Renal Failure Research Articles

Beyond Blood Sugar: Low Awareness of Kidney Disease among Type 2 Diabetes Mellitus Patients in Dalmatia—Insights from the First Open Public Call

Background and Objectives: Kidney disease (KD) is a common complication of diabetes mellitus (DM) associated with adverse outcomes of renal failure, cardiovascular disease, and mortality. The aim of this study was to determine the prevalence and awareness of the KD among the DM type 2 (T2DM) patients. Materials and Methods: This cross-sectional study was conducted at the University Hospital of Split between November and December of 2023 during an open call for DM patients. For each participant, blood and urine samples, along with relevant medical information, were collected, and adherence to the Mediterranean diet (MeDi) was assessed using the Mediterranean Diet Service Score (MDSS). Furthermore, blood pressure was measured, along with body composition and anthropometric parameters. Results: Of 252 T2DM patients with a median age of 67 years (IQR: 60–73), 130 (51.6%) were women. The median duration of T2DM was 10 years (IQR: 6–20). Despite the fact that 80.95% of total participants reported receiving dietary guidelines from any source, only 53.2% reported adhering to the suggested instructions, while according to the MDSS, only 7.2% adhered to the MeDi. The median body mass index was 27.6 kg/m2 (24.2–31), with 70.1% of participants overweight or obese. Only 6% of participants believed they had KD, but after blood and urine sample analysis, 31% were found to have KD. Conclusions: This study highlights a significant gap in awareness of KD, low adherence to MeDi, and a high prevalence of obesity among T2DM patients. Due to the increasing number of T2DM patients, it is crucial to improve healthy lifestyle education and make modifications within this group, as well as perform regular screening for KD and medical check-ups.

Associations between Kidney Disease Progression and Metabolomic Profiling in Stable Kidney Transplant Recipients—A 3 Year Follow-Up Prospective Study

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = −0.250 and p = 0.04, citric acid with r = −0.296 and p = 0.014, formic acid with r = −0.349 and p = 0.004, and glycine with r = −0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Early Renal Outcomes Following Heart Transplantation Using Organs Procured After Circulatory Death.

Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited. Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation. Posttransplantation renal outcomes included estimated glomerular filtration rate at 1 week, 4 weeks, and 16 weeks, and the incidence of acute kidney injury (AKI) and renal replacement therapy within 1 week. The analysis included 225 patients (55 recipients of DCD). Baseline characteristics were comparable between recipients of DCD and DBD. Renal outcomes within 1 week posttransplantation in recipients of DCD were similar to recipients of DBD, including percent change in estimated glomerular filtration rate (-37.9% [-58.6 to -6.2] versus -31.9% [-52.4 to -9.9]; P=0.91), incidence of AKI (47.3% versus 46.5%; P>0.99) and incidence of renal replacement therapy (3.6% versus 4.7%; P>0.99). Recipients of DCD with AKI within 1 week ("early AKI") did not recover to baseline estimated glomerular filtration rate (75.8 [60.2-91.3] mL/min per 1.73 m2) by week 16 (59.3 [46.9-73.6] mL/min per 1.73 m2; P=0.002), whereas recipients without early AKI exhibited comparable estimated glomerular filtration rate to baseline by week 4 (84.5 [70.8-98.5] mL/min per 1.73 m2; P=0.084). Similar trends were observed in recipients of DBD. Recipients of DCD demonstrated similar renal outcomes compared with recipients of DBD, supporting the ongoing use of DCD transplantation. Early AKI was associated with persistent renal dysfunction for recipients of both DCD and DBD.

SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation

Background/Objectives: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods: Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results: The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial–mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions: Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis.

Sirt6 ameliorates high glucose-induced podocyte cytoskeleton remodeling via the PI3K/AKT signaling pathway

