Renal Failure Research Articles

Biochemical variations in patients with renal failure: A comparative study

Biochemical variations in patients with renal failure: A comparative study

Cardiogenic shock in general intensive care unit: a Nationwide prospective analysis of epidemiology and outcome

Abstract Background Cardiogenic shock (CS) is a life-threatening disease burdened by a mortality up to 50%. The epidemiology has changed with non-ischemic aetiologies being predominant although data was mainly derived from patients admitted to dedicated acute cardiac care. We report the epidemiology and outcome of patients with CS admitted to general intensive care unit (ICU). Methods Prospective multicentric epidemiological study including 314 general ICU adhering to the GiViTI Nationwide registry from 2011 to 2018, excluding cardiac arrest. The primary endpoint of the study was mortality. The association between clinical factors and mortality was evaluated using a logistic regression model. The Odds Ratios of the covariates quantify their association with mortality during hospitalization. Results 11052 patients admitted to general ICU (incidence 2.17%; median age 72 (IQR [66-81]), 38.7% were women) with CS were included. Fourthy-seven percent of patients had more than 3 organ insufficiency at the time of admission. The most common CS aetiologies were: left heart failure LHF- 5247–47.5%), acute myocardial infarction (AMI - 3612–32.6%); right heart failure (RHF- 515–4.6%) and biventricular failure (532- 4.8%). 85.5% were mechanically ventilated during the ICU hospitalization. The overall ICU mortality was 44.8%, increasing to 53.4% during the hospitalization in the index hospital and to 54.3% at the latest hospital. RHF-CS patients exhibited the highest mortality risk (OR: 1.19 95% CI [0.94 − 1.50]; p < 0.001), followed by biventricular-CS OR 1.04 95% CI [0.82–1.32]. Respiratory failure (OR 1.13 [95%CI 1.08–1.19]), coagulation disorder (1.17 (95% CI 1.1–1.24), renal dysfunction (OR 1.55 [95% CI 1.50-1.61] and neurological alteration (OR 1.45 [95% CI 1.39–1.50]) were associated with worsen outcome along with severe hypotension (systolic blood pressure < 70 mmHg- OR 2.35 95% CI [2.06–2.67]), increasing age (OR 2.21 95% CI [2.01–2.42] and longer ICU stay prior to admission (2-fold increase for each 4.7 days). Conclusions In the general ICU the aetiology of CS, excluding cardiac arrest, remains characterized mostly by LHF with RHF-CS burdened by higher mortality. Multiorgan failure at admission and longer hospital stay before ICU admission predispose to worsen outcome.

Cardiovascular events in crush syndrome: on-site therapeutic strategies and pharmacological investigations

Crush syndrome often occurs after severe crush injury caused by disasters or accidents, and is associated with high mortality and poor prognosis. Cardiovascular complications, such as cardiac arrest, hypovolemic shock, and hyperkalemia-related cardiac dysfunction, are the primary causes of on-site death in crush syndrome. Prehospital evaluation, together with timely and correct treatment, is of great benefit to crush syndrome patients, which is difficult in most cases due to limited conditions. Based on current data and studies, early fluid resuscitation remains the most important on-site treatment for crush syndrome. Novel solutions and drugs used in fluid resuscitation have been investigated for their effectiveness and benefits. Several drugs have proven effective for the prevention or treatment of cardiovascular complications in crush syndrome, such as hypovolemic shock, hyperkalemia-induced cardiac complications, myocardial ischemia/reperfusion injury, ventricular dysfunction, and coagulation disorder experimentally. Moreover, these drugs are beneficial for other complications of crush syndrome, such as renal dysfunction. In this review, we will summarize the existing on-site treatments for crush syndrome and discuss the potential pharmacological interventions for cardiovascular complications to provide clues for clinical therapy of crush syndrome.

Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats

BACKGROUND: Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SS CD247 −/− (Dahl SS CD247 knockout rat; lacking T cells), and SS p67phox−/− (Dahl SS p67 phox [NOX2 (NADPH oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states. METHODS: We assessed blood pressure and renal damage phenotypes in SS, SS CD247−/− , and SS p67phox−/− rats during primigravida and multigravida states. To investigate the contribution of NOX2 in T cells, we performed adoptive transfers of splenocytes or CD4 + T cells from either SS or SS p67phox−/− donors into SS CD247−/− recipients to determine pregnancy-specific alterations in phenotype. RESULTS: Multigravida SS rats developed significant pregnancy-induced renal damage and renal functional impairment associated with elevated maternal mortality rates, whereas deletion of T cells or NOX2 garnered protection. During primigravida states, this attenuation in renal damage was observed, with the greatest protection in the SS p67phox−/− rat. To demonstrate that NOX2 in T cells contributes to adverse pregnancy phenotypes, adoptive transfer of SS splenocytes into SS CD247−/− rats resulted in significant pregnancy-induced renal damage, whereas transfer of SS p67phox−/− splenocytes garnered protection. Specifically, the transfer of SS CD4 + T cells resulted in pregnancy-induced proteinuria and increases in uterine artery resistance index, an effect not seen with the transfer of SS p67phox−/− CD4 + T cells. CONCLUSIONS: T cells and NOX2-derived reactive oxygen species, thus, contribute to end-organ damage in both primigravida and multigravida pregnancies in the SS rat leading to increases in maternal mortality.

Divide and Save: A Critical Care Air Transport Team Case With Prolonged Field Care

ABSTRACT Critical care air transport teams (CCATTs) specialize in providing intensive medical and postoperative resuscitative care during air evacuations. In a 2014 mission, a seasoned CCATT was urgently deployed to evacuate 6 American service members with gunshot wounds. Despite only having 2 hours of premission preparation and no further injury or treatment details, CCATT secured additional equipment, medications, and blood supply. Upon arrival to a foreign nonmilitary hospital, they discovered that American ground commanders had lost trust in local medical capabilities. One patient experienced prolonged extremity tourniquet time and surgical delay. This led to acute renal failure, preventing immediate evacuation without continuous renal replacement therapy (CRRT). Deviating from the standard procedure, the CCATT obtained permission to split their team. The CCATT nurse attended 5 stabilized patients during unregulated critical care air transport with plans to swiftly return with CRRT equipment for the critical sixth patient. The physician and respiratory therapist remained at the foreign hospital for 2 days to provide prolonged field care. This case demonstrates the evolving mission scope of CCATT, which may encompass ground triage, prolonged field care, unregulated movement, and atypical CCATT equipment such as CRRT, occasionally necessitating a split team construct. To adapt to these evolving needs, updated policies and training now incorporate these diverse CCATT concepts, emphasizing the importance of flexibility in en route critical care missions.

Cohort profile: the PRIMETIME 1 (PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy) cohort – a longitudinal Danish nationwide study of individuals with diabetes and a performed kidney biopsy

PurposeIndividuals with diabetes and chronic kidney disease are at high risk of kidney failure, cardiovascular events and premature mortality and more research is warranted to further improve the prevention and...

Attributes of Pathological Fractures in a Nigerian myeloma cohort

Multiple Myeloma (MM) is a plasma cell tumor usually characterized by lytic bone lesions. Pathological Fracture (PF) is a debilitating condition that usually affects a patient’s psychomotor functions, treatment modality, morbidity, and outcome. We evaluated the associations, characteristics, and impact of PF on survival in a group of Nigerian myeloma cohort. A 10-year (2011-2021) retrospective review of MM data from Nigerian tertiary hospital haemato-oncology unit to evaluate attributes of PFs in myeloma cohort. Sixty-six patients had MM of which 23 had PF while forty-three had no fractures. Of the number with PF, 18 had lytic bone lesions, while 20 had bone pains. Monoclonal Immunoglobulin G was predominant followed by Immunoglobulin A. Significant correlations existed between hemoglobin level (r=0.446, p=0.002); platelet count (r=-0.347, p=0.041), serum calcium (r=0.471, p=0.006) and bone pains; as well as between urea level (r=-0.787, p=001), creatinine level (r=-0.853, p=0.001) and renal impairment respectively. PFs are associated with diabetes, peptic ulcer disease, hypertension, nephropathy, and arthritis. Bortezomib-based regimen was the choice treatment. Overall survival was 16 (69.6%) with 7 (30.4%) mortality. PF is common amongst the myeloma cohort with the spine being the most common site. It is associated with significant comorbidities like hypertension, diabetes, peptic ulcer disease, and paraplegia and is characterized by severe debilitating bone pains, anemia, hypercalcemia, raised plasma monoclonal immunoglobulin, renal impairment, loss of man-hour at work, and psychosocial imbalance. The impact of the fracture has increased morbidity and mortality and has reduced the median survival duration to as low as 4 years.

