies may sometimes come back / Pericardite Constritiva relacionada a diálise: velhos inimigos podem, às vezes, voltar

ABSTRACT Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Several heart conditions have been associated with CKD, including myocardial and pericardial diseases. This paper describes a case of Dialysis-related constrictive pericarditis in a patient diagnosed with sudden hypotension during a hemodialysis session. A 65-year-old man diagnosed with hypertension, diabetes, obesity, and cirrhosis on hemodialysis for two years complained of symptoms during one of his sessions described as malaise, lipothymia, and confusion. The patient had a record of poor compliance with the prescribed diet and missed dialysis sessions. He was sluggish during the physical examination, and presented hypophonetic heart sounds, a blood pressure of 50/30mmHg, and a prolonged capillary refill time. The patient was referred to the intensive care unit and was started on antibiotics and vasoactive drugs. His workup did not show signs of infection, while electrocardiography showed low QRS-wave voltage. His echocardiogram showed signs consistent with a thickened pericardium without pericardial effusion. Cardiac catheterization showed equalization of diastolic pressures in all heart chambers indicative of constrictive pericarditis. The patient underwent a pericardiectomy. Examination of surgical specimens indicated he had marked fibrosis and areas of dystrophic calcification without evidence of infection, consistent with Dialysis-related constrictive pericarditis. Hypotension for unknown causes must be considered in the differential diagnosis of dialysis patients.

RESUMO A doença cardiovascular é a principal causa de morte em pacientes com doença renal crônica (DRC). Várias formas de acometimento cardíaco têm sido associadas. à DRC, incluindo doenças miocárdicas e pericárdicas. Este artigo descreve um caso de pericardite constritiva relacionada a em um paciente diagnosticado com hipotensão súbita durante uma sessão de hemodiálise. Um homem de 65 anos com diagnósticos prévios de hipertensão, diabetes, obesidade e cirrose em hemodiálise por dois anos queixou-se de sintomas durante uma de suas sessões, descritos como mal-estar, lipotímia e confusão mental. Apresentava histórico de baixa adesão à dieta prescrita e faltas frequentes às sessões de diálise. Ele estava fraco durante o exame físico e apresentava bulhas cardíacas hipofonéticas, pressão arterial de 50/30mmHg e tempo de enchimento capilar prolongado. O paciente foi encaminhado para a unidade de terapia intensiva e iniciou o tratamento com antibióticos e drogas vasoativas. Investigação laboratorial não mostrou sinais de infecção, enquanto o eletrocardiograma mostrou baixa voltagem de complexo QRS. Seu ecocardiograma evidenciou sinais consistentes com um pericárdio espessado, sem derrame pericárdico. O cateterismo cardíaco mostrou equalização das pressões diastólicas em todas as câmaras cardíacas, indicativo de pericardite constritiva. O paciente foi submetido a uma pericardiectomia. O exame anatomopatológico mostrou sinais de acentuada fibrose acentuada fibrose e áreas de calcificação distrófica sem evidência de infecção, consistente com pericardite constritiva relacionada a por diálise. A hipotensão por causas desconhecidas deve ser considerada no diagnóstico diferencial de pacientes em diálise.

Atypical hemolytic uremia syndrome in a young adult male

Atypical hemolytic uremia syndrome (aHUS) is a rare and life-threatening disease, characterized by the same triad of hemolytic anemia, thrombocytopenia, and renal failure as seen in HUS. It differs in its etiology, being caused by a dysregulation of the complement pathway rather than Shiga-like toxin-producing Escherichia coli. Prognosis is poor, with 50% of cases progressing to end-stage renal disease (ESRD) and 25% succumbing in the acute phase. The treatment of choice is therapeutic plasma exchange which can lower mortality. Monoclonal antibody drugs such as eculizumab, which suppress the dysregulated complement pathway, help to prevent complement-mediated kidney injury. We report the case of a young adult male who presented with thrombocytopenia and worsening acute kidney injury and was diagnosed with aHUS based on high lactic dehydrogenase, low complement C3, and haptoglobin, as well as renal biopsy showing thrombotic microangiopathy

