Vortioxetine is a multimodal antidepressant approved for the treatment of major depressive episodes. As part of the overall European risk-management plan, we aimed to fill data gaps on relevant missing information such as the extent of vortioxetine use in special populations and assessment of selected potential risks.

This non-interventional post-authorization safety study used longitudinal administrative claims/medical records data from 10,358 patients newly prescribed vortioxetine in Finland, Spain, and the Netherlands (EU-PAS register: EUPAS19199).

Elderly patients (≥75 years) accounted for 3-14% of the assessed populations, while off-label pediatric prescribing was low (0.1-0.5%). Patients with a comorbid diagnosis of mania/hypomania accounted for 0.4-10% of the population, while patients with comorbid neurological conditions accounted for ≤3% of patients. The median prescribed daily vortioxetine dose was 10mg and mean exposure was 72-238 days. The proportions of patients who had one of the events of interest (suicidal events, epilepsy, convulsions/seizures, severe renal or hepatic events) recorded during vortioxetine exposure were all ≤1%.

In this European healthcare database study, the extent and characteristics of vortioxetine use were in line with clinical trial experience and the current label. Analyses of events, including those of special interest, did not raise any new safety concerns.

The development of diagnostic definitions for acute kidney disease in outpatients (AKDOPT) remains an unattained goal because of consensus gaps and data silos in health-care systems.

Our team developed the Acute Kidney Injury Detection System (AKIDS) to screen for undiagnosed AKDOPT using National Health Insurance MediCloud data and institutional electronic medical records. The criteria for AKDOPT were a >50% change in maximum and minimum serum creatinine levels or a >35% change in corresponding estimated glomerular filtration rate values within the 180 days before an appointed outpatient visit. In this retrospective cohort study, the associations between AKDOPT and composite kidney outcome (CKO; e.g., end-stage kidney disease, a >40% drop in estimated glomerular filtration rate, or a 2-fold or more increase in serum creatinine), all-cause mortality, and de novo non-dialysis chronic kidney disease (CKD-ND) were evaluated using multivariable Cox proportional hazards models.

Of 79,838 eligible adult patients screened by the AKIDS, 12,510 (15.7%) have AKDOPT. The adjusted absolute risk increases for 1-year incident CKO, mortality, and de novo CKD-ND for patients with AKDOPT relative to those without are 79.0 (95% confidence interval 78.9-79.1), 25.3 (25.2-25.3), and 54.8 (54.7-54.9) per 1000 patients, respectively. The adjusted hazard ratios for 1-year CKO, mortality, and de novo CKD-ND are 16.2 (14.2-18.5), 2.6 (2.4-2.9), and 3.5 (3.1-3.9), respectively.

By integrating the national-local data using the AKIDS, this study comprehensively characterizes a previously unrecognized phenotype, AKDOPT, illustrating the potential of healthcare big data in transforming global approaches to AKD patterns and prevention.

Background: Although lactated Ringer's (LR) solution is widely used in managing patients with acute kidney injury (AKI), its specific impact on mortality remains unclear. This retrospective cohort study aimed to evaluate the effects of LR administration on survival outcomes in severely ill patients with AKI. Methods: Critically ill patients with AKI were identified using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Propensity score matching (PSM) was employed to address baseline discrepancies between patients who received LR and those who did not. The association of LR administration with survival, duration of hospitalization and intensive care unit (ICU) stay, requirement for renal replacement therapy (RRT), renal function recovery, and hyperkalemia was analyzed using restricted mean survival time (RMST), logistic regression, and linear regression models. Results: A total of 5620 patients with AKI were included. Following PSM, LR administration was associated with prolonged survival at 28 and 90 days compared to non-LR use (28-day survival increase: 1.12 days, 95% confidence interval [CI] 0.62-1.63, p < 0.001; 90-day survival increase: 3.73 days, 95% CI 1.70-5.76, p < 0.001). The survival benefit became more pronounced, with higher LR use linked to more remarkable 90-day survival. However, LR administration did not significantly affect renal function recovery or hyperkalemia incidence. Conclusion: Administering LR to critically ill patients with AKI was associated with improved survival at both 28 and 90 days.

Acute kidney injury (AKI) is a frequent yet often overlooked complication. This study examines the incidence, unrecognized rate, and outcomes of AKI in adults at a large public Chinese hospital from 2010 to 2023. AKI rates were calculated, and outcomes were assessed using follow-up records. Multivariate logistic regression identified risk factors for unrecognized AKI. Among 2,790,540 patients, 5,080 met the AKI criteria, with an overall incidence of 0.18% (0.78% in hospitalizations, 0.05% in outpatients). The unrecognized AKI was 76.3%. In this group, 75% were stage 1, 16.7% stage 2, and 8.3% stage 3. Orthopedics had the highest unrecognized rate (94.5%) and ICUs the lowest (55.77%). Unrecognition of AKI improved from 90.3% in 2010-2011 to 70.2% in 2022-2023. AKI stage progression was linked to poorer survival. Patients with recognized AKI recovered faster than those with unrecognized AKI (8.0 vs. 9.0 days, p < 0.001). The mean follow-up time was 15.8 days, with similar rates at 28 and 90 days post-AKI for both groups. Risk factors for unrecognized AKI included lower AKI stage, baseline creatinine, absence of shock/heart disease/hypertension, and non-nephrology/surgery admissions. Non-nephrology physicians' unfamiliarity with AKI guidelines may contribute to low awareness. Improved early detection and monitoring in high-risk groups are needed.

Causes and risk factors for community-acquired acute kidney injury (CA-AKI) have not been thoroughly studied. The aim of this study was to examine the risk factors for CA-AKI.

In this prospective study, we examined serum creatinine from all individuals visiting a university hospital's emergency department (ED) over an 11-month period for the presence of AKI defined according to the KDIGO criteria. Patients with AKI were invited to participate. Randomly selected controls (1:2) were paired according to age, sex, and date of admission. Participants answered questions about their medical history and medication use, including over-the-counter (OTC) drugs. Conditional logistic regression was used to identify factors associated with AKI.

