The influence of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life of patients with sarcopenia receiving haemodialysis: a randomised controlled trial.

OBJECTIVE: To study the effect of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life in patients with sarcopenia receiving maintenance haemodialysis (MHD). METHODS: Eligible patients with sarcopenia in our hospital were randomly assigned to a control group (n = 24) and an intervention group (n = 25). The control group received conventional dialysis treatment, while the intervention group underwent mindfulness meditation combined with progressive muscle relaxation training during the interdialysis period in addition to conventional dialysis treatment. The effect of the intervention was evaluated after 12 weeks. RESULTS: There were no significant differences in the baseline values of various parameters between the two groups. Exercise capacity (sit-to-stand test,handgrip,time to 10 sit-ups) significantly improved in the intervention group after 12 weeks (32.68 ± 8.32 vs 26.50 ± 6.83; 37.42 ± 10.12 vs 28.12 ± 8.51; 19.8 ± 5.40 vs 25.29 ± 7.18) (p < 0.05). In terms of the kidney disease quality of life (KDQOLTM) score, all other dimensions except sexual function, social functioning, burden of kidney disease and work status dimensions showed significant improvement compared to the baseline (p < 0.05). In the control group, only the dialysis staff encouragement (DSE) and patient satisfaction (PS) dimensions showed slight improvements compared to the baseline (p > 0.05). When compared with the control group, the intervention group showed significant improvements in 10 dimensions of exercise capacity and KDQOLTM scores for physical function, role-physical, general health, energy, symptom/problem list, sleep, DSE, pain, cognitive function, emotional well-being and patient PS after 12 weeks (61.30 ± 5.38 vs 42.98 ± 5.73; 57.50 ± 3.55 vs 50.70 ± 3.62) (p < 0.05). Some inflammatory markers, such as the levels of interleukin-6 and high-sensitivity C-reactive protein (30.29 ± 2.96 vs 17.65 ± 3.22; 8.93 ± 0.99 vs 3.02 ± 0.34), showed a decrease during the intervention, while albumin and prealbumin levels were significantly increased compared with the baseline (30.62 ± 1.65 vs 35.60 ± 1.68; 0.32 ± 0.05 vs 0.44 ± 0.07) (p < 0.05). CONCLUSION: Combined intervention training can improve the motor ability and quality of life of patients with sarcopenia within a short period of time.

Effect of regulated vitamin D increase on vascular markers in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

AIM: The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to assess the effect of regulated vitamin D increase on vascular markers in patients with CKD. DATA SYNTHESIS: We searched PubMed, Web of Science, Embase and ClinicalTrials.gov from database inception up until July 21, 2023. We included randomized controlled trials assessing the effects of using vitamin D and its analogues on vascular function in patients with CKD. Fixed-effects and random-effects model analyses were performed using weighted mean difference effects for each trial by heterogeneity (I2) assessment. Primary outcomes encompassed blood flow-mediated dilation (FMD)、pulse wave velocity (PWV) and augmentation index (AIx). FINDINGS: From 1964 records we selected 12 trials, 5 (n = 331) on FMD, 8 (n = 626) on PWV and 4 (n = 393) on AIx. Vitamin D and VDRA supplementation failed to significantly improve FMD (WMD 1.68%; 95% CI -0.18 to 3.53; P = 0.08; I2 = 88%)、PWV (WMD -0.41 m/s; 95%CI -0.95 to 0.13; P = 0.14; I2 = 57%)and AIx (WMD -0.53%; 95%CI -1.69 to 0.63; P = 0.37; I2 = 0%). Subgroup analysis revealed that 2 µg paricalcitol significantly improved FMD (WMD 2.09%; 95%CI 1.28 to 2.90; P < 0.00001); I2 = 0%), as did cholecalciferol (WMD 5.49%; 95% CI 4.35 to 6.63; P < 0.00001). CONCLUSION: Supplementation vitamin D and VDRA are associated with improved vascular function as measured by FMD, but not arterial stiffness as measured by PWV and AIx, tentatively suggesting that regulating the increase of vitamin D could not potentially reduce the incidence of cardiovascular disease.