Is Total Joint Arthroplasty an Effective and Safe Option for Psoriatic Arthritis Patients? A Scoping Review

Recent advancements in the treatment of psoriatic arthritis (PsA) have improved patient outcomes, but many still experience disease progression, potentially leading to joint replacement surgery. In this scoping review, we examine the relationship between PsA and orthopedic surgery, focusing on the risks and temporal trends of total hip arthroplasty (THA) and total knee arthroplasty (TKA), the prevalence of postoperative complications, and the effectiveness of these procedures in PsA. The included studies suggest that PsA patients have an overall higher risk of undergoing THA and TKA compared to the general population, but with temporal trends showing a decreased risk for patients diagnosed in recent years. Acute complications, such as renal failure, stroke, and postoperative infections, may be more common in PsA patients than in those with osteoarthritis after THA and TKA. No significant differences were found in pain, function, or satisfaction between PsA, skin psoriasis, and osteoarthritis patients after THA. A key conclusion from our review is the need to strengthen the collaboration between rheumatologists and orthopedic surgeons, as interdisciplinary evaluation is crucial for improving the outcomes of PsA patients undergoing orthopedic surgery.

Simultaneous Percutaneous Coronary Intervention (PCI) and Endovascular Aneurysm Repair (EVAR): A Preliminary Report

Background: Performing percutaneous coronary intervention (PCI) and endovascular aneurysm repair (EVAR) at the same time represents a groundbreaking development in the multidisciplinary treatment of cardiovascular disease. This combined PCI–EVAR approach bridges a critical gap by offering treatment for patients who have both coronary artery disease and aortic aneurysms. This innovative strategy exemplifies the evolving landscape of cardiovascular care, providing a new solution for complex clinical situations that previously required separate procedures. Methods: Six patients with critical coronary artery lesions and asymptomatic infrarenal aortic aneurysms (AAAs) ≥ 6 cm diameter, as well as one patient with critical coronary artery lesions and endoleak type 1A with aneurysms ≥ 6 cm, underwent simultaneous coronary artery revascularization through percutaneous intervention (PCI) and endovascular aneurysm repair (EVAR). The occurrence of any intraoperative or postoperative complication was considered to be the primary endpoint of the study, including the abortion or failure of either PCI or EVAR, bleeding requiring a conversion to open surgical procedures, the failure of local anesthesia, postoperative myocardial or lower limb ischemia, and a postoperative serum creatinine level of >125 mmol/L or of >180 mmol/L in patients affected by chronic renal failure. The overall length of the procedure, X-ray exposure, the quantity of iodine contrast medium administered, and the length of recovery were considered to be secondary endpoints. Results: Postoperative complications included two episodes of acute renal failure in the two patients already affected by chronic renal failure, which were easily resolved with adequate daily hydration and the elimination of nephrotoxic drugs. In no cases did cardiac ischemia or lower limb ischemia occur. The average procedure duration was 198 min (range: 180–240 min), the average fluoroscopy duration was 41.7 min (range: 35–50 min), the average amount of iodinated contrast medium was 34.8 mL (range: 30–40 mL), and the mean length of hospitalization was 2.7 days (range: 2–5 days). Conclusions: In selected patients, this surgical approach has demonstrated safety, reduced hospitalization times, minimized risks associated with complications from the untreated condition if procedures were performed at different times, and facilitated the effective management of intraoperative complications due to the presence of a multidisciplinary team. However, the limited number of patients necessitates further research.

Renal impairment: to refer or not to refer to endocrinologist?

Renal impairment: to refer or not to refer to endocrinologist?

Evaluation of knowledge and attitude concerning augmented renal clearance among physicians and clinical pharmacists in Al-Ain, UAE: A cross-sectional study