Of 602 AKI cases identified, 512 participated in the study. AKI cases were significantly more likely than controls to have used nonsteroidal anti-inflammatory drugs (NSAIDs) (26.0 % vs 18.0 %, p = 0,001) in the week preceding the ED visit, particularly OTC NSAIDs (23.3 % vs 15.9 %, p < 0.001). AKI was associated with a recent history of vomiting (OR 2.52 [95 %CI 1.87-3.39]), diarrhea (1.30 [1.00-1.70]) and urinary retention (1.92 [1.36-2.72]), use of non-selective NSAIDs (1.84, [1.37-2.48]), RAAS blockers (1.63 [1.21-2.19]), and diuretics (1.53 [1.13-2.08]), and a history of diabetes (1.42 [1.04-1.94]), CKD (1.36 [1.01-1.83]) and smoking (1.72 [1.24-2.37]).

Events in the setting of acute illness and medication use, including OTC NSAIDs, may play a greater role in the development of CA-AKI than comorbid conditions. Frequent use of OTC NSAIDs is a concern and should be addressed in view of serious adverse effects.

The transient receptor potential ankyrin 1 (TRPA1) channels, characterized as nonselective cation channels with permeability to calcium ions (Ca2 +), are part of the extensive family of transient receptor potential (TRP) channels. Research has demonstrated that TRPA1 channels function as sensors for oxidative stress in the renal tubules. Additionally, TRPA1 expression has increased in renal tissue following ischemia-reperfusion (IR). There is also a significant correlation between IR-induced renal injury and TRPA1 expression. This study investigated the effects of selective TRPA1 agonist ASP7663 and selective TRPA1 antagonist HC-030031 on renal IR injury. A total of 40 rats were divided into four groups: control, IR, IR+ASP7663, and IR + HC-030031. The rat kidneys were exposed to 45 min of ischemia, followed by 24 h of reperfusion. TRPA1 agonist ASP7663 and selective TRPA1 antagonist HC-030031 were administered intraperitoneally to the treatment groups with renal IR. HC-030031 administration reduced the elevated kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cre) caused by renal IR. HC-030031 administration reduced the increased histopathological damage in renal tissue due to IR. It also reduced renal tissue interleukin-1beta (IL-1β), interleukin-6 (IL-6), toll-like receptor-4 (TLR-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor-alpha (TNF-α), and caspase-3 levels. In this study, TRPA1 antagonist HC-030031 showed a protective behavior on renal IR injury by averting inflammation and apoptosis. After further studies, TRPA1 inhibition may be a new treatment strategy to prevent renal IR injury.

Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study aimed to clarify the characteristics and risk factors for AKI in this population.

This retrospective observational study was performed with the clinical data of all outpatients and inpatients aged ≥ 65 years at the time of enrolment at Kochi Medical School Hospital between 1 January 1981 and 31 December 2021. The primary cohort was divided into those aged 65-74 and ≥ 75 years. The primary outcome was the occurrence of AKI.

Of 83,822 patients, 38,333 were included in the 65-74-year-old group, whereas 45,489 were included in the ≥ 75-year-old group. Prevalences of the first AKI event in the 65-74-year-old and ≥ 75-year-old groups were 11.9% and 12.4%, respectively. Overall, lower estimated glomerular filtration rate, lower albumin level, lower or higher level of serum uric acid, and histories of diabetes mellitus, chronic heart failure, ischaemic heart disease, non-ischaemic heart disease, cerebrovascular disease, cancer, and liver disease were independent risk factors for an AKI event. The risk factors for AKI unique to each cohort were using non-steroidal anti-inflammatory drugs (NSAIDs) and loop diuretics (L-DI), and histories of hypertension (HT) and vascular diseases (VD) in men aged 65-74 years; using NSAIDs, angiotensin-converting enzyme inhibitors (ACEIs), L-DI and other diuretics (O-DI), and histories of HT and VD in men aged ≥ 75 years; using NSAIDs and O-DI and not using angiotensin-receptor blockers (ARBs), and a history of HT in women aged 65-74 years; and use of L-DI and a history of VD in women aged ≥ 75 years. Presence of proteinuria was a risk factor for developing AKI.

Many AKI risk factors reported thus far are associated with AKI development. However, there are differences in the effects of the renin-angiotensin system inhibitors, ACEIs, and ARBs (ARBs may be protective). Additionally, the U-shaped relationship between AKI onset and uric acid levels differs between sexes in the elderly population, similar to other age groups, but this sex difference disappears in the very elderly population. Pre-existing chronic kidney disease is a risk factor for the development of AKI.

Acute kidney injury (AKI) is common. An AKI episode may disrupt the normal mineral bone balance maintained by normal kidney function, thereby modifying the risk of developing bone fractures. However, it remains unclear whether an AKI episode is associated with the risk of bone fractures.

Using retrospective cohort study from an Australian Local Health District, we examined the association between an AKI episode and bone fractures using patient data between 2008 and 2017. Time-varying Cox proportional hazards and propensity-matched analysis were used to examine the association. Sensitivity analyses were undertaken to capture the impact of confirmed AKI status and AKI severity.

Of 123 426 included patients, 14 549 (12%) had an AKI episode and 12 505 (10%) had a bone fracture. In the unadjusted analysis, AKI was associated with bone fractures [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.88-2.11]. This association persisted in the adjusted analysis (HR 1.50, 95% CI 1.41-1.59) and propensity-matched dataset (HR 1.71, 95% CI 1.59-1.83). The sensitivity analysis yielded similar results, with the AKI patients having a higher risk of fractures compared with no AKI patients in the adjusted analysis (HR 1.34, 95% CI 1.25-1.43) and in the propensity-matched dataset (HR 1.44, 95% CI 1.33-1.55). Similar results were seen in the subsidiary sensitivity analysis excluding patients without baseline creatinine. We did not find an increased risk of bone fractures with increasing AKI severity (P = .7). Interaction tests demonstrated a significant association between sex and age category with AKI status and fractures, but not CKD stage or osteoporosis.