Plasma D-dimer levels are associated with disease progression in diabetic nephropathy: a two-center cohort study.

BACKGROUND: This study aimed to investigate the relationship between plasma D-dimer levels, clinicopathological features, and clinical outcomes in patients with biopsy-proven diabetic nephropathy (DN). METHODS: A total of 137 patients with biopsy-proven DN were enrolled in this two-center cohort study. Patients were stratified into tertiles based on plasma D-dimer levels. We investigated the relationship between plasma D-dimer levels and clinical outcomes, including a composite of death, a 40% decline in estimated glomerular filtration rate (e-GFR) from baseline, or end-stage renal disease (ESRD) (defined as e-GFR < 15 mL/min/1.73 m2 or need for renal replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), assessed using Cox regression models with adjustment for confounders. RESULTS: At baseline, the mean age was 52.61 ± 11.63 years, and the mean e-GFR was 58.02 ± 28.77 mL/min/1.73 m2. During a median 26-month follow-up period, 65 (47% of patients) achieved clinical outcomes. Compared with the low plasma D-dimer level group, those with higher plasma D-dimer levels were more likely to have higher 24-h proteinuria (p = .002), lower e-GFR (p = .001), lower hemoglobin (p = .001), a higher glomerular lesion class (p = .03), and higher interstitial fibrosis and tubular atrophy (IFTA) scores (p = .002). After adjustment for demographic, DN-specific covariates, and treatments, it was observed that a higher tertile of plasma D-dimer was nonlinearly associated with an increased risk of the clinical outcomes (Hazard Ratio (HR) for tertile 2 vs. 1, 1.7; 95% Confidence Interval (CI), 0.80-3.75; HR for tertile 3 vs. 1, 2.2; 95% CI, 0.93-5.27; p for trend = .001) in the Cox proportional hazards models. CONCLUSION: In this study, DN patients with higher levels of plasma D-dimer had higher 24-h proteinuria, lower e-GFR, a higher glomerular lesion class, and higher IFTA scores. Furthermore, a high level of plasma D-dimer was nonlinearly associated with DN progression.

ROCK1 activates mitochondrial fission leading to oxidative stress and muscle atrophy.

Chronic kidney disease (CKD) is often associated with protein-energy wasting (PEW), which is characterized by a reduction in muscle mass and strength. Although mitochondrial dysfunction and oxidative stress have been implicated to play a role in the pathogenesis of muscle wasting, the underlying mechanisms remain unclear. In this study, we used transcriptomics, metabolomics analyses and mouse gene manipulating approaches to investigate the effects of mitochondrial plasticity and oxidative stress on muscle wasting in mouse CKD models. Our results showed that the expression of oxidative stress response genes was increased, and that of oxidative phosphorylation genes was decreased in the muscles of mice with CKD. This was accompanied by reduced oxygen consumption rates, decreased levels of mitochondrial electron transport chain proteins, and increased cellular oxidative damage. Excessive mitochondrial fission was also observed, and we found that the activation of ROCK1 was responsible for this process. Inducible expression of muscle-specific constitutively active ROCK1(mROCK1ca)exacerbated mitochondrial fragmentation and muscle wasting in CKD mice. Conversely, ROCK1 depletion (ROCK1-/-) alleviated these phenomena. Mechanistically, ROCK1 activation promoted the recruitment of Drp1 to mitochondria, thereby facilitating fragmentation. Notably, the pharmacological inhibition of ROCK1 mitigated muscle wasting by suppressing mitochondrial fission and oxidative stress. Our findings demonstrate that ROCK1 participates in CKD-induced muscle wasting by promoting mitochondrial fission and oxidative stress, and pharmacological suppression of ROCK1 could be a therapeutic strategy for combating muscle wasting in CKD conditions.

