Elevated Serum Creatinine Research Articles

Low T3 Syndrome is Associated with Imbalance of Bone Turnover Biomarker in Patients with Type 2 Diabetes.

To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome). This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome. The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), β C-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level. This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.

Clinicopathological characteristics and outcomes of patients with unexplained renal impairment: A single center study

BackgroundChronic kidney disease (CKD) is a growing health problem. About 20% of CKD patients have undetermined causes. Data describing histopathological patterns of unexplained impaired kidney functions in Egypt are lacking. We aimed to identify the clinicopathological characteristics and short-term outcomes of adult cases with unexplained impaired kidney functions. MethodsWe conducted a prospective study in Assiut University Hospital from August 2018 to May 2022. It included patients with unexplained elevated serum creatinine (serum creatinine>115μmol/L) who underwent renal biopsies. Descriptive statistics were used to summarize data on patient demographics, histopathological patterns, and outcomes after three months. Clinical trial registration number: NCT03586531. ResultsOverall, 210 native renal biopsies were included in the analysis. Glomerular diseases were the most common pathological finding (n=88, 44.9%), amyloidosis and FSGS were the most prevalent glomerular pathology (15.2%, 14.3%, respectively). Chronic kidney disease of unknown etiology (CKDu) was diagnosed in 8.1% of the cases; histology suggestive of genetic origin was found in 2.5%, and LECT amyloidosis was found in 3.8% of the cases. Poor outcomes were observed in 43.6% of the patients i.e., renal replacement therapy or death. Treatment strategies were changed based on the biopsy findings in 86 patients (40%). ConclusionAmyloidosis and FSGS were the most common causes of unexplained renal impairment. CKDu is not uncommon in Egypt, and more preventive measures are needed. This study supports the irreplaceable role of renal biopsy in disease diagnosis, treatment decisions, and predicting prognosis even in advanced stages.

A novel mutation in HNF1B promotes ferroptosis-mediated renal mesangial cells fibrosis

Maturity onset diabetes of the young type 5(MODY5) is typically attributed to mutations in the HNF1B gene, which encodes transcription factors that play a significant role in kidney development and function maintenance. In this study, we identified a novel HNF1B gene mutation (c.445C>A) in a young male MODY5 patient exhibiting elevated serum creatinine levels and albuminuria. Through transfection of wild type and mutant HNF1B plasmids into mouse mesangial cells (MMCs), we investigated the impact on molecular indicators related to proliferation, fibrosis and oxidative stress. The results revealed that the HNF1B novel mutation promoted the expression of fibronectin, type 1 collagen, and CyclinD1, as well as increasing cellular oxidative stress and susceptibility to ferroptosis in MMCs. Our findings established a novel association between HNF1B mutant diseases and mesangial cell proliferation and fibrosis, suggesting that mutations of HNF1B may contribute to the progression of renal function in MODY5 patients. Additionally, our results implicate potential therapeutic targets for restraining fibrosis.

Predicting the risk of colorectal cancer among diabetes patients using a random survival forest-guided approach.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Diabetes and CRC share many overlapping lifestyle risk factors such as obesity, heavy alcohol use, and diet. This study aims to develop a risk scoring system for CRC prediction among diabetes patients using routine medical records. A retrospective cohort study was conducted using electronic health records of Hong Kong. Patients who received diabetes care in public general outpatient clinics between 2010 and 2019 and had no cancer history were identified, and followed up until December 2019. The outcome was diagnosis of CRC during follow-up. For model building, predictors were first selected using random survival forest, and weights were subsequently assigned to selected predictors using Cox regression. Of the 386,325 patients identified, 4,199 patients developed CRC during a median follow-up of 6.2 years. The overall incidence rate of CRC was 1.93 per 1000 person-years. In the final scoring system, age, waist-to-hip ratio, and serum creatinine were included as predictors. The C-index on test set was 0.651 (95%CI: 0.631-0.669). Elevated serum creatinine (≥127 µmol/L) could be a potential important predictor of increased CRC risk. While obesity is a well-known risk factor for CRC, renal dysfunction could be potentially linked to an elevated risk of CRC among diabetes patients. Further studies are warranted to explore whether renal function could be a potential parameter to guide screening recommendation for diabetes patients.