AKI is associated with a greater risk of bone fractures. This could have implications for managing and screening for bone disease in patients post-AKI episode. This association should be examined in other cohorts and populations for verification.

Patients with non-diabetic hypoglycemia have a poorer prognosis than those with diabetic hypoglycemia. However, the factors associated with prognosis remain unclear. Therefore, this study aimed to identify the prognostic factors for non-diabetic hypoglycemia. This is a retrospective study of patients hospitalized for severe hypoglycemia with blood glucose ≤ 3.0 mmol/L (54 mg/dL) due to non-diabetic hypoglycemia between April 2008 and June 2023. Additionally, the underlying cause of hypoglycemia was identified, and the factors associated with mortality were examined. Of the 134 hospitalized patients, 126 were analyzed, excluding cases of multiple or scheduled hospitalizations. The most common causes of hypoglycemia were malnutrition (n = 79, 62.7%), alcohol intake (n = 27, 21.4%), and hypothermia (n = 27, 21.4%); 76 (60.3%) patients had multiple associated factors. Of the 126 patients, 52 died within 90 days. In the multivariate analysis, the estimated glomerular filtration rate (eGFR) (< 30 mL/min/1.73 m2) was independently associated with death [odds ratio (OR) 5.78, 95% confidence interval (CI) 1.69-19.8], whereas blood glucose (OR 0.95, 95% CI 0.92-0.99), serum albumin (OR 0.27, 95% CI 0.12-0.59), and alcohol intake (OR 0.03, 95% CI 0.004-0.34) were associated with survival. Moreover, age (OR 1.0, 95% CI 0.97-1.04) was not associated with death. Patients with non-diabetic hypoglycemia had a very high mortality. Low eGFR, blood glucose levels, and serum albumin levels at admission were associated with 90-day mortality, and alcohol intake was associated with survival.

The increasing admissions of very elderly patients to intensive care units (ICUs) over recent decades highlight a growing need for understanding acute kidney injury (AKI) in this population. Although these individuals are potentially at high risk for AKI and adverse outcomes, data on AKI in this population is scarce. This study investigates the AKI incidence and outcomes of critically-ill patients aging at least 90 years.

This retrospective cohort study conducted at the Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Germany (2008-2020), investigates AKI incidence and outcomes between 2008 and 2020 in critically-ill patients aged ≥ 90 years. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using creatinine dynamics and/or urine output. Primary endpoint was overall mortality after 1 year. Secondary endpoints were in-hospital mortality, length of ICU and hospital stay.

During the study period 92,958 critically-ill patients were treated and 1108 were ≥ 90 years. Of these, 1054 patients had available creatinine values and were included in the present study. AKI occurred in 24.4%, mostly classified as mild (17.5%). AKI was independently associated with a significant increase in overall mortality (HR 1.21, 95 %-CI: 1.01-1.46), in-hospital mortality (OR 2, 1.41-2.85), length of ICU (+2.8 days, 2.3-3.3) and hospital stay (+2.3 days, 0.9-3.7). Severity escalated these effects, but even mild AKI showed significance. Introducing urine-based criteria increased incidence but compromised mortality prediction.

AKI is a frequent complication in very elderly critically-ill patients. Occurrence of AKI at any stage was associated with increased mortality. Predictive ability applied to AKI defined by creatinine but not urine output. Careful attention of creatinine dynamics is essential in very elderly ICU-patients.

Acute kidney injury (AKI) affects 10-15% of hospitalised patients and arises after severe infections, major surgeries, or exposure to nephrotoxic drugs. AKI diagnosis based on creatinine level changes lacks specificity and may be delayed. MicroRNAs are short non-coding RNA secreted by all cells. This review of studies measuring miRNAs in AKI aimed to verify miRNAs as diagnostic markers. The study included data from patients diagnosed with AKI due to sepsis, ischaemia, nephrotoxins, radiocontrast, shock, trauma, and cardiopulmonary bypass. Out of 71 studies, the majority focused on AKI in sepsis patients, followed by cardiac surgery patients, ICU patients, and individuals receiving nephrotoxic agents or experiencing ischaemia. Studies that used untargeted assays found 856 differentially regulated miRNAs, although none of these were confirmed by more than one study. Moreover, 68 studies measured miRNAs by qRT-PCR, and 2 studies reported downregulation of miR-495-3p and miR-370-3p in AKI patients with sepsis after the AKI diagnosis. In three studies, upregulation of miR-21 was reported at the time of the AKI diagnosis with a significant pooled effect of 0.56. MiR-21 was also measured 19-24 h after cardiac surgery in three studies. However, the pooled effect was not significant. Despite the considerable research into miRNA in AKI, there is a knowledge gap in their applicability as diagnostic markers of AKI in humans.

It remains unclear whether the incidence of post-operative acute kidney injury (PO-AKI) has been reduced despite the recent emphasis on its early recognition and prevention in clinical practice. We aimed to investigate the trend in the incidence of PO-AKI and to identify the associated factors affecting its changes.

We gathered clinical data from patients who underwent non-cardiac major surgeries at three referral hospitals from 2005 to 2020. PO-AKI was defined as KDIGO AKI criteria within 7 days after surgery. Severe PO-AKI (S-PO-AKI) was defined as stage 2 or 3 AKI. The temporal change of PO-AKI was evaluated by joinpoint regression analysis and multivariable logistic regression based on a 3-year interval.

Among 138 235 patients, 8156 (5.9%) PO-AKI and 1127 (0.8%) S-PO-AKI occurred, respectively. The patients enrolled in recent years were older and more were women. They had more comorbidities and a higher PO-AKI risk compared with those included in past years. As time passed, the PO-AKI incidence decreased from 8.6% in 2005-07 to 5.1% in 2017-20, whereas S-PO-AKI incidence did not change (0.8% to 0.9%). In joinpoint analysis, PO-AKI incidence tended to decrease with annual percentage change (APC) of -4.2% per year [95% confidence interval (CI) -5.5% to -2.8%, P-value <.001), although S-PO-AKI did not (APC 0.9%, 95% CI -1.1 to 2.9%, P-value = .347). Similarly, the overall PO-AKI incidence decreased but S-PO-AKI did not, even after adjusting covariables.