Background Podocyte injury plays an important role in the occurrence and progression of diabetic kidney disease (DKD), which leads to albuminuria. Cytoskeletal remodeling is an early manifestation of podocyte injury in DKD. However, the underlying mechanism of cytoskeletal remodeling has not been clarified. Histone deacetylase sirtuin6 (Sirt6) has been found to play a key role in DKD progression, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway directly regulates the cytoskeletal structure of podocytes. Whereas, the relationship between Sirt6, the PI3K/AKT pathway and DKD progression remains unclear. Methods Renal injury of db/db mice was observed by PAS staining and transmission electron microscope. Expression of Sirt6 in the glomeruli of db/db mice was detected by immunofluorescence. UBCS039, a Sirt6 activator, was used to explore the renal effects of Sirt6 activation on diabetic mouse kidneys. We also downregulating Sirt6 expression in podocytes using the Sirt6 inhibitor, OSS_128167, and induced upregulation of Sirt6 using a recombinant plasmid, after which the effects of Sirt6 on high glucose (HG)-induced podocyte damage were assessed in vitro. Podocyte cytoskeletal structures were observed by phalloidin staining. The podocyte apoptotic rate was assessed by flow cytometry, and PI3K/AKT signaling activation was measured by Western blotting. Results Db/db mice exhibited renal damage including elevated urine albumin-to-creatinine ratio (ACR), increased mesangial matrix, fused podocyte foot processes, and thickened glomerular basement membrane. The expression of Sirt6 and PI3K/AKT pathway components was decreased in db/db mice. UBCS039 increased the expressions of Sirt6 and PI3K/AKT pathway components and ameliorated renal damage in db/db mice. We also observed consistent Sirt6 expression was in HG-induced podocytes in vitro. Activation of the PI3K/AKT pathway via a Sirt6 recombinant plasmid ameliorated podocyte cytoskeletal remodeling and apoptosis in HG-treated immortalized human podocytes in vitro, whereas Sirt6 inhibition by OSS_128167 accelerated HG-induced podocyte damage in vitro. Conclusions Sirt6 protects podocytes against HG-induced cytoskeletal remodeling and apoptosis through activation of the PI3K/AKT signaling pathway. These findings provide evidence supporting the potential efficacy of Sirt6 activation as a promising therapeutic strategy for addressing podocyte injury in DKD.

Sepsis associated acute kidney injury is common among Aboriginal and Torres Strait Islanders with septic shock and has poor outcomes: A nested cohort study.

Exploration of the incidence and outcomes of Acute Kidney Injury (AKI) broadly, and sepsis associated AKI specifically, in Aboriginal and Torres Strait Islander (First Nations) people has been limited. We compared a nested cohort of First Nations people drawn from a multinational randomised controlled trial of hydrocortisone in septic shock, to a cohort matched for age, sex and severity of illness. Acute Kidney Injury was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as well as incident use of kidney replacement therapy (KRT). Major Adverse Kidney Events (MAKE) were described as the composite of death, new dialysis requirement or persisting kidney dysfunction at hospital discharge. A cohort of 57 Aboriginal and/or Torres Strait Islander patients with septic shock was identified. 91.2% (52) of the First Nations cohort met KDIGO criteria for Stage 1 AKI or greater and 63% (36) met Stage 3 criteria. 59.6% (34) of the First Nations required dialysis as compared to 45.6% (26) in the matched cohort. 60.7% (34) of First Nations participants met criteria for MAKE at hospital discharge. The proportions requiring dialysis at 6, 12 and 24 months were 8.3%, 9.1% and 6.9% respectively. The incidences of AKI and MAKE reported in this First Nations cohort are substantially higher than in previously published cohorts of patients with sepsis, even those that use sensitive definitions of AKI. Measures to promote better management of infectious diseases in First Nations communities are required.

Comparison of the Effect of Omega-3 vs. MCT Supplementation on Iron-Related Indices in Patients Undergoing Dialysis.

Chronic kidney disease (CKD), characterized by progressive kidney failure, significantly increases mortality and comorbidity risks such as anemia. This study contrasts the impacts of omega-3 and medium-chain triglycerides (MCT) oil on levels of iron, ferritin, total iron-binding capacity (TIBC), hemoglobin (Hb), and transferrin saturation in patients with CKD undergoing dialysis. This interventional trial was conducted on 120 patients with CKD undergoing dialysis in Rasht, Iran. For 8weeks, the omega-3 group was orally administered three 1000-mg capsules of omega-3 fatty acid supplement, and the MCT group was administered three 1000-mg capsules containing MCT oil daily. Serum concentrations of ferritin, iron, TIBC, Hb, and transferrin saturation were assessed pre-intervention and after the intervention. There was a significant increase in serum iron levels in the MCT group compared to the omega-3 group (103.72 ± 57.8vs. 77.48±40.13; P = 0.031). No effect was found regarding other iron-related factors such as TIBC, Hb, transferrin saturation, and ferritin levels. The results of our study indicated that taking MCT oil increased serum iron levels compared to omega-3 supplementation in patients with CKD undergoing dialysis. Further research is needed to better understand the potential benefits of MCT oils in patients with CKD.

