Changes In Kidney Function Research Articles

Procedural sedative effect of remimazolam in ICU patients on invasive mechanical ventilation: a randomised, prospective study

BackgroundInvasive procedures and environmental factors in the intensive care unit (ICU) may cause anxiety and discomfort in patients, who often require sedation therapy. The aim of this study was to assess the safety of remimazolam tosilate for procedural sedation in ICU patients receiving mechanical ventilation following endotracheal intubation. Eighty patients from a single centre were randomly assigned to either the propofol group or the remimazolam group. Blood tests were conducted to evaluate changes in lactate, blood lipids, liver and kidney function, and inflammatory markers, and patients’ vital signs were observed over several periods. This study compared the incidence of delirium, the impact on liver and kidney function, circulatory effects, and changes in blood lipids between the two groups. These findings have optimised the selection of medications, providing ICU patients with more options for sedation therapy.MethodsIn this single-centre randomised controlled trial, intubated patients were randomly assigned to the remimazolam group or the propofol group. Under the same analgesic regimen, the two groups received remimazolam and propofol for procedural sedation.ResultsOur primary outcome was the mean arterial pressure (MAP), which significantly differed on Days 4 and 7 (P = 0.021, control group vs. experimental group = 85.23 ± 11.24 vs. 94.36 ± 13.18, P = 0.023, 83.55 ± 8.94 vs. 92.66 ± 7.02). With respect to liver and kidney function, the ∆AST value in the remimazolam group was significantly lower than that in the control group on Day 7 (P = 0.023). There were significant differences in triglyceride (TG) levels on Days 4 and 7 (P = 0.020) and in the ∆LDL on Day 7 (P = 0.027). Furthermore, the rates of dyslipidaemia and delirium in the remimazolam group were lower than those in the propofol group (85.0%, n = 40 vs. 90.0%, n = 40; 27.5%, n = 40 vs. 55%, n = 40).ConclusionRemimazolam is a novel benzodiazepine that has demonstrated promising applications in general anaesthesia and procedural sedation; however, its use in ICU sedation is still in the early stages of research. Current evidence suggests that remimazolam is a safe sedative that is particularly well suited for patients with haemodynamic instability. Large sample-size randomised clinical trials are warranted.

Attempts To Achieve Standardized Definitions To Characterize Changes In Kidney Function In The Context Of Heart Failure Clinical Trials: From The Heart Failure Collaboratory

Attempts To Achieve Standardized Definitions To Characterize Changes In Kidney Function In The Context Of Heart Failure Clinical Trials: From The Heart Failure Collaboratory

Luteolin alleviated calcium oxalate crystal induced kidney injury by inhibiting Nr4a1-mediated ferroptosis

BackgroundThe global incidence of calcium oxalate (CaOx) kidney stones is rising, and effective treatments remain limited. Luteolin (Lut), a naturally flavonoid present in several plants, is recognized for its anti-inflammatory, anti-injury, and neuroprotective effects. However, its effects on CaOx kidney stone formation and the associated kidney damage are still unknown. ObjectiveOur study seeks to explore the therapeutic impact of Lut on kidney injury and renal fibrosis caused by CaOx crystal and to elucidate the underlying mechanisms. MethodsCaOx stone models were established in mice via intraperitoneal injection of glyoxylate (Gly, 100 mg/kg) for 12 days. Lut (50 mg/kg or 100 mg/kg) was administered intraperitoneally 7 days before and with the period of Gly treatment. Kidney function and histopathology changes in renal tissues were assessed. RNA sequencing was used to explore potential mechanisms between the model and Lut treatment groups. Molecular docking simulations evaluated the interaction between Lut and the downstream target Nr4a1. Moreover, Nr4a1 knockout mice and knockdown plasmids were used to validate the mechanism of Lut in the treatment of CaOx crystal-induced kidney injury. ResultsLut significantly mitigated kidney injury and renal fibrosis induced by CaOx crystal, as evidenced by improved kidney function, histopathology staining and Western blot analysis. Lut treatment also significantly inhibited lipid peroxidation and mitochondrial injury. In vitro experiments further demonstrated that Lut treatment alleviated injury and fibrosis in HK-2 cells. Mechanistically, RNA sequencing and molecular docking simulations indicated that Lut binds to Nr4a1 to regulate ferroptosis, thereby alleviating kidney injury induced by CaOx crystal. Overexpression of Nr4a1 negated Lut's beneficial effects, whereas Nr4a1 knockout exhibited a protective effect against kidney injury. ConclusionLut exerts its protective effects by inhibiting ferroptosis via targeting Nr4a1-Slc7a11-GPX4 pathway, alleviating kidney injury and renal fibrosis caused by CaOx crystal deposition.

