Bromadiolone may cause severe acute kidney injury through severe disorder of coagulation: a case report.

BACKGROUND: Bromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning. CASE PRESENTATION: A 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient's serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient's kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL. CONCLUSION: Bromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Automated Electronic Alert for the Care and Outcomes of Adults With Acute Kidney Injury: A Randomized Clinical Trial.

Importance: Despite the expansion of published electronic alerts for acute kidney injury (AKI), there are still concerns regarding their effect on the clinical outcomes of patients. Objective: To evaluate the effect of the AKI alert combined with a care bundle on the care and clinical outcomes of patients with hospital-acquired AKI. Design, Setting, and Participants: This single-center, double-blind, parallel-group randomized clinical trial was conducted in a tertiary teaching hospital in Nanjing, China, from August 1, 2019, to December 31, 2021. The inclusion criteria were inpatient adults aged 18 years or older with AKI, which was defined using the Kidney Disease: Improving Global Outcomes creatinine criteria. Participants were randomized 1:1 to either the alert group or the usual care group, which were stratified by medical vs surgical ward and by intensive care unit (ICU) vs non-ICU setting. Analyses were conducted on the modified intention-to-treat population. Interventions: A programmatic AKI alert system generated randomization automatically and sent messages to the mobile telephones of clinicians (alert group) or did not send messages (usual care group). A care bundle accompanied the AKI alert and consisted of general, nonindividualized, and nonmandatory AKI management measures. Main Outcomes and Measures: The primary outcome was maximum change in estimated glomerular filtration rate (eGFR) within 7 days after randomization. Secondary patient-centered outcomes included death, dialysis, AKI progression, and AKI recovery. Care-centered outcomes included diagnostic and therapeutic interventions for AKI. Results: A total of 2208 patients (median [IQR] age, 65 [54-72] years; 1560 males [70.7%]) were randomized to the alert group (n = 1123) or the usual care group (n = 1085) and analyzed. Within 7 days of randomization, median (IQR) maximum absolute changes in eGFR were 3.7 (-6.4 to 19.3) mL/min/1.73 m2 in the alert group and 2.9 (-9.2 to 16.9) mL/min/1.73 m2 in the usual care group (P = .24). This result was robust in all subgroups in an exploratory analysis. For care-centered outcomes, patients in the alert group had more intravenous fluids (927 [82.6%] vs 670 [61.8%]; P < .001), less exposure to nonsteroidal anti-inflammatory drugs (56 [5.0%] vs 119 [11.0%]; P < .001), and more AKI documentation at discharge (560 [49.9%] vs 296 [27.3%]; P < .001) than patients in the usual care group. No differences were observed in patient-centered secondary outcomes between the 2 groups. Conclusions and Relevance: Results of this randomized clinical trial showed that the electronic AKI alert did not improve kidney function or other patient-centered outcomes but changed patient care behaviors. The findings warrant the use of a combination of high-quality interventions and AKI alert in future clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03736304.

A marked elevation in serum creatinine/cystatin C ratio may indicate pseudo-acute kidney injury due to urinary ascites: a case report and literature review.

BACKGROUND: Urinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes. CASE PRESENTATION: We reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient's kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites. CONCLUSIONS: This case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney protection. The current murine experiments show that IL-1R1 activation in the proximal tubule exacerbates toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorates AKI by restoring VEGFA-dependent endothelial cell viability. Using this information, future delivery strategies can maximize the protective effects of blocking IL-1R1 while mitigating unwanted actions of IL-1R1 manipulation. BACKGROUND: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. IL-1R1 is expressed on some myeloid cell populations and on multiple kidney cell lineages, including tubular and endothelial cells. Pharmacological inhibition of the IL-1R1 does not consistently protect the kidney from injury, suggesting there may be complex, cell-specific effects of IL-1R1 stimulation in AKI. METHODS: To examine expression of IL-1 and IL-1R1 in intrinsic renal versus infiltrating immune cell populations during AKI, we analyzed single-cell RNA sequencing (scRNA-seq) data from kidney tissues of humans with AKI and mice with acute aristolochic acid exposure. We then investigated cell-specific contributions of renal IL-1R1 signaling to AKI using scRNA-seq, RNA microarray, and pharmacological interventions in mice with IL-1R1 deletion restricted to the proximal tubule or endothelium. RESULTS: scRNA-seq analyses demonstrated robust IL-1 expression in myeloid cell populations and low-level IL-1R1 expression in kidney parenchymal cells during toxin-induced AKI. Our genetic studies showed that IL-1R1 activation in the proximal tubule exacerbated toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorated aristolochic acid-induced AKI by restoring VEGFA-dependent endothelial cell viability and density. CONCLUSIONS: These data highlight opposing cell-specific effects of IL-1 receptor signaling on AKI after toxin exposure. Disrupting pathways activated by IL-1R1 in the tubule, while preserving those triggered by IL-1R1 activation on endothelial cells, may afford renoprotection exceeding that of global IL-1R1 inhibition while mitigating unwanted actions of IL-1R1 blockade.