Research progress on the relationship between serum magnesium and survival and prognosis of uremic maintenance dialysis patients / 中国综合临床

With the gradual maturity of renal replacement therapy technology, prolonging life span and improving quality of life of patients with uremia have become the ultimate management goals. In recent years, many studies at home and abroad have suggested that hypomagnesemia has an adverse effect on the prognosis of dialysis patients, which may be related to an increased risk of death. We understand the correlation between blood magnesium and blood pressure, cardiovascular disease, bone metabolism and vascular calcification, point out that blood magnesium may become one of the control indicators to reduce the mortality of dialysis patients, and explore its new clinical application.

Analysis of changes in serum metabolites of uremia patients based on ultra-high performance liquid chromatography-mass spectrometry / 中华肾脏病杂志

Objective:To analyze the changes in serum metabolites of patients with uremia using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), and provide a theoretical basis for the prevention and treatment of uremia.Methods:Uremia patients from the Department of Nephrology, the Affiliated Hospital of Southwest Medical University, and the volunteers from the Health Examination Center were enrolled in this study. According to the inclusion and exclusion criteria, 20 uremia patients (experimental group) and 20 volunteers (control group) were screened out. UHPLC-MS was used to detect the metabolites in the serum of subjects from the two groups, and difference analysis was made to screen the different metabolites, followed by correlation analysis and pathway enrichment study.Results:A total of 412 metabolites were identified by UHPLC-MS. Principal components analysis (PCA) proved that these metabolites could distinguish the control group and the experimental group well. The criteria [variable importance for the projection (VIP)>1, fold changes (FC)>1.25 or FC<0.8 and P value<0.05] was set to screen those significantly different metabolites. Finally, 28 significantly different metabolites were screened out, of which 18 metabolites increased significantly, the other 10 different metabolites decreased significantly. Correlation analysis results proved a certain correlation among 28 different metabolites and the experimental group and control group samples, and between the 28 differential metabolites themselves. Enrichment analysis found that 28 different metabolites might enrich the catecholamine biosynthetic pathway, and pathway analysis suggested that 28 different metabolites might affect glutamate, aspartame acid and glutamate metabolic pathways. Conclusion:Based on metabonomic analysis, some metabolites in the serum of patients with uremia have changed, which can affect some metabolic pathways, thus affecting the pathophysiological process of patients with uremia.

Prevalence of uremic pruritus and related factors in patients undergoing hemodialysis / 中国基层医药

Objective:To investigate the prevalence of uremic pruritus and related factors in patients undergoing hemodialysis.Methods:A total of 212 patients with uremia who undergo hemodialysis in the First Affiliated Hospital of Xiamen University in March 2021 were included in this cross-sectional study. Data including gender, age and blood biochemical indicators were collected. The 5D itch scale was used to evaluate skin itch in patients. The included patients were divided into pruritus and no pruritus groups according to evaluation results. Related indicators were compared between the two groups. Binary logistic regression analysis of skin itch related factors was performed.Results:According to 5D itch scale evaluation results, 129 patients (60.85%) of the 212 patients had no skin pruritus, and 83 patients (39.15%) had skin pruritus. In the pruritus group, age, hypersensitive C-reactive protein, alkaline phosphatase, brain natriuretic peptide, ferritin were 63.0 (51.0, 72.0) years, 1.66 (0.30, 7.85) mg/L, 93.0 (70.0, 118.0) U/L, 192.0 (84.9, 446.4) ng/L and 421.0 (291.6, 577.6) μg/L, respectively, which were significantly higher than 53.0 (42.0, 63.0) years, 0.40 (0.30, 1.88) mg/L, 79.0 (62.0, 99.0) U/L, 143.3 (65.8, 256.5) ng/L, 356.8 (203.3, 528.4) μg/L in the pruritus group ( Z = -3.14, -3.96, -3.05, -2.88, -2.11, all P < 0.05). Increased hypersensitive C-reactive protein, brain natriuretic peptide, ferritin levels ( Wald = 14.58, 4.17, 4.23, all P < 0.05) were independent risk factors for uremic pruritus. Conclusion:Uremic pruritus remains a serious problem in patients undergoing hemodialysis. Increased hypersensitive C-reactive protein, ferritin, brain natriuretic peptide levels are independent risk factors for uremic pruritus. In clinical work, physicians should focus on strengthening the early identification of patients, optimizing treatment measures, and improving the quality of life of patients.

