Probability Of Acute Kidney Injury Research Articles

Prostaglandin Transporter and Dipeptidyl Peptidase-4 as New Pharmacological Targets in the Prevention of Acute Kidney Injury in Diabetes: An In Vitro Study.

The probability of acute kidney injury (AKI) is higher in septic diabetic patients, which is associated with, among other factors, proximal tubular cell (PTC) injury induced by the hypoxic/hyperglycemic/inflammatory microenvironment that surrounds PTCs in these patients. Here, we exposed human PTCs (HK-2 cells) to 1% O2/25 mM glucose/inflammatory cytokines with the aim of studying the role of prostaglandin uptake transporter (PGT) and dipeptidyl peptidase-4 (DPP-4, a target of anti-hyperglycemic agents) as pharmacological targets to prevent AKI in septic diabetic patients. Our model reproduced two pathologically relevant mechanisms: (i) pro-inflammatory PTC activation, as demonstrated by the increased secretion of chemokines IL-8 and MCP-1 and the enhanced expression of DPP-4, intercellular leukocyte adhesion molecule-1 and cyclo-oxygenase-2 (COX-2), the latter resulting in a PGT-dependent increase in intracellular prostaglandin E2 (iPGE2); and (ii) epithelial monolayer injury and the consequent disturbance of paracellular permeability, which was related to cell detachment from collagen IV and the alteration of the cell cytoskeleton. Most of these changes were prevented by the antagonism of PGE2 receptors or the inhibition of COX-2, PGT or DPP-4, and further studies suggested that a COX-2/iPGE2/DPP-4 pathway mediates the pathogenic effects of the hypoxic/hyperglycemic/inflammatory conditions on PTCs. Therefore, inhibitors of PGT or DPP-4 ought to undergo testing as a novel therapeutic avenue to prevent proximal tubular damage in diabetic patients at risk of AKI.

Development of a novel score (RENSAFE) to determine probability of acute kidney injury and renal functional decline post surgery: A multicenter analysis

ObjectiveTo create and validate 2 models called RENSAFE (RENalSAFEty) to predict postoperative acute kidney injury (AKI) and development of chronic kidney disease (CKD) stage 3b in patients undergoing partial (PN) or radical nephrectomy (RN) for kidney cancer. MethodsPrimary objective was to develop a predictive model for AKI (reduction >25% of preoperative eGFR) and de novo CKD≥3b (<45 ml/min/1.73m2), through stepwise logistic regression. Secondary outcomes include elucidation of the relationship between AKI and de novo CKD≥3a (<60 ml/min/1.73m2). Accuracy was tested with receiver operator characteristic area under the curve (AUC). ResultsAKI occurred in 452/1,517 patients (29.8%) and CKD≥3b in 116/903 patients (12.8%). Logistic regression demonstrated male sex (OR = 1.3, P = 0.02), ASA score (OR = 1.3, P < 0.01), hypertension (OR = 1.6, P < 0.001), R.E.N.A.L. score (OR = 1.2, P < 0.001), preoperative eGFR<60 (OR = 1.8, P = 0.009), and RN (OR = 10.4, P < 0.0001) as predictors for AKI. Age (OR 1.0, P < 0.001), diabetes mellitus (OR 2.5, P < 0.001), preoperative eGFR <60 (OR 3.6, P < 0.001) and RN (OR 2.2, P < 0.01) were predictors for CKD≥3b. AUC for RENSAFE AKI was 0.80 and 0.76 for CKD≥3b. AKI was predictive for CKD≥3a (OR = 2.2, P < 0.001), but not CKD≥3b (P = 0.1). Using 21% threshold probability for AKI achieved sensitivity: 80.3%, specificity: 61.7% and negative predictive value (NPV): 88.1%. Using 8% cutoff for CKD≥3b achieved sensitivity: 75%, specificity: 65.7%, and NPV: 96%. ConclusionRENSAFE models utilizing perioperative variables that can predict AKI and CKD may help guide shared decision making. Impact of postsurgical AKI was limited to less severe CKD (eGFR<60 ml/min 71.73m2). Confirmatory studies are requisite.

