Search

Background: Previous investigations identified a connection between air pollution and kidney diseases. Nevertheless, there is a lack of comprehensive evidence on the long-term risks posed by air pollution with respect to acute kidney injury (AKI) and AKI-related death. Methods: This prospective cohort analysis included 414,885 UK Biobank (UKB) participants who did not exhibit AKI at the study's outset. AKI was defined based on ICD-10 codes recorded for hospitalized patients. Cox proportional hazards models were used to assess the association between prolonged exposure to air pollutants (particulate matter with diameters of 2.5 micrometers or less (PM2.5), between 2.5 and 10 micrometers (PM2.5−10), and 10 micrometers or less (PM10), along with nitrogen dioxide (NO2) and nitrogen oxides (NOx)) and the risk of AKI and AKI-related death, adjusting for potential confounders including sex, age, ethnicity, education, income, lifestyle factors, and relevant clinical covariates. Restricted cubic splines were applied to evaluate non-linear dose-response relationships, and stratified analyses were performed to explore potential effect modification across subgroups. Results: Over an average follow-up duration of 11.7 years, 14,983 cases of AKI and 326 cases of AKI-related death were diagnosed. Quartile analysis showed individuals exposed to higher levels of these air pollutants had a significantly higher risk of developing AKI and AKI-related death compared to those in the lowest quartile (all P < 0.05). The RCS curves depicting the relationship between PM2.5, PM2.5−10, PM10, NO2, NOx, and the risk of AKI showed a significant departure from linearity (P for non−linearity < 0.05), while the relationships between PM2.5, NO2, NOx, and the risk of AKI-related death did not exhibit a significant departure from linearity (P for non−linearity > 0.05). Sensitivity analyses confirmed the robustness of our findings. Conclusion: Our study reveals a direct association between prolonged air pollution exposure and elevated risks of both AKI and AKI-related death. These findings offer scientific validation for the adoption of environmental and public health measures directed towards the reduction of air pollution. Such initiatives could potentially ease the impact associated with AKI and AKI-related death. [ABSTRACT FROM AUTHOR]

Introduction: Chloride is the most abundant extracellular anion; however, abnormalities of serum chloride (dyschloremia) are often overlooked. This study aimed to study the association of dyschloremia with AKI and major adverse kidney events at Day 30 (MAKE30) in critically ill patients with sepsis. Materials and Methods: This prospective single‐center cohort study included adult patients with sepsis admitted in a tertiary care hospital in India. Patients with advanced chronic kidney disease, requiring dialysis at admission, or with hospital stay of less than 72 h were excluded. Hyperchloremia and hypochloremia were defined as chloride levels of > 110 mEq/L and < 95 mEq/L, respectively. The primary outcome measure was MAKE30—a composite of death, need for dialysis, or sustained loss of kidney function at Day 30. Results: In a cohort of 400 patients with a mean age of 60 (±15) years, AKI was seen in 301 (75.2%) and MAKE30 in 171 (42.8%). Hyperchloremia and hypochloremia were seen in 19.3% (n = 77) and 32.3% (n = 129), respectively, in the first 72 h of ICU stay. Hypochloremia, but not hyperchloremia, was independently associated with both MAKE30 (OR: 2.56, 95% CI: 1.13–5.79; p = 0.024) and new‐onset or worsening AKI (OR: 2.52, 95% CI: 1.17–5.41; p = 0.019). There was no association between hyperchloremia and either MAKE30 (OR: 1.07, 95% CI: 0.43–2.69; p = 0.882) or new‐onset/worsening AKI (OR: 0.89, 95% CI: 0.38–2.09; p = 0.781). Conclusion: Hypochloremia, but not hyperchloremia, was associated with MAKE30 in this cohort of critically ill patients with sepsis. Trial Registration: Clinical Trial Registry identifier: CTRI//2022/02/040519 [ABSTRACT FROM AUTHOR]

Background: Gastrojejunostomy junction perforation is a rare yet critical complication associated with enteral tube placement, presenting unique challenges in patients with a history of Roux-en-Y gastric bypass surgery. Case presentation: A 63-year-old white female with a complex medical history, including heart failure, atrial fibrillation, stage 4 chronic kidney disease, and prior Roux-en-Y gastric bypass surgery in 2015, experienced a significant decline in her health. She was discharged to a skilled nursing facility after a fall but deteriorated rapidly in the 2 weeks before admission. She presented with symptoms of failure to thrive, abdominal/back pain, inability to eat or drink, constipation, and stool incontinence. Lab tests showed anemia, electrolyte imbalances, and acute kidney injury. Imaging confirmed Roux-en-Y gastric bypass anatomy and a small hiatal hernia. Despite treatment attempts, her condition worsened. Nutrition discussions led to a temporary Dobhoff tube placement, considering her Roux-en-Y gastric bypass history, with plans for a gastrostomy tube. However, Dobhoff tube placement posed challenges, and imaging later revealed perforation near the gastrojejunostomy junction. After consulting with the family, the decision was made to transition the patient to comfort care due to her overall condition. Yearly education of staff about Roux-en-Y gastric bypass anatomy and updated Dobhoff placement protocol was implemented with physician oversight. Further imaging protocol in a patient who had had a Roux-en-Y gastric bypass was updated to include fluoroscopic guidance when endoscopic placement was unavailable. Conclusions: This case highlights the intricacies of managing patients with Roux-en-Y gastric bypass history and underscores the need for meticulous planning and consideration of anatomical variations when performing procedures involving the gastrointestinal tract and the importance of involving multiple healthcare disciplines in complex decision-making and preventive measures to enhance patient safety in similar cases. [ABSTRACT FROM AUTHOR]