Background Kidney function assessment is crucial in critical illness patients and is required before administering renally excreted medication, especially antibiotics and antiepileptics. Conventional clinical practice often focuses on renal impairment with low creatinine clearance (CrCl) and overlooks the augmented renal clearance (ARC), which is defined by (CrCl) more than 130 ml/min. This typical demonstration neglects individuals who experience hyperfunctioning kidneys. Among critically ill patients, the prevalence of (ARC) is approximately 20% to 65% of cases. This study aims to evaluate physicians’ and clinical pharmacists’ knowledge about ARC-associated risk factors, antibiotic regimen modification in ARC patients, and attitudes towards ARC workshops and guidelines in Al-Ain, UAE. Methods A cross-sectional, online self-administered survey-based study was designed to achieve this study’s aim. The questionnaire was constructed on profound literature analysis, validated, and piloted. The survey was emailed to physicians and pharmacists working in two hospitals, private and governmental, and distributed through different social media platforms over three months, December 2022—February 2023. Results Of the 92 complete responses (32 clinical pharmacists, 60 physicians), 57 (61.9%), were aware of ARC, but 72 (78%) demonstrated poor knowledge overall. Clinical pharmacists had a higher mean rank of knowledge than the physician’s group. Meanwhile, 70 (76.1%) participants were unaware of the eGFR threshold to determine ARC. There is a noticeable positive attitude toward seeking more information about antibiotic dose adjustment in ARC patients at 85 (92%) of the respondents. Remarkably, only 28 (30.4%) were directly involved with ARC patients’ treatment plans. Conclusion In conclusion, clinical pharmacists showed better knowledge than physicians. However, overall, the participating healthcare providers lacked knowledge about ARC, so a reliable source of information regarding ARC should be utilized. Future research could explore the implementation of professional development workshops for healthcare providers and national guidelines and then assess their impact on patient outcomes.

Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (GN). To date, treatment of most patients with ANCA-GN relies on non-specific immunosuppressive agents, which may have serious adverse effects and be only partially effective. Here, using spatial and single-cell transcriptome analysis, we characterize inflammatory niches in kidney samples from 34 patients with ANCA-GN and identify proinflammatory, cytokine-producing CD4+ and CD8+ T cells as a pathogenic signature. We then utilize these transcriptomic profiles for digital pharmacology and identify ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, as the strongest therapeutic drug to use. Moreover, four patients with relapsing ANCA-GN are treated with ustekinumab in combination with low-dose cyclophosphamide and steroids, with ustekinumab given subcutaneously (90 mg) at weeks 0, 4, 12, and 24. Patients are followed up for 26 weeks to find this treatment well-tolerated and inducing clinical responses, including improved kidney function and Birmingham Vasculitis Activity Score, in all ANCA-GN patients. Our findings thus suggest that targeting of pathogenic T cells in ANCA-GN patients with ustekinumab might represent a potential approach and warrants further investigation in clinical trials.

Predictive Value of the Naples Prognostic Score for Cardiovascular Outcomes in Patients With Chronic Kidney Disease Receiving Percutaneous Coronary Intervention

The Naples prognostic score (NPS) is a novel multidimensional inflammatory and nutritional assessment system in cancer patients. However, its significance in patients with chronic kidney disease (CKD) after percutaneous coronary intervention (PCI) remains unclear. The study has a single-center, retrospective design and included 631 patients with CKD who underwent index PCI between 2019 and 2022. All participants were divided into 2 groups according to the NPS (Low-risk group: n = 209; High-risk group: n = 422) and followed up until November 2022. The primary endpoint was Major Adverse Cardiac Events (MACE). NPS predicted MACE events better than other scores, besides, high-risk NPS with severe renal dysfunction (RD) group (MODEL 2) had superior MACE diagnostic efficiency than NPS high-risk group lonely. (NPS: AUC: 0.605, P < .001; MODEL 2: AUC: 0.624, P < .001, respectively). Kaplan–Meier survival analysis of two groups showed that high-risk group had higher incidence of MACE ( P < .001). Meanwhile, high-risk group had higher MACE events [adjusted Hazard Ratio (aHR) 2.013, 95% CI 1.294, 3.132; P = .002]. NPS is an independent prognostic factor for CKD patients undergoing index PCI before operation whose predictive value for survival prognosis is better than other nutritional and inflammatory indicators. Compared with low NPS, patients with high NPS have a relatively poor prognosis.