Contrast-Enhanced Ultrasound (CEUS) and Ultra-Microangiography (UMA) in Critically Ill Children with Acute Kidney Injury.

Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.

Biomarker-based acute kidney injury sub-phenotypes refine risk assessment in children undergoing cardiac surgery.

Pediatric cardiac surgery-associated acute kidney injury (CS-AKI) is common with variable association with outcomes, possibly because transient serum creatinine (SCr) elevations are unrelated to kidney disease. Sub-phenotypes of CS-AKI with biomarker integration may provide prognostic enrichment. This study aims to determine if combining early postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr into sub-phenotypes strengthens associations with AKI and outcomes. We hypothesized that patients with early subclinical (uNGAL + , SCr -) or damage (uNGAL + , SCr +) CS-AKI would have more postoperative day 2-4 KDIGO-defined AKI and worse clinical outcomes than patients with early functional AKI (uNGAL - , SCr +). Two-center prospective observational study evaluating combinations of early uNGAL (8-12h from ICU admission, ≥ 150ng/mL) and early postoperative (≤ 8h of admission) KDIGO SCr-defined AKI to predict CS-AKI on postoperative days (POD) 2-4. Four CS-AKI phenotypes were derived (uNGAL - /SCr - ; uNGAL + /SCr - ; uNGAL - /SCr + and uNGAL + /SCr +). The primary outcome was POD2-4 KDIGO SCr-defined CS-AKI. Secondary outcomes included ventilator and intensive care unit-free days (maximum 28). Four hundred seventy-six patients (median age 4.8 [IQR 1.4-30.4] months, 39% female) were included. POD2-4 AKI occurred in 44 (9.2%). 27% were uNGAL + /SCr - and 0.4% (n = 2) uNGAL + /SCr + . The adjusted odds of POD2-4 AKI was ninefold higher (aOR: 9.09, 95%CI: 3.84-21.53) in uNGAL + /SCr - when compared to uNGAL - /SCr - . uNGAL + /SCr - was associated with fewer ventilator-free (aOR: 0.30, 95%CI: 0.19-0.48) and ICU-free days (aOR: 0.41, 95%CI: 0.26-0.66) when compared to uNGAL - /SCr - . Early postoperative uNGAL, regardless of SCr elevation, refines risk assessment for pediatric POD2-4 CS-AKI and associated morbidity, enabling earlier AKI identification and prognostics.

Cardioprotective action of apocynin in isoproterenol‐induced cardiac damage is mediated through Nrf‐2/HO‐1 signaling pathway

AbstractThis investigation evaluated the therapeutic benefit of apocynin in isoproterenol (ISO)‐induced cardiac damage in rats. ISO‐administered male Wistar rats were treated with apocynin for 2 weeks. Blood plasma and left ventricle of heart tissues were collected and analyzed for oxidative stress‐related parameters such as malondialdehyde (MDA), advanced oxidation protein product (AOPP), and nitric oxide (NO). The activities of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase were also measured. The gene expressions of oxidative stress‐related proteins such as Nrf‐2, HO‐1, and HO‐2 in cardiac tissues were also measured. In silico studies like molecular docking and molecular dynamics were also performed to detect how apocynin interacts with NADPH and nitric oxide synthase at the molecular level. This investigation revealed significant elevation of serum transferase enzymes and creatinine kinase‐Muscle Brain (CK‐MB) activities in ISO‐administered rats compared to the control. Apocynin effectively normalized the serum transferases and CK‐MB activities in the blood of ISO‐stressed rats. Moreover, ISO‐induced elevations of MDA, NO, and AOPP levels were also suppressed by apocynin treatment. Consistently, apocynin restored the reduced SOD and catalase activities in ISO‐administered rats. This restoration of enzyme activity might be due to the increased expression of Nrf‐2 and HO‐1 and reduced expression of iNOS and TNF‐α in ISO‐administered rats. Histological analysis revealed that apocynin treatment ameliorated the mononuclear cell adherence and fibrosis in the cardiac tissue of ISO‐administered rats. Computational studies also support the experimental findings. This study demonstrates that apocynin prevents ISO‐induced cardiac injury not only by preventing inflammation but also by empowering the antioxidant defense system.