Pharmacological action and clinical evaluation of difelikefalin, a new drug for the treatment of uremic pruritus / 中国基层医药

Uremic pruritus is one of the skin complications that perplex patients with end-stage renal disease undergoing hemodialysis or peritoneal dialysis. Because the specific pathogenesis is not clear, there is no unified treatment plan in the world. In August 2021, the US Food and Drug Administration approved the use of difelikefalin (under the trade name Korsuva) for the treatment of moderate to severe pruritus associated with chronic kidney disease in adult patients undergoing hemodialysis. Studies have shown that difelikefalin can remarkably reduce the intensity of pruritus and improve sleep and pruritus-related quality of life. The recommended dose of difelikefalin is 0.5 μg/kg, and difelikefalin is well tolerated and has high safety. This paper reviews the pharmacological effects, pharmacokinetics, clinical efficacy and safety of difelikefalin.

Alteraciones tromboelastográficas en pacientes con urgencia dialítica / Thromboelastographic alterations in patients with dialytic urgency

Resumen Antecedentes: la enfermedad renal cursa con alteraciones de la hemostasia, lo que aumenta el riesgo de eventos trombóticos y hemorrágicos. Objetivo: describir las anormalidades de la coagulación en pacientes con urgencia dialítica según tromboelastografía y pruebas convencionales. Materiales y métodos: serie de casos de 60 pacientes adultos con urgencia dialítica. Se tomaron muestras de sangre previas al implante de catéter de hemodiálisis o de diálisis peritoneal y se procesaron para tromboelastografía y pruebas convencionales. Resultados: en la interpretación global del tromboelastograma se identificó estado hipercoagulable en 60 % de los pacientes. En el análisis individual de parámetros del trazado se demostraron alteraciones en la fase enzimática con ángulo-α, aumentado en el 61,7 % y tiempo R acortado en el 58,3 % de los casos, alteraciones en la fase celular con MA y G aumentados en cerca del 45 % y alteraciones en la estabilidad con hiperfibrinolisis en el 18 %. El aPTT estaba prolongado en 23,7 %. Conclusiones: en la interpretación global de la tromboelastografía de pacientes con urgencia dialítica, el hallazgo más frecuente es el estado hipercoagulable. En el análisis individual se encontraron alteraciones en todas las fases de la coagulación, siendo la más frecuente la formación acelerada del coágulo, seguida por aumento de la fuerza de este. La tromboelastografía debería ser considerada como una prueba enfocada en la cabecera del paciente para la valoración de la hemostasia en estos pacientes.

Abstract Background: Kidney disease causes alterations of hemostasis increasing the risk of thrombotic and hemorrhagic events. Objective: Describe coagulation abnormalities in patients with kidney disease and dialytic urgency according to thrombelastography and conventional tests. Materials and methods: Case series of 60 patients hospitalized due to dialytic urgency. Blood samples were taken prior to implantation hemodialysis catheter or peritoneal catheter, processed for thrombelastography and conventional tests. Results: In the global interpretation of the thrombelastography hypercoagulable state was identified in 60% of the patients. In the individual analysis of the parameters of the plot, alterations in the enzymatic phase were demonstrated with an increased angle-α in 61.7% and shortened R time in 58.3% of the cases, alterations in the cellular phase with increased MA and G by about 45% and hyperfibrinolysis in 18%. The aPTT was prolonged by 23.7% of cases. Conclusions: In the overall interpretation of the thrombelastography of patients with dialytic urgency, the most frequent disorder was the hypercoagulable state. In the individual analysis, alterations were found in all the phases of coagulation, the most frequent being the accelerated formation of the clot, followed by an increase in strength. Thrombelastography should be considered as point-of-care test for the assessment of hemostasis in these patients.