Effect of an intensive lifestyle intervention on cystatin C-based kidney function in adults with overweight and obesity: From the PREDIMED-Plus trial.

Large-scale trials evaluating a multicomponent lifestyle intervention aimed at weight loss on kidney function are lacking. This was a post hoc analysis of the "PREvención con DIeta MEDiterránea-Plus" (PREDIMED-Plus) randomized controlled trial, including patients with overweight/obesity and metabolic syndrome, measured cystatin C and creatinine. Participants were randomly assigned (1:1) to an intensive weight loss lifestyle intervention (intervention group [IG]) consisting of an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support, or a control group (CG) receiving ad libitum MedDiet recommendations. The primary outcome was between-group differences in cystatin C-based kidney function (cystatin C-based estimated glomerular filtration rate-eGFRcys-and combined cystatin C-creatinine-based eGFR-eGFRcr-cys) change from baseline to 12 and 36 months. Secondary outcomes included between-group differences in creatinine-based eGFR (eGFRcr) and urinary albumin-to-creatinine ratio (UACR) change and the predictive capacity of these formulas at baseline for new-onset chronic kidney disease (CKD). A total of 1909 participants (65±5 years, 54% men) were included. Twelve-month decline in eGFRcys, eGFRcr-cys, and eGFRcr was greater in the CG compared to the IG, with between-group differences of -1.77mL/min/1.73m2 [95% confidence interval -2.92 to -0.63], -1.37 [-2.22 to -0.53], and -0.91 [-1.74 to -0.71], respectively. At 36 months, the decline in eGFRcr-cys and eGFRcr was greater in the CG. No between-group differences in UACR were found. Significant adjusted areas under the curve for baseline eGFRcys and eGFRcr-cys were observed for incident CKD at 36 months, which were similar to those foreGFRcr and UACR. In older adults with overweight/obesity and metabolic syndrome, the PREDIMED-Plus intervention may be an optimal approach to preserve kidney function.

The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial.

Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hoc study of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2 or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2 in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

A nationwide questionnaire study evaluated kidney injury associated with Beni-koji tablets in Japan.

Red yeast rice, traditionally used in Asian cuisine and increasingly marketed as a dietary supplement for cholesterol management, has recently been linked to kidney dysfunction in Japan. In late 2023 to early 2024, multiple cases involving specific Beni-koji (red yeast rice) tablets from three different Beni-koji preparations, prompted a safety reevaluation. Although citrinin, a known nephrotoxin of red yeast rice, was not produced by the implicated strains, new safety concerns emerged. Here, we aimed to investigate the clinical, laboratory, and pathological features of affected patients with a two-phase nationwide survey of Japanese nephrologists. The initial survey captured clinical presentations, while the follow-up survey tracked changes in kidney function and gathered pathological data. Statistical analyses included trend assessments across estimated glomerular filtration rate (eGFR) categories and mixed-effects models for eGFR trajectories. Of 192 patients, 94.1% presented with low eGFR (under 60 ml//min/1.73m2). Laboratory findings revealed characteristics of Fanconi syndrome, including hypokalemia, hypophosphatemia, hypouricemia, glycosuria, and metabolic acidosis. Creatine kinase levels were not elevated suggesting no rhabdomyolysis related kidney injury. Kidney biopsies showed predominant tubulointerstitial changes, with 50% exhibiting tubulointerstitial nephritis and 32% showing tubular necrosis. Glomerular changes were less prominent. Following product discontinuation and treatment, Fanconi syndrome-related parameters improved significantly. However, 87% of patients still had eGFR under 60 ml/min/1.73m2 at the last observation. Our findings underscore the need for long-term follow-up of affected individuals and highlight the importance of rigorous safety evaluations for dietary supplements. Further research is necessary to establish definitive causal relationships and long-term outcomes.