Adult-Onset IgA Vasculitis Complicated by Kidney Failure at Disease Onset in a Nepalese Patient: A Case Report

Introduction: Immunoglobulin A (IgA) vasculitis, previously known as Henoch-Schönlein purpura, is an immune complex-mediated small vessel vasculitis primarily affecting children. While rare in adults, it can present with more severe manifestations, particularly involving the kidneys. This case report details the presentation and management of adult-onset IgA vasculitis with significant renal involvement.  Case Report: A 43-year-old male with a history of bipolar disorder presented with facial swelling, shortness of breath, and decreased urine output following an upper respiratory infection. Initial investigations revealed elevated blood pressure and renal impairment. Despite supportive treatment, his condition worsened, leading to a referral to a tertiary care center. He exhibited symptoms consistent with IgA vasculitis, including joint pain, rash, and nephrotic-range proteinuria. The diagnosis was confirmed through a skin biopsy and 24-hour urine collection. The patient was treated with intravenous methylprednisolone, oral prednisone, and an ACE inhibitor. His renal function improved with this regimen.  Discussion: Adult-onset IgA vasculitis can present with severe kidney involvement, including nephrotic-range proteinuria and elevated serum creatinine, which are associated with poorer outcomes compared to pediatric cases. The patient's management, involving glucocorticoids and an ACE inhibitor, aligns with current treatment recommendations for significant renal involvement. Long-term prognosis in adults remains challenging, with a higher risk of end-stage kidney disease compared to children. Vigilant monitoring and tailored treatment strategies are crucial for improving outcomes.  Conclusion: This case underscores the potential severity of adult- onset IgA vasculitis and highlights the importance of early diagnosis and aggressive management to mitigate long- term renal complications. Ongoing research is necessary to refine treatment approaches and enhance outcomes for adults with this condition.

Predicting prolonged length of stay following revision total knee arthroplasty: A national database analysis using machine learning models

BackgroundAs the number of revision total knee arthroplasty (TKA) continues to rise, close attention has been paid to factors influencing postoperative length of stay (LOS). The aim of this study is to develop generalizable machine learning (ML) algorithms to predict extended LOS following revision TKA using data from a national database. Methods23,656 patients undergoing revision TKA between 2013 and 2020 were identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients with missing data and those undergoing re-revision or conversion from unicompartmental knee arthroplasty were excluded. Four ML algorithms were applied and evaluated based on their (1) ability to distinguish between at-risk and not-at-risk patients, (2) accuracy, (3) calibration, and (4) clinical utility. ResultsAll four ML predictive algorithms demonstrated good accuracy, calibration, clinical utility, and discrimination, with all models achieving a similar area under the curve (AUC) (AUCLR=AUCRF=AUCHGB=0.75, AUCANN=0.74). The most important predictors of prolonged LOS were found to be operative time, preoperative diagnosis of sepsis, and body mass index (BMI). ConclusionsML models developed in this study demonstrated good performance in predicting extended LOS in patients undergoing revision TKA. Our findings highlight the importance of utilizing nationally representative patient data for model development. Prolonged operative time, preoperative sepsis, BMI, and elevated preoperative serum creatinine and BUN were noted to be significant predictors of prolonged LOS. Knowledge of these associations may aid with patient-specific preoperative planning, discharge planning, patient counseling, and cost containment with revision TKA.