Introduction: Up to 40% of patients with typical hemolytic-uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia and acute kidney injury (AKI), develop long-term consequences, most prominently chronic kidney disease (CKD). The transition from AKI to CKD, particularly in the context of HUS, is not yet fully understood. The objective of this study was to establish and characterize a Shiga toxin (Stx)-induced long-term HUS model to facilitate the study of mechanisms underlying the AKI-to-CKD transition. Methods: C57BL/6J mice were subjected to 5, 10, 15, or 20 ng/kg Stx on days 0, 3, and 6 of the experiment and were sacrificed on day 14 or day 21 to identify the critical time of turnover from the acute to the chronic state of HUS disease. Results: Acute disease, indicated by weight loss, plasma neutrophil gelatinaseassociated lipocalin (NGAL) and urea, and renal neutrophils, diminished after 14 days and returned to sham level after 21 days. HUS-associated hemolytic anemia transitioned to non-hemolytic microcytic anemia along with unchanged erythropoietin levels after 21 days. Renal cytokine levels indicated a shift towards pro-fibrotic signaling, and interstitial fibrosis developed concentration-dependently after 21 days. While Stx induced the intrarenal invasion of pro-inflammatory M1 and pro-fibrotic M2 macrophages after 14 days, pro-fibrotic M2 macrophages were the dominant phenotype after 21 days. Conclusion: In conclusion, we established and characterized the first Stxinduced long-term model of HUS. This tool facilitates the study of underlying mechanisms in the early AKI-to-CKD transition following HUS and allows the testing of compounds that may protect patients with AKI from developing subsequent CKD. [ABSTRACT FROM AUTHOR]

Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various 'remote organs' such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats. Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery is associated with a lower morbidity than open surgery. No recent data compared kidney cancer surgery in the French population using the National Health Insurance database (PMSI-MCO). Aims: We explore and compare the surgical morbidity rates between laparoscopic and open laparotomy for kidney cancer. Methods: The initial length of stay and complications parameters during the three postoperative months were described for renal cancer in every French center in 2018. We compared Relative Risks (RR [95% CI]) between laparoscopic and open surgery for both radical and partial nephrectomy. Results: Among 8,162 patients, 3,525 had a radical nephrectomy, 978 open, 2,547 laparoscopic surgeries; 4,637 patients had partial nephrectomies, 1,778 open 2,859 laparoscopic surgeries. For radical surgery, the most common complications were urinary infections (7.8%), acute renal failure (8.9%), sepsis (8.4%), bleeding (9.3%), and postoperative anemia (5.9%); the RR for laparoscopic versus open surgery were respectively 0.68 [0.54;0.86], 0.71 [0.57;0.88], 0.69 [0.55;0.86], 0.83 [0.66;1.03], 0.56 [0.43;0.73]. For partial nephrectomies, the most common complications were urinary infections (7.7%), bleeding (11.6%), and postoperative anemia (5.8%), with RR of 0.71 [0.58;0.87], 0.61 [0.52;0.71], and 0.64 [0.51;0.81]. The mean length of stay was 7.7 for open radical nephrectomy, 6.3 for laparoscopic radical nephrectomy, 7.5 for open partial nephrectomy, and 5 for laparoscopic partial nephrectomy. Conclusions: The laparoscopic approach had fewer postoperative complications and a shorter length of stay than open surgery for partial and radical nephrectomy. The PMSI analysis provided an exhaustive description of surgical practice for kidney cancer and surgical complications in France. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI. Methods: Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied. Results: Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23–7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08–1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50–2.87, p = 0.69). Conclusions: The analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in cirrhotic patients, especially in the intensive care unit (ICU), and is often associated with poor prognosis. Albumin is often used for plasma volume expansion, but its efficacy in cirrhotic patients with AKI [excluding hepatorenal syndrome (HRS)] is debated. This study aimed to assess the impact of albumin therapy on prognosis in ICU patients with cirrhosis and non-HRS AKI. Methods: A retrospective analysis was conducted using the MIMIC-IV 2.2 database. The primary endpoint was 28-day mortality. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics between the albumin and non-albumin groups. Results: A total of 1,623 patients were included, with 586 receiving albumin. After IPTW, the sample sizes were 1,713 in the non-albumin group and 1,490 in the albumin group. Albumin administration was associated with higher rates of AKI recovery at 48 h but did not improve 28-daymortality in the overall cohort. Further analysis revealed that using 5% albumin concentration was associated with improved 28-day mortality (HR 0.68; 95% CI 0.49-0.95; p = 0.025), whereas 25% albumin did not show benefit. In patients with high bilirubin levels, albumin treatment significantly reduced 28-day mortality. However, albumin therapy may increase 28-day mortality in certain subgroups, including patients with chronic kidney disease and baseline albumin levels >3.3 g/dL. Conclusion: Although albumin therapy improved 28-day mortality in some cases, it may also increase mortality in certain subgroups. The use of albumin in critically ill patients with cirrhosis and AKI should be approached with greater consideration of its risks and benefits. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the relationship between heat and emergency hospital admissions (EHAs) in Switzerland using clinically relevant metrics. Methods: Applying distributed lag non-linear models, we investigated temperatureadmission associations between May and September 1998--2019 for various disease groups, by age class and gender. We estimated the relative risk (RR) for moderate (29°C) and extreme (34°C) daily maximum temperatures relative to disease-specific optimum temperature, and calculated attributable fractions (AFs) for hot days and the following week. We also calculated the total number of heat-related EHAs. Results: We attributed 31,387 (95% confidence interval: 21,567--40,408) EHAs to aboveoptimal temperatures, 1.1% (0.7%--1.4%) of the total. Extreme temperatures increased the EHA risk for mental, infectious and neurological diseases. We observed particularly high AFs due to extreme heat for dehydration (85.9%, 95% CI: 82.4%--88.8%) and acute kidney injury (AKI, 56.1%, 95% CI: 45.3%--64.7%). While EHA risk generally increased with age, we also found high RRs for infectious diseases in children (0--15 years) and AKI in young adults (15--64 years). Conclusion: Hot weather increases the EHA risk in Switzerland. Therefore a comprehensive clinical and public health response is needed. [ABSTRACT FROM AUTHOR]

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and ß-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities. [ABSTRACT FROM AUTHOR]

Unilateral Nephrectomy is one of the most common treatments for surgical diseases of the kidney but often results in postsurgical acute kidney injury (AKI). In the current study, we aimed to investigate the risk factors for AKI in patients who have received Unilateral Nephrectomy. We retrospectively analysed 528 patients who underwent Unilateral Nephrectomy for different etiologies between January 2013 and December 2018 at the Affiliated Hospital of Qingdao University. We recorded the prevalence and severity of AKI, age, gender, diabetes, body mass index (BMI), hypertension, preoperative renal function, etiology, performed surgically, anaemia, albumin, coagulation, lactate dehydrogenase, nitrogen (BUN), and uric acid. Univariate and multivariate logistic regression analyses were used to investigate the predictors of AKI in patients with Unilateral Nephrectomy. Overall, 218 of the 528 patients (41.2%) developed AKI during their hospitalisation. Univariate analysis showed that AKI was significantly associated with gender (male, OR = 1.866, P = 0.001), overweight (OR = 2.19, P = 0.0002), and surgical approach (OR = 1.7, P = 0.018), while multivariate logistic regression analysis showed that male gender (OR = 1.953, P = 0.001), overweight (OR = 2.176, P = 0.001), and preoperative renal function (OR = 0.507, P = 0.001) were independent factors for AKI. Regression analysis among different etiologies showed significant differences in postoperative AKI. After Unilateral nephrectomy, AKI is more likely to occur in overweight male patients with normal kidney function. AKI occurred more frequently in patients who are kidney donors, but rarely in those with non-function kidneys. [ABSTRACT FROM AUTHOR]