Tolerability and Safety of Miltefosine for the Treatment of Cutaneous Leishmaniasis

Miltefosine, an orally administered drug, is an important component of the therapeutic arsenal against visceral and mucosal forms of leishmaniasis. However, data regarding the safety and tolerability of miltefosine treatment for cutaneous leishmaniasis (CL) are relatively limited. The aim of this study was to evaluate the tolerability, safety, and adverse events (AEs) of miltefosine treatment in patients with CL. In this cohort study, we reviewed the medical records of all miltefosine-treated patients between 1 January 2016 and 31 December 2022, at Israel Defense Forces military dermatology clinics and the dermatology and Tropical Medicine Clinics at Chaim Sheba Medical Center, Ramat-Gan, Israel. A total of 68 patients (54 males, 79%) with a median age of 30.3 ± 15.6 years (range: 18–88) were included in this study. Leishmania species were identified as L. major (n = 37, 54.4%), L. tropica (n = 12, 17.6%), L. braziliensis (n = 18, 26.5%), and L. infantum (n = 1, 1.5%) using polymerase chain reaction (PCR). Miltefosine tablets were administered orally at a dose of 50 mg, three times daily, for 28 days. Overall, 44 patients (65%) completed the 28-day treatment, and the remaining patients required dose reduction or early discontinuation of treatment. AEs (of any degree) were common, reported in 91% of patients. Both previously reported and previously unreported AEs were documented. Gastrointestinal symptoms (66.1%) and malaise (23.5%) typically occurred during the first two weeks of treatment and tended to subside. Other AEs, including acute renal failure (20.6%), sudden and severe pleuritic chest pain (7.6%), acne exacerbation (11.8%), suppuration of CL lesions (17.8%), and AEs related to the male genitourinary system (39.6% of males), typically occurred towards the end of treatment. The latter included testicular pain, epididymitis, diminution or complete absence of ejaculate, inability to orgasm, and impotence. Severe AEs necessitated treatment discontinuation (29.4%) or hospitalization (10.3%). URTI-like symptoms, arthritis, cutaneous eruption, pruritus, and laboratory abnormalities were also observed. Overall, the cure rate (for all patients combined) evaluated 3 months after the completion of treatment was 60%. The tolerability of miltefosine treatment for CL is low. Close clinical and laboratory monitoring is required during treatment, as severe AEs are not uncommon. As new insights regarding its toxicities emerge, further studies are required to define the role of miltefosine in the treatment of CL.

Diagnostic and Prognostic Utilities of Pancreatic Stone Protein in Patients with Suspected Sepsis

Background/Objectives: Pancreatic stone protein (PSP) is an emerging biomarker of sepsis that is secreted from pancreas sensing remote organ damages. We explored the diagnostic and prognostic utilities of PSP in patients with suspected sepsis. Methods: In a total of 285 patients (suspected sepsis, n = 148; sepsis, n = 137), we compared PSP with procalcitonin (PCT) and sequential organ failure assessment (SOFA) score. Sepsis diagnoses were explored using receiver operating characteristic curve analyses with area under the curves (AUCs). Clinical outcomes (in-hospital mortality, 30-day mortality, and kidney replacement therapy [KRT]) were explored using the Kaplan–Meier method and a multivariate analysis with hazard ratio (HR). Results: PCT and PSP were comparable for sepsis diagnosis (AUC = 0.71–0.72, p < 0.001). The sepsis proportion was significantly higher when both biomarkers increased than when either one or both biomarkers did not increase (89.0% vs. 21.3–47.7%, p < 0.001). Each biomarker quartile (Q1–Q4) differed significantly according to their SOFA score (all p < 0.001). Compared with Q1, the Q2–Q4 groups showed worse clinical outcomes (p = 0.002–0.041). Both biomarkers added to the SOFA score showed higher HRs than the SOFA score alone (3.3–9.6 vs. 2.8–4.2, p < 0.001–0.011), with nearly 2.5-fold higher HR (9.6 vs. 4.2) for predicting KRT. Conclusions: Although PCT and PSP did not independently predict clinical outcomes in the multivariate analysis, PSP demonstrated diagnostic and prognostic utilities in patients with suspected sepsis, especially for predicting kidney dysfunction. PSP, alone or in combination with PCT, would be a valuable tool that can be added to clinical assessments.

Postoperative early laboratory changes and follow-up process of patients underwent hyperthermic intrathoracic chemotherapy

BackgroundThe aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30.MethodsThe study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure.ResultsOut of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery.ConclusionAlthough there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.

Recent advances in the understanding of the peritoneal membrane.