The Role of MicroRNA in the Pathogenesis of Acute Kidney Injury.

Acute kidney injury (AKI) describes a condition associated with elevated serum creatinine levels and decreased glomerular filtration rate. AKI can develop as a result of sepsis, the nephrotoxic properties of several drugs, and ischemia/reperfusion injury. Renal damage can be associated with metabolic acidosis, fluid overload, and ionic disorders. As the molecular background of the pathogenesis of AKI is insufficiently understood, more studies are needed to identify the key signaling pathways and molecules involved in the progression of AKI. Consequently, future treatment methods may be able to restore organ function more rapidly and prevent progression to chronic kidney disease. MicroRNAs (miRNAs) are small molecules that belong to the non-coding RNA family. Recently, numerous studies have demonstrated the altered expression profile of miRNAs in various diseases, including inflammatory and neoplastic conditions. As miRNAs are major regulators of gene expression, their dysregulation is associated with impaired homeostasis and cellular behavior. The aim of this article is to discuss current evidence on the involvement of miRNAs in the pathogenesis of AKI.

An evaluation of the empirical vancomycin dosing guide in pediatric cardiology

BackgroundHigher doses of vancomycin are currently prescribed due to the emergence of bacterial tolerance and resistance. This study aimed to evaluate the efficacy and safety of the currently adopted vancomycin dosing guide in pediatric cardiology.MethodsThis was a single-center prospective cohort study with pediatric cardiac patients, younger than 14 years, from June 2020 to March 2021. The patients received intravenous vancomycin (40 mg/kg/day divided every 6–8 h) according to the department’s vancomycin medication administration guide (MAG) for at least three days.ResultsIn total, 88 cardiac patients were included, with a median age of 0.82 years (IQR: 0.25–2.9), and 51 (58%) received cardiopulmonary bypass surgery (CPB). The majority (71.6%, n = 61) achieved a serum vancomycin level within the therapeutic range (7–20 mg/L). Infants, young children, and children exposed to CPB surgery had an increased incidence of subtherapeutic vancomycin levels, [7 (29.2%); P = 0.033], [13 (54.2%); P = 0.01], and [21 (87.5%); P = 0.009] respectively. After the treatment, 8 (10%) patients had an elevated Serum creatinine (SCr) and 2 (2.5%) developed acute kidney injury (AKI). However, no significant difference was found between the patients developing AKI or an elevated SCr and the group who did not, in terms of clinical, therapeutic, and demographic characteristics, except for the decreased incidence of SCr elevation in patients receiving an ACE inhibitor, [4 (36.4%); P = 0.036].ConclusionOur institution followed MAG recommendations; however, subtherapeutic serum concentrations were evident in infants, young children, and CPB patients. Strategies to prevent AKI should be investigated, as the possible causes have not been identified in this study.

Association of Neighborhood Social Determinants of Health with Acute Kidney Injury during Hospitalization.