Background At present, the relationship between the Triglyceride-glucose index (TyG index) and Acute kidney injury (AKI) in traumatic brain injury patients in the Intensive Care Unit (ICU) is still unclear. Currently, the relationship between TyG index and AKI occurred within 7 days in the ICU is a highly researched and trending topic. Objective In this study, we conducted in-depth exploration of the relationship between the development of AKI in traumatic brain injury (TBI) patients in the ICU and changes in TyG index, as well as its relevance. Methods A cross-sectional study was conducted with a total of 492 individuals enrolled in the Medical Information Mart for Intensive Care IV(MIMIC-IV) database. Multivariate model logistic regression, smoothed curve fitting and forest plots were utilized to confirm the study objectives. The predictive power of the TyG index for outcome indicators was assessed using subject work characteristics (ROC) curves. As well as comparing the Integrated Discriminant Improvement Index and the Net Reclassification Index of the traditional forecasting model with the addition of the TyG index. Results Of all eligible subjects, 55.9% were male and the incidence of AKI was 59.3%. There was a statistically significant difference in the incidence of AKI within 7 days in the ICU between the different TyG index groups. The difference between TyG index and the risk of AKI within 7 days in the ICU remained significant after adjustment for logistic multifactorial modeling (OR = 2.07, 95% CI = 1.41–3.05, P < 0.001). A similar pattern of associations was observed in subgroup analyses (P values for all interactions were greater than 0.05). The addition of TyG index to the traditional risk factor model improved the predictive power of the risk of AKI within 7 days in ICU (P < 0.05). Conclusion The findings of this study demonstrate a strong association between the TyG index and the occurrence of AKI within 7 days in ICU patients. The TyG index can potentially be used as a risk stratification tool for early identification and prevention of AKI. Implementing preventive strategies targeting patients with a high TyG index may help reduce the burden of AKI in the ICU. Further prospective studies are warranted to validate these findings and explore the clinical utility of the TyG index in AKI prevention. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion 2,3‐bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney.A tubular‐specific, doxycycline‐inducible Bpgm‐knockout mouse model was generated. Histological, immunofluorescence, and proteomic analyses were conducted to examine the localization of BPGM expression and the impact of its knockout on kidney structure and function. In vitro studies were performed to investigate the metabolic consequences of Bpgm knockdown under osmotic stress.BPGM expression was localized to the distal nephron and was absent in proximal tubules. Inducible knockout of Bpgm resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed involvement of BPGM in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation. In vitro, Bpgm knockdown led to enhanced glycolysis, decreased reactive oxygen species elimination capacity under osmotic stress, and increased apoptosis. Furthermore, interactions between nephron segments and immune cells in the kidney suggested a mechanism for propagating stress signals from distal to proximal tubules.BPGM fulfills critical functions beyond the erythrocyte in maintaining glucose metabolism in the distal nephron. Its absence leads to metabolic imbalances, increased oxidative stress, inflammation, and ultimately kidney injury. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and despite the availability of multiple treatments, striking a balance between long-term efficacy and side effects remains a major clinical challenge. B-cell-directed therapy has attracted much attention because of its unique mechanism of action. Belimumab and obinutuzumab, as representative drugs for B-cell-directed therapy, have shown their respective advantages for SLE treatment. However, data on combination therapy with obinutuzumab and belimumab are currently unavailable. Case presentation: We present the severe case report of a patient who was diagnosed with lupus nephritis (LN) with gastrointestinal involvement and developed acute renal failure. The patient responded to the first dose of obinutuzumab but failed to achieve a complete response to LN. The repeated use of obinutuzumab was limited by persistently low IgG levels and frequent infections. This is a real-world challenge that must be addressed. Therefore, the patient was subsequently treated with a novel sequential regimen of obinutuzumab followed by belimumab. After 18 months of follow-up, the patient achieved a complete clinical response with a favourable safety profile, along with the conversion of all autoantibodies from positive to negative and sustained negativity. To date, the patient has achieved a dual clinical and serological response. Conclusion: There is a reason to believe that this novel combination regimen could be developed as a therapeutic strategy, with the expectation of balancing efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Methods: Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Results: Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. Conclusions: During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane‐coated metal‐organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney‐targeting ability, and low membrane permeability. The engineered irisin‐mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin‐encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia‐reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI. [ABSTRACT FROM AUTHOR]

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single‐cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI‐to‐CKD model of unilateral ischemia‐reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co‐localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro‐repair subsets, whereas infiltrating monocyte‐derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling‐associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin‐like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI‐to‐CKD transition, which could be a potential therapeutic target for preventing CKD development. [ABSTRACT FROM AUTHOR]

Background and purpose: This comparative systematic review and meta-analysis investigated the incidence of ischemic stroke in intermediate-to-high-risk patients undergoing transcatheter aortic valve replacement versus surgical aortic valve replacement. Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines, searching PubMed, Google Scholar, Embase, Web of Science, and Cochrane CENTRAL databases from their inception to December 2023. The evaluated outcomes were primarily incidence of stroke and transient ischemic attack (TIA), along with other secondary safety end-points at 30 days and 1 year post-procedure. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for each study, employing a random-effects model for data synthesis irrespective of heterogeneity. Statistical heterogeneity was assessed using I2 statistics. All statistical analyses were conducted using Review Manager. Results: We screened 8028 articles and included 8 studies consisting of 5 randomized controlled trials and 3 observational studies. The studies examining 30-day and 1-year stroke incidence found no significant difference between TAVR and SAVR patients (OR 0.83, 95% CI 0.59 to 1.17, p = 0.30, OR 0.92, 95% CI 0.64 to 1.33, p = 0.67, respectively). Both TAVR and SAVR also had a comparable risk of having a transient ischemic attack within 30 days (OR 0.93, 95% CI 0.24 to 3.63, p = 0.92, I2 52%) and 1 year (OR 1.15, 95% CI 0.72 to 1.82, p = 0.56, I2 0%) following the procedure. Regarding safety endpoints, TAVR had lower rates of all-cause mortality and acute kidney injury at 1 year post-procedure, but a higher incidence of major vascular complications at both 30 days and 1 year compared with SAVR. Conclusion: The results suggest that TAVR and SAVR have comparable outcomes for both TIA and stroke incidence at 30 days and 1 year post-procedure, but display varying safety profiles in intermediate-to-high surgical risk patients. [ABSTRACT FROM AUTHOR]