Severe fluctuation in mean perfusion pressure is associated with increased risk of in-hospital mortality in critically ill patients with central venous pressure monitoring: A retrospective observational study.

BACKGROUND: The mean perfusion pressure (MPP) was recently proposed to personalize tissue perfusion pressure management in critically ill patients. Severe fluctuation in MPP may be associated with adverse outcomes. We sought to determine if higher MPP variability was correlated with increased mortality in critically ill patients with CVP monitoring. METHODS: We designed a retrospective observational study and analyzed data stored in the eICU Collaborative Research Database. Validation test was conducted in MIMIC-III database. The exposure was the coefficient of variation (CV) of MPP in the primary analyses, using the first 24 hours MPP data recorded within 72 hours in the first ICU stay. Primary endpoint was in-hospital mortality. RESULTS: A total of 6,111 patients were included. The in-hospital mortality of 17.6% and the median MPP-CV was 12.3%. Non-survivors had significantly higher MPP-CV than survivors (13.0% vs 12.2%, p<0.001). After accounting for confounders, the highest MPP-CV in decile (CV > 19.2%) were associated with increased risk of hospital mortality compared with those in the fifth and sixth decile (adjusted OR: 1.38, 95% Cl: 1.07-1.78). These relationships remained remarkable in the multiple sensitivity analyses. The validation test with 4,153 individuals also confirmed the results when MPP-CV > 21.3% (adjusted OR: 1.46, 95% Cl: 1.05-2.03). CONCLUSIONS: Severe fluctuation in MPP was associated with increased short-term mortality in critically ill patients with CVP monitoring.

Acute kidney injury in advanced lung cancer patients treated with PD-1 inhibitors: a single center observational study.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy is now the stand of care for lung cancer. Due to the low incidence, the study of acute kidney injury (AKI) in lung cancer patients treated with ICIs was hardly reported. We focused on the incidence, characteristics, risk factors, and mortality of AKI in advanced lung cancer patients receiving PD-1 inhibitors. METHODS: We reviewed advanced lung cancer patients receiving PD-1 inhibitors between January 2018 to August 2020 at Jiangsu Province Hospital. Patients were followed up for 6 months. We used the logistic regression model to evaluate risk factors for AKI, and Kaplan-Meier method to assess the association between AKI and mortality. RESULTS: A total of 305 advanced lung cancer patients treated with PD-1 inhibitors. The median age was 64 years and 80.6% of patients were male. The incidence of AKI was 10.2%, and the incidence of ICI-AKI was 4.6%. Multivariate analysis showed that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 2.509; 95% CI 1.053-5.974) and renin-angiotensin-aldosterone system (RAAS) inhibitors (OR 2.656; 95% CI 1.091-6.466) were risk factors for AKI. In addition, concomitant use of NSAIDs (OR 5.170; 95% CI 1.087-24.595) and RAAS inhibitors (OR 5.921; 95% CI 1.871-18.737), and the occurrence of extra-renal immune-related adverse events (OR 4.726; 95% CI 1.462-15.280) were significantly associated with ICI-AKI. ICI-AKI was not associated with mortality while severe AKI was associated with higher risk of mortality. CONCLUSION: AKI is common in advanced lung cancer patients treated with PD-1 inhibitors. The characteristics and risk factors of ICI-AKI were similar to those previously reported in other solid organ malignancies treated with ICIs. Severe AKI may indicate higher mortality.

Increased mean perfusion pressure variability is associated with subsequent deterioration of renal function in critically ill patients with central venous pressure monitoring: a retrospective observational study.

PURPOSE: The mean perfusion pressure (MPP) was recently proposed to personalized management tissue perfusion pressure in critically ill patients. Increased MPP variability (MPPV) may be associated with organ injuries. Our objective was to determine if increased MPPV was associated with subsequent deterioration of renal function in critically ill patients. METHODS: We analyzed data stored in the eICU-CRD and MIMIC-IV databases. The exposure was MPPV, measured as the coefficient of variation (CV) using the MPP data of the first 24 h after first ICU admission. The primary endpoint was deterioration of renal function, defined as new-onset or progress of acute kidney injury between 24 and 72 h after ICU admission. RESULTS: The study population consisted of 8,590 patients from eICU-CRD and 6,723 patients from MIMIC-IV database. A total of 28.4% and 30.2% of the study population experienced deteriorated renal function, respectively. Patients with deteriorated renal function had significantly higher median MPP-CV compared with those without (12.2% vs 11.5% and 12.8% vs 12.5%, p < .001). In fully adjusted multivariate logistic models, higher MPP-CV (adjusted OR per 1-SD, 1.08; 95% CI, 1.02-1.13 and adjusted OR per 1-SD, 1.06; 95% CI, 1.00-1.12, respectively) was significantly associated with greater risk of primary endpoint. The pooled analyses showed heterogeneity in patients with cardiac surgery, medical sepsis and others. CONCLUSION: Increased MPPV was associated with an increased risk of subsequent deterioration of renal function in critically ill patients with central venous pressure monitoring. Maintaining stable MPP may reduce the risk of renal function deterioration.

Association of Serum 25 (OH) Vitamin D With Chronic Kidney Disease Progression in Type 2 Diabetes.

Objectives: Growing evidence demonstrated that vitamin D levels had been linked to type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in light of various extraskeletal effects. Therefore, the present study aimed to evaluate the association of 25-hydroxyvitamin D [25(OH)D] level with the clinicopathological features and CKD progression in T2DM. Methods: A total of 182 patients with T2DM with CKD stages 1 through 4 (G1-G4) were retrospectively included. Identification of the serum 25(OH)D level associated with CKD progression was executed by Kaplan-Meier survival analysis and Cox proportional hazards models. We further performed sensitivity analyses with a time-weighted average (TWA) of the serum 25(OH)D level in 75 participants to reinforce the findings. Results: The median serum 25(OH)D level was 26 (IQR, 14; 39) nmol/L in the study participants. Median follow-up time was 42 months, during which 70 (38%) patients confronted CKD progression. Cumulative kidney outcomes were significantly higher in the lowest tertile of the serum 25(OH)D level in Kaplan-Meier analyses (P < 0.001). Consistently, the analyses of Cox proportional hazards regression models indicated a significantly greater risk for CKD progression in the lowest tertile of the serum 25(OH)D level compared with the highest tertile of the serum 25(OH)D level (P = 0.03). These relationships remained robust with further sensitivity analysis of data with TWA of the serum 25(OH)D level, showing an independent association between lower TWA of the serum 25(OH)D level and an unfavorable renal outcome in patients with T2DM with CKD. Conclusions: Our findings demonstrated that patients with T2DM with a decreased 25(OH)D level had deteriorated renal function. Both lower levels of baseline and TWA of serum 25(OH)D were associated with an increased risk of CKD progression in patients with T2DM, which suggested that the long-term maintenance of optimal vitamin D levels from early in life might be associated with reduced future risk of CKD development in T2DM.

Incidence, predictors and 6-month overall outcome of acute kidney injury in Chinese patients receiving PD-1 inhibitors.

Aim: To explore the incidence, risk factors and overall outcome of the first episode of immune checkpoint inhibitor-related acute kidney injury (ICI-AKI) in Chinese patients receiving PD-1 inhibitors. Methods: Data for patients receiving PD-1 inhibitors at Jiangsu Province Hospital between December 2017 and January 2020 were retrospectively reviewed. Results: A total of 5.6% of 551 patients receiving PD-1 inhibitors developed ICI-AKI. Concomitant use of NSAIDs, ICI cycles and extrarenal immune-related adverse events may be independently associated with ICI-AKI. ICI-AKI may not be a risk factor for increased mortality or worse progression-free survival. Conclusions: ICI-AKI is relatively rare and its occurrence may not affect the overall 6-month outcome of patients receiving PD-1 inhibitors. Further studies are needed to verify these findings.

Immune checkpoint inhibitors (ICIs) have been more and more commonly used in patients with cancer. Therefore, it is important to understand the immune-related adverse events (irAEs), including immune-related renal adverse events, caused by ICIs. In this article, the authors explore the incidence, clinical features, risk factors and overall outcome of immune checkpoint inhibitor related-acute kidney injury (ICI-AKI) in Chinese patients treated with PD-1 inhibitors for the first time. Among 551 patients treated with PD-1 inhibitors, 65 patients experienced AKI and 31 patients experienced ICI-AKI. Patients with ICI-AKI may be more likely to receive nonsteroidal anti-inflammatory drugs, to receive PD-1 inhibitors for longer cycles or to experience extrarenal immune-related adverse events prior to or concomitant with ICI-AKI. The occurrence of ICI-AKI may not affect the survival time or disease progression of patients with cancer.

Value of urine/serum Neutrophil gelatinase-associated lipocalin ratio in distinguishing acute kidney injury from chronic kidney disease.

OBJECTIVE: This study was performed to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker would be helpful for differentiation acute kidney injury (AKI) from chronic kidney disease (CKD) in kidney malfunction patients from the nephrology department. METHODS: This retrospective study included 355 patients admitted from the nephrology department with modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) < 60 ml/min/1.73 m2. The subjects were categorized into AKI group (n = 204) and CKD group (n = 151). A propensity-matched analysis, incorporating 17 variables, was performed to control potential selection bias. RESULTS: Urinary NGAL (uNGAL) level in the AKI group was higher than in the CKD group (372.10 (170.10-690.63) vs 88.10 (52.00-238.80), P < 0.001), but there was no significant difference in serum NGAL (sNGAL). Both sNGAL and uNGAL had a correlation with MDRD eGFR in total patients, AKI patients, and CKD patients. The propensity-matched analysis enrolled 75 patients in each group. In matched AKI group, sNGAL was lower (401.20 (239.10-616.00) vs 468.50 (305.00-709.40), P = 0.049) and uNGAL was elevated (284.00 (136.90-690.90) vs 203.70 (69.20-596.00), P = 0.032), compared with the matched CKD group. In all patients (n = 355), the ratio of uNGAL and sNGAL (u/s NGAL), fractional excretion of NGAL (Fe NGAL) discriminated AKI from CKD (area under the curve, 0.803 and 0.790, respectively). After stratified kidney function, the sub-analyses found that u/s NGAL and Fe NGAL were shown to differ substantially between the AKI group and CKD group (all P < 0.01). The u/s NGAL ratio always had the highest AUC area in the sub-analyses. CONCLUSIONS: u/s NGAL might be helpful to discriminate AKI from CKD in kidney malfunction patients admitted to the nephrology department. Further confirmatory studies might be warranted.

Ratio of Overhydration and Extracellular Water Versus Ratio of Extracellular Water and Body Cell Mass in the Assessment of Fluid Status in Patients With Acute Kidney Injury Requiring Kidney Replacement Therapy: A Cohort Study.

OBJECTIVES: The aim of this study is to analyze the association between the ratio of overhydration and extracellular water (OH/ECW) and the ratio of extracellular water and body cell mass (ECW/BCM) measured by bioelectrical impedance and outcomes of patients with acute kidney injury (AKI) requiring kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed using a body composition monitor before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors mainly included OH/ECW and ECW/BCM. The association between all-cause mortality and predictors were analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study with a median follow-up of 39 (interquartile range 8-742) days. The 28-day mortality, 90-day mortality, and 1-year mortality were 46.7%, 54.6%, and 60.5%, respectively. A high ratio of OH/ECW (adjusted hazard ratio per standard deviation, 1.45; 95% confidence interval = 1.15-1.82, P = .002) and a high ratio of ECW/BCM (adjusted hazard ratio per standard deviation, 1.33, 95% confidence interval = 1.07-1.64, P = .009) before KRT were associated with all-cause mortality during follow-up. Higher ECW/BCM rather than OH/ECW at 7th day was associated with poorer outcomes. Furthermore, a reduction of OH/ECW with an increase of ECW/BCM had higher 1-year mortality as compared to others (85.7% vs. 51.2%, P = .004) in patients who survived 7 days after KRT initiation. CONCLUSIONS: ECW/BCM performed better than OH/ECW in assessment of fluid status in AKI patients requiring KRT. This study suggested that a simple reduction of OH/ECW without decreasing ECW/BCM may not improve outcomes.

Association of Serum Sclerostin Level, Coronary Artery Calcification, and Patient Outcomes in Maintenance Dialysis Patients.

OBJECTIVE: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. METHODS: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. RESULTS: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605-0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. CONCLUSIONS: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.

The Association of an Early Net Ultrafiltration Rate and 28-Day Mortality in Patients Receiving Continuous Kidney Replacement Therapy.

Background: An early net ultrafiltration (NUF) rate may be associated with prognosis in patients receiving continuous kidney replacement therapy (CKRT). In this study, we tested whether high or low early NUF rates in patients treated with CKRT were associated with increased mortality. Methods: We conducted a retrospective, observational study among all patients in the Medical Information Mart for Intensive Care IV database who received CKRT for more than 24 h within 14 days after intensive care unit admission. We defined the early (initial 48 h) NUF rate as the amount of fluid removal per hour adjusted by the patients' weight and took it as a classified variable (low rate: <1.6, moderate rate: 1.6-3.1 and high rate: > 3.1 ml/kg/h). The association between 28-day mortality and the NUF rate was analyzed by logistic regression and mediation analyses. Results: A total of 911 patients were included in our study. The median NUF rate was 2.71 (interquartile range 1.90-3.86) ml/kg/h and the 28-day mortality was 40.1%. Compared with the moderate NUF rate, the low NUF rate (adjusted odds ratio 1.56, 95% CI 1.04-2.35, p = 0.032) and high NUF rate (adjusted odds ratio 1.43, 95% CI 1.02-2.01, p = 0.040) were associated with higher 28-day mortality. The putative effect of high or low NUF rates on 28 day mortality was not direct [adjusted average direct effects (ADE) for a low NUF rate = 0.92, p = 0.064; adjusted ADE for a high NUF rate = 1.03, p = 0.096], but mediated by effects of the NUF rate on fluid balance during the same period [adjusted average causal mediation effects (ACME) 0.96, p = 0.010 for a low NUF rate; adjusted ACME 0.99, p = 0.042 for a high NUF rate]. Moreover, we found an increase trend in the NUF rate corresponding to the lowest mortality when fluid input increased. Conclusion: Compared with NUF rates between 1.6-3.1 ml/kg/h in the first 48 h of CKRT, NUF rates > 3.1 and <1.6 ml/kg/h were associated with higher mortality.

Comparative Prevalence of Acute Kidney Injury in Chinese Patients Receiving Vancomycin with Concurrent ß-Lactam Antibiotics: A Retrospective Cohort Study.

PURPOSE: The combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and ß-lactam antibiotics. METHODS: This retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of ß-lactam antibiotics in combination with vancomycin. FINDINGS: In all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65-11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50-4.35), PTZ (OR = 2.86; 95% CI, 1.92-4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80-3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64-3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups. IMPLICATIONS: The prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.

The Effect of Coronary Angiography Timing on Cardiac Surgery Associated Acute Kidney Injury Incidence and Prognosis.

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury. Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results. Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017-1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316-8.986) and diabetes (OR = 2.522, 95%CI: 1.439-4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results. Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.

Body Composition Analysis as a Predictor of Prognosis for Patients With Acute Kidney Injury Requiring Kidney Replacement Therapy.

OBJECTIVES: The aim of this study is to investigate the association between body composition, measured by bioelectrical impedance analysis, and outcomes in patients with acute kidney injury (AKI) receiving kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed by body composition analysis before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors included lean tissue index (LTI), fat tissue index, and body cell mass index (BCMI). The association between all-cause mortality and predictors was analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study, with a 28-day mortality of 46.7% and 1-year mortality of 60.5%. LTI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.66, P < .001) and BCMI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.67, P < .001) on day 7 after initiation of KRT, rather than before KRT, were associated with mortality during follow-up. LTI and BCMI before KRT were associated with 28-day mortality rather than 1-year mortality. CONCLUSIONS: LTI and BCMI before KRT were associated with short-term prognosis, and those on day 7 after KRT initiation were associated with intermediate mortality in patients with AKI requiring KRT.

Comparative Performance of Body Composition Parameters in Prediction of Death in Hospitalized Patients on Maintenance Hemodialysis: A Cohort Study.

We compared the prognostic value of nutritional or volumetric parameters measured by body composition in hospitalized patients on maintenance hemodialysis. We conducted a cohort study to assess the association of different parameters of body composition with all-cause mortality in inpatients admitted to our nephrology department from January 2014 to December 2016. Of the 704 study patients, 160 (22.7%) died during a median follow-up of 33 months. In multivariate adjusted Cox models, higher ratio of extracellular water to body cell mass (ECW/BCM) (adjusted HR per 1-SD, 1.49; 95% CI, 1.19 to 1.85), lower lean tissue index (LTI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.57 to 0.86) and lower body cell mass index (BCMI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.58 to 0.85) were associated with a significantly greater risk of death. When these parameters were added to the fully adjusted model, BCMI performed best in improving the predictability for all-cause mortality (integrated discrimination improvement = 0.02, P = 0.04; net reclassification index = 0.11, P = 0.04). Among body composition indexes, ECW/BCM was the most relevant fluid volume indices to mortality and BCMI and LTI were the most relevant nutritional status indices to mortality in maintenance hemodialysis patients.

Effects of parathyroidectomy on tumoral calcinosis in uremic patients with secondary hyperparathyroidism.

BACKGROUND: Tumoral calcinosis (TC) is a rare disease derived from uremic secondary hyperparathyroidism (SHPT). However, parathyroidectomy (PTX) seems to be ineffective at relieving TC in some patients. In this study, we investigated the relationship between PTX and TC shrinkage. METHODS: We retrospectively followed up nine TC patients who underwent PTX, dividing them into two groups: those with TC size reduced by > 80% were in the "effective group" (group A), and the rest in the "ineffective group" (group B). RESULTS: We enrolled nine patients (7 men; mean age 38.6 ± 10.9 years) with SHPT-related TC. One patient with calciphylaxis was excluded due to sudden death. The efficiency of PTX in causing TC regression was 62.5% (5 patients in group A). Group A had a shorter overall duration of TC (6 [5.5, 6.0] vs. 9 [8.0, 10.0] months; P = 0.02) and higher serum levels of alkaline phosphatase (ALP; 408.0 [217.9, 1101.7] vs. 90.8 [71.0, 102.1] pg/ml; P = 0.03) and high-sensitivity C-reactive protein (hs-CRP; 82.7 [55.0, 112.4] vs. 3.1 [3.1, 4.5] mg/l; P = 0.02). Average calcium supplementation within 1 week of surgery was significantly greater in group A than in group B (96.8 [64.1, 105.3] vs. 20.1 [13.1, 32.7] g; P = 0.04). Patients in both the groups demonstrated similar serum phosphate levels before PTX, but these levels were higher in group B than in group A at follow-up times (3 months, P = 0.03; 6 months, P = 0.03). CONCLUSIONS: The shorter duration of pre-existing TC and higher ALP levels before PTX, as well as lower serum phosphate levels after PTX, were correlated with effective SHPT-TC shrinkage.

Comparison of different equations for estimated glomerular filtration rate in Han Chinese patients with chronic kidney disease.

AIM: To understand the agreement, precision, and accuracy between other estimated glomerular filtration rate (eGFR) equations and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation (EPI_Cr_CysC). MATERIALS AND METHODS: We conducted a cross-sectional study of 1,913 CKD patients. The eGFRs were calculated separately by creatinine clearance rate and Cockcroft-Gault equation corrected for standard body surface area (Ccr_BSA and eCcr_BSA); CKD-EPI creatinine equation (EPI_Cr); CKD-EPI cystatin C equation (EPI_CysC); EPI_Cr_CysC equation; Modification of Diet in Renal Disease (MDRD) Study equation with standardized serum creatinine; and full-age spectrum creatinine equation (FAS). The EPI_Cr_CysC equation was used as the reference. RESULTS: When compared with the EPI_Cr_CysC equation, the EPI_Cr equation achieved the highest agreement in eGFRs (Lin's concordance correlation coefficient = 0.936, 95% confidence interval (CI) = 0.930, 0.941). eCcr_BSA and EPI_Cr equations achieved the first and second highest percentage agreement in the accurate classification of CKD stage (72.55 vs. 71.25%). The MDRD equation had minimal bias and was closely followed by the EPI_Cr equation (median difference = -1.3, 95% CI = -2.0, -0.8 vs. median difference = 2.5, 95% CI = 1.7, 3.3 mL/min/1.73m2). The EPI_CysC and EPI_Cr equations achieved the first and second highest precision (interquartile range (IQR) of the difference = 12.2, 95% CI = 11.6, 12.9 vs. IQR of the difference = 15.5, 95% CI = 14.7, 16.3 mL/min/1.73m2). The EPI_Cr and MDRD equations performed similarly and both had the highest accuracy at 30% (1 - P30 = 18.6, 95% CI = 16.9, 20.4 vs. 1 - P30 = 18.6, 95% CI = 16.8, 20.3%). CONCLUSION: For assessment of renal function, the EPI_Cr equation performed the best and remained an acceptable alternative to the EPI_Cr_CysC equation in the absence of cystatin C.
.

New modes of continuous renal replacement therapy using a refiltering technique to reduce micronutrient loss.

INTRODUCTION: Micronutrient depletion is a major drawback of high-dose continuous renal replacement therapy (CRRT). We tested two novel CRRT modes, double-filtration hemofiltration (DHF) and dialysate-recycling hemodiafiltration (DHDF), aimed at reducing micronutrient loss while maintaining a high clearance rate of midsized solutes comparable to that of high-volume hemofiltration (HVHF). METHODS: Forty patients with renal failure requiring CRRT were randomly assigned to receive predilutional standard-volume hemofiltration (SVHF, effluent rate 35 mL/kg/h), predilutional HVHF (100 mL/kg/h), DHF (35 mL/kg/h), and DHDF (30 mL/kg/h). In the two novel modes of CRRT, part of the high-volume primary effluent fluid produced by a high-flux filter (AV600S) was refiltered by two low-flux filters (15 L) for recycling as replacement fluid in DHF and dialysate in DHDF, while the remainder was discarded as final effluent fluid. Specimens were collected for measurement of trace elements, folic acid, amino acids (AAs), ß2-microglobulin, cystatin C, and creatinine and for calculation of solute clearance. FINDINGS: The clearance of 17 AAs, phosphorus, folic acid, copper, and zinc by DHF and DHDF was much lower than that by HVHF and comparable to that by SVHF. The estimated amount of AA loss by SVHF, HVHF, DHF, and DHDF was 10.3 (7.2-13.4) g/d, 22.1 (17.8-24.0) g/d, 10.6 (8.6-14.0) g/d, and 10.0 (8.6-11.4) g/d, respectively. Clearance of cystatin C and ß2-microglobulin by DHF and DHDF was much greater than that by SVHF and equal to that by HVHF. DISCUSSION: Compared to HVHF, DHF, and DHDF have an equal capacity for removal of large solutes but show substantially reduced micronutrient loss.