Acute kidney injury (AKI) is common among hospitalized patients. However, the contribution of social determinants of health (SDOH) to AKI risk remains unclear. This study evaluated the association between neighborhood measures of SDOH and AKI development and recovery during hospitalization. This is a retrospective cohort study of adults without end-stage kidney disease admitted to a large southern U.S. healthcare system from 10/2014 to 9/2017. Neighborhood SDOH measures included: 1) Socioeconomic status: Area Deprivation Index (ADI) scores, 2) Food access: Low Income Low Access (LILA) scores, 3) Rurality: Rural Urban Commuting Area (RUCA) scores, and (4) Residential segregation: dissimilarity and isolation scores. The primary study outcome was AKI based on serum creatinine (SCr)-KDIGO criteria. Our secondary outcome was lack of AKI recovery (requiring dialysis or elevated SCr at discharge). The association of SDOH measures with AKI was evaluated using generalized estimating equation models adjusted for demographics and clinical characteristics. Among 26,769 patients, 26% developed AKI during hospitalization. Compared with those who did not develop AKI, those who developed AKI were older (median 60 vs. 57 years), more commonly men (55% vs. 50%), and more commonly self-identified as Black (38% vs. 33%). Patients residing in most disadvantaged neighborhoods (highest ADI tertile) had 10% (95%CI: 1.02-1.19) greater adjusted odds of developing AKI during hospitalization than counterparts in least disadvantaged areas (lowest ADI tertile). Patients living in rural areas had 25% higher adjusted odds of lack of AKI recovery by hospital discharge (95% CI: 1.07, 1.46). Food access and residential segregation were not associated with AKI development or recovery. Hospitalized patients from the most socioeconomically disadvantaged neighborhoods and from rural areas had higher odds of developing AKI and not recovering from AKI by hospital discharge, respectively. A better understanding of the mechanisms underlying these associations is needed to inform interventions to reduce AKI risk during hospitalization among disadvantaged populations.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

Updates on the Association Between Anemia and Heart Failure: A Systematic Review.

This systematic review aims to investigate the potential relationship between anemia and heart failure (HF) by summarizing existing literature on the topic. A comprehensive search was performed using four major databases, PubMed, Scopus, Web of Science, and ScienceDirect, to find the relevant literature. Ten studies, including a total of 2,828 participants, with 1,451 (51.3%) males, were included in this review.Iron deficiency anemia was the most prevalent type in the included studies; however, two studies included megaloblastic anemia. The prevalence of anemia in patients diagnosed with HF ranged from 33.3% to 69.8%, with a total prevalence of 1,643 (58.1%). Hypertension, diabetes mellitus, chronic kidney disease, and atrial fibrillation were the most commonly associated comorbidities in patients with HF. Anemia patients had a considerably higher risk of mortality than those without anemia. Anemia served as a marker of disease severity rather than an independent predictor of death in congestive individuals. Anemia was substantially correlated with elevated serum creatinine, left ventricular hypertrophy, and left atrial enlargement. According to the findings of this review, anemia has a significant impact on the prognosis of HF. In patients with HF, anemia may be a reliable indicator of both short- and long-term all-cause mortality as well as the rates of all-cause HF events. Future and ongoing research may provide vital information that may help guide clinical judgments in the future.

Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery.

We performed a clinical trial in non-muscle invasive urothelial cancer (NMIUC) patients randomized (2:1) to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib or placebo (either orally once weekly x 3 doses prior to scheduled surgery) to assess for a difference in EGFR phosphorylation in tumor adjacent normal urothelium <24 hours post-study dose and tolerance of weekly erlotinib. Thirty-seven volunteers (6 female/31 male, mean age 70, 35 white/2 non-white) with confirmed or suspected NMIUC were enrolled into either erlotinib (n=24; 900 mg-13, 600 mg-11) or placebo (n=13). Immunohistochemical assessment of phosphorylated and total EGFR in adjacent normal urothelium (20 erlotinib; 9 placebo) or tumor (21 erlotinib and 11 placebo subjects) at study end observed no significant difference between those receiving erlotinib or placebo. This was also true for other assessed tissue biomarkers (phosphorylated ERK, ERK, e-cadherin, p53 and Ki67). Adverse events were more common, in a dose-related fashion, in participants receiving erlotinib, e.g. 38% experienced Grade 1 with rare grade 2 diarrhea and skin toxicity vs 8% in placebo. Clinically insignificant, but statistically significant (p=0.001) elevations in serum total bilirubin and creatinine were observed in erlotinib participants. Serum erlotinib and metabolite concentrations (OSI-420) confirmed compliance in all erlotinib subjects and did not significantly differ between the 600 and 900 mg doses. Despite compelling pre-clinical and clinical data for targeted EGFR inhibition in bladder cancer prevention, these data do not support the use of weekly erlotinib to prevent progression of NMI bladder cancer.