Case report: A case report of Alport syndrome caused by a novel mutation of COL4A5.

Alport syndrome (#308940) is an X-linked genetic disease with clinical manifestations, such as hematuria, proteinuria, renal insufficiency, and end-stage renal disease. The disease is characterized by the thinning of the glomerular basement membrane in the early stages and the thickening of the glomerular basement membrane in the late stages and may be associated with ocular lesions and varying degrees of sensorineural deafness. Herein, we report a case of Alport syndrome caused by a de novo mutation in COL4A5. The patient was a young male with clinical manifestations of hematuria and massive proteinuria who was diagnosed with Alport syndrome based on renal pathology and genetic testing.

Acute kidney injury in patients with cancer receiving anti-PD-1/PD-L1 antibodies: incidence, risk factors, and prognosis.

Anti-PD-1/PD-L1 antibodies are widely used in anti-cancer therapy. While they have improved cancer prognoses, immune-related adverse events, which can cause acute kidney injury (AKI), cannot be ignored. The purpose of this retrospective cohort study was to assess the incidence, risk factors, and prognosis of AKI associated with anti-PD-1/PD-L1 antibodies. Patients who received anti-PD-1/PD-L1 antibody treatment at our hospital between January 2018 and December 2022 were enrolled. Clinical information, combined medications, concomitant diseases, tumor types, and laboratory indicators were collected from patient records, and the incidence of AKI was determined. The risk factors for AKI were assessed using univariate and multivariate logistic regression analyses. Overall, 1418 patients were enrolled. The median follow-up time was 112 days and 92 (6.5%) developed AKI. The median time from the initial anti-PD-1/PD-L1 antibody treatment to AKI was 99.85 days. Head and neck cancer and combined use of diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), lower hemoglobin level, and other types of chemotherapeutic drugs were independent risk factors for AKI. The complete recovery, partial recovery, non-recovery, and unknown AKI rates were 7.6%, 28.3%, 52.2%, and 11.9%, respectively. Kidney biopsies were performed on two patients with AKI and pathology confirmed diagnosis of acute tubulointerstitial nephritis. In this cohort, AKI was not uncommon in patients treated with anti-PD-1/PD-L1 antibodies; therefore, it is necessary to monitor renal function and identify AKI early, especially in patients with head and neck tumors. Improving anemia and minimizing the use of diuretics, NSAIDs, and chemotherapeutics may reduce AKI.

Panax notoginseng saponins inhibits NLRP3 inflammasome-mediated pyroptosis by downregulating lncRNA-ANRIL in cardiorenal syndrome type 4.

OBJECTIVE: Cardiorenal syndrome type 4 (CRS4) is a complication of chronic kidney disease. Panax notoginseng saponins (PNS) have been confirmed to be efficient in cardiovascular diseases. Our study aimed to explore the therapeutic role and mechanism of PNS in CRS4. METHODS: CRS4 model rats and hypoxia-induced cardiomyocytes were treated with PNS, with and without pyroptosis inhibitor VX765 and ANRIL overexpression plasmids. Cardiac function and cardiorenal function biomarkers levels were measured by echocardiography and ELISA, respectively. Cardiac fibrosis was detected by Masson staining. Cell viability was determined by cell counting kit-8 and flow cytometry. Expression of fibrosis-related genes (COL-I, COL-III, TGF-ß, α-SMA) and ANRIL was examined using RT-qPCR. Pyroptosis-related protein levels of NLRP3, ASC, IL-1ß, TGF-ß1, GSDMD-N, and caspase-1 were measured by western blotting or immunofluorescence staining. RESULTS: PNS improved cardiac function, and inhibited cardiac fibrosis and pyroptosis in a dose-dependent manner in model rats and injured H9c2 cells (p < 0.01). The expression of fibrosis-related genes (COL-I, COL-III, TGF-ß, α-SMA) and pyroptosis-related proteins (NLRP3, ASC, IL-1ß, TGF-ß1, GSDMD-N, and caspase-1) was inhibited by PNS in injured cardiac tissues and cells (p < 0.01). Additionally, ANRIL was upregulated in model rats and injured cells, but PNS reduced its expression in a dose-dependent manner (p < 0.05). Additionally, the inhibitory effect of PNS on pyroptosis in injured H9c2 cells was enhanced by VX765 and reversed by ANRIL overexpression, respectively (p < 0.05). CONCLUSION: PNS inhibits pyroptosis by downregulating lncRNA-ANRIL in CRS4.