Acetazolamide Therapy and Kidney Function in Persons with Non-albuminuric Diabetes Mellitus Type 1

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower the risk of kidney failure in persons with type 2 diabetes. The presumed mechanism of action is through greater delivery of sodium to the distal tubule, activation of tubuloglomerular feedback which lowers glomerular filtration rate (GFR) and intra-glomerular pressure. SGLT2is are not approved for use in persons with type 1 diabetes due to the risk of diabetic ketoacidosis. Acetazolamide, a proximal tubule diuretic, delivers more sodium to the distal nephron, and may activate tubuloglomerular feedback in a similar way to SGLT2is without a higher risk of diabetic ketoacidosis. The kidney effects and safety of acetazolamide in persons with type 1 diabetes have not been well studied. Methods: We conducted a dose-escalation trial to determine the effects of 3 dosages of oral acetazolamide (62.5mg, 125mg, and 250mg, all twice-daily) in 12 persons with type 1 diabetes. Participants were treated for 2 weeks followed by a 2-week washout before exposure to the next dosage level. Blood and urine chemistries, as well as iohexol measured GFR, were assessed before and after each treatment interval. We aimed to identify a dose that maximized measured GFR reductions while minimizing adverse effects. Results: The mean age was 46±17 years, 100% were White, and 75% were female. The mean measured GFR was 89±18ml/min/1.73m2 at baseline. Acetazolamide reduced measured GFR by 15% (95% CI 9, 21), 14% (95% CI 7, 21), and 15% (95% CI 10, 21) after 2 weeks at the 62.5mg, 125mg, and 250mg twice-daily dosage levels respectively. The measured GFR reduction was fully reversed after each 2-week washout. Serum bicarbonate was reduced by 2.3, 4.2 and 4.4 mEq/L with escalating doses, and no episodes of hypokalemia (< 3.5 mEq/L) were observed. Conclusions: Among persons with type 1 diabetes and preserved kidney function, acetazolamide caused an acute, reversible reduction in measured GFR without effects on glucose metabolism.

Acute Kidney Injury after Isolated Coronary Bypass Surgery

AbstractAcute kidney injury (AKI) is among the most serious of the common postoperative complications of cardiac surgeries, which can increase the short- and long-term morbidity and mortality of patients. This study aimed to examine possible risk factors that lead to AKI. We sought to compare our AKI rates to national averages in coronary artery bypass grafting (CABG) reported by the Society of Thoracic Surgeons (STS). We reviewed our institution's data for renal failure in CABG procedures performed between January 1, 2020, and June 30, 2023. From the database, we identified 1,068 CABG patients and reviewed demographics, nonmodifiable conditions, and modifiable risk factors. The STS database uses the Risk, Injury, Failure, Loss, and End-stage renal disease definition for renal failure. Of our patient sample, 14 (1.3%) experienced renal failure. The national rate for AKI after isolated CABG was 1.9% in 2023. Chronic lung disease was a risk factor for AKI development. The mean perfusion, cross-clamp, ventilator times, and hospital stay increased in AKI patients. All patients who suffered from AKI had undergone perioperative blood transfusion. Our single-center experience with renal failure is slightly better than the national average. In our population, chronic lung disease and lower preoperative ejection fractions were associated with increased rates of AKI. Modifiable risk factors in our population included perioperative blood transfusion and increased perfusion/cross-clamp times. Lastly, AKI patients spent longer time on ventilators, increased lengths of stay, and increased postoperative mortality.