The incidence of PO-AKI has decreased recently despite the increase in known risk factors; however, the incidence of S-PO-AKI has not decreased in recent years.

ClinicalTrials.gov Identifier: NCT05986474. Name of registry: Development of Synthetic Medical Data Generation Technology to Predict Postoperative Complications. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05986474. Date of registration: 14 August 2023. Date of enrollment of the first participant to the trial: 27 September 2022, retrospectively registered.

Acute kidney injury (AKI) is a frequent complication in critical patients, leading to a worse prognosis. Although its consequences are worse among critical patients, AKI is also associated with less favorable outcomes in non-critical patients. Therefore, understanding the magnitude of the problem in these patients is crucial, yet there is a scarcity of evidence in non-critical settings, especially in resource limited countries. Hence, the study aimed at determining the incidence and predictors of hospital acquired acute kidney injury (HAAKI) in non-critical medical patients who were admitted at a large tertiary hospital in Ethiopia.

A retrospective chart review study was conducted from September 25, 2022 to January 20, 2023 among 232 hospitalized non-critical medical patients admitted to St. Paul's Hospital Millennium Medical College between January 2020 and January 2022. The incidence of HAAKI was estimated using incidence density per total person day (PD) observation of the study participants. To identify predictors of HAAKI, a log binomial regression model was fitted at a p value of ≤0.05. The magnitude of association was measured using adjusted relative risk (ARR) with its 95% CI.

During the median follow-up duration of 11 days (IQR, 6-19 days), the incidence of HAAKI was estimated to be 6.0 per 100 PD (95% CI = 5.5 to 7.2). Significant predictors of HAAKI were found to be having type 2 diabetes mellitus (ARR = 2.36, 95% CI = 1.03, 5.39, p-value=0.042), and taking vancomycin (ARR = 3.04, 95% CI = 1.38, 6.72, p-value=0.006) and proton pump inhibitors (ARR = 3.80, 95% CI = 1.34,10.82, p-value=0.012).

HAAKI is a common complication in hospitalized non-critical medical patients, and is associated with a common medical condition and commonly prescribed medications. Therefore, it is important to remain vigilant in the prevention and timely identification of these cases and to establish a system of rational prescribing habits.

Sepsis and acute kidney injury (AKI) are two major public health concerns that contribute significantly to illness and death worldwide. Early diagnosis and prompt treatment are essential for achieving the best possible outcomes. To date, there are no specific clinical, imaging, or biochemical indicators available to diagnose sepsis, and diagnosis of AKI based on the KDIGO criterion has limitations. To improve the diagnostic process for sepsis and AKI, it is essential to continually evolve our understanding of these conditions. Delays in diagnosis and appropriate treatment can have serious consequences. Sepsis and AKI often occur together, and patients with kidney dysfunction are more prone to developing sepsis. Therefore, identifying potential biomarkers for both conditions is crucial. In this review, we talk about the main biomarkers that evolve the diagnostic of sepsis and AKI, namely neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and cell-free DNA.

Acute kidney injury (AKI) is a common critical illness in hospitalized patients, characterized by a rapid decline in kidney function over a short period, which can seriously endanger the patient's life. Currently, there is a lack of precise and universal AKI diagnostic biomarkers in clinical practice. In this study, weighted gene coexpression network analysis (WGCNA), differential expression analysis, univariate and multivariate logistic regression analyses, receiver operating characteristic (ROC) curves, and immune cell infiltration were performed to identify apoptosis-related biomarkers that can be used for AKI diagnosis. Three core apoptosis-related genes (ARGs), CBFB, EGF and COL1A1, were identified as AKI biomarkers. More importantly, an apoptosis-related signature containing three hub ARGs was validated as a diagnostic model. The hub genes exhibited good correlations with glomerular filtration rate (GFR) and serum creatinine (SCr) in the Nephroseq kidney disease database. Additionally, CIBERSORT immune infiltration analysis indicated that these core ARGs may affect immune cell recruitment and infiltration in AKI patients. Subsequently, we investigated the alteration of the expression levels of three core ARGs in AKI samples using single-cell RNA sequencing analysis and analyzed the cell types that mainly expressed these ARGs. More importantly, the expression of core ARGs was validated in folic acid- and cisplatin-induced AKI mouse models. In summary, our study identified three diagnostic biomarkers for AKI, explored the roles of ARGs in AKI progression and provided new ideas for the clinical diagnosis and treatment of AKI.

Acute renal failure (ARF) is a huge threat to the lives of most patients in intensive care units, and there is currently no satisfactory treatment strategy. SRY-box transcription factor 4 (SOX4) plays a key role in the development of various diseases, but its effect on ARF is unknown. Therefore, this study aimed to explore the relationship between SOX4 and ARF. Blood samples were collected from 20 ARF patients and 20 healthy volunteers. We also established an ARF rat model by excising the right kidney and ligating the left renal artery, and SOX4 knockdown in ARF rats was achieved down by means of lentiviral infection. Subsequently, we used quantitative polymerase chain reaction and western bolt assays to detect the expression levels of SOX4 and nuclear factor-κB (NF-κB) signaling pathway-related proteins in human blood or rat renal tissue and hematoxylin and eosin and terminal deoxynucleotidyl transferase (TdT) 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling staining to observe the pathological changes and apoptosis of renal tissue. Enzyme-linked immunosorbent assay and biochemical kits were used to measure the levels of renal function-related indicators (blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin) and inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha), as well as changes in oxidative stress-related indicators (malondialdehyde [MDA], superoxide dismutase [SOD], and reactive oxygen species [ROS]) in rat serum. SOX4 expression levels in blood samples from ARF patients and renal tissue from ARF rats were significantly higher compared with those in healthy volunteers and control rats, respectively. ARF model rats displayed the typical ARF phenotype, while SOX4 silencing significantly improved pathological injury and apoptosis of renal tissue in ARF rats. Moreover, SOX4 silencing significantly inhibited increased levels of renal function-related indicators and inflammatory factors and reduced the level of excessive oxidative stress (MDA and ROS were upregulated, and SOD was downregulated) in ARF rats. SOX4 also reduced the activity of the NF-κB signaling pathway in ARF samples. Thus, SOX4 knockdown may reduce oxidative stress, the inflammatory response, and apoptosis by reducing the activity of the NF-κB signaling pathway, thereby improving renal injury in ARF rats.