Background: Radical cystectomy (RC) is a major surgery associated with a high morbidity rate. Perioperative fluid management according to enhanced recovery after surgery (ERAS) protocols aims to maintain patients in an optimal euvolemic state while exposing them to acute kidney injury (AKI) in the event of hypovolemia. Postoperative AKI is associated with severe morbidity and mortality. Our main objective was to determine the association between perioperative variables, including some component of ERAS protocols, and occurrence of postoperative AKI within the first 30 days following RC in patients presenting bladder cancer. Our secondary objective was to evaluate the association between a postoperative AKI and the occurrence or worsening of a chronic kidney disease (CKD) within the 2 years following RC. Methods: We conducted a retrospective observational study in a referral cancer center in France on 122 patients who underwent an elective RC for bladder cancer from 01/02/2015 to 30/09/2019. The primary endpoint was occurrence of AKI between surgery and day 30. The secondary endpoint was survival without occurrence or worsening of a postoperative CKD. AKI and CKD were defined by KDIGO (Kidney Disease: Improving Global Outcomes) classification. Logistic regression analyse was used to determine independent factors associated with postoperative AKI. Fine and Gray model was used to determine independent factors associated with postoperative CKD. Results: The incidence of postoperative AKI was 58,2% (n = 71). Multivariate analysis showed 5 factors independently associated with postoperative AKI: intraoperative restrictive vascular filling < 5ml/kg/h (OR = 4.39, 95%CI (1.05–18.39), p = 0.043), postoperative sepsis (OR = 4.61, 95%CI (1.05–20.28), p = 0.043), female sex (OR = 0.11, 95%CI (0.02–0.73), p = 0.022), score SOFA (Sequential Organ Failure Assessment) at day 1 (OR = 2.19, 95%CI (1.15–4.19), p = 0.018) and delta serum creatinine D1 (OR = 1.06, 95%CI (1.02–1.11), p = 0.006). During the entire follow-up, occurrence or worsening of CKD was diagnosed in 36 (29.5%). A postoperative, AKI was strongly associated with occurrence or worsening of a CKD within the 2 years following RC even after adjustment for confounding factors (sHR = 2.247, 95%CI [1.051–4.806, p = 0.037]). Conclusion: A restrictive intraoperative vascular filling < 5ml/kg/h was strongly and independently associated with the occurrence of postoperative AKI after RC in cancer bladder patients. In this context, postoperative AKI was strongly associated with the occurrence or worsening of CKD within the 2 years following RC. A personalized perioperative fluid management strategy needs to be evaluated in these high-risk patients. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (I/R) is an important inducer of acute kidney injury (AKI), and triggers the generation of reactive oxygen species (ROS) and the expression of matrix metalloproteinase 2 (MMP2), exacerbating kidney damage. Given the immense potential of vitamin E (VitE) as a natural fat-soluble antioxidant in kidney protection, we designed the nanoparticles (NPs) that could dual respond to ROS and MMP2, aiming to accurately deliver VitE to renal injury cells. The NPs utilized Gel-SH as a sensitive receptor for MMP2 and diselenide as a sensitive receptor for ROS, while PEG2k modification enhanced biocompatibility and prevented phagocytosis mediated by the mononuclear phagocyte system. The amphiphilic Gel-SH and diselenide encapsulate the liposoluble VitE and self-assemble into the NPs with a hydrodynamic size of 69.92 nm. Both in vivo and in vitro experiments based on these NPs show good biocompatibility and the ability of target renal injury cells. In vivo kidney I/R injury models and in vitro cell hypoxia/reoxygenation models, the NPs have demonstrated effects in reducing oxidative stress and alleviating AKI. Notably, VitE can preferentially react with peroxyl radical (LOO•) than polyunsaturated fatty acid (PUFA), inhibiting the formation of carbon centered radical (L•), thereby blocking the chain reaction between PUFA and LOO• in ferroptosis. The NPs also inhibit the transition from AKI to chronic kidney disease, with few side effects. Thus, the NPs with dual-responsiveness to MMP2 and ROS for targeted delivery of VitE to renal injury cells exhibit remarkable effects in inhibiting ROS and the chain reactions of ferroptosis, making it a promising therapeutic agent against AKI caused by I/R. [ABSTRACT FROM AUTHOR]

Simplified rapid hydration has been proven to be non-inferior to standard hydration in preventing contrast-associated acute kidney injury among chronic kidney disease patients undergoing coronary angiography. The current investigation aimed to further confirm the feasibility and safety of the newly proposed hydration method-simplified rapid hydration (SH) in each risk stratification by Mehran risk score (MRS). Eligible patients (n = 954) randomized to the SH group and standard hydration group were allocated into 2 groups based on MRS: low to moderate-risk and high to very high-risk groups. Primary endpoints were the incidence of contrast-associated acute kidney injury (CA-AKI) and acute heart failure (AHF) (SH vs standard hydration). Secondary endpoints included serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), and C-reactive protein (CRP) at 24 h, 48 h, and 72 h after PCI procedure, and the incidence of major adverse cardiac events (MACE). MRS was associated with a higher incidence of CA-AKI (OR = 1.101, 95%CI 1.049–1.156, P < 0.001). In the low to moderate-risk and high to very-high-risk groups, the incidence of CA-AKI in the SH and standard hydration group was 3.3% versus 4.9% (P = 0.5342), 10% versus 12% (P = 0.6392), respectively. Meanwhile, there might be subtle differences in renal function indexes and inflammatory indicators between SH and the control group at different time points. The preventive effect of SH in CA-AKI was similar to standard hydration regardless of MRS-guided risk stratification. [ABSTRACT FROM AUTHOR]