Mechanism of lncRNA-ANRIL/miR-181b in autophagy of cardiomyocytes in mice with uremia by targeting ATG5.

OBJECTIVES: This study is to investigate whether the cardiac microvascular endothelial cells (CMECs) can regulate the autophagy of cardiomyocytes (CMs) by secreting lncRNA-ANRIL/miR-181b exosomes, thus participating in the occurrence of uremic cardiovascular disease (CVD). METHODS: A 5/6 nephrectomy uremia model was established, with the mice injected with ANRIL-shRNA lentivirus vector, miR-181b agomir, and related control reagents, containing the serum creatinine and urea nitrogen measured. The renal tissue sections of mice were stained with Periodic Acid-Schiff (PAS), TUNEL, and Hematoxylin-Eosin (HE) performed on myocardial tissue sections of mice. ANRIL-shRNA, miR-181b mimics, and related control reagents were transfected into CMECs, in which the exosomes were extracted and co-cultured with CMs. The expressions of ANRIL, miR-181b and ATG5 were detected by qRT-PCR, and the expressions of autophagy related proteins by Western blot, as well as the binding of ANRIL and miR-181b by the double luciferase reporter gene experiment. RESULTS: ANRIL down-regulation or miR-181b up-regulation can increase the weight of mice with uremia, as well as the expressions of p62 and miR-181b, and reduce the content of serum creatinine and urea nitrogen, the damage of kidney and myocardial tissues, the number of apoptotic cells in myocardial tissues, as well as the expressions of ANRIL, ATG5, Beclin1, and LC3. CMs can absorb the exosomes of CMECs. Compared with IS+ CMEC-Exo group, the expressions of ANRIL and ATG5 in CMs of IS+ CMEC-Exo + sh lncRNA ANRIL and IS+CMEC-Exo+miR-181b mimics groups was down-regulated, as well as the expressions of ATG5, Beclin1, and LC3, while miR-181b expression was up-regulated as well as P62 expression. CONCLUSIONS: CMECs can regulate autophagy of CMs by releasing exosomes containing ANRIL and miR-181b.

Highlighted Prospects of an IgM/IgG Antibodies Test in Identifying Individuals With Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

CONTEXT.­: Covert severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections could be seeding new outbreaks. How to identify asymptomatic SARS-CoV-2 infections early has become a global focus. OBJECTIVE.­: To explore the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies detection, nucleic acid tests, and computed tomography (CT) scanning to identify asymptomatic SARS-CoV-2 infection. DESIGN.­: The clinical data of 389 individuals with close contacts, including in general characteristics, SARS-CoV-2 etiology, serum-specific IgM and IgG antibody detection and CT imaging results, were systematically analyzed. RESULTS.­: The present study showed that only 89 of 389 individuals with close contacts were positive after the first nucleic acid test, while 300 individuals were still negative after 2 nucleic acid tests. Among the 300 individuals, 75 did not have pneumonia, and the other 225 individuals had pulmonary imaging changes. A total of 143 individuals were eventually diagnosed as having asymptomatic infection through IgM antibody and IgG antibody detection. The sensitivity, specificity, and false-negative rate of IgM and IgG antibody detection were approximately 97.1% (347 of 357), 95.3% (204 of 214), and 4.67% (10 of 214), respectively. It also indicated that during approximately 2 weeks, most individuals were both IgM positive and IgG positive, accounting for 68.57% (72 of 105). During approximately 3 weeks, the proportion of IgM-positive and IgG-positive individuals decreased to 8.57% (9 of 105), and the proportion of IgM-negative and IgG-positive individuals increased to 76.19% (80 of 105). CONCLUSIONS.­: There are highlighted prospects of IgM/IgG antibody detection as a preferred method in identifying the individuals with asymptomatic SARS-CoV-2 infection, especially combined with nucleic acid tests and pulmonary CT scanning.