The adoption of the 2021 CKD-EPIcr equation for glomerular filtration rate (GFR) estimation provided a race-free eGFR calculation. However, the discriminative performance for AKI risk has been rarely validated. We aimed to evaluate the differences in acute kidney injury (AKI) prediction or reclassification power according to the three eGFR equations.

We performed a retrospective observational study within a tertiary hospital from 2011 to 2021. Acute kidney injury was defined according to KDIGO serum creatinine criteria. Glomerular filtration rate estimates were calculated by three GFR estimating equations: 2009 and 2021 CKD-EPIcr, and EKFC. In three equations, AKI prediction performance was evaluated with area under receiver operator curves (AUROC) and reclassification power was evaluated with net reclassification improvement analysis.

A total of 187,139 individuals, including 27,447 (14.7%) AKI and 159,692 (85.3%) controls, were enrolled. In the multivariable regression prediction model, the 2009 CKD-EPIcr model (continuous eGFR model 2, 0.7583 [0.755-0.7617]) showed superior performance in AKI prediction to the 2021 CKD-EPIcr (0.7564 [0.7531-0.7597], < 0.001) or EKFC model in AUROC (0.7577 [0.7543-0.761], < 0.001). Moreover, in reclassification of AKI, the 2021 CKD-EPIcr and EKFC models showed a worse classification performance than the 2009 CKD-EPIcr model. (- 7.24 [- 8.21-- 6.21], - 2.38 [- 2.72-- 1.97]).

Regarding AKI risk stratification, the 2009 CKD-EPIcr equation showed better discriminative performance compared to the 2021 CKD-EPIcr equation in the study population.

To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.

Acute kidney injury (AKI) is caused by a sudden loss of renal function, resulting in the build-up of waste products and a significant increase in mortality and morbidity. It is commonly diagnosed in critically ill patients, with its occurrence estimated at up to 50% in patients hospitalized in the intensive critical unit. Despite ongoing efforts, the death rate associated with AKI has remained high over the past half-century. Thus, it is critical to investigate novel therapy options for preventing the epidemic. Many studies have found that inflammation and Toll-like receptor-4 (TLR-4) activation have a significant role in the pathogenesis of AKI. Noteworthy, challenges in the search for efficient pharmacological therapy for AKI have arisen due to the multifaceted origin and complexity of the clinical history of people with the disease. This article focuses on kidney injury's epidemiology, risk factors, and pathophysiological processes. Specifically, it focuses on the role of TLRs especially type 4 in disease development.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.

Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing. This study in US Veterans with diabetes mellitus and proteinuria demonstrated an association between ACEi/ARB use and lower mortality. This association was more pronounced with earlier post-AKI ACEi/ARB use and was not meaningfully affected by initiating ACEis/ARBs before versus after recovery from AKI.

Optimal use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) after AKI is uncertain.

Using data derived from electronic medical records, we sought to estimate the association between ACEi/ARB use after AKI and mortality in US military Veterans with indications for such treatment (diabetes and proteinuria) while accounting for AKI recovery. We used ACEi/ARB treatment after hospitalization with AKI (defined as serum creatinine ≥50% above baseline concentration) as a time-varying exposure in Cox models. The outcome was all-cause mortality. Recovery was defined as return to ≤110% of baseline creatinine. A secondary analysis focused on ACEi/ARB use relative to AKI recovery (before versus after).

Among 54,735 Veterans with AKI, 31,146 deaths occurred over a median follow-up period of 2.3 years. Approximately 57% received an ACEi/ARB <3 months after hospitalization. In multivariate analysis with time-varying recovery, post-AKI ACEi/ARB use was associated with lower risk of mortality (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.72 to 0.77). The association between ACEi/ARB use and mortality varied over time, with lower mortality risk associated with earlier initiation ( P for interaction with time <0.001). In secondary analysis, compared with those with neither recovery nor ACEi/ARB use, risk of mortality was lower in those with recovery without ACEi/ARB use (aHR, 0.90; 95% CI, 0.87 to 0.94), those without recovery with ACEi/ARB use (aHR, 0.69; 95% CI, 0.66 to 0.72), and those with ACEi/ARB use after recovery (aHR, 0.70; 95% CI, 0.67 to 0.73).

This study demonstrated lower mortality associated with ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI, regardless of recovery. Results favored earlier ACEi/ARB initiation.

This study aims to investigate the factors affecting development of acute kidney injury (AKI) in patients with severe hypothyroidism.

This retrospective observational study involved patients with primary hypothyroidism and thyroid stimulating hormone (TSH) levels of more than 50 mIU/L at their review in the endocrinology outpatient clinic, between January 2015 and April 2021. Factors affecting the development of AKI were examined by logistic regression analysis.

A total of 100 patients, 20 (11 male (M), 9 female (F)) in the AKI (case) group and 80 (23 M, 57 F) patients in control group, were included in our study. The median age of the case group (56 years, interquartile range (IQR) 44.3-68.5) was significantly higher than the control group (49 years, IQR 32.3-60; p = 0.027), and the ratio of males to females was significantly higher in the case group (p = 0.001). Multivariate logistic regression analyses showed that hypothyroidism diagnosed after the age of 60 years (odds ratio (OR) 59.674, 95% confidence intervals (CI) 5.955-598.031; p = 0.001), free triiodothyronine (FT3) < 1.3 pg/mL (OR 17.151, 95% CI 2.491-118.089; p = 0.004) and creatine kinase (CK) > 1000 U/L (OR 1.522, 95% CI 1.602-82.848; p = 0.015) were predictors for the development of AKI in patients with severe hypothyroidism.