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101–153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1–3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15–22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106–159) µmol/L post-COVID-19 infection and 128 (101–161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection. [ABSTRACT FROM AUTHOR]

Purpose: Diverting ileostomy is related to postoperative high-output stoma (HOS) leading to kidney injury. The purpose of our study was to clarify the risk factors for ileostomy-associated kidney injury, which is kidney injury starting after the first operation to ileostomy closure after colorectal tumor surgery with diverting ileostomy. Methods: Between January 2013 and December 2020, 442 patients who underwent colorectal tumor surgery (cancer, neuroendocrine tumor, and leiomyosarcoma) following diverting ileostomy formation were included. We used the KDIGO (Kidney Disease Improving Global Outcomes) guidelines, which defines the acute kidney injury (AKI) to classify patients with ileostomy-associated kidney injury. The definition of AKI was (i) serum creatinine (sCr) ≥ 0.3 mg/dL or (ii) sCr ≥1.5-fold the preoperative level. Multivariate analyses were performed to identify the independent risk factors for kidney injury. Results: Kidney injury developed in 99/442 eligible patients (22.4%). Patients in the kidney injury group were older age, male sex, high American Society of Anesthesiologists Physical Status Classification System (ASA-PS) score, hypertension, cardiovascular diseases, diabetes. The preoperative hemoglobin, albumin, prognostic nutritional index (PNI), and creatinine clearance (CCr) were lower, and the maximum wound length was more extended than the non-kidney injury group. The median highest daily stoma output was significantly higher in the kidney injury group. The postoperative white blood cell (WBC) and C-reactive protein (CRP) levels were also high in the kidney injury group. The univariate analysis showed older age, male sex, high ASA-PS score, hypertension, cardiovascular diseases, and diabetes were the risk factors for kidney injury. The multivariate analysis revealed that age 70 or older, ASA-PS III/IV, hypertension, and HOS ≥2000 ml/day were independent risk factors for kidney injury. Conclusions: Surgeons should consider diverting colostomy creation for patients with risk factors such as age 70 or older, ASA-PS III/IV, and hypertension. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion The concomitant use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs.The data analyzed were obtained from the JMDC hospital‐based administrative claims database between April 2014 and August 2022. Histamine‐2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin‐angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log‐rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time‐varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates.After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92–3.63, p = 0.08).Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade‐off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs. [ABSTRACT FROM AUTHOR]

Objective To characterize the relationship between gut microbiota and neonatal acute kidney injury biomarkers based on the gut-kidney axis. Study Design The Pubmed database was primarily searched to include relevant literature on gut microbiota and neonatal acute kidney injury biomarkers, which was subsequently organized and analyzed and a manuscript was written. Results Gut microbiota was associated with neonatal acute kidney injury biomarkers. These biomarkers included TIMP-2, IGFBP-7, VEGF, calbindin, GST, B2MG, ghrelin, and clusterin. Conclusion The gut microbiota is strongly associated with neonatal acute kidney injury biomarkers, and controlling the gut microbiota may be a potential target for ameliorating neonatal acute kidney injury. Key Points There is a bidirectional association between gut microbiota and AKI. Gut microbiota is closely associated with biomarkers of nAKI. Manipulation of gut microbiota may improve nAKI. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) presents a significant clinical challenge due to its rapid progression to kidney failure, resulting in serious complications such as electrolyte imbalances, fluid overload, and the potential need for renal replacement therapy. Early detection and prediction of AKI can improve patient outcomes through timely interventions. This review was conducted as a narrative literature review, aiming to explore state-of-the-art models for early detection and prediction of AKI. We conducted a comprehensive review of findings from various studies, highlighting their strengths, limitations, and practical considerations for implementation in healthcare settings. We highlight the potential benefits and challenges of their integration into routine clinical care and emphasize the importance of establishing robust early-detection systems before the introduction of artificial intelligence (AI)-assisted prediction models. Advances in AI for AKI detection and prediction are examined, addressing their clinical applicability, challenges, and opportunities for routine implementation. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms. Methods: 56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-a) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR. Results: 654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI. Discussion: This study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock. [ABSTRACT FROM AUTHOR]

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% (n = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4–8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53–2.60]; P < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17–2.40]; P = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38–1.93]; P < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42–2.55]; P < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29–4.18]; P < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality. [ABSTRACT FROM AUTHOR]

Background: Coronary artery bypass grafting is associated with a high occurrence of postoperative cardiopulmonary complications. Preliminary evidence suggested that enhanced recovery after surgery can effectively reduce the occurrence of postoperative cardiopulmonary complications. However, enhanced recovery after surgery with systematic integration of cardiopulmonary rehabilitation (ERAS-CaRe) into for Coronary artery bypass grafting has not been evaluated so far. We thus design the ERAS-CaRe randomized-controlled trial to evaluate possible superiority of embedding cardiopulmonary rehabilitation in ERAS over ERAS alone as well as to investigate effects of differential timing of cardiopulmonary rehabilitation within enhanced recovery after surgery (pre-, post-, perio-operative) on post-operative cardiopulmonary complications following Coronary artery bypass grafting surgery. Methods: ERAS-CaRe is a pragmatic, randomized-controlled, parallel four-arm, clinical trial. Three hundred sixty patients scheduled for Coronary artery bypass grafting in two Chinese hospitals will be grouped randomly into (i) Standard enhanced recovery after surgery or (ii) pre-operative ERAS-CaRe or (iii) post-operative ERAS-CaRe or (iv) perio-operative ERAS-CaRe. Primary outcome is the occurrence of cardiopulmonary complications at 10 days after Coronary artery bypass grafting. Secondary outcomes include the occurrence of other individual complications including cardiac, pulmonary, stroke, acute kidney injury, gastrointestinal event, ICU delirium rate, reintubation rate, early drainage tube removal rate, unplanned revascularization rate, all-cause mortality, ICU readmission rate, plasma concentration of myocardial infarction-related key biomarkers etc. Discussion: The trial is designed to evaluate the hypothesis that a cardiopulmonary rehabilitation based enhanced recovery after surgery program reduces the occurrence of cardiopulmonary complications following Coronary artery bypass grafting and to determine optimal timing of cardiopulmonary rehabilitation within enhanced recovery after surgery. The project will contribute to increasing the currently limited knowledge base in the field as well as devising clinical recommendations. Trial registration: The trial was registered at the Chinese Clinical Trials Registry on 25 August 2023 (ChiCTR2300075125; date recorded: 25/8/2023, https://www.chictr.org.cn/). [ABSTRACT FROM AUTHOR]

Backgrounds: Crush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures. Methods: Mice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols. Results: The results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state. Conclusion: We successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI. [ABSTRACT FROM AUTHOR]

Introduction: Cisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatininduced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear. Methods: To investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques. Results: Here, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin. Discussion: Our study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodResultsConclusions\nSHORT ABSTRACTTo review the utility of galectin-3 (Gal-3) as a biomarker for postoperative adverse outcomes in patients undergoing cardiac surgery.This review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic database search was conducted in October 2023. Studies that measured pre- and/or postoperative plasma Gal-3 levels in adult patients undergoing cardiac surgery were included. Primary outcomes included postoperative morbidity and mortality.Out of 391 studies screened, eight studies met the inclusion criteria. Two of the three studies showed that preoperative plasma levels of Gal-3 were associated with acute kidney injury (AKI) after cardiac surgery. Two of the three studies reported a significant increase in preoperative Gal-3 levels in patients who developed postoperative atrial fibrillation (POAF). The addition of Gal-3 to the EuroSCORE II model was found to statistically improve the prediction of both AKI and POAF. Three of the five studies suggested that Gal-3 levels can predict postoperative mortality. Finally, one study suggested that lower preoperative Gal-3 levels was associated with a higher likelihood of achieving left ventricular reverse remodeling (LVRR) after surgery.Gal-3 may play a promising role in predicting adverse outcomes in patients undergoing cardiac surgery. The addition of Gal-3 to clinical risk prediction scores may improve their discriminatory power in this group of patients. Future studies are warranted to justify its incorporation into routine clinical practice.Galectin-3 (Gal-3) is an inflammatory protein that has recently emerged in literature as a potential biomarker for predicting mortality and cardiovascular events in cardiac surgery patients. Our review article consolidates landmark studies on the association between Gal-3 and several post-surgery outcomes such as kidney injury, atrial fibrillation, mortality, and left ventricular remodeling in adult patients. Incorporating Gal-3 in established clinical risk models such as the Society of Thoracic Surgeons (STS) scores and EuroSCORE may improve their predictive ability in diverse patient populations. [ABSTRACT FROM AUTHOR]

The article from the New England Journal of Medicine discusses a case of a 37-year-old man with fever, myalgia, jaundice, and respiratory failure. The patient's symptoms developed rapidly, leading to hospitalization and a series of diagnostic tests. Ultimately, the patient was diagnosed with icteric leptospirosis, a rare but serious bacterial infection transmitted through contaminated water or soil. Treatment with doxycycline was successful, and the patient recovered after a 14-day course of antibiotics. The article highlights the challenges in diagnosing and managing leptospirosis, especially in areas where the disease is not common. [Extracted from the article]

COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04–1.15) and a C-index of 0.82 (95% CI 0.72–0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21–8.36) and C-index of 0.91 (95% CI 0.87–0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM's importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions. [ABSTRACT FROM AUTHOR]

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-β and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin. [ABSTRACT FROM AUTHOR]

Background : Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration–time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. Methods: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. Discussion: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. Trial registration: Eudract number: 2019–004538-40. Registered on 2020–09-08 ClinicalTrials.gov NCT046666948. Registered on 2020–11-28 [ABSTRACT FROM AUTHOR]

Background Aims Study design Results Conclusions Relevance to Clinical Practice Pheochromocytoma can occur in patients with multiple endocrine neoplasia type 2, placing them at increased risk of tumour recurrence after surgical resection. Therefore, management of pheochromocytoma in these patients is a clinical challenge.We aim to present and discuss the nursing management of patient with recurrent pheochromocytoma.Case studies. We reviewed and retrieved the necessary information from the medical records.A 34‐year‐old female with a history of medullary thyroid carcinoma and pheochromocytoma complicated by cardiomyopathy, who had undergone surgical resections 6 years ago, presented with abdominal pain for 1 day and was diagnosed with recurrent bilateral pheochromocytoma, hypertensive crisis, acute heart failure, and acute renal failure. Eight hours after hospital admission, she experienced sudden cardiac arrest and received cardiopulmonary resuscitations. She was then supported under extracorporeal membrane oxygenation and continuous renal replacement therapy (CRRT). The adrenal tumour was successfully treated with absolute ethanol ablation followed by gelatin sponge particle embolization, a management approach which has not been reported previously. She had a satisfactory recovery.A comprehensive nursing management approach, including prone ventilation; safe transportation; close cardiopulmonary monitoring; pre‐, intra‐ and post‐procedure care; individualized early rehabilitation; and psychological supports, should be applied to improve the prognoses in patients with similar medical conditions.Bilateral adrenal pheochromocytoma can be managed by absolute ethanol ablation followed by gelatin sponge particle embolization. Comprehensive nursing management, including a team effort regarding patient positioning, transportation, close monitoring, early rehabilitation and psychological support, should be provided during the peri‐procedure period. [ABSTRACT FROM AUTHOR]

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up. [ABSTRACT FROM AUTHOR]

Diquat poisoning is a fatal condition that is becoming increasingly common. The mortality risk of patients taking lethal doses of diquat is extremely high. It typically leads to rapid dysfunction of multiple organs, including the kidneys, heart, lungs, and brain. Acute kidney injury is usually the first manifestation of this poisoning. However, the optimal treatment strategy for diquat poisoning remains uncertain. Additionally, the mechanism of multiple organ dysfunction syndrome caused by diquat poisoning may resemble the progression of sepsis. In this report, we present 3 cases of diquat poisoning, all of which resulted in death. We emphasize that acute kidney injury is the primary cause of death, and suggest that some strategies used in the treatment of sepsis could be beneficial in managing diquat poisoning-induced acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT. Methods: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa. Results: Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function. Conclusions: Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing. [ABSTRACT FROM AUTHOR]