Elevation of Urinary Liver-Type Fatty Acid-Binding Protein Is a Harbinger of Poor Patient Prognosis after Allogeneic Stem Cell Transplantation

Several recent studies have demonstrated that urinary levels of liver-type fatty acid-binding protein (L-FABP) can be used to stratify the prognosis of cardiac disease, cardiac intensive care unit admission, cirrhosis, and coronavirus disease 2019. Our initial prospective study revealed that urinary L-FABP (uL-FABP) was associated with a high probability of acute kidney injury after stem cell transplantation (SCT); however, the relevance of elevated uL-FABP to the prognosis of patients undergoing SCT remains to be determined. We aimed to investigate whether uL-FABP levels can be used to stratify patient prognosis after SCT. To achieve this aim, we conducted a new long-term follow-up study using data from patients enrolled in our preceding prospective cohort study. Patients were classified into high and low uL-FABP groups based on levels measured at baseline (ie, before initiating the conditioning regimen), using an uL-FABP cutoff of 8.4 μg/gCr, which was determined based on data from healthy adults. uL-FABP levels were also measured on days 0, 7, and 14 after SCT. Cox proportional hazard regression was used to examine the effects of each factor on survival outcomes, and Fine-Gray regression was used in the presence of competing risks. Multivariate analysis incorporating confounders was then performed for factors with P < .1 in univariate analysis. In total, 20 of 84 patients (23.8%), 57 of 84 patients (67.9%), 34 of 49 patients (69.4%), and 34 of 46 patients (73.9%) were classified into the high uL-FABP group at baseline and on days 0, 7, and 14, respectively. The 5-year overall survival (OS) rate was 23.9% in the high uL-FABP group and 68.9% in the low uL-FABP group. The multivariate analysis identified a high uL-FABP level at baseline as a significant prognostic factor for poor OS (hazard ratio [HR], 3.54; P=.002). The 5-year cumulative incidence rate for nonrelapse mortality (NRM) was 50.0% in the high uL-FABP group and 19.9% in the low uL-FABP group. In the multivariate analysis, high uL-FABP at baseline was a significant prognostic factor for NRM (HR, 3.37; P=.01). uL-FABP levels did not significantly stratify the cumulative incidence of relapse (HR, 2.13; P=.11). uL-FABP levels on days 0, 7, and 14 were not significant predictors of survival. High uL-FABP level before initiation of conditioning significantly influences OS and NRM following SCT, whereas a high uL-FABP level at any point after the conditioning regimen does not. Our results show that measuring uL-FABP level at baseline may be a simple way to predict survival in patients undergoing SCT.

Impact of timing of urgent coronary artery bypass grafting following coronary angiography on acute kidney injury

ObjectivesPrior studies have examined the association between timing of cardiac surgery after coronary angiography with risk of acute kidney injury, but this remains controversial. The purpose of this study was to investigate the association between interval from coronary angiography to urgent coronary artery bypass grafting with acute kidney injury, and to examine this possible effect in patients with preexisting kidney disease. MethodsPatients from a single institution undergoing urgent, isolated coronary artery bypass grafting within 7 days of coronary angiography were included. Patients were subdivided by chronic kidney disease stage and angiography-to-surgery interval. Locally estimated scatterplot smoothing was used to evaluate the functional relationship of the probability of acute kidney injury and time interval. Adjusted odds ratios were calculated for each time interval group compared against the Day 0 to 1 interval group, controlling for multiple covariates. Analyses were repeated for each chronic kidney disease subgroup. ResultsA total of 2249 patients were included in this study. There were 271 (12.0%) patients with postoperative acute kidney injury. Plots demonstrated a decreasing risk of kidney injury from Day 0 to 1 to Day 3 following coronary angiography. Adjusted odds ratios also showed a significant decrease in risk of kidney injury on Day 3 compared with Day 0 to 1. Analyses repeated for each chronic kidney disease stage showed similar trends. ConclusionsFor patients undergoing urgent coronary artery bypass grafting, there is a decreased risk of kidney injury in those having surgery on day 3 after coronary angiography compared with those having surgery on Day 0 to 1, regardless of preexisting kidney disease.