We recommend close follow-up and monitoring of patients with AKI caused by severe hypothyroidism if patients who are diagnosed at age > 60 years, CK > 1000 U/L or FT3 < 1.3 pg/mL.

Published works have reported the impact of a nephrologist intervention on outcomes for patients with hospital-acquired acute kidney injury (HA-AKI), however little is known about the clinical characteristics of patients with community-acquired acute kidney injury (CA-AKI) and the impact of nephrology interventions on outcomes in these patients.

A retrospective study on all adult patients admitted to a large tertiary care hospital in 2019 who were identified to have CA-AKI were followed from hospital admission to discharge. Clinical characteristics and outcomes of these patients were analysed by receipt of nephrology consultation. Statistical analysis included descriptive, simple Chi-squared/Fischer Exact test, independent samples t-test/Mann-Whitney U test and logistic regression.

182 patients fulfilled the study inclusion criteria. Mean age was 75 ± 14 years, 41% were female, 64% had stage 1 AKI on admission, 35% received nephrology input and 52% had achieved recovery of kidney function by discharge. Higher admission and discharge serum creatinine (SCr) (290.5 vs 159 and 173 vs 109 µmol/L respectively, p =  < 0.001), and younger age (68 vs 79, p =  < 0.001) were associated with nephrology consultations, whilst length of hospitalisation, mortality and rehospitalisation rates were not significantly different between the two groups. At least 65% were recorded to be on at least one nephrotoxic medication.

Our findings provide a snapshot of current practice where close to two-thirds of hospitalised patients with CA-AKI had a mild form of AKI that was associated with good clinical outcomes. While higher SCr on admission and younger age were predictors of receiving a nephrology consultation, nephrology consultations did not have any impact on outcomes.

In older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI.

We used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities.

Out of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1-29.6); higher for men than women (33.9 (29.5-38.7) vs. 21.2 (18.1-24.6)). IR (CI) were lowest for persons aged 70-75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities.

AKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

AKI is associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19); however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied.

Electronic health record data were obtained from 53 health systems in the United States in the National COVID Cohort Collaborative. We selected hospitalized adults diagnosed with COVID-19 between March 6, 2020, and January 6, 2022. AKI was determined with serum creatinine and diagnosis codes. Time was divided into 16-week periods (P1-6) and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality.

Of a total cohort of 336,473, 129,176 (38%) patients had AKI. Fifty-six thousand three hundred and twenty-two (17%) lacked a diagnosis code but had AKI based on the change in serum creatinine. Similar to patients coded for AKI, these patients had higher mortality compared with those without AKI. The incidence of AKI was highest in P1 (47%; 23,097/48,947), lower in P2 (37%; 12,102/32,513), and relatively stable thereafter. Compared with the Midwest, the Northeast, South, and West had higher adjusted odds of AKI in P1. Subsequently, the South and West regions continued to have the highest relative AKI odds. In multivariable models, AKI defined by either serum creatinine or diagnostic code and the severity of AKI was associated with mortality.

The incidence and distribution of COVID-19-associated AKI changed since the first wave of the pandemic in the United States.

This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_08_08_CJN0000000000000192.mp3.

Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU.

Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury?

This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission.

Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy.

VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

There is increasing global incidence of acute kidney injury (AKI) and significant short- and long-term impacts on patients.

To determine incidence and outcomes of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among inpatients in the Australian healthcare setting using modern health information systems.

A retrospective cohort study of adult patients admitted to a quaternary hospital in Melbourne, Australia, between 1 January 2018 and 31 December 2019 utilising an electronic data warehouse. Participants included adult patients admitted for >24 h who had more than one serum creatinine level recorded during admission. Kidney transplant and maintenance dialysis patients were excluded. Main outcomes measured included AKI, as classified by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, hospital length of stay and 30-day mortality.

A total of 6477 AKI episodes was identified across 43 791 admissions. Of all AKI episodes, 77% (n = 5011), 15% (n = 947) and 8% (n = 519) were KDIGO stage 1, 2 and 3 respectively. HA-AKI accounted for 55.9% episodes. Patients required intensive care unit admission in 22.7% (n = 1100) of CA-AKI and 19.3% (n = 935) of HA-AKI, compared with 7.5% (n = 2815) of patients with no AKI (P = 0.001). Patients with AKI were older with more co-morbidities, particularly chronic kidney disease (CKD). Length of stay was longer in CA-AKI (8.8 days) and HA-AKI (11.8 days) compared with admissions without AKI (4.9 days; P < 0.001). Thirty-day mortality was increased with CA-AKI (10.2%) and HA-AKI (12.8%) compared with no AKI (3.7%; P < 0.001).

The incidence of AKI detected by the electronic data warehouse was higher than previously reported. Patients who experienced AKI had greater morbidity and mortality. CKD was an important risk factor for AKI in hospitalised patients.

Patients hospitalized with AKI have higher subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality than their counterparts without AKI, but these higher risks may be due to differences in prehospitalization patient characteristics, including the baseline level of estimated glomerular filtration rate (eGFR), the rate of prior eGFR decline, and the proteinuria level, rather than AKI itself.

Among 2177 adult participants in the Chronic Renal Insufficiency Cohort study who were hospitalized in 2013-2019, we compared subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality between those with serum creatinine-based AKI (495 patients) and those without AKI (1682 patients). We report both crude associations and associations sequentially adjusted for prehospitalization characteristics including eGFR, eGFR slope, and urine protein-creatinine ratio (UPCR).