Background: Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Results: Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77–0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85–0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82–0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05). Conclusions: As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI. Trial registration: Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1. Highlights: The mFRI is a rapid, cost-effective and easily accessible biomarker. The mFRI exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers and cytokines in cardiac surgical patients with mild to moderate AKI. Combining the functional biomarker mFRI with a urinary injury biomarker (uNAG or uNGAL) enhanced predictive accuracy for adverse renal outcomes. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) frequently occurs as a complication of cardiac surgery and cardiopulmonary bypass (CPB). Its prevalence and severity are determined by various preoperative and intraoperative factors. The aim of this study was to examine the risk factors for AKI following on-pump coronary artery bypass grafting (CABG). Methods: A retrospective analysis of clinical records from a single medical center was performed. The primary determinant for AKI analysis was the creatinine-level changes within the first 48 h after surgery. Records of 120 patients from a prospective cohort study were examined. Results: An AKI incidence of 26% occurred in the study cohort. The univariate analysis revealed that patients who developed AKI had notably higher EuroSCORE II values (2.00 ± 0.98 vs. 1.49 ± 0.74, p = 0.006) and higher initial levels of urea (7.62 ± 2.94 vs. 6.12 ± 1.71, p = 0.002) and creatinine (0.108 ± 0.039 vs. 0.091 ± 0.016, p = 0.003). Additionally, they exhibited a more frequent occurrence of initial albumin levels below 40 g/l (9 (34.6%) vs. 11 (14.9%) cases, p = 0.030) and a lower initial hemoglobin level (137.8 ± 13.2 g/l vs. 146.6 ± 13.6 g/l, p = 0.005) in comparison to patients without this complication. Moreover, those with AKI had a significantly longer hospital stay duration (14.3 ± 5.45 days vs. 12.6 ± 3.05 days, p = 0.048). Logistic regression indicated one risk factor, oxygen delivery during CPB, that correlated with the onset of AKI in the early postoperative period. Conclusion: The prevalence of AKI was higher among patients with a higher EuroSCORE II, lower preoperative hemoglobin, increased preoperative levels of creatinine and urea, infrequent albumin levels below 40 g/L, diminished oxygen delivery during CPB, and greater need for RBC transfusion and furosemide, but it did not correlate with the duration of CPB. [ABSTRACT FROM AUTHOR]

Background: Desmopressin 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). Methods: We 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. Results: A 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. Conclusion: In 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Globally, the primary causes of mortality and morbidity related to kidney ailments can be classified as Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD). Biomarker detection can have great potential to improve survival, lower mortality, and reduce the cost of treatment of kidney diseases. Considering the chronic nature of CKD, non-invasive identification and monitoring have proven to be useful. Biosensors and more specifically lateral flow test strips (LFTs) are regarded as the most desirable point-of-care instruments which have shown promise in elevating the healthcare industry to a new level. The major aspects of an ideal point-of-care (POC) lateral flow test include its cost effectiveness, high sensitivity and specificity, ease of use, quick result delivery, and quality control. This review provides a detailed account of recent developments, challenges, and opportunities in renal biomarker detection using LFTs including various approaches for sensitivity enhancement along with potential future advancements in POC and LFT kits. [ABSTRACT FROM AUTHOR]

Patients critically afflicted with coronavirus disease 2019 (COVID‐19) often need intensive care unit (ICU) admission, despite comprehensive vaccination campaigns. The challenges faced by healthcare systems in low‐middle‐income countries, including limited infrastructure and resources, play a pivotal role in shaping the outcomes for these patients. This study aimed to meticulously compare outcomes between COVID‐19 vaccinated and nonvaccinated patients admitted to the ICU. In addition, demographic factors and the ICU course influencing mortality were also assessed. A retrospective review of records from the COVID‐ICU of Aga Khan University Hospital spanning July 2021–March 2022 included 133 patients. Statistical analyses, encompassing the Mann–Whitney U‐test and chi‐square/Fisher exact test, discerned quantitative and qualitative differences. Stepwise multivariable logistic regression models with forward selection identified factors associated with hospital mortality. Results revealed comparable cohorts: vaccinated (48.13%) and nonvaccinated (51.87%). Vaccinated individuals, characterized by advanced age and higher Charlson Comorbidity Index, exhibited more critical disease (89.1%; p value: 0.06), acute respiratory distress syndrome (96.9%; p value: 0.013) and elevated inflammatory markers. Despite these differences, both cohorts exhibited similar overall outcomes. Factors such as decreased PaO2/FiO2 ratio on admission and complications during ICU stay were significantly associated with in‐hospital mortality. In conclusion, despite advanced age and increased frailty among vaccinated patients, their mortality rate remained comparable to nonvaccinated counterparts. These findings underscore the pivotal role of vaccination in mitigating severe outcomes within this vulnerable population. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of preoperative HbA1c levels on postoperative complications in coronary heart disease patients undergoing coronary artery bypass grafting (CABG). Methods: From September 2020 to November 2022, 98 patients with coronary heart disease who were preparing to receive CABG treatment in a cardiac surgery department of a certain hospital were included in the study using the retrospective analysis. According to the preoperative serum hemoglobin A1C (HbA1c) test results, patients were divided into a low-level group (HbA1c < 5.7%, 20 cases), a medium level group (HbA1c: 5.7% ~ 7.0%, 59 cases), and a high level group (> 7%, 19 cases). The surgical outcomes and postoperative complications among the three groups were compared. Results: There was no statistically significant difference in the number of bypass grafts, mechanical ventilation time, and hospitalization time among the three groups of patients (P > 0.05). The high-level group stayed in the ICU longer than the other two groups, while the middle level group had a longer stay than the low-level group (P < 0.05). Within one year of postoperative follow-up, the occurrence of postoperative complications was 20.00%, 32.20%, and 47.37%, respectively, with no statistically significant difference (P > 0.05). Among them, the incidence of acute kidney injury in the high-level group was higher than that in the other groups (P < 0.05), but the correlation difference between the middle and low level groups is P > 0.05. The incidence of infection in the middle level group was higher than that in the low level group (P < 0.05), but the incidence of infection in the high and low level groups was P > 0.05 compared to the medium level group. Conclusion: For patients with coronary heart disease undergoing CABG, the higher the preoperative HbA1c level, the longer their postoperative stay in the ICU, and the higher the risk of acute renal function damage. [ABSTRACT FROM AUTHOR]