The efficiency of peritoneal dialysis (PD) as a life-sustaining replacement therapy for patients with kidney failure relies on the integrity and function of the peritoneal membrane. Here, we review the most recent advances in the understanding of the peritoneal membrane and its role in PD. A recent update of the ISPD guidelines proposed a revised definition of membrane dysfunction, emphasizing the importance of fluid balance in patients treated with PD and identified three main mechanisms leading to insufficient peritoneal ultrafiltration (UF). The Bio-PD study, the first genomewide association study in PD, demonstrated that 20% of the interindividual variability in the peritoneal solute transfer rate is genetically determined, and identified several loci of potential relevance for peritoneal transport. A candidate-gene approach identified and characterized a common and functional variant in the promoter of the AQP1 gene associated with water transport and clinical outcomes in PD. Innovative strategies to preserve the integrity of the peritoneal membrane and to enhance UF are also discussed, including the use of gliflozins; steady glucose concentration PD; modulation of GLUT proteins; and cytoprotective additives. A comprehensive understanding of the peritoneal membrane and of the mechanisms driving UF may help individualizing PD prescription and improving outcomes in patients treated with PD.

Different growth patterns in two siblings with Schimke immuno-osseous-dysplasia.

Schimke immuno-osseous-dysplasia (SIOD) is an autosomal recessive systemic disease due to pathogenic variants in SMARCAL1. Manifestations include nephrotic syndrome (NS), kidney failure, T-cell dysfunction, vaso-occlusive disease, and disproportionate short stature, a general feature of this disease. Here, we present a markedly different growth pattern in two brothers with SIOD sharing the same homozygous R561C missense variant. The index patient presented at the age of 11years with NS and severely disproportionate short stature, followed by kidney failure at the age of 16, and severely reduced adult height (z-score - 8.0). In contrast, the younger brother showed normal growth until the age of 8years. Mild proteinuria was noted at the age of 4.5, followed by NS at 9.5years, kidney failure at 11years, progressive disproportionate stature, and reduced adult height (z-score - 4.5). Both brothers had comparable disproportion in adulthood (sitting height index z-score - 0.88 and - 1.44, respectively).

Comparison of uric acid elevation between aspirin-ticagrelor and aspirin-clopidogrel during dual antiplatelet therapy.

This study investigated whether serum uric acid levels are more elevated in the aspirin-ticagrelor group than in the aspirin-clopidogrel group. Materials and Materials and methods: We conducted a retrospective cohort study with patients between 2013 and 2020. Baseline and maximum serum uric acid levels within a 6-month follow-up period were analyzed to determine the increase in both groups. A total of 41,877 patients were enrolled. A statistically significant elevation of serum uric acid levels was found in the aspirin-ticagrelor group compared to the aspirin-clopidogrel group (odds ratio (OR; 95% confidence interval (CI)) = 1.36 (1.15 - 1.60), p < 0.001). Kidney dysfunction and diuretic use were also identified as risk factors for uric acid elevation. Monitoring serum uric acid levels is recommended during aspirin-ticagrelor therapy, especially in patients with kidney dysfunction or those using diuretics.

4-Octyl itaconate attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis

Objectives: The aim of this study was to investigate the mechanism of itaconate’s potential effect in diabetic kidney disease. Methods: Renal immune responsive gene 1 (IRG1) levels were measured in db/db mice and streptozotocin (STZ) + high-fat diet (HFD)-induced diabetic mice. Irg1 knockout mice were generated. db/db mice were treated with 4-octyl itaconate (4-OI, 50 mg/kg), a derivative of itaconate, for 4 weeks. Renal function and morphological changes were investigated. Ultrastructural alterations were determined by transmission electron microscopy. Results: Renal IRG1 levels were reduced in two diabetic models. STZ+HFD-treated Irg1 knockout mice exhibited aggravated renal tubular injury and worsened renal function. Treatment with 4-OI lowered urinary albumin-to-creatinine ratio and blood urea nitrogen levels, and restored renal histological changes in db/db mice. It improved mitochondrial damage, increased expressions of peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the renal cortex of db/db mice. These were confirmed in vitro; 4-OI improved high glucose-induced abnormal mitochondrial morphology and TFAM expression in HK-2 cells, effects that were inhibited by PGC-1α silencing. Moreover, 4-OI reduced the number of apoptotic cells in the renal cortex of db/db mice. Further study showed that 4-OI increased renal Nrf2 expression and decreased oxidative stress levels in db/db mice. In HK-2 cells, 4-OI decreased high glucose-induced mitochondrial ROS production, which was reversed by Nrf2 silencing. Nrf2 depletion also inhibited 4-OI-mediated regulation of PGC-1α, TFAM, and mitochondrial apoptotic protein expressions. Conclusions: 4-OI attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis.