Increased Risk Of Acute Kidney Injury Research Articles

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Intraoperative fluid management is not predictive of AKI in major pancreatic surgery: a retrospective cohort study

BackgroundPancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery.MethodsThis retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018–December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes.ResultsAKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8–35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4–16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality.ConclusionIn this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study

BackgroundAging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. MethodsA case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1–7 days and 181–187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. ResultsThe study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70–4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47–5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15–26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82–66.64). ConclusionsNSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

Association between intraoperative hyperglycemia/hyperlactatemia and acute kidney injury following on-pump cardiac surgery: a retrospective cohort study.

Despite the long-lasting notion about the substantial contribution of intraoperative un-stabilization of homeostasis factors on the incidence on acute kidney injury (AKI), the possible influence of intraoperative glucose or lactate management, as a modifiable factor, on the development of AKI remains inconclusive. To investigated the relationship between intraoperative hyperglycemia, hyperlactatemia, and postoperative AKI in cardiac surgery. A retrospective cohort study was conducted among 4,435 adult patients who underwent on-pump cardiac surgery from July 2019 to March 2022. Intraoperative hyperglycemia and hyperlactatemia were defined as blood glucose levels >10 mmol/L and lactate levels >2 mmol/L, respectively. The primary outcome was the incidence of AKI. All statistical analyses, including t tests, Wilcoxon rank sum tests, chi-square tests, Fisher's exact test, Kolmogorov-Smirnov test, logistic regression models, subgroup analyses, collinearity analysis, and receiver operating characteristic analysis, were performed using the statistical software program R version 4.1.1. Among the 4,435 patients in the final analysis, a total of 734 (16.55%) patients developed AKI after on-pump cardiac surgery. All studied intraoperative metabolic disorders was associated with increased AKI risk, with most pronounced odds ratio (OR) noted for both hyperglycemia and hyperlactatemia were present intraoperatively [adjusted OR 3.69, 95% confidence intervals (CI) 2.68-5.13, p < 0.001]. Even when hyperglycemia or hyperlactatemia was present alone, the risk of postoperative AKI remained elevated (adjusted OR 1.97, 95% CI 1.50-2.60, p < 0.001). The presence of intraoperative hyperglycemia and hyperlactatemia may be associated with postoperative acute kidney injury (AKI) in patients undergoing on-pump cardiac surgery. Proper and timely interventions for these metabolic disorders are crucially important in mitigating the risk of AKI.

The risk of acute kidney injury in colorectal cancer survivors: an english population-based matched cohort study

BackgroundColorectal cancer survival has improved in recent decades but there are concerns that survivors may develop kidney problems due to adverse effects of cancer treatment or complications of the cancer itself. We quantified the risk of acute kidney injury (AKI) in colorectal cancer survivors compared to people with no prior cancer.MethodsRetrospective matched cohort study using electronic health record primary care data from the Clinical Practice Research Datalink GOLD linked to hospital data in England (HES-APC). Individuals with colorectal cancer between 1997–2018 were individually matched on age, sex, and GP practice to people with no prior cancer. We used Cox models to estimate hazard ratios for an incident hospital diagnosis of AKI in colorectal cancer survivors compared to individuals without cancer, overall and stratified by time since diagnosis adjusted for other individual-level factors (adj-HR).ResultsTwenty thousand three hundred forty colorectal cancer survivors were matched to 100,058 cancer-free individuals. Colorectal cancer survivors were at increased risk of developing AKI compared to people without cancer (adj-HR = 2.16; 95%CI 2.05–2.27). The HR was highest in the year after diagnosis (adj-HR 7.47, 6.66–8.37), and attenuated over time, but there was still increased AKI risk > 5 years after diagnosis (adj-HR = 1.26, 1.17–1.37). The association between colorectal cancer and AKI was greater for younger people, men, and those with pre-existing chronic kidney disease.ConclusionsColorectal cancer survivors were at increased risk of AKI for several years after cancer diagnosis, suggesting a need to prioritise monitoring, prevention, and management of kidney problems in this group of cancer survivors.

Association between Premorbid Renin-Angiotensin-Aldosterone System Blockade and the Risk of Acute Kidney Injury in Critically Ill Patients.

Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are commonly used for hypertension and cardiovascular diseases. However, whether their use increases the risk of acute kidney injury (AKI) and should be discontinued during acute illness remains controversial. This retrospective study enrolled 952 dialysis-free patients who were admitted to intensive care units (ICUs) between 2015 and 2017, including 476 premorbid long-term (> 1 month) ACEi/ARB users. Propensity score matching was performed to adjust for age, gender, comorbidities, and disease severity. The primary endpoint was the occurrence of AKI during hospitalization, and the secondary endpoint was mortality or dialysis within 1 year. Compared with non-users, the ACEi/ARB users were not associated with an increased AKI risk during hospitalization [66.8% vs. 70.4%; hazard ratio (HR): 1.13, 95% confidence interval (CI): 0.97-1.32, p = 0.126]. However, the ACEi/ARB users with sepsis (HR: 1.29, 95% CI: 1.04-1.60, p = 0.021) or hypotension (HR: 1.21, 95% CI: 1.02-1.14, p = 0.034) were found to have an increased AKI risk in subgroup analysis. Nevertheless, compared with the non-users, the ACEi/ARB users were associated with a lower incidence of mortality or dialysis within 1 year (log-rank p = 0.011). Premorbid ACEi/ARB usage did not increase the incidence of AKI, and was associated with a lower 1-year mortality and dialysis rate in patients admitted to ICUs. Regarding the results of subgroup analysis, renin-angiotensin-aldosterone system blockade may still be safe and beneficial in the absence of sepsis or circulation failure. Further large-scale studies are needed to confirm our findings.

Biomarkers in acute kidney injury - the search for the "renal troponin"

The prognosis of acute kidney injury (AKI) is poor, partly due to significant limitations of the current functional marker-based definition, which results in too small therapeutic window to treat AKI. Therefore, AKI biomarkers are needed to detect AKI earlier. Classical filtration markers are serum creatinine and cystatin C, which, however, show clear limitations for AKI prediction. Early AKI markers are divided into damage markers and "stress" markers. The latter indicate a pre-injury phase with increased AKI risk. The one "renal troponin" will probably never be found because of heterogeneous renal structure and heterogeneous causes of AKI. However, AI-based models with inclusion of biomarkers could significantly improve AKI prediction and prognosis.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

Acute Kidney Injury in Patients With Suspected Pulmonary Embolism: A Retrospective Study of the Incidence, Risk Factors, and Outcomes in a Tertiary Care Hospital in Saudi Arabia.

BackgroundPulmonary embolism (PE) is a known cause of morbidity and mortality. A diagnosis of PE is made by computed tomography pulmonary angiogram (CTPA) or a ventilation-perfusion (V/Q) scan. This study aimed to assess the incidence and predictors of acute kidney injury (AKI) in patients with suspected PE.MethodsThis study was a retrospective study including patients with suspected PE who underwent a CTPA and/or a V/Q scan from 2015 to 2020. The patients were grouped into CTPA or V/Q scan. Creatinine levels were obtained before and after the procedure. AKI was defined based on an increased serum creatinine by 0.3 mg/dL within 48 hours.ResultsA total of 752 patients were included in the study. The majority (n = 688) underwent a CTPA as a diagnostic modality in patients suspected to have pulmonary embolism (PE), and a V/Q scan was used in 73 patients. Of the 752 patients, there were eight patients who underwent both diagnostic modalities. PE was diagnosed in 121 (16.1%) patients. The incidence of AKI was observed in 15.8%. PE was suspected more frequently in the female group (n = 481, 64%), with a 50% reduction of AKI risk, compared with the male group (p-value = 0.004, OR = 0.522, 95% CI = 0.337-0.81). The presence of diabetes mellitus (DM) and hypertension (HTN) was associated with AKI (p-value < 0.001). Of the AKI group, 43 (36.1%) patients had malignancy. The presence of malignancy was a predictor of increased AKI risk (p-value = 0.014, OR = 1.74, 95% CI = 1.21-2.70). A small proportion (2.1%, n = 16) required dialysis. Patients who developed AKI had a 30-day mortality of 20.2% compared with 5.1% for the group without AKI.ConclusionIn our sample, clinicians suspected PE more frequently in the female group. The overall incidence rate of AKI in patients suspected of having PE was 16.1%. The presence of diabetes mellitus and hypertension was associated with AKI. However, DM and HTN were not predictors of AKI. The risk of AKI requiring dialysis was relatively low (2.1%). There was no relationship between the diagnostic modalities and PE, and AKI, suggesting that clinicians overestimate the fear of contrast-induced AKI (CI-AKI).

Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Could Provide Better Accuracy Than Creatinine in Predicting Acute Kidney Injury Development in Critically Ill Patients.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development (n = 98) or not (n = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not (p < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002–1.008), p < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.

MO368THE INCIDENCE AND RISK FACTORS FOR ACUTE KIDNEY INJURY IN PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A REAL-LIFE STUDY

Abstract Background and Aims The immune checkpoint inhibitors (ICIs) became a vital part of cancer treatment. The ICIs seem to be safer than chemotherapy for kidneys in clinical trials. However, recent observational studies from high-resource settings pointed out the possible underreporting of renal adverse events like acute kidney injury (AKI) in the clinical trials due to focusing only to the renal immune-related adverse events. Additionally, clinical trials generally enroll a fitter population with lesser comorbidities and include mostly treatment-naive patients making studies in real-life cohorts imperative for evaluating the AKI rates during ICI treatment. From these points, we aimed to evaluate the AKI rates and predisposing factors in ICI-treated patients. Method This retrospective study has evaluated the data of adult metastatic cancer patients treated with ICIs in Hacettepe University Cancer Center from 01.2014 to 12.2019. All patients other than the ones treated within the context of clinical trials or followed in other institutions after the first dose of ICIs were included. Baseline demographics, cancer types, patient weight and heights, ICI type and the number of cycles, serum creatinine and the estimated GFR values under treatment, regular medications, and comorbidities were recorded. AKI was defined by Kidney Disease Improving Global Outcomes criteria. The predisposing factors to AKI development were evaluated with the univariate and multivariate analyses. Results A total of 147 patients were included in the analyses. Median age was 61 [interquartile range (IQR) 51-67], and 69.4% of the patients were male. Patients were given a median of 8 (IQR 5-17) ICI cycles. Patients with melanoma (24.5%), non-small cell lung cancer (15%), and renal cell carcinoma (25.9%) comprised almost 2/3 of the cohort and 72.8% of the patients were treated with nivolumab. Hypertension was the most common comorbidity (38.1%), followed by chronic kidney disease (21.2%) and type 2 diabetes (19.7%). Median Charlson Comorbidity Index (CCI) was 8 (7-9). Median follow-up was 10.3 (IQR 6.3-19.4) months, and patients had median 9 (IQR 5-18) serum creatinine measurements. During the follow-up, 28 patients (19%) had at least one AKI episode with multiple AKI episodes in 3 patients (10.7%). The median time to AKI development was 2.53 (IQR 1.39-6.19) months. Almost all AKI events were mild (grade 1 or 2 in 27/28) and reversible (25/28). In univariate analyses, coronary artery disease (CAD) (p=&amp;lt;0.001), chronic kidney disease (CKD) (p=0.002), previous nephrectomy (p=0.015), iodinated contrast exposure in the week before immunotherapy (p=0.035), the use of renin-angiotensin-aldosterone system inhibitors (p=0.046) or proton pump inhibitors (PPI) (p=0.041) was associated with an increased AKI risk. The association between diabetes (p=0.067), higher CCI (9 vs. ≥9, p=0.107), baseline lactate dehydrogenase levels (p=0.177), and performance status (ECOG 0 vs. ≥1, p=0.235) and AKI risk did not reach statistical significance. In multivariate analyses, patients with CKD (OR: 3.719, 95% CI: 1.375- 10.057, p=0.010) or CAD (OR: 4.774, 95% CI: 1.803- 12.641, p=0.002) had increased AKI risk. Additionally, regular PPI use (OR: 2.734, 95% CI: .991- 7.542, p=0.052) had borderline statistical significance for AKI development. The development of AKI was not associated with decreased survival (HR: 0.726, 95% CI: 0.409-1.291, p=0.276). Conclusion In this study, we observed AKI development under ICIs in almost one in five cancer patients. The increased AKI rates in patients with CAD, CKD, or regular PPI use pointed out the need for better onco-nephrology collaboration in all ICI-treated patients, with a particular emphasis in these high-risk patients.

Non-steroidal anti-inflammatory drug-associated acute kidney injury: does short-term NSAID use pose a risk in hospitalized patients?

While renal risk associated with short-term use of non-steroidal anti-inflammatory drugs (NSAID) has been anecdotally documented, no conclusive evidence is available on the renal safety, especially among hospitalized patients with reduced renal function. This study is to evaluate the risk of acute kidney injury (AKI) associated with NSAID use in hospital. A retrospective matched cohort study utilizing electronic health records from two large academic tertiary-care hospitals was conducted. We defined AKI based on changes in SCr according to published AKI criteria. The hospital acquired AKI risk associated with inpatient NSAID use was assessed using a time-dependent Cox proportional hazard regression in pooled cohort as well as two sub cohorts stratified by baseline renal function. A total of 18,794 admissions were included in the final cohort. Of 9397 admissions exposed to NSAIDs, 7914 and 1483 admissions were in the "without" and "with baseline renal impairment" cohort, with the same number of matching non-exposed admissions in each of the stratified cohort. The AKI incidences were 6 and 22 events per 1000 patient-days in "without" and "with preexisting renal impairment" cohort, respectively. The adjusted analyses suggested that NSAID use increased AKI risk in patients with preexisting renal impairment (hazard ratio [HR]: 1.38 [1.04-1.83]) but not in the patients without preexisting renal impairment (HR: 0.83 [95% CIs: 0.63-1.08]) or in the pooled cohort (HR: 1.01 [95% CIs: 0.83-1.24]). Our findings suggested that NSAID use is associated with an increased risk of AKI in the hospitalized patients with preexisting renal impairment but the association is not statistically significant in those who have preserved renal function. Further randomized controlled trials are needed to validate these observational findings.

Higher total ultrafiltration volume during cardiopulmonary bypass-assisted infant cardiac surgery is associated with acute kidney injury and fluid overload.

Ultrafiltration (UF) is used for fluid removal during and after infant cardiopulmonary bypass (CPB) surgery to reduce fluid overload. Excessive UF may have the opposite of its intended effect, resulting in acute kidney injury (AKI), oliganuria, and fluid retention. This is a single-center, retrospective review of infants treated with conventional and/or modified UF during CPB surgery. UF volume was indexed to weight. AKI was defined using serum creatinine "Kidney Disease Improving Global Outcome (KDIGO)" criteria. Fluid balance was defined according to: [Formula: see text]. Peak fluid overload was determined on postoperative day 3. Multivariable logistic regression adjusted for multiple covariates was used to explore associations with UF, AKI, and fluid overload. Five hundred thirty subjects < 1 year of age underwent CPB-assisted congenital heart surgery with UF. Sixty-four (12%) developed postoperative AKI. On multivariable regression, higher indexed total UF volume was associated with increased AKI risk (OR 1.11, 95% CI=1.04-1.19, p = 0.003). UF volume > 119.9 mL/kg did not reduce peak fluid overload. Subjects with AKI took longer to reach a negative fluid balance (2 vs. 3 days, p = 0.04). Those with more complex surgery were at highest AKI risk (STAT 3 [25-75 percentile: 3-4] in AKI group versus STAT 3 [25-75 percentile: 2-4] in non-AKI group, p = 0.05). AKI was reduced in subjects undergoing more complex surgery and treated with UF volume < 119.9 mL/kg. Judicious use of UF in more complex congenital cardiac surgery reduces the risk of AKI.

Risk of Acute Kidney Injury andClostridioides difficileInfection With Piperacillin/Tazobactam, Cefepime, and Meropenem With or Without Vancomycin

Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an anti-pseudomonal beta-lactam (AP-BL). These agents vary in risk for adverse events, including acute kidney injury (AKI) and Clostrioides difficile infection (CDI). Studies have only examined these risks separately; thus, our objective was to evaluate AKI and CDI risks simultaneously with AP-BL in the same patient cohort. This retrospective cohort study included 789 200 Veterans Health Administration medical admissions from 1 July 2010 through 30 June 2016. The antimicrobials examined were vancomycin, cefepime, piperacillin/tazobactam, and meropenem. Cox proportional hazards regression was used to contrast risks for AKI and CDI across individual target antimicrobials and vancomycin combination therapies, including adjustment for known confounders. With respect to the base rate of AKI among patients who did not receive a target antibiotic (4.6%), the adjusted hazards ratios for piperacillin/tazobactam, cefepime, and meropenem were 1.50 (95% CI: 1.43-1.54), 1.00 (.95-1.05), 0.92 (.83-1.01), respectively. Co-administration of vancomycin increased AKI rates (data not shown). Similarly, against the base rate of CDI (0.7%), these ratios were 1.21 (1.07-1.36), 1.89 (1.62-2.20), and 1.99 (1.55-2.56), respectively. Addition of vancomycin had minimal impact on CDI rates (data not shown). Piperacillin/tazobactam increased AKI risk, which was exacerbated by concurrent vancomycin. Cefepime and meropenem increased CDI risk relative to piperacillin/tazobactam. Clinicians should consider the risks and benefits of AP-BL when selecting empiric regimens. Further well-designed studies evaluating the global risks of AP-BL and patient specific characteristics that can guide empiric selection are needed.