Impact of Warm Ischemia on Acute Kidney Injury After Robotic Partial Nephrectomy Stratified by Baseline Kidney Function.

Objectives: To evaluate the differences in baseline chronic kidney disease (CKD) status in correlations between warm ischemic time (WIT) and acute kidney injury (AKI) or acute/chronic renal function change after robot-assisted partial nephrectomy (RAPN). Methods: This study retrospectively recruited 1290 patients from a multi-institutional RAPN database. The patients were grouped into four preoperative CKD categories: CKD Group 1 (CKDG1), CKD Group 2 (CKDG2), CKD Group 3a (CKDG3a), and CKD Group 3b (CKDG3b). The correlation between WIT and the probability of AKI was assessed according to the baseline CKD grade, together with changes in serum creatinine (sCr) at the postoperative maximum and chronic renal function. Results: AKI was not observed in the CKDG1 group. The probability of AKI at WIT = 30 minutes was 5.6% for CKDG2, 8.5% for CKDG3a, and 11.6% for CKDG3b (all p < 0.05). WIT was an independent predictor of AKI occurrence in the multivariate model for these three CKD groups. Significant weak correlations were observed between WIT and sCr change for all four groups, with R2 = 0.22 for CKDG1, R2 = 0.16 for CKDG2, R2 = 0.03 for CKDG3a, and R2 = 0.09 for ≥CKDG3b. For chronic renal function, correlations were significant in CKDG2, CKDG3a, and ≥CKDG3b, yet R2 was considered small in all cases (<0.1). Conclusions: The association between extended WIT and the probability of AKI increased in patients with more severe baseline CKD. The correlation between WIT and renal function was significant, yet clinically modest.

Does Monitoring Total and Free PolymyxinB1 Plasma Concentrations Predict PolymyxinB-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients.

IntroductionThe correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-induced acute kidney injury (AKI) in critically ill patients.MethodsCritically ill patients who used PMB and met the criteria were enrolled. The total plasma concentration and plasma binding of PMB1 and PMB2 were analysed by liquid chromatography–tandem mass spectrometry and equilibrium dialysis.ResultsA total of 89 patients were finally included, and AKI developed in 28.1% of them. The peak concentration of PMB1 (Cmax (B1)) (adjusted odds ratio (AOR) = 1.68, 95% CI 1.08–2.62, p = 0.023), baseline BUN level (AOR = 1.08, 95% CI 1.01–1.16, p = 0.039) and hypertension (AOR = 3.73, 95% CI 1.21–11.54, p = 0.022) were independent risk factors for PMB-induced AKI. The area under the ROC curve of the model was 0.799. When Cmax (B1) was 5.23 μg/ml or more, the probability of AKI was higher than 50%. The ratio of PMB1/PMB2 decreased after PMB preparation entered into the body. The protein binding rate in critically ill patients indicated significant individual differences. Free Cmax (B) and free Cmax (B1) levels in the AKI group were significantly (p < 0.05) higher than those in the non-AKI group. Total and free concentrations of PMB in patients showed a positive correlation.ConclusionsBoth the ROC curve and logistic regression model showed that Cmax (B1) was a good predictor for the probability of PMB-induced AKI. Early therapeutic drug monitoring (TDM) of PMB should be considered in critically ill patients. Compared with Cmin (B), Cmax (B) and Cmax (B1) may be helpful for the early prediction of PMB-induced AKI in critically ill patients.