Beta-Lactam Antibiotic Exposure During Pediatric Extracorporeal Membrane Oxygenation: Retrospective Cohort Analysis of Drug Levels Using Standard Dosing, 2018–2020

Objectives: Children on extracorporeal membrane oxygenation (ECMO) are at high risk of infection that may worsen prognosis. Even though treatment with beta-lactam antibiotics is frequent, dosing is not adapted to altered pharmacokinetic and pharmacodynamic characteristics of children on ECMO. There is, therefore, a risk of inadequate drug levels when using standard dosing. In this study, we aimed to describe beta-lactam exposures of children on ECMO using current dosing and to identify factors associated with inadequate exposure. The optimal pharmacokinetic/pharmacodynamic target was considered as a plasma concentration four times above the minimum inhibitory concentration throughout the dosing interval target. Design: Two-center retrospective cohort study. Setting: Two PICUs in Paris, France. Patients: Children (from birth to 18 yr) undergoing venovenous or venoarterial ECMO, from 2018 to 2020. Interventions: None. Measurements and Main Results: There were 57 patients who received 11 different beta-lactams, with 226 plasma concentrations analyzed. A total of 32 infections were documented. Overall, 133 of 226 concentrations (58.8%) were insufficient, primarily in samples from children younger than 28 days (p = 0.035), with low body weight (p = 0.013), or in instances of hypoalbuminemia (p = 0.011) and increased renal clearance (p = 0.032). Supratherapeutic concentrations were observed in 25 of 226 samples (11.1%), associated with being taken from patients with renal impairment (p < 0.01). Conclusions: In this retrospective cohort of pediatric ECMO cases, there is an associated risk of underexposure when prescribing conventional dosing of beta-lactams, which are likely associated with renal impairment and fluid overload. Prospective testing of therapeutic drug monitoring combined with pharmacokinetic/pharmacodynamic models should be tested as a risk-reduction strategy in this vulnerable population.

Safety of in-hospital parenteral anti-osteoporosis therapy following a hip fracture: a retrospective cohort

Abstract Purpose To assess the safety of Zoledronic acid (ZOL) and Denosumab (Dmab) administered following hip fracture in a hospital setting. Methods Patients older than 65 years were treated by a Fracture Liaison Service following hip fracture. Generally, patients who had a GFR>35 ml/min, were treated with ZOL, whereas patients who had previously received bisphosphonates or had a GFR between 20-35 ml/min, were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/d), renal functional impairment (0.5 mg/dl or more increase in serum creatinine) within 30 days of treatment, or a fever (>38˚C) within 48 hours of drug administration. Results Two hundred and twenty-eight and 134 patients were treated with ZOL and Dmab respectively. Mean body temperature was elevated following ZOL administration (0.18 degrees Celsius P<0.001) but remained below 38° Celsius. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups respectively (P=0.009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab group respectively (P=0.8). Pre-treatment calcium above 9.3 mg/dl was associated with a lower risk of post-treatment hypocalcemia (OR 0.30 95% CI-0.13-0.68, P=0.004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Post-treatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab.

Predictive role of cardiopulmonary bypass exposure indexed to body surface area on postoperative organ dysfunction: a retrospective cohort study.

Long cardiopulmonary bypass times are associated with adverse postoperative outcomes and increased healthcare resources use. It is likely that this effect is pronounced in smaller patients. Previous studies have been criticized for not taking into consideration that prolonged bypass times are often due to higher complexity. The purpose of this study was to investigate the relationship between bypass index (bypass time/body surface area) and adverse postoperative events. Single-centre, retrospective cohort study including 2413 patients undergoing cardiac surgery on cardiopulmonary bypass from June 2018 to April 2020. Length of hospital stay, as surrogate marker of post-operative morbidity, was selected as primary outcome. The strength of association between BI and the primary outcome was assessed with linear regression analysis. Secondary outcomes included new onset renal, pulmonary or cardiac rhythm dysfunction. The predictive value of bypass index was assessed with linear regression analysis; univariate and multiple regression were used to assess the strength of association between Bi and the secondary outcomes. Bypass index was predictive for length of stay at univariate (RR 1.004, p < 0.001) and at multivariable (RR 1.003, p < 0.001) analysis. The association between bypass index and new renal (mean difference 14.1 min/m2, p < 0.001) and cardiac rhythm dysfunction (mean difference 12.6 min/m2) was significant. This was not true of postoperative lung dysfunction (mean difference -1.5 min/m2, p = 0.293). Bypass index, calculated as total bypass time/patient body surface area, is predictive of postoperative morbidity and resource utilization after cardiac surgery on pump.