Acute kidney injury as a prognostic marker in severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14–36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan–Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan–Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.

Impact of sympathetic hyperactivity induced by brain microglial activation on organ damage in sepsis with chronic kidney disease

BackgroundSympathetic nerve activity (SNA) plays a central role in the pathogenesis of several diseases such as sepsis and chronic kidney disease (CKD). Activation of microglia in the paraventricular nucleus of the hypothalamus (PVN) has been implicated in SNA. The mechanisms responsible for the adverse prognosis observed in sepsis associated with CKD remain to be determined. Therefore, we aimed to clarify the impact of increased SNA resulting from microglial activation on hemodynamics and organ damage in sepsis associated with CKD.Methods and resultsIn protocol 1, male Sprague–Dawley rats underwent either nephrectomy (Nx) or sham surgery followed by cecal ligation and puncture (CLP) or sham surgery. After CLP, Nx-CLP rats exhibited decreased blood pressure, increased heart rate, elevated serum creatinine and bilirubin levels, and decreased platelet count compared to Nx-Sham rats. Heart rate variability analysis revealed an increased low to high frequency (LF/HF) ratio in Nx-CLP rats, indicating increased SNA. Nx-CLP rats also had higher creatinine and bilirubin levels and lower platelet counts than sham-CLP rats after CLP. In protocol 2, Nx-CLP rats were divided into two subgroups: one received minocycline, an inhibitor of microglial activation, while the other received artificial cerebrospinal fluid (CSF) intracerebroventricularly via an osmotic minipump. The minocycline-treated group (Nx-mino-CLP) showed attenuated hypotensive and increased heart rate responses compared to the CSF-treated group (Nx-CSF-CLP), and the LF/HF ratio was also decreased. Echocardiography showed larger left ventricular dimensions and inferior vena cava in the Nx-mino-CLP group. In addition, creatinine and bilirubin levels were lower and platelet counts were higher in the Nx-mino-CLP group compared to the Nx-CSF-CLP group.ConclusionsIn septic rats with concomitant CKD, SNA was significantly enhanced and organ dysfunction was increased. It has been suggested that the mechanism of exacerbated organ dysfunction in these models may involve abnormal systemic hemodynamics, possibly triggered by activation of the central sympathetic nervous system through activation of microglia in the PVN.

Correlation between neuropsychiatric systemic lupus erythematosus and immunological markers: a real-world retrospective study.

This study aimed to investigate disparities in clinical profiles and autoantibody patterns between patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort and to identify risk factors associated with NPSLE in the Chinese population. SLE patients were retrospectively reviewed from two tertiary hospitals. The relationships between NPSLE and immunological biomarkers were explored. Among the 945 SLE patients, 75 (7.94%) were diagnosed with NPSLE. The most prevalent NP manifestations involved cognitive disorder (30.67%), headache (26.67%), seizure disorder (26.67%), and psychosis (26.67%).We observed significant associations between psychosis and anti-β2GPI antibodies (F = 6.092, p = 0.015), polyneuropathy and anti-Scl70 antibodies (F = 20.161, p < 0.001), demyelinating syndrome and anti-cardiolipin antibodies (F = 6.637, p = 0.011), myasthenia gravis and anti-RNP (F = 5.864, p = 0.017), and anti-Smith antibodies (F = 5.096, p = 0.026). Multivariate logistics analysis showed that anti-prothrombin (aPT) IgM antibodies (OR = 10.985, CI 1.279-94.343, p = 0.029), age (OR = 1.169, CI 1.032-1.325, p = 0.014), and serum creatinine (SCr) (OR = 1.014, CI 1.003-1.025, p = 0.009) were independent risk factors of NPSLE, while anti-Sjogren syndrome antigen B (SSB) antibodies (OR 0.023, CI 0.002-0.622, p = 0.023) and high complement C3 (OR = 0.001, CI 0-0.045, p < 0.001) indicated reduced risk of NPSLE. Various neuropsychiatric manifestations in SLE were found to be correlated with specific autoantibodies. Independent risk factors for NPSLE included aPT IgM antibodies, age, and elevated serum creatinine, while the absence of anti-SSB antibodies and low complement C3 levels were associated with increased risk. •Significant associations were found between specific autoantibodies and neuropsychiatric symptoms, shedding light on potential biomarkers for predicting and understanding NPSLE. •The study identifies independent risk factors for NPSLE in the Chinese population, including the presence of anti-prothrombin IgM antibodies, older age, elevated serum creatinine, and lower complement C3 levels.