Disruptive technologies for hemodialysis: medium and high cutoff membranes. Is the future now? / Tecnologias disruptivas para hemodiálise: membranas de ponto de corte médio e alto. O futuro é agora?

Abstract In the past decade, a new class of hemodialysis (HD) membranes (high retention onset class) became available for clinical use. The high cutoff (HCO) and the medium cutoff (MCO) membranes have wider pores and more uniformity in pore size, allowing an increased clearance of uremic toxins. Owing to the mechanism of backfiltration/internal filtration, middle molecules are dragged by the convective forces, and no substitution solution is needed. The HCO dialyzer is applied in septic patients with acute kidney injury requiring continuous kidney replacement therapy. The immune response is modulated thanks to the removal of inflammatory mediators. Another current application for the HCO dialyzer is in hematology, for patients on HD secondary to myeloma-kidney, since free light chains are more efficiently removed with the HCO membrane, reducing their deleterious effect on the renal tubules. In its turn, the MCO dialyzer is used for maintenance HD patients. A myriad of clinical trials published in the last three years consistently demonstrates the ability of this membrane to remove uremic toxins more efficiently than the high-flux membrane, an evolutionary disruption in the HD standard of care. Safety concerns regarding albumin loss as well as blood contamination from pyrogens in the dialysate have been overcome. In this update article, we explore the rise of new dialysis membranes in the light of the scientific evidence that supports their use in clinical practice.

Resumo Na última década, uma nova classe de membranas de hemodiálise (HD) (classe de início de alta retenção) tornou-se disponível para uso clínico. As membranas de ponto de corte alto (HCO) e ponto de corte médio (MCO) têm poros mais largos e maior uniformidade no tamanho dos poros, permitindo uma maior depuração de toxinas urêmicas. Devido ao mecanismo de retrofiltração/filtração interna, as moléculas médias são arrastadas pelas forças convectivas, não sendo necessária uma solução de substituição. O dialisador de HCO é aplicado em pacientes sépticos com lesão renal aguda que requerem terapia renal substitutiva contínua. A resposta imunológica é modulada graças à remoção de mediadores inflamatórios. Outra aplicação atual para o dialisador de HCO é em hematologia, para pacientes em HD secundária ao rim do mieloma, uma vez que as cadeias leves livres são removidas mais eficientemente com a membrana de HCO, reduzindo seu efeito deletério sobre os túbulos renais. Por sua vez, o dialisador de MCO é utilizado para pacientes em HD de manutenção. Uma miríade de ensaios clínicos publicados nos últimos três anos demonstra consistentemente a capacidade desta membrana de remover toxinas urêmicas de forma mais eficiente do que a membrana de alto fluxo, uma ruptura evolutiva no padrão de cuidado em HD. As preocupações de segurança em relação à perda de albumina, bem como a contaminação do sangue por pirogênios no dialisato foram superadas. Neste artigo de atualização, exploramos o surgimento de novas membranas de diálise à luz das evidências científicas que apoiam seu uso na prática clínica.

Relación entre el índice urémico y la función renal en pacientes con enfermedad renal crónica y en personas sanas

Objetivo : Evaluar la relación entre el índice urémico (IU) y la función renal medida por el aclaramiento de creatinina (ClCr) en personas sanas y en pacientes con enfermedad renal crónica (ERC); asimismo, comparar con la función renal extrapolada según la creatinina sérica y la calculada por algunas fórmulas recomendadas en la literatura internacional. Material y métodos : Estudio transversal, de correlación, analítico y observacional. Se incluyeron pacientes atendidos de forma ambulatoria en el Hospital Cayetano Heredia, Lima, Perú entre junio del 2018 y junio del 2019. Se realizó correlación de Pearson entre el IU y el ClCr; para la comparación de las medias del IU, creatinina sérica y las fórmulas estandarizadas en función al ClCr estratificado se utilizó el test de ANOVA y el eta cuadrado. Resultados: El IU de la población fue 4,37 ± 4,99 mg/dl y presentó correlación lineal cuadrática estadísticamente significativa con el ClCr (r=-0,74, p=0,000). Asimismo, el IU y el Log IU mostraron un valor predictivo el ClCr superior a la creatinina sérica y a las diversas fórmulas recomendadas en la literatura. El IU presentó correlación significativa con el potasio sérico y su fracción excretoria de forma relevante en comparación con la creatinina sérica. Conclusiones: El IU es un indicador del estado metabólico y nutricional que refleja el ClCr con una precisión estadísticamente significativa en la persona sana y en el paciente con distintos grados de ERC. Además, traduce aspectos relevantes de la función tubular renal.