New insights on genetic background of major diabetic vascular complications

BackgroundBy 2045, it is expected that 693 million individuals worldwide will have diabetes and with greater risk of morbidity, mortality, loss of vision, renal failure, and a decreased quality of life due to the devastating effects of macro- and microvascular complications. As such, clinical variables and glycemic control alone cannot predict the onset of vascular problems. An increasing body of research points to the importance of genetic predisposition in the onset of both diabetes and diabetic vascular complications.ObjectivesPurpose of this article is to review these approaches and narrow down genetic findings for Diabetic Mellitus and its consequences, highlighting the gaps in the literature necessary to further genomic discovery.Material and methodsIn the past, studies looking for genetic risk factors for diabetes complications relied on methods such as candidate gene studies, which were rife with false positives, and underpowered genome-wide association studies, which were constrained by small sample sizes.ResultsThe number of genetic findings for diabetes and diabetic complications has over doubled due to the discovery of novel genomics data, including bioinformatics and the aggregation of global cohort studies. Using genetic analysis to determine whether diabetes individuals are at the most risk for developing diabetic vascular complications (DVC) might lead to the development of more accurate early diagnostic biomarkers and the customization of care plans.ConclusionsA newer method that uses extensive evaluation of single nucleotide polymorphisms (SNP) in big datasets is Genome-Wide Association Studies (GWAS).

Trauma Compendium: Management of the Entrapped Patient – a position statement and resource document of NAEMSP

ABSTRACT Entrapped patients may be simply entombed or experiencing crush injury or entanglement. Patients with trauma who are entrapped are at higher risk of significant injury than patients not entrapped. Limited access and prolonged scene times further complicate patient management. Although patient entrapment is a significant focus of specialty teams, such as urban search & rescue (US&R) teams that operate as local, regional, and/or national resources in response to complex scenes and disaster scenarios, entrapment is a regular occurrence in routine EMS response. Therefore, all EMS clinicians must have the training and skills to manage entrapped patients and to support medically-directed rescue throughout the extrication process. NAEMSP recommends: EMS clinicians must perform a timely and thorough primary and secondary assessment and reassessments in parallel with dynamic extrication planning; the environment may require adaption of standard assessment techniques and devices. EMS clinicians should establish early, clear, and ongoing communications with rescue personnel to ensure a coordinated patient-centered medically directed approach to extrication. Communication with the patient should be frequent, clear, and reassuring. EMS clinicians should immediately take measures to effectively prevent and manage hypothermia. EMS clinicians should recognize airway management in the entrapped patient is always challenging. When required, advanced airway placement should be performed by the most experienced operator with proficiency in multiple modalities and alternative techniques in limited access situations. In entrapped patients who are experiencing or are at risk for crush syndrome, EMS clinicians should initiate large-volume (i.e., 1-1.5 liters/hour for adults and 20 milliliters/kilogram/hour for pediatric patients for the initial 3-4 hours) fluid resuscitation with crystalloid, preferably normal saline, as early as possible and prior to extrication. In entrapped patients who are experiencing or are at risk for crush syndrome, EMS clinicians should administer medications to mitigate risks of hyperkalemia, infection, and renal failure, early and prior to extrication. Tourniquet application should be considered in the setting of the crushed extremity as a potential adjunct to medical optimization before extrication of some patients. Patients with prolonged entrapment with the potential for severe injuries require complex resuscitation and may benefit from EMS physician management on scene. EMS systems should consider an early EMS physician response to entrapped patients.

Impact of COVID-19 on Psychiatric Patients: The Role of Vaccination, Comorbidities, and Biomarkers in Clinical Outcomes

Background/Objectives: The COVID-19 pandemic has posed significant challenges, particularly for individuals residing in psychiatric facilities. This study aims to investigate the impact of COVID-19 on psychiatric patients, focusing on factors such as their vaccination status, comorbidities, medication regimens, and biomarkers like C-reactive protein (CRP) and ferritin. Methods: This retrospective study analyzed 100 patients with confirmed SARS-CoV-2 infections admitted to the private psychiatric clinic “Asclepius of Upper Volos” from March 2020 to March 2023. The data collected included sociodemographic characteristics, vaccination status, symptom severity, medication regimens, and levels of CRP and ferritin. Statistical analyses using IBM SPSS Statistics version 29 included Pearson’s chi-square tests, Student’s t-tests, and a survival time analysis via the log-rank test to assess associations between clinical characteristics and outcomes. Results: Among the participants, 64% were female and 74% received two doses of the COVID-19 vaccine. The majority experienced mild symptoms, with a survival rate of 74%. Statistically significant findings include a higher survival rate among vaccinated individuals (98.6%) versus unvaccinated individuals (1.4%, p &lt; 0.001). Comorbidities like chronic obstructive pulmonary disease (COPD), coronary artery disease, and renal failure were associated with severe symptoms and higher mortality rates. Higher ferritin levels were significantly associated with poorer outcomes, with survivors having a mean ferritin level of 246.2 (SD = 150.3) compared to the 416.9 (SD = 215.9) seen in non-survivors (p &lt; 0.001). Similarly, mean CRP levels were lower in survivors (1.58, SD = 1.96) than in non-survivors (3.46, SD = 2.92), with a p-value of 0.002. Conclusions: The findings underscore the importance of tailored health protocols and continued support for this vulnerable population. Enhanced strategies for managing comorbidities and utilizing biomarkers can aid in better predicting and improving psychiatric patient outcomes.

Trimetazidine protects against acute indomethacin-induced gastric mucosal, hepatic, and renal injury in rats

Background: Peptic ulcers are increasingly reported as a challenging disease in clinical settings. Several medications are employed in the management of peptic ulcers. Thus far, there is no medication devoid of any adverse effects that may achieve a 100% curative rate or provide a total remedy for the ailment. Aim: We aimed to examine the healing effects of trimetazidine against indomethacin-induced gastric ulcers in albino rats. Methodology: A total of 25 rats were used, divided into five groups (each group contained five rats): a negative control group that was only treated with distilled water, a positive control group that was only treated with a single dose of indomethacin (30 mg/kg) orally, a group that received indomethacin (30 mg/kg) and low doses of trimetazidine (17.5 mg/kg) orally, a group that received indomethacin (30 mg/kg) and medium doses of trimetazidine (35 mg/kg) orally, and a group that received indomethacin (30 mg/kg) and high doses of trimetazidine (52.5 mg/kg) orally. The induction of gastric ulcers occurred on the first day of the experiment through the administered indomethacin and, subsequently, the rats were treated orally with either trimetazidine or distilled water, three times daily, for 7 days. Serum urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels were measured. Stomachs were excised from the rats’ bodies and opened along the greater curvature; they were then rinsed with saline, extended on a white corkboard, and examined macroscopically. The stomach tissues were also processed in order to generate microscopic slides for microscopical examination. Results: Indomethacin administration caused multiple ulcerations in the gastric mucosa, significant elevations in serum urea, creatinine, AST, and ALT levels, and a significant reduction of the serum albumin levels. The treatment with trimetazidine significantly healed the indomethacin-induced gastric ulcers. Conclusion: The present study indicates that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin can induce substantial gastric ulcers, which may be linked to a direct toxic effect on the histological architecture of the gastric linings in addition to the reduction of blood flow to gastric mucosa; this effect can be treated by administration of trimetazidine. Ultimately, this study suggests that administering the optimal dosage of trimetazidine can be advantageous in treating stomach ulcers caused by NSAIDs. Moreover, the study suggests that the indomethacin-induced liver and renal dysfunction can also be alleviated by the use of trimetazidine.

Desmopressin use in major cardiac surgery is associated with renal impairment: a retrospective single-center analysis

BackgroundDesmopressin acetate (1-deamino-8-d-arginine vasopressin—DDAVP) is a analogue of the antidiuretic hormone vasopressin. DDAVP is suggested to reduce bleeding after cardiac surgery using cardiopulmonary bypass. The aim of this study was to determine if DDAVP has any negative impact on renal function leading to acute kidney injury (AKI) and therefore increases the need for renal replacement therapy (RRT).MethodsWe performed a retrospective single institutional cohort analysis of 2,179 patients undergoing elective and urgent cardiac surgery with CPB from 2017 to 2021. Logistic regression analysis was used to investigate any association between DDAVP, the incidence of AKI KDIGO class 3 and the need for RRT, respectively. The model was adjusted for relevant covariates, including preexisting renal impairment, pharmacological hemodynamic support with vasopressors, complexity of the surgery and postoperative lactate. Secondary outcomes included, in hospital mortality and the need for allogenic blood transfusion.ResultsA total of 992 (45.5%) patients received DDAVP intraoperatively during surgery or shortly thereafter. The use of DDAVP was associated with a significant increase in in AKI KDIGO class 3 (OR 2.27; 95% CI 1.46–3.55; p < 0,001) and the need for RRT (OR 2.19; 95%CI 1.48–3.24; p < 0,001). Both findings persisted after covariate adjusting. No increased in-hospital mortality was associated with DDAVP.ConclusionIn cardiac surgery, the use of DDAVP was associated with an increased rate of server AKI and the requirement for RRT. Given the severity of the potential harm associated with DDAVP, an evidence-based reevaluation is needed to enable an accurate risk and benefit assessment.

Semaglutide in patients with kidney failure and obesity undergoing dialysis and wishing to be transplanted: A prospective, observational, open-label study.

Chronic kidney disease (CKD) and obesity are major global health challenges, eventually leading to kidney replacement therapy (KRT), but body mass index (BMI) thresholds hinder kidney transplantation. Glucagon-like peptide-1 receptor agonists induce weight loss, thereby offering attractive treatment options; however, their safety and efficacy have not been systematically investigated in patients undergoing dialysis. We conducted a prospective 12-week, open-label trial with 13 patients who had a BMI ≥ 30.00 kg/m2, were undergoing dialysis (12 haemodialysis and 1 peritoneal dialysis) and had not been listed for transplantation due to their weight. Semaglutide was administered once weekly subcutaneously, and the dose was increased from 0.25 mg to 0.5 mg and then to 1 mg. Study endpoints included change in body weight and BMI (primary - statistically evaluated by repeated measures analysis of variance [ANOVA]), side effects, adverse events, blood parameters and patient-reported outcomes (secondary). At baseline, the mean age ± standard deviation of patients was 64.0 ± 6.4 years, the mean weight was 113.9 ± 16.6 kg, and the mean BMI was 37.3 ± 3.9 kg/m2. At week 12, average weight reduction under semaglutide treatment was 4.6 ± 2.4 kg and ranged from 2.0 to 9.7 kg (p < 0.001 for weight and BMI reduction across the study period). One patient discontinued treatment due to nausea/vomiting, two patients died of unrelated causes and six patients reported side effects. Approximately 9 months after the treatment started, three patients were able to seriously reconsider being listed for transplantation. Semaglutide treatment resulted in significant reduction in weight and BMI in patients with obesity undergoing dialysis, while maintaining an acceptable side effect profile comparable to that of the non-dialysis population.

USP15 inhibits hypoxia-induced IL-6 signaling by deubiquitinating and stabilizing MeCP2.

Methyl-CpG binding protein 2 (MeCP2) is an important X-linked DNA methylation reader and a key heterochromatin organizer. The expression level of MeCP2 is crucial, as indicated by the observation that loss-of-function mutations of MECP2 cause Rett syndrome, whereas an extra copy spanning the MECP2 locus results in MECP2 duplication syndrome, both being progressive neurodevelopmental disorders. Our previous study demonstrated that MeCP2 protein expression is rapidly induced by renal ischemia-reperfusion injury (IRI) and protects the kidney from IRI through transcriptionally repressing the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 signaling pathway. However, the mechanisms underlying the upregulation of MeCP2 have remained elusive. Here, by using two hypoxia cell models, hypoxia and reoxygenation and cobalt chloride stimulation, we confirmed that the removal of lysine 48-linked ubiquitination from MeCP2 prevented its proteasome-dependent degradation under hypoxic conditions. Through unbiased screening based on a deubiquitinating enzymes library, we identified ubiquitin-specific protease 15 (USP15) as a stabilizer of MeCP2. Further studies revealed that USP15 could attenuate hypoxia-induced MeCP2 degradation by cleaving lysine 48-linked ubiquitin chains from MeCP2, primarily targeting its C-terminal domain. Consistently, USP15 inhibited hypoxia-induced signal transducer and activator of transcription 3 activation, resulting in reduced transcription of IL-6 downstream genes. In summary, our study reveals an important role for USP15 in the maintenance of MeCP2 stability and the regulation of IL-6 signaling.

Acute renal failure requiring renal replacement therapy secondary to rhabdomyolysis due to rosuvastatin

Acute renal failure requiring renal replacement therapy secondary to rhabdomyolysis due to rosuvastatin