Compared with patients hospitalized without AKI, those with hospitalized AKI had lower eGFR prehospitalization (42 versus 49 ml/min per 1.73 m 2 ), faster chronic loss of eGFR prehospitalization (-0.84 versus -0.51 ml/min per 1.73 m 2 per year), and more proteinuria prehospitalization (UPCR 0.28 versus 0.16 g/g); they also had higher prehospitalization systolic BP (130 versus 127 mm Hg; P < 0.01 for all comparisons). Adjustment for prehospitalization patient characteristics attenuated associations between AKI and all three outcomes, but AKI remained an independent risk factor. Attenuation of risk was similar after adjustment for absolute eGFR, eGFR slope, or proteinuria, individually or in combination.

Prehospitalization variables including eGFR, eGFR slope, and proteinuria confounded associations between AKI and adverse cardiovascular outcomes, but these associations remained significant after adjusting for prehospitalization variables.

Cisplatin is widely used as an anti-neoplastic agent but is limited by its nephrotoxicity. The use of mesenchymal stem cells (MSCs) for the management of acute kidney injury (AKI) represents a new era in treatment but effective homing of administered cells is needed. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on cisplatin-induced AKI in rats after directed migration by electric field (EF). Forty-eight adult male albino rats were equally classified into four groups: control, cisplatin-treated, cisplatin plus BM-MSCs, and cisplatin plus BM-MSCs exposed to EF. Serum levels of IL-10 and TNF-α were measured by ELISA. Quantitative real-time PCR analysis for gene expression of Bcl2, Bax, caspase-3, and caspase-8 was measured. Hematoxylin and eosin (H&E) staining, periodic acid Schiff staining, and immunohistochemical analysis were also done. MSC-treated groups showed improvement of kidney function; increased serum levels of IL-10 and decreased levels of TNF-α; and increased mRNA expression of Bcl2 and decreased expression of Bax, caspase-3, and caspase-8 proteins comparable to the cisplatin-injured group. EF application increased MSCs homing with significant decrease in serum urea level and caspase-3 gene expression together with significant increase in Bcl2 expression than occurred in the MSCs group. Restoration of normal kidney histomorphology with significant decrease in immunohistochemical expression of caspase-3 protein was observed in the BM-MSCs plus EF group compared to the BM-MSCs group. EF stimulation enhanced the MSCs homing and improved their therapeutic potential on acute cisplatin nephrotoxicity.

BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of biomarkers in murine models of repair and atrophy after ischemic reperfusion injury (IRI).RESULTSAfter 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney atrophy in mice after IRI.CONCLUSIONSustained tissue injury and inflammation, and slower restoration of tubular health, are associated with higher risk of kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.FUNDINGNIH and NIDDK (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, K01DK120783, and R01DK093771).

AKI is a major clinical complication leading to high mortality, but intensive research over the past decades has not led to targeted preventive or therapeutic measures. In rodent models, caloric restriction (CR) and transient hypoxia significantly prevent AKI and a recent comparative transcriptome analysis of murine kidneys identified kynureninase (KYNU) as a shared downstream target. The present work shows that KYNU strongly contributes to CR-mediated protection as a key player in the de novo nicotinamide adenine dinucleotide biosynthesis pathway. Importantly, the link between CR and NAD+ biosynthesis could be recapitulated in a human cohort.

Clinical practice lacks strategies to treat AKI. Interestingly, preconditioning by hypoxia and caloric restriction (CR) is highly protective in rodent AKI models. However, the underlying molecular mechanisms of this process are unknown.

Kynureninase (KYNU) knockout mice were generated by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and comparative transcriptome, proteome and metabolite analyses of murine kidneys pre- and post-ischemia-reperfusion injury in the context of CR or ad libitum diet were performed. In addition, acetyl-lysin enrichment and mass spectrometry were used to assess protein acetylation.

We identified KYNU as a downstream target of CR and show that KYNU strongly contributes to the protective effect of CR. The KYNU-dependent de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway is necessary for CR-associated maintenance of NAD+ levels. This finding is associated with reduced protein acetylation in CR-treated animals, specifically affecting enzymes in energy metabolism. Importantly, the effect of CR on de novo NAD+ biosynthesis pathway metabolites can be recapitulated in humans.

CR induces the de novo NAD+ synthesis pathway in the context of IRI and is essential for its full nephroprotective potential. Differential protein acetylation may be the molecular mechanism underlying the relationship of NAD+, CR, and nephroprotection.

Acute kidney injury (AKI) is common. An episode of AKI may modify the risk of developing kidney stones by potential long-term effects on urine composition. We aimed to investigate the association between AKI and the risk of kidney stone presentations.

The retrospective cohort study used patient data (1 January 2008-31 December 2017), from an Australian Local Health District, which included AKI diagnosis, demographics, comorbidities and kidney stone admissions. Time-varying Cox proportional hazards and propensity-matched analysis were used to determine the impact of AKI on the risk of kidney stones. To address possible population inhomogeneity in comparisons between no AKI and hospitalized AKI, sub-group analysis was done comparing inpatient and outpatient AKI versus no AKI, to assess consistency of association with future stones. Sensitivity analysis was undertaken to capture the impact of a known AKI status and AKI severity.

Out of 137 635 patients, 23 001 (17%) had an AKI diagnosis and 2295 (2%) had kidney stone presentations. In the unadjusted analysis, AKI was associated with kidney stones, with AKI used as a time-varying exposure, [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.16-1.50)]. Both inpatient-AKI (HR 1.19, 95% CI 1.01-1.39) and outpatient-AKI (HR 1.59, 95% CI 1.30-1.94) were significantly associated with future stones compared to no AKI subjects. This association persisted in the adjusted analysis (HR 1.45, 95% CI 1.26-1.66), propensity-matched dataset (HR 1.67, 95% CI 1.40-1.99) and sensitivity analysis. There was a dose-response relationship with higher stages of AKI being associated with a greater risk of kidney stones.

In a large cohort of patients, AKI is associated with a greater risk of kidney stones, which increases with higher stages of AKI. This association should be examined in other cohorts and populations for verification.

The occurrence of acute and chronic kidney diseases has been rising in the last decades. Although drug use is a common risk factor for impaired kidney function, changes in utilization of potential nephrotoxic drugs have received little attention.

To describe temporal trends in the utilization of potentially nephrotoxic drugs in Denmark between 1999 and 2021.

Specific drugs known or suspected to be nephrotoxic were identified in the literature. Data on the sold defined daily doses (DDDs) of potentially nephrotoxic drugs between 1999 and 2021 were retrieved using the Danish Register of Medical Product Statistics. Trends in sales of DDDs per 1000 inhabitants per day were tabulated and illustrated graphically.

From 1999 to 2021, the total sale of all selected drugs increased from 286 to 457 DDDs per 1000 inhabitants per day. The overall sale reached a preliminary peak in 2012 with 449 DDDs per 1000 inhabitants per day and remained relatively stable thereafter until reaching an all-time high in 2021 with 457 DDDs per 1000 inhabitants per day. Contributing with the majority in volume, sales of drugs inhibiting the renin-angiotensin-aldosterone system (RAAS) increased dramatically throughout the period. The same was observed for acetaminophen, methotrexate, tacrolimus, and iodinated contrast dye. In contrast, the sales of diuretics, acetylsalicylic acid, and ciclosporin decreased during the last decade of the study period.

From 1999-2021 considerable changes in sales of potentially nephrotoxic drugs were observed. In general, the sales increased, in volume predominated by RAAS inhibiting drugs. This increase in sales of potential nephrotoxins could contribute to an increasing occurrence of kidney diseases.

Arachidonoyl ethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are the most studies endocannabinoids. AEA and 2-AG are degraded by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes, respectively. FAAH and MAGL enzymes are widely expressed in many tissues, including kidney. Recent works have depicted that AEA and 2-AG levels are associated with ischemia-reperfusion (IR) injury. In this study, we investigated the effects of MAGL inhibitor KML29 and FAAH inhibitor URB597 against kidney IR injury.

The kidneys of the rats underwent ischemia for 45 min and then reperfusion for 24 h. KML29 and URB597 were administered intraperitoneally with kidney IR to two different treatment groups.

IR application increased serum blood urea nitrogen (BUN), creatinine (Cre), interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels, while these parameters were decreased following KML29 and URB597 administration. KML29 and URB597 administration also reduced the increased toll-like receptor-4 (TRL-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), caspase-3 levels and histopathological damage in kidney tissue.

Our results reveal that MAGL inhibitor KML29 and FAAH inhibitor URB597 have a protective effect on kidney IR injury by preventing apoptosis and inflammation. Inhibition of MAGL and FAAH may be a new therapeutic strategy to prevent kidney IR injury.

The concept of acute kidney disease (AKD) implies kidney damage that results in a significant decrease in glomerular filtration rate, including acute kidney injury (AKI), but that is not persistent enough to meet the criteria of chronic kidney disease (CKD). While a few studies have shown associations between AKD and the risk of adverse outcomes, there is still a lack of evidence from resource-limited settings.

All hospitalized patients at the study hospital during 2017 were retrospectively reviewed. Diagnosis of AKI, AKD, and CKD was based on the diagnostic algorithm proposed by KDIGO. Patients were followed up for 2 years to determine their risks of mortality, development of CKD, and progression of pre-existing CKD.

A total of 9800 patients were included in the analysis, 26.1% of whom had pre-existing CKD, while AKD without AKI was found in 8% and 7% of individuals with and without pre-existing CKD, respectively. Patients with AKD without AKI were associated with higher in-hospital mortality than those without pre-existing CKD [adjusted hazard ratio (aHR) of 2.50; 95% CI 1.43, 4.37] and with pre-existing CKD (aHR 1.79; 95% CI 1.16, 2.76). The incidence of new CKD was higher in the group of AKD without AKI than in the AKI group (34.8 vs. 14.7%).

In a resource-limited setting, AKD is associated with short- and long-term mortality and CKD progression, especially in individuals with pre-existing CKD.

Sepsis remains the most common cause of acute kidney injury (AKI) and is associated with a high mortality. This study aims to identify laboratory, clinical and demographic factors that are associated with the different stages of AKI in sepsis.

We studied patients >18 years who met Sepsis-3 criteria between July 10, 2009 and September 7, 2019 using ordinal logistic regression to determine the factors associated with different stages of AKI. Sensitivity analyses for development of any stage vs no AKI and, separately, the factors associated with receipt of kidney replacement therapy were also done.

Of 31,228 patients meeting Sepsis-3 criteria, 4684 (15%) developed AKI. Of the AKI patients, 53% were KDIGO stage 1, 9% stage 2, and 37% stage 3, with 27% of AKI patients receiving kidney replacement therapy (Stage 3b). Several comorbidities, mechanical ventilation, and pre-sepsis creatinine levels were associated with AKI occurrence and severity. Positive blood culture was associated with a higher risk (OR 1.10 [1.06, 1.15], p < 0.001), while positive respiratory, urine, and wound cultures were associated with lower risks of developing AKI and with lower severity.

Presepsis creatinine levels, mechanical ventilation, comorbidities, and positive blood cultures were associated with AKI.

All cell types must maintain homeostasis under periods of stress. To prevent the catastrophic effects of stress, all cell types also respond to stress by inducing protective pathways. Within the cell, the endoplasmic reticulum (ER) is exquisitely stress-sensitive, primarily because this organelle folds, posttranslationally processes, and sorts one-third of the proteome. In the 1990s, a specialized ER stress response pathway was discovered, the unfolded protein response (UPR), which specifically protects the ER from damaged proteins and toxic chemicals. Not surprisingly, UPR-dependent responses are essential to maintain the function and viability of cells continuously exposed to stress, such as those in the kidney, which have high metabolic demands, produce myriad protein assemblies, continuously filter toxins, and synthesize ammonia. In this mini-review, we highlight recent articles that link ER stress and the UPR with acute kidney injury (AKI), a disease that arises in ∼10% of all hospitalized individuals and nearly half of all people admitted to intensive care units. We conclude with a discussion of prospects for treating AKI with emerging drugs that improve ER function.