Background: Signal transducer and activator of transcription 3 (STAT3), a multifaceted transcription factor, modulates host immune responses by activating cellular response to signaling ligands. STAT3 has a pivotal role in the pathophysiology of kidney injury by counterbalancing resident macrophage phenotypes under inflammation conditions. However, STAT3's role in acute kidney injury (AKI), particularly in macrophage migration, and in chronic kidney disease (CKD) through fibrosis development, remains unclear. Methods: Stattic (a JAK2/STAT3 inhibitor, 5 mg/kg or 10 mg/kg) was administered to evaluate the therapeutic effect on LPS-induced AKI (L-AKI) and LPS-induced CKD (L-CKD), with animals sacrificed 6–24 h and 14 days post-LPS induction, respectively. The immune mechanisms of STAT3 blockade were determined by comparing the macrophage phenotypes and correlated with renal function parameters. Also, the transcriptomic analysis was used to confirm the anti-inflammatory effect of L-AKI, and the anti-fibrotic role was further evaluated in the L-CKD model. Results: In the L-AKI model, sequential increases in BUN and blood creatinine levels were time-dependent, with a marked elevation of 0–6 h after LPS injection. Notably, two newly identified macrophage subpopulations (CD11bhighF4/80low and CD11blowF4/80high), exhibited population changes, with an increase in the CD11bhighF4/80low population and a decrease in the CD11blowF4/80high macrophages. Corresponding to the FACS results, the tubular injury score, NGAL, F4/80, and p-STAT3 expression in the tubular regions were elevated. STAT3 inhibitor injection in L-AKI and L-CKD mice reduced renal injury and fibrosis. M2-type subpopulation with CD206 in CD11blowF4/80high population increased in the Stattic-treated group compared with that in the LPS-alone group in the L-AKI model. Additionally, STAT3 inhibitor reduced inflammation driven by LPS-stimulated macrophages and epithelial cells injury in the co-culture system. Transcriptomic profiling identified 3 common genes in the JAK-STAT, TLR, and TNF signaling pathways and 11 common genes in the LPS with macrophage response. The PI3K-AKT (IL-6, Akt3, and Pik3r1) and JAK-STAT pathways were determined as potential Stattic targets. Further confirmation through mRNA and protein expressions analyses showed that Stattic treatment reduced inflammation in the L-AKI and fibrosis in the L-CKD mice. Conclusions: STAT3 blockade effectively mitigated inflammation by retrieving the CD11blowF4/80high population, further emphasizing the role of STAT3-associated macrophage-driven inflammation in kidney injury. Plain English summary: This study investigated the role of STAT3 in LPS-induced acute kidney injury (AKI) and its prolonged pathophysiological effect. In a mouse model, blocking STAT3 with Stattic reduced inflammation and fibrosis, decreased the levels of inflammatory and extracellular matrix (ECM) substances, reduced the number of certain immune cells (macrophages), and influenced specific genes related to inflammation. The findings suggest that targeting STAT3 is a promising approach to treat AKI and CKD by controlling the inflammation and the immune response as well as ECM accumulation. This study provides novel insights into AKI and CKD progression and will facilitate the development of new treatments for kidney injuries at various stages. [ABSTRACT FROM AUTHOR]

Backgound: People with diabetes are much more likely to develop acute kidney injury (AKI) than people without diabetes. Low 25-hydroxy-vitamin D [25(OH)D] concentrations increased the risk of AKI in specific populations. Few studies have explored the relationship between the 25(OH)D level and AKI in patients with diabetes. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and the risk of AKI in patients with diabetes, and to evaluate whether the 25(OH)D level could be a good prognostic marker for AKI progression. Methods: A total of 347 patients with diabetes were retrospectively reviewed. The primary endpoint was the first event of AKI. The secondary endpoint is need-of-dialysis. AKI patients were further followed up for 6 months with the composite endpoint of end-stage renal disease (ESRD) or all-cause death. Kaplan–Meier survival analysis and Cox proportional hazards models were used. Results: During a median follow-up of 12 weeks (12.3 ± 6.7), 105 incident AKI were identified. The middle and high tertiles of baseline 25(OH)D levels were associated with a significantly decreased risk of AKI and dialysis compared to the low tertile group (HR = 0.25, 95% CI 0.14–0.46; HR = 0.24, 95% CI 0.13–0.44, respectively, for AKI; HR = 0.15; 95% CI 0.05–0.46; HR = 0.12; 95% CI 0.03–0.42, respectively, for dialysis). Sensitivity analysis revealed similar trends after excluding participants without history of CKD. Furthermore, AKI patients with 25(OH)D deficiency were associated with a higher risk for ESRD or all-cause death (HR, 4.24; 95% CI, 1.80 to 9.97, P < 0.001). Conclusion: A low 25 (OH) vitamin D is associated with a higher risk of AKI and dialysis in patients with diabetes. AKI patients with 25(OH)D deficiency were associated with a higher risk for ESRD or all-cause death. [ABSTRACT FROM AUTHOR]

Introduction: Glomerular diseases, encompassing primary and secondary forms, pose significant morbidity and mortality risks. Despite their impact, little is known about critically ill patients with primary glomerulopathy admitted to the intensive care unit (ICU). Methods: We conducted a case‒control study of patients with primary glomerulopathy using the Medical Information Mart for Intensive Care IV database. Demographic, clinical, and outcome data were collected. Logistic regression and mediation analysis were performed to identify predictors of hospital and long-term mortality. Results: Among 50,920 patients, 307 with primary glomerulopathy were included. Infectious and cardiovascular-related causes were the main reasons for ICU admission, with sepsis being diagnosed in more than half of the patients during their ICU stay. The hospital mortality rate was similar to that of the control group, with a long-term mortality rate of 29.0% three years post-ICU discharge. Reduced urine output and serum albumin were identified as independent predictors of hospital mortality, while serum albumin and the Charlson comorbidity index were significantly associated with long-term mortality. Notably, although acute kidney injury was frequent, it was not significantly associated with mortality. Additionally, reduced urine output mediates nearly 25% of the association between serum albumin and hospital mortality. Conclusion: Critically ill patients with primary glomerulopathy exhibit unique characteristics and outcomes. Although hospital mortality was comparable to that of the control group, long-term mortality remained high. The serum albumin concentration and Charlson Comorbidity Index score emerged as robust predictors of long-term mortality, highlighting the importance of comprehensive risk assessment in this population. The lack of an association between acute kidney injury and mortality suggests the need for further research to understand the complex interplay of factors influencing outcomes in this patient population. [ABSTRACT FROM AUTHOR]