Gitelman syndrome caused by a rare homozygous mutation in the SLC12A3 gene: A case report.

BACKGROUND: Gitelman syndrome (GS) is an unusual, autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. It is caused by mutations in the solute carrier family 12 member 3 (SLC12A3) gene resulting in disordered function of the thiazide-sensitive NaCl co-transporter. To date, many types of mutations in the SLC12A3 gene have been discovered that trigger different clinical manifestations. Therefore, gene sequencing should be considered before determining the course of treatment for GS patients. CASE SUMMARY: A 55-year-old man was admitted to our department due to hand numbness and fatigue. Laboratory tests after admission showed hypokalemia, metabolic alkalosis and renal failure, all of which suggested a diagnosis of GS. Genome sequencing of DNA extracted from the patient's peripheral blood showed a rare homozygous mutation in the SLC12A3 gene (NM_000339.2: chr16:56903671, Exon4, c.536T>A, p.Val179Asp). This study reports a rare homozygous mutation in SLC12A3 gene of a Chinese patient with GS. CONCLUSION: Genetic studies may improve the diagnostic accuracy of Gitelman syndrome and improve genetic counseling for individuals and their families with these types of genetic disorders.

Repeated and progressive rhabdomyolysis due to a novel carnitine palmitoyltransferase II gene variant in an adult male: A case report.

INTRODUCTION: The occurrence of repeated and progressive rhabdomyolysis is rare in clinical settings, particularly in adults. The pathogenesis of rhabdomyolysis is often overlooked due to its rapid recovery. Carnitine palmitoyltransferase (CPT) II deficiency could be a rare etiology of repetitive nontraumatic rhabdomyolysis, and several mutations of CPT II have been reported. PATIENT CONCERNS: A 41-year-old man presented with high fever, general malaise, myalgia, dyspnea, and dark-colored urine, and then progressed to anuria. In the past 15 years, he experienced dark-colored urine twice due to exercise and high fever. Physical examination revealed oliguria, suppurated tonsils, poor hemoglobin saturation, alert consciousness, normal neurological signs and reflexes, hypertension, and tachypnea. Laboratory investigations showed positive test results for inflammation, high serum myogenic enzyme levels, and evidence of acute kidney injury (AKI). DIAGNOSES: Investigations revealed an extremely high serum myogenic enzyme levels and impaired renal function with serum creatinine level of 510 µmol/L, consistent with the diagnosis of rhabdomyolysis, AKI stage 3, and acute respiratory distress syndrome. High levels of acylcarnitine in the serum confirmed the diagnosis of CPT II deficiency. In addition, whole exome sequencing (WES) was conducted in the patient and his mother. INTERVENTIONS: Intubation, ventilator support, and hemodialysis were the major therapeutic interventions at the peak of disease progression. He was then administered valsartan tablets at a dosage of 80 mg per day and L-carnitine supplements. OUTCOMES: WES conducted in the patient and his mother revealed 2 novel mutations of CPT II (c.482G>A and c.1493G>T) in this patient. The patient recovered from the severe AKI but the renal function remained impaired at chronic kidney disease stage 3a. CONCLUSION: Thus, gene examination can help to understand the etiology of repetitive nontraumatic rhabdomyolysis. Accurate diagnosis can be beneficial for providing an individualized treatment for patients with repeated and progressive rhabdomyolysis.

The nuclear phosphatase SCP4 regulates FoxO transcription factors during muscle wasting in chronic kidney disease.