Evaluation of the Risk Factors for Acute Kidney Injury in Neonates Exposed to Antenatal Indomethacin.

Evidence is limited about important maternal and neonatal risk factors that affect neonatal renal function. The incidence of acute kidney injury (AKI) and identification of associated risk factors in neonates exposed to antenatal indomethacin was studied. A retrospective cohort of neonates exposed to antenatal indomethacin within 1 week of delivery was analyzed for development of AKI up to 15 days of life. Adjusted hazard ratios (HRs) and 95% CIs for AKI risk were calculated in time-dependent Cox proportional hazards models. Among 143 neonates with mean gestational age of 28.3 ± 2.4 weeks, AKI occurred in 62 (43.3%), lasting a median duration of 144 hours (IQR, 72-216 hours). Neonates with AKI had greater exposure to postnatal NSAIDs (48.4% vs 9.9%, p < 0.001) and inotropes (37.1% vs 3.7%, p < 0.001) compared with neonates without AKI. In multivariable-adjusted models, increased AKI risk was observed with antenatal indomethacin doses received within 24 to 48 hours (HR, 1.6; 95% CI, 1.28-1.94; p = 0.036) and <24 hours (HR, 2.33; 95% CI, 1.17-4.64; p = 0.016) prior to delivery. Further, postnatal NSAIDs (HR, 2.8; 95% CI, 1.03-7.61; p = 0.044), patent ductus arteriosus (HR, 4.04; 95% CI, 1.27-12.89; p = 0.018), and bloodstream infection (HR, 3.01; 95% CI, 1.37-6.60; p = 0.006) were associated significantly with increased risk of AKI following antenatal indomethacin. Neonates with AKI experienced more bloodstream infection, severe intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, and longer hospitalization. Extended risk of AKI with antenatal indomethacin deserves clinical attention among this population at an already increased AKI risk.

Clinical Experience with High-Dose Polymyxin B against Carbapenem-Resistant Gram-Negative Bacterial Infections-A Cohort Study.

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340–34,884 IU/kg/day) and 14 days (IQR, 7–28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6–13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00–1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03–4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.

Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes

BackgroundImmune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving...

Estimating the risk of acute kidney injury associated with use of diuretics and renin angiotensin aldosterone system inhibitors: A population based cohort study using the clinical practice research datalink

BackgroundThe risk of acute kidney injury (AKI) attributable to renin angiotensin aldosterone (RAAS) inhibitors and diuretics remains unclear.MethodsWe conducted a prospective cohort study using the Clinical Practice Research Datalink (2008–2015) linked to Hospital Episode Statistics – Admitted Patient Care and Office for National Statistics mortality data. Patients were included if they had one or more chronic diagnoses requiring medication. Exposed patients had a first ever prescription for RAAS inhibitors/diuretics during the study period. AKI risk associated with exposure was determined by multivariable Cox regression, propensity score-adjusted Cox regression and a prior event rate ratio (PERR) analysis.ResultsOne hundred forty thousand nine hundred fifty-two individuals were included. Increased AKI risk in the exposed group was demonstrated in both the multivariable and propensity score-adjusted cox regressions (HR 1.23 (95% CI 1.04–1.45) and HR 1.24 (1.05–1.47) respectively). The PERR analysis provided a similar overall hazard ratio with a wider confidence interval (HR 1.29 (0.94–1.63)). The increased AKI risk in the exposed group was present only in those receiving two or more antihypertensives. Absolute AKI risk was small.ConclusionsRAAS inhibitors/diuretics result in an increased risk of AKI. The absolute increase in AKI risk is small, however, and needs to be considered in the context of any potential benefits.

1244. Evaluation of Intraoperative Topical Vancomycin and the Incidence of Acute Kidney Injury

BackgroundThe use of intraoperative topical vancomycin (VAN) is a strategy aimed to prevent surgical site infections (SSI). Although there is evidence to support its efficacy in SSI prevention following orthopedic spine surgeries, data describing its safety, specifically acute kidney injury (AKI) risk, is limited. The purpose of this study was to determine the AKI incidence associated with intraoperative topical VAN.MethodsThis is a retrospective cohort study reviewing patient encounters where intraoperative topical VAN was administered from February 2018 to July 2018. All adult patients ( ≥18 years) that received topical VAN in the form of powder, beads, rods, paste, cement spacers, or unspecified topical routes were included. Patient encounters were excluded for AKI or renal replacement therapy (RRT) at baseline, ≤ 2 serum creatinine values drawn after surgery, and/or if irrigation was the only topical formulation given. The primary outcome was the percentage of patients who developed AKI after intraoperative topical VAN administration. AKI was defined as an increase in serum creatinine (SCr) ≥50% from baseline, an increase in SCr >0.5 from baseline, or0 if RRT was initiated after topical VAN was given. Secondary outcomes included analysis of AKI risk factors and SSI incidence. AKI risk factors were analyzed using a multivariable logistic regression model.ResultsA total of 589 patient encounters met study criteria. VAN powder was the most common formulation (40.9%), followed by unspecified topical routes (30.7%) and beads (9.9%%). Nonspinal orthopedic surgeries were the most common procedure performed 46.7%. The incidence of AKI was 8.7%. In a multivariable logistic regression model, AKI was associated with concomitant systemic VAN (OR 3.39, [3.39–6.22]) and total topical VAN dose. Each doubling of the topical dose was associated with increased odds of developing AKI (OR = 1.42, [1.08–1.86]). The incidence of SSI was 5.3%.ConclusionAKI rates associated with intraoperative topical VAN are comparable to that of systemic VAN. Total topical vancomycin dose and concomitant systemic VAN was associated with an increased AKI risk. Additional analysis is warranted to compare these patients to a similar population that did not receive topical VAN.Disclosures All authors: No reported disclosures.

Baseline Predictors of Renal Failure in Transcatheter Aortic Valve Implantation.

Acute kidney injury (AKI) post transcatheter aortic valve implantation (TAVI) is associated with worsened short- and long-term outcomes. We sought to identify significant baseline predictors of AKI and establish a high-risk group within patients enrolled in the multicenter SWISS-TAVI cohort. A total of 526 patients who underwent TAVI were included in our analysis. Patients on hemodialysis were excluded. Within the first week after valve implantation, fifty patients (9.5%) developed AKI. There was a significantly higher prevalence of diabetes mellitus in the AKI group (45% vs 28%; P=.02). The odds ratio (OR) for patients suffering from diabetes mellitus who developed AKI was 1.9 after multivariable binary regression analysis (95% confidence interval, 1.018-3.553; P=.04). Chronic kidney disease (CKD) stage ≥4 was more prevalent in the AKI group (26% vs 14%; P=.04). Every 1 mg/dL creatinine above normal level at baseline increased AKI risk by a factor of 1.6 (OR, 1.605; 95% CI, 1.111-2.319; P=.01). Age, gender, body mass index, history of dyslipidemia, and history of hypertension were similar between the groups. In the diabetic population of 155 patients (29.5%), AKI developed in 22 patients (14.2%), compared with the non-diabetic population of 370 patients (70.5%), where AKI developed in 27 patients (7.3%). In the diabetic population, an elevation by 1 mg/dL in baseline creatinine was an independent predictor of developing kidney injury (OR, 2.061; 95% CI, 1.154-3.683; P=.02, while in non-diabetic patients, neither baseline glomerular filtration rate, CKD grade, STS score, EuroScore II, ACEF score, nor procedural contrast usage were predictors of AKI. Diabetics with CKD stage ≥4 (as defined by the Kidney Disease: Improving Global Outcomes criteria) constitute a high-risk group for developing AKI after TAVI. In this high-risk subgroup, baseline creatinine in combination with amount of contrast agent used were strong risk factors for developing AKI. AKI in non-diabetics was less predictable by baseline characteristics.