The incidence and trends of proteinuria, azotemia and hypertension in cats receiving toceranib phosphate.

This retrospective study aimed to determine the incidence and trends of proteinuria, elevations in serum creatinine and urea, and systolic blood pressure in cats undergoing treatment with toceranib. In total, 32 cats treated with toceranib for malignancies were analyzed. Cats were included if urinalysis and urine protein:creatinine ratio (UPC) measurements were available at 28 days (T1) and 56 days (T2) after starting the treatment. Cats with concurrent lower urinary tract disease, including urinary tract malignancy, were excluded. Friedman's ANOVA compared variables between time points, and the Spearman test assessed the correlation between treatment duration and UPC. The median starting dose of toceranib was 2.68 mg/kg (range 1.7-3.9). In total, 15 (46.9%) cats received concurrent non-steroidal anti-inflammatory drugs. The most commonly treated tumors were oral squamous cell carcinoma (n = 10) and mast cell tumor (n = 5). None of the 32 cats developed progressive proteinuria or azotemia during the follow-up period (median 56 days; range 56-336). Notably, UPC and serum creatinine were significantly lower at T2 compared with baseline (P = 0.012 and 0.001, respectively). Among the four cats with baseline proteinuria, UPC decreased over time with or without concurrent telmisartan treatment (n = 2). All four of these cats experienced a reduction in tumor size with toceranib concurrently with their decreased UPC. There was no significant correlation between UPC and the duration of toceranib treatment (P = 0.089). Blood pressure was not significantly different over the assessed time points. The incidence of proteinuria, renal azotemia and hypertension in cats treated with toceranib for neoplasia appears to be low. Toceranib may be a viable treatment option even in cats with pre-existing proteinuria or renal disease, with careful monitoring of trends recommended.

Epidemiologic pattern and factors associated with adverse outcomes of diabetic ketoacidosis in medical intensive care units of a tertiary care centre in India

AimDiabetic ketoacidosis (DKA) is a dreadful complication of diabetes mellitus characterized by a biochemical triad of hyperglycemia, ketosis, and metabolic acidosis. The clinic-epidemiologic pattern and outcomes of DKA in the Indian subcontinent are largely unexplored, yet understanding them is crucial for optimizing management strategies. MethodsA total of 138 patients admitted with a DKA diagnosis were reviewed retrospectively over two years. Patient demographics, clinical history, laboratory findings, precipitating factors, and intensive care management were extracted from case files. Clinical outcomes were classified as either discharge or death. Data analysis was performed using SPSSv29. ResultsThe mean age of the patients was 41.54 (16) years; 77 (55.79 %) were female, 56.52 % had type 1, 23.19 % had type 2, and 20.29 % had pancreatic diabetes. Non-compliance with infection (21.02 %), and pancreatitis (21.01 %) were common DKA triggers. Severity was assessed by pH, anion gap, and bicarbonate levels. The overall mortality rate was 11.59 %. Factors significantly associated with mortality included age >60 years, >3 previous DKA episodes, hypokalaemia, elevated serum creatinine, and altered sensorium. ConclusionThese findings emphasize the importance of demographics and risk factors in assessing DKA mortality risk, aiding early identification and targeted interventions for high-risk patients.