TOXICOLOGICAL IMPACT OF DICLOFENAC SODIUM: HEMATOLOGICAL, BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN MALE RATS

Background: Long-term administration of diclofenac sodium can lead to harmful effects on body tissues, causing cellular injuries that include changes in kidney function and contributing to the development of immune mechanisms against kidney tissues. This study aimed to evaluate the toxic effects of diclofenac sodium on hematological and biochemical parameters, as well as histopathological changes in the kidneys of experimental animals. Methods: Forty male Albino-Aster mice were divided into four groups: control and three groups administered diclofenac sodium orally at doses of 20.5, 45 and 56.25 mg/kg body weight for 20 days. Blood samples were collected for hematological and biochemical analyses and kidney tissues were examined histopathologically. Results: Diclofenac sodium administration caused a significant decrease in red blood cells, hemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular hemoglobin concentration, as well as a significant increase in platelets and total white blood cells. Serum alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase were significantly elevated. Histopathological examination revealed congestion, inflammation, glomerular abnormalities, tubular necrosis and vascular changes in the kidney tissues, with the severity increasing with higher doses. Conclusion: Diclofenac sodium administration at different doses can cause significant alterations in hematological and biochemical parameters, as well as histopathological changes in the kidneys of male rats, indicating potential adverse effects on animal tissues. Caution is recommended in the clinical use of diclofenac sodium and the lowest effective dose and duration should be used to achieve the desired therapeutic effect.

Clinical significance of elevated serum cardiac troponin T and associated risk factors in patients diagnosed with acute ischemic stroke

Objective: We explored the clinical significance and associated risk factors of increased levels of serum cardiac troponin T (cTnT) in individuals suffering from acute ischemic stroke (AIS). Methods: Our study subjects consisted of patients who were admitted with AIS within 48 hours of its onset. These study participants were categorized based on their levels of cTnT into two groups: normal cTnT group and elevated cTnT group. We collected and subjected a range of data to statistical analysis, including general clinical traits, medical history, laboratory test results, electrocardiograms, imaging scans, and medical records like the National Institute of Health Stroke Scale (NIHSS) scores of the patients. Results: Out of the 232 patients diagnosed with AIS, 84 individuals (36.21%) exhibited raised levels of cTnT. When comparing this elevated cTnT cohort to the group with regular cTnT levels, those with elevated cTnT were older [with a median age of 76 year (interquartile range: 67 to 83) as compared to 70 year interquartile range: 61 to 79), P = 0.002], and they presented with higher NIHSS scores upon admission [8.5 (interquartile range: 4 to 14) compared to 5 (interquartile range: 2 to 9), p = 0.002]. In addition, a larger percentage of patients in the elevated cTnT group had both coronary artery disease (23.81% vs. 7.43%, P < 0.001) and cardiac insufficiency (25.00% vs. 3.38%, P < 0.001) as comorbidities. Meanwhile, the elevated cTnT group also displayed a higher occurrence of electrocardiogram abnormalities, including bundle branch block (29.76% vs. 9.46%, P < 0.001) and atrial fibrillation (32.14% vs. 11.49%, P < 0.001), in comparison to the normal cTnT group. The clinical data and related laboratory indicators of patients were collected for risk factor analysis, which showed that bundle branch block [odds ratio (OR) = 4.17, 95% confidence interval (95%CI) = 1.43–12.16), log to base 10 N-terminal pro-brain natriuretic peptide (Log10NT-proBNP; OR = 3.41, 95%CI = 1.62-7.16), cystatin C (OR = 6.86, 95%CI = 2.01–23.43), and neutrophil/lymphocyte ratio (OR = 1.13, 95%CI = 1.02–1.25) were independent risk factors for elevated cTnT in patients with AIS. Conclusions: Older patients with AIS who had higher levels of cTnT exhibited more severe neurological impairments and a greater number of comorbidities. Furthermore, an elevated cTnT in patients with AIS may be linked to cardiac insufficiency, changes in kidney function, and signs of inflammation.

The Safety of Multiple-Dose Liquid Blend Containing Kava and Kratom in Healthy Adults.

This study investigates the safety of three different daily dosages of a liquid blend containing kava and kratom (Feel Free® Classic Tonic {FFCT}) in healthy adults over six consecutive days of supplementation. Both kava and kratom have been used traditionally for hundreds of years, but there is limited data on the combined safety of these ingredients. In this randomized, double-blind, placebo-controlled trial, the participants were assigned to receive one of three daily dosages of FFCT or placebo. Safety assessments included the monitoring of vital signs, clinical chemistry, hematology, and withdrawal symptoms using the Clinical Opiate Withdrawal Scale (COWS) and the Subjective Opiate Withdrawal Scale (SOWS). The results indicate that FFCT was safe, with mild to moderate adverse events (AEs) such as nausea, headaches, and fatigue, particularly in the high-dosage (HD) group. No significant changes in liver or kidney function were noted, and all vital signs remained within normal physiological ranges although some statistically significant changes in blood pressure (BP) and respiratory rate (RR) were observed. There were no clinically significant observations in COWS or SOWS scores despite a small but statistically significant increase in COWS total score in the high-dose group on day 7. Overall, FFCT appears safe for short-term use in healthy adults, with no significant impact on vital signs, laboratory values, or withdrawal symptoms.

Rate of decline in kidney function with age: a systematic review

ObjectiveTo determine the distribution of kidney function values as measured by glomerular filtration rate (GFR), and the rate of decline with age in male and female healthy subjects without pre-existing...

Radiographic and tomographic findings of excretory urography of avian kidneys after induced nephropathy in broiler chicken as a model.

Although kidney diseases have a high prevalence, initial recognition and diagnosis of renal disease are complicated in avian medicine. The aim of this study is to assess the intraosseous excretory urography (IOEU) in order to introduce a new method for evaluation of kidney's function in broilers as a primary model of birds. A total of 10 male broiler chickens at the age of 20 days were included and evaluated with plain and serial post-contrast radiography and computed tomography (CT) scan to check the time and concentration of the contrast media (CM) passage from the kidney. In the next step, after the nephropathy induction with gentamicin, plain and serial post-contrast radiography and CT scan were repeated. After the necropsy, kidney samples were sent for histopathology evaluation, and statistical analysis of data obtained from image analysis was conducted. After nephropathy induction, all of the chickens exhibited increase in kidney size and in histopathological evaluation, all the samples (30 of 30) showed severe tubular necrosis and mild glomerulopathy. In the IOEU, the average time to create the maximum concentration of CM, the average time to decrease the CM concentration from the kidney and the time of the complete clearance of CM indicated a significant incensement after nephropathy compared to the time before it. Intraosseous excretory urography (IOEU) is a safe contrast imaging modality and can be useful in the assessment of the urinary system in chickens to check the changes in kidney size and function.

Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined. To assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM. This retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024. The primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR >20%). Among 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was -5 mlL/min/1.73 m2 (-12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; P < .001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; P < .001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; P < .001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m2 [51-77] vs 61 mL/min/1.73 m2 [49-77]; P = .41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; P < .001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (P for interaction = .93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (P for interaction = .97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; P < .001). In this retrospective cohort study, decline in kidney function was frequent in patients with ATTR-CM and was consistently associated with an increased risk of mortality, even after adjusting for established markers of worsening ATTR-CM. eGFR decline represents an independent marker of ATTR-CM disease progression that could guide treatment optimization in clinical practice.

Kidney hyperfiltration and mitochondrial changes are associated with eGFR decline in young people with type 1 diabetes.

To examine the relationship between kidney hyperfiltration during adolescence and subsequent changes in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) in a young cohort of participants with type 1 diabetes. Additionally, to explore urinary mitochondrial DNA:nuclear DNA ratio (mtDNA:nDNA) as a marker of metabolic stress and its association with early changes in kidney function. Eighty adolescents were studied at baseline [mean (SD) age 14.2 (1.5) years; mean diabetes duration 6.7 (3.0) years] and followed up 9.2 (1.3) years later. Blood pressure, HbA1c, lipids, eGFR, UACR and heart rate variability were assessed at each visit. Urinary mtDNA:nDNA was measured by quantitative PCR (qPCR). Overall, 4.2% of participants had diabetic kidney disease (DKD) at follow-up. Hyperfiltration at baseline (>135 mL/min/1.73m2) was seen in 31% of adolescents and was associated with a decline in eGFR at follow-up when adjusted for sex, diabetes duration and HbA1c [hyperfiltration -1.46 (3.07) mL/min/1.73 m2/year vs non-hyperfiltration -0.51 (2.48) mL/min/1.73m2/year, P=0.02]. Participants with hyperfiltration also had higher odds of undergoing rapid eGFR decline (>3 mL/min/1.73m2/year) compared to those without hyperfiltration [OR 14.11, 95% CI (2.30-86.60), P=0.004]. Baseline urinary mtDNA:nDNA was significantly associated with both greater annual rate of eGFR decline and rapid eGFR decline in univariable but not multivariable modelling. Hyperfiltration during adolescence is significantly associated with greater reduction in eGFR and higher risk of rapid eGFR decline after ∼9 years, following transition into young adulthood in type 1 diabetes. Urinary mtDNA:nDNA measured during adolescence may be a novel predictor of early changes in kidney function.

Glucagon receptor activation contributes to the development of kidney injury.

The underlying causes of diabetic kidney disease are still largely unknown. New insights into the contributing causes of diabetic nephropathy are important to prevent this complication. Hyperglycemia and hypertension are some of the risk factors for diabetic nephropathy. However, the incidence of diabetic nephropathy is increasing despite efforts to normalize blood glucose levels and blood pressure. Therefore, other factors should be investigated as causes of diabetic nephropathy. We investigated whether long-term increased plasma levels of glucagon contribute to the development of pathophysiological changes in kidney function as seen in patients with diabetic nephropathy. Using mouse models of chronic activation and inactivation of glucagon receptor signaling, we investigated whether glucagon is involved in changes in renal function, renal structure, and transcriptional changes. We found several histopathological changes in the kidney, such as thickening of the parietal layer of Bowman's capsule, glomerular mesangial cell expansion, and significant albuminuria in the mice with activated glucagon receptor signaling. Opposite effects on mesangial area expansion and the development of albuminuria were demonstrated in mice with glucagon receptor inactivation. RNA sequencing data revealed that transcription of genes related to fatty acid metabolism, podocytes, Na+-K+-ATPase, and sodium/glucose transport was significantly changed in mice with activated glucagon receptor signaling. These data implicate that glucagon receptor signaling is involved in the development of kidney injury, as seen in type 2 diabetes, and that glucagon receptor is a potential therapeutic target in the treatment of diabetes. NEW & NOTEWORTHY This study suggests that the glucagon receptor is a potential therapeutic target in the treatment of diabetic kidney disease. We show, in mice, that long-term treatment with a glucagon analog showed not only pathophysiological changes and changes in renal function but also transcriptional changes in the kidneys, whereas opposite effects were demonstrated in mice with glucagon receptor inactivation. Therefore, the use of glucagon in a treatment regimen requires investigation of possible metabolic and renal abnormalities.

Post-hoc analysis of the CARES trial suggests delayed progression of chronic kidney disease in patients with gout during urate-lowering therapy

Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD- EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57–0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.

Zhuangyao Jianshen Wan ameliorates senile osteoporosis in SAMP6 mice through Modulation of the GCN5L1-mediated PI3K/Akt/wnt signaling pathway

BackgroundSenile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. However, there is currently no effective treatment for SOP. The Zhuangyao Jianshen Wan (ZYJSW) pill is traditionally believed to possess kidney-nourishing and bone-strengthening effects, demonstrating efficacy in treating fractures. Despite this, its effectiveness and mechanism in SOP remain unclear. This study aims to investigate the therapeutic potential of ZYJSW in treating SOP in senescence accelerated mouse prone 6 (SAMP6, P6) mice, and elucidate the underlying mechanisms. MethodsFour-month-old SAMP6 mice were categorized into six groups: the model group (SAMP6), low, medium, and high-dose ZYJSW treatment groups, calcitriol treatment (positive control 1) group, and metformin treatment (positive control 2) group. Gastric administration was carried out for 15 weeks, and a normal control group comprising four-month-old Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Changes in body weight, liver and kidney function, bone protective effects, and muscle quality were evaluated using various assays, including H&E staining, Goldner staining, bone tissue morphology analysis, Micro-CT imaging, and biomechanical testing. Qualitative analysis and quality control of ZYJSW were performed via LC-MS/MS analysis. To explore mechanisms, network pharmacology and proteomics were employed, and the identified proteins were validated by Western blotting. ResultsOral administration of ZYJSW to P6 mice exerted preventive efficacy against osteopenia, impaired bone microstructure, and poor bone and muscle quality. ZYJSW attenuated the imbalance in bone metabolism by promoting bone formation, as evidenced by the upregulation of key factors such as Runt-related transcription factor 2 (RUNX2), Bone Morphogenetic Protein (BMP2), Osteoprotegerin (OPG) and Osteocalcin (OCN), while simultaneously inhibiting bone resorption through the downregulation of TNF receptor associated factor 6 (TRAF6), Tartrate resistant acid phosphatase (TRAP), Receptor activator for nuclear factor-κB ligand (RANKL) and Cathepsin K (CTSK). Additionally, ZYJSW enhanced muscle structure and function by counteracting the elevation of Ubiquitin (Ub), Muscle RING-finger protein-1 (Murf-1), F-Box Protein 32 (FBOX32), and Myogenin (Myog). Network pharmacology predictions, proteomics analysis corroborated by published literature demonstrated the role of ZYJSW involving in safeguarding mitochondrial biogenesis. This was achieved by suppressing GCN5L1 expression, contributing to the heightened expression of TFAM, PGC-1α, and nuclear respiratory factor-1 (NRF-1) proteins. ZYJSW also positively modulated Wnt signaling pathways responsible for bone formation, due to regulating expressions of key components like β-catenin, GSK-3β, and LRP5. In addition, ZYJSW causes the downregulation of the PI3K/Akt pathway by inhibiting the phosphorylation of both PI3K and Akt. ConclusionsThe study highlights the significance of ZYJSW in preserving the health of both bone and muscle in P6 mice, potentially through the regulation of the GCN5L1-mediated PI3K/Akt/Wnt signaling pathway. The translational potential of this articleOur research provides evidence and a mechanistic rationale for ZYJSW as a candidate for SOP treatment, offering insights for further exploration and strategy development.

Alfacalcidol-Induced Kidney Injury in Patients with Severe Motor and Intellectual Disabilities.

Patients with severe motor and intellectual disabilities (SMID) often experience insufficient physical activity, leading to osteoporosis. The active form of vitamin D is commonly prescribed for the prevention or treatment of osteoporosis. We observed four cases of kidney injury believed to be associated with the administration of 1α-OH vitamin D (alfacalcidol) preparations. This study employed a case series design to investigate change in kidney function in SMID patients following administration or discontinuation of alfacalcidol. We retrospectively analyzed data of 23 SMID patients (sex: 10 males, 13 females; age range: 27 to 74 y), and assessed kidney function, serum calcium, and albumin levels. Data was grouped into A: 16 cases collected both before starting alfacalcidol administration and during alfacalcidol administration; and into B: 11 cases collected during alfacalcidol administration and after discontinuation of alfacalcidol administration. Of the 23 patients, four were assigned into both group A and group B. Of the 16 cases in group A, six showed ≥30% decreased kidney function. Of the 11 cases in group B, the median values of modified Cr-eGFR were 43.0 and 65.1 mL/min/1.73 m2, respectively (p=0.008), indicating a significant improvement in kidney function. It is essential for practitioners to understand that osteoporosis may ordinarily occur in SMID patients due to reduced bone stimulation. Thus caution must be exercised when administering active vitamin D preparations to this population, as they carry a risk of kidney organ damage despite having no direct effect on bone health.

Proenkephalin improves risk prediction in acute coronary syndromes: derivation and external validation of the KID-ACS risk score

Abstract Background Early assessment of renal and mortality risk in patients with acute coronary syndromes (ACS) is essential to guide treatment decisions according to international guidelines. Circulating proenkephalin (PENK) is a stable opioid metabolite with fast response to changes in kidney function. Purpose This study examined the predictive value of PENK for acute kidney injury (AKI) and mortality in patients presenting with acute coronary syndromes (ACS). Methods Plasma PENK levels were measured using a validated sandwich immunoassay in a prospective multicentre ACS cohort from Switzerland (n = 4 787) and in validation cohorts from the UK (n = 1 141) and Czechia (n = 920). A biomarker-enhanced risk score for simultaneous prediction of both in-hospital acute kidney injury (AKI) and 30-day death (KID-ACS score) with model coefficients adjusted to the outcome was derived and externally validated. In the development of the in-hospital AKI model, patients from one participating study centre were reserved for external validation (Swiss validation cohort). Results Circulating PENK ranked among the top predictors of renal outcomes and mortality in patients with ACS. Accounting for established risk factors and risk models, circulating PENK levels at presentation were independently associated with in-hospital AKI (per log2 increase: adjusted odds ratio [OR] 1.56, 95% CI 1.14 – 2.12, P = 0.005) and with 30-day mortality (per log2 increase: adjusted OR 2.69, 95% CI 1.89 – 3.84, P &amp;lt; 0.001). Dynamic changes in PENK levels within the first 12-24 hours after presentation were strongly and independently associated with in-hospital AKI (increase vs. decrease: adjusted OR 2.83, 95% CI 1.98 – 4.05, P &amp;lt; 0.001). The simple 6-item KID-ACS risk score for in-hospital AKI and 30-day mortality integrates PENK levels at presentation and showed an AUC of 0.72 (95% CI 0.68 – 0.76) for in-hospital AKI, and of 0.91 (95% CI 0.87 – 0.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS had similarly high performance for in-hospital AKI (Swiss validation cohort: AUC 0.73, 95% CI 0.70 – 0.77; Czech validation cohort: 0.74, 95% CI 0.68 – 0.80) and 30-day mortality (UK validation cohort: AUC of 0.87, 95% CI 0.82 – 0.91; Czech validation cohort: 0.91, 95% CI 0.87 – 0.94). The simple 6-item KID-ACS score was non-inferior to established risk models and significantly outperformed the CA-AKI risk score in predicting in-hospital AKI (Zurich cohort: delta AUC 0.11, 95% CI 0.07 – 0.15, P = 0.001) and the GRACE 2.0 in predicting 30-day mortality (UK cohort: delta AUC 0.05, 95% CI 0.01 – 0.09, P = 0.027). Conclusions Circulating PENK was identified as independent predictor of in-hospital AKI and 30-day mortality in patients with ACS. The simple 6-item KID-ACS risk score integrates circulating PENK levels and provides a novel tool for simultaneous assessment of renal and mortality risk in patients presenting with ACS.Independent Predictive Value PENKPerformance and validation of KID-ACS

Incident HFpEF and time-dependent changes in markers of LVDD severity in women and men with pre-clinical LVDD

Abstract Background Over time, left ventricular diastolic dysfunction (LVDD) can progress towards heart failure with preserved ejection fraction (HFpEF). Yet, the identification of those at high risk of progression is challenging, and guidance on follow-up or preventive treatment is lacking. Purpose To study the incidence of HFpEF and changes over time in markers of LVDD severity in women and men with pre-clinical LVDD. In addition, we evaluate whether blood pressure and kidney function affect progression of LVDD. Methods We reinvited 146 participants from the HELPFul study (58% women and 42% men) with pre-clinical LVDD after a median follow-up of 4.3 [IQR: 3.9-4.7] years (Figure 1). The follow-up measurements were similar to baseline and encompassed a structured interview, physical examination, blood draw, electrocardiogram and (exercise) echocardiography. We determined HFpEF incidence and report changes over time in cardiovascular risk factors as well as echocardiographic characteristics and biomarkers of LVDD. Additionally, we studied whether changes in blood pressure and kidney function affected LVDD progression using generalized mixed models. LVDD progression was defined as an increase in plasma NT-proBNP levels and HFA-PEFF major functional and morphological abnormalities. All analyses were performed for women and men combined as well as stratified by sex. Results Fifteen (10%) of the 146 participants developed HF of whom 13 had HFpEF (9 women and 4 men) during follow-up. Over time, systolic and diastolic blood pressure levels remained stable while mean kidney function (eGFR) declined from 89±14 to 81±17 mL/min/1.73m2. Median NT-proBNP plasma levels increased from 71 [IQR: 44, 120] to 100 [IQR: 51, 157] pg/mL. The prevalence of major functional abnormalities according to the HFA-PEFF score increased from 84 to 91%, while the prevalence of morphological abnormalities increased from 25% to 39% (Figure 2). A higher systolic blood pressure in women and a higher diastolic blood pressure in men was associated with an increase in NT-proBNP plasma levels over time. Additionally, lower eGFR levels were related to increased NT-proBNP plasma levels over time in both men and women. There was a significant rise in the prevalence of major functional and morphological abnormalities with time, but blood pressure and kidney function did not affect this change over time. Conclusions A small proportion of women and men with preclinical LVDD developed incident HF over a 5-year follow-up period. High blood pressure and reduced kidney function were associated with increased levels of NT-proBNP over time. This highlights the need to further explore cardiorenal protection as a method to prevent HFpEF.Study design and HF outcomesLongitudinal changes in LVDD markers

Effectiveness of a fixed combination of empagliflozin with metformin in reduction of cardiovascular risk in patients with uncontrolled arterial hypertension and decompensated type 2 diabetes mellitus

Objective is to study the effectiveness of a fixed combination of empagliflozin and metformin in reducing cardiovascular risk in patients with uncontrolled arterial hypertension (AH) and decompensated type 2 diabetes mellitus (DM). Materials and methods. 36 patients with uncontrolled AH and decompensated type 2 diabetes mellitus aged 45 to 60 were examined. Before inclusion in the study, all patients received standard antihypertensive (angiotensin‑converting enzyme (ACE) inhibitor or angiotensin‑II receptor blocker (ARB) in combination with a calcium channel blocker and a thiazide‑like diuretic), glucose‑lowering (metformin) and hypolipidemic (atorvastatin) therapy. However, target levels of blood pressure (BP), glycated haemoglobin (HbA1c) and lipids were not achieved. After the initial examination, all patients were prescribed a fixed combination of empagliflozin and metformin at a dose of 12.5 mg/1000 mg 1—2 times a day, and antihypertensive and hypolipidemic therapy was continued. Re‑examination was carried out after 20 weeks. In the work, a statistical analysis of the obtained data was carried out using standard methods using Microsoft Excel 7.0 and SPSS 19.0 application packages. Results. The transfer of the examined patients from previous ineffective hypoglycemic therapy to a fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy made it possible to achieve the target levels of HbA1c in 69% of patients and target BP levels in 64%. The frequency of reaching target BP levels in the subgroup of patients who received ARB was significantly higher than in the subgroup of patients who received ACE inhibitors. The specified therapy contributed to a significant reduction in body weight, reaching the target levels of low‑density lipoprotein cholesterol (LDL‑C) and non‑high‑density lipoprotein cholesterol (Non‑HDL‑C) in more than a third of patients, and reducing the severity of albuminuria in some patients. The tested therapy, in general, led to reduction in cardiovascular risk and did not cause side effects that could lead to discontinuation of treatment. Conclusions. The fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy in patients with uncontrolled hypertension and decompensated type 2 diabetes mellitus contributed to the achievement in the vast majority of patients of the target levels of HbA1c in the blood and BP levels, reduced body weight, positive changes in lipid metabolism and kidney function, and demonstrated the possibility of a significant reduction in cardiovascular risk. A more pronounced decrease in BP was detected in the case of a fixed combination of empagliflozin and metformin with ARB compared to ACE inhibitors in this category of patients.