SUMMARY Objective : To evaluate the relationship between uremic index (UI) and renal function measured by creatinine clearance (CrCl) in persons with normal renal function and in those with chronic renal failure (CRF), as well as to compare the renal function extrapolated from serum creatinine and that calculated with equations internationally recommended. Methods : A cross sectional study was conducted including patients attended in outpatient clinics at Hospital Cayetano Heredia in Lima from June 2018 to June 2019. Pearson's correlation between UI and CrCl was calculated; comparison of means of UI, serum creatinine and standard equations was done by ANOVA and eta square. Results: the overall UI was 4.37 ± 4.99 mg/dl and correlated linearly with CrCl (r=-0.74, p=0.000). The UI and the log UI were significantly more predictive of CrCl than serum creatinine and the international equations used. The UI correlated significantly with serum potassium than serum creatinine. Conclusions : The UI is a good indicator of the metabolic and nutritional status in persons With normal renal function and with CRF and reflects more accurately the CrCl.

AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients / O acúmulo de AGEs está relacionado à degeneração muscular e calcificação vascular em pacientes em diálise peritoneal

Abstract Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Resumo Histórico: Pacientes com doença renal crônica (DRC) são afetados pela dinapenia, sarcopenia e calcificação vascular. Produtos finais da glicação avançada (AGEs) podem se acumular em pacientes em diálise peritoneal (DP) e favorecer a sarcopenia por meio de alterações em ligações cruzadas do colágeno, quebra da proteína muscular e calcificação das células do músculo liso arterial por meio da ativação da p38-MAPK. O objetivo deste estudo é explorar as relações entre AGEs, degeneração muscular e calcificação da artéria coronária. Métodos: Este foi um estudo clínico observacional em pacientes com DRC submetidos à DP, no qual foram medidos os AGEs séricos e teciduais (AGEs-sAF), a carga cumulativa de glicose, a força muscular e testes funcionais, ultrassonografias musculares com elastografia, quantificação do cálcio da artéria coronária (CAC), e a densidade muscular por tomografia computadorizada multislice. Resultados: 27 pacientes com idade entre 48±16 anos, tempo de diálise entre 27±17 meses, tinham níveis de AGEs-sAF de 3,09±0,65 UA (elevado em 13 [87%] pacientes), níveis de força de preensão de 26,2±9,2 kg (11 [42%] pacientes com dinapenia), velocidade de marcha de 1,04±0,3 m/s (anormal em 14 [58%] pacientes) e teste "timed-up-and-go" (TUG) de 10,5±2,2s (anormal em 7 [26%] pacientes). Foram detectadas correlações entre os níveis AGEs-sAF e a elastografia do reto femoral (R=-0,74; p=0,02), a elastografia tibial anterior (R= -0,68; p=0,04) e a CAC (R=0,64; p=0,04). A carga cumulativa de glicose se correlacionou com a elastografia do reto femoral (R=-0,6; p=0,02), as concentrações séricas de hemoglobina glicada se correlacionaram com a densidade muscular do psoas (R= -0,58; p=0,04) e o CAC se correlacionou com a densidade do músculo psoas (R=-0,57; p=0,01) e a densidade do músculo quadrado lombar (R=-0,63; p=0,005). Conclusões: O estudo revelou associações entre o acúmulo de AGEs e menor rigidez/densidade muscular. Foram observadas associações que ligavam parâmetros de degeneração muscular com a calcificação vascular.