Chronic kidney disease (CKD) and related inflammatory responses stimulate protein-energy wasting, a complication causing loss of muscle mass. Primarily, muscle wasting results from accelerated protein degradation via autophagic/lysosomal and proteasomal pathways, but mechanisms regulating these proteolysis pathways remain unclear. Since dephosphorylation of FoxOs regulates ubiquitin/proteasome protein metabolism, we tested whether a novel nuclear phosphatase, the small C-terminal domain phosphatase (SCP) 4, regulates FoxOs signaling and, in turn, muscle wasting. In cultured mouse myoblast cells, SCP4 overexpression stimulated proteolysis, while knockdown of SCP4 prevented the proteolysis stimulated by inflammatory cytokines. SCP4 overexpression led to nuclear accumulation of FoxO1/3a followed by increased expression of catabolic factors including myostatin, Atrogin-1, and MuRF-1, and induction of lysosomal-mediated proteolysis. Treatment of C2C12 myotubes with proinflammatory cytokines stimulated SCP4 expression in an NF-κB-dependent manner. In skeletal muscle of mice with CKD, SCP4 expression was up-regulated. Similarly, in skeletal muscle of patients with CKD, SCP4 expression was significantly increased. Knockdown of SCP4 significantly suppressed FoxO1/3a-mediated expression of Atrogin-1 and MuRF-1 and prevented muscle wasting in mice with CKD. Thus, SCP4 is a novel regulator of FoxO transcription factors and promotes cellular proteolysis. Hence, targeting SCP4 may prevent muscle wasting in CKD and possibly other catabolic conditions.

Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney disease.

BACKGROUND: Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF-1/insulin signalling and increases in glucocorticoids, myostatin and/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation. METHODS: Using in vitro and in vivo models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone. RESULTS: Using cultured C2C12 myotubes to study muscle wasting, we found that exposure to glucocorticoids cause loss of cell proteins plus an increase in myostatin; both responses are significantly suppressed by ursolic acid. Results from promoter and ChIP assays demonstrated a mechanism involving ursolic acid blockade of myostatin promoter activity that is related to CEBP/δ expression. In mouse models of CKD-induced or dexamethasone-induced muscle wasting, we found that ursolic acid blocked the loss of muscle mass by stimulating protein synthesis and decreasing protein degradation. These beneficial responses included decreased expression of myostatin and inflammatory cytokines (e.g. TGF-ß, IL-6 and TNFα), which are initiators of muscle-specific ubiquitin-E3 ligases (e.g. Atrogin-1, MuRF-1 and MUSA1). CONCLUSIONS: Ursolic acid improves CKD-induced muscle mass by suppressing the expression of myostatin and inflammatory cytokines via increasing protein synthesis and reducing proteolysis.

CKD Stimulates Muscle Protein Loss Via Rho-associated Protein Kinase 1 Activation.

In patients with CKD, muscle wasting is common and is associated with morbidity and mortality. Mechanisms leading to loss of muscle proteins include insulin resistance, which suppresses Akt activity and thus stimulates protein degradation via the ubiquitin-proteasome system. However, the specific factors controlling CKD-induced suppression of Akt activity in muscle remain undefined. In mice with CKD, the reduction in Akt activity in muscle exceeded the decrease in upstream insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity, suggesting that CKD activates other pathways that suppress Akt. Furthermore, a CKD-induced increase uncovered caspase-3 activity in muscle in these mice. In C2C12 muscle cells, activated caspase-3 cleaves and activates Rho-associated protein kinase 1 (ROCK1), which enhances the activity of phosphatase and tensin homolog (PTEN) and reduces Akt activity. Notably, constitutive activation of ROCK1 also led to increased caspase-3 activity in vitro. In mice with either global ROCK1 knockout or muscle-specific PTEN knockout, CKD-associated muscle proteolysis was blunted. These results suggest ROCK1 activation in CKD and perhaps in other catabolic conditions can promote loss of muscle protein via a negative feedback loop.