Association of Neighborhood Resources and Race and Ethnicity With Readmissions for Diabetic Ketoacidosis at US Children’s Hospitals

The Child Opportunity Index 2.0 (COI) assesses neighborhood resources and conditions that influence health. It is unclear whether the COI scores are associated with health outcomes by race and ethnicity among children with type 1 diabetes (T1D). To determine whether COI categories are associated with diabetes-related outcomes by race and ethnicity, including readmissions for diabetic ketoacidosis (DKA) and co-occurring acute kidney injury (AKI) or cerebral edema (CE). This cross-sectional study included children discharged with a primary diagnosis of T1D with DKA between January 1, 2009, and December 31, 2018. Merged data were obtained from the Pediatric Health Information System and COI. Participants included children and adolescents younger than 21 years with an encounter for DKA. Data were analyzed from April 29, 2021, to January 5, 2022. Neighborhood opportunity, measured with the COI as an ordered, categorical score (where a higher score indicates more opportunity), and race and ethnicity. The primary outcome was readmission for DKA within 30 and 365 days from an index visit. Secondary outcomes included the proportion of encounters with AKI or CE. Mixed-effects logistic regression was used to generate probabilities of readmission, AKI, and CE for each quintile of COI category by race and ethnicity. A total of 72 726 patient encounters were identified, including 38 924 (53.5%) for girls; the median patient age was 13 (IQR, 9-15) years. In terms of race and ethnicity, 600 (0.8%) of the encounters occurred in Asian patients, 9969 (13.7%) occurred in Hispanic patients, 16 876 (23.2%) occurred in non-Hispanic Black (hereinafter Black) patients, 40 129 (55.2%) occurred in non-Hispanic White (hereinafter White) patients, and 5152 (7.1%) occurred in patients of other race or ethnicity. The probability of readmission within 365 days was significantly higher among Black children with a very low COI category compared with Hispanic children (risk difference, 7.8 [95% CI, 6.0-9.6] percentage points) and White children (risk difference, 7.5 [95% CI, 5.9-9.1] percentage points) at the same COI category. Similar differences were seen for children with very high COI scores and across racial groups. The COI category was not associated with AKI or CE. However, race and ethnicity constituted a significant factor associated with AKI across all COI categories. The probability of AKI was 6.8% among Black children compared with 4.2% among Hispanic children (risk difference, 2.5 [95% CI, 1.7-3.3] percentage points) and 4.8% among White children (risk difference, 2.0 [95% CI, 1.3-2.6] percentage points). These results suggest that Black children with T1D experience disparities in health outcomes compared with other racial and ethnic groups with similar COI categories. Measures to prevent readmissions for DKA should include interventions that target racial disparities and community factors.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes.Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Candidates for area under the concentration–time curve (AUC)-guided dosing and risk reduction based on analyses of risk factors associated with nephrotoxicity in vancomycin-treated patients

Compared with vancomycin trough concentration (Cmin)-guided dosing, area under the concentration-time curve (AUC)-guided dosing is associated with decreased acute kidney injury (AKI). However, whether Cmin-guided or AUC-guided dosing should be used in patients other than those with serious MRSA infections remains uncertain. The purposes of this multicentre study were to identify risk factors for early- and late-phase vancomycin-induced AKI and to identify candidates for AUC-guided dosing, rather than Cmin-guided dosing, who require a more accurate dose titration to reduce the AKI risk. A multivariate logistic regression analysis was applied to identify risk factors for AKI. Additionally, the cut‑off day for AKI onset, cut-off Cmin for AKI, safe Cmin for reduced AKI risk and probability of AKI were calculated. In total, 8.4% (159/1882) of patients developed AKI. AKI occurred within the first 7 days of therapy (early phase) in the vast majority of patients. Significant risk factors for AKI during the early phase were identified as Cmin > 20 mg/L, ICU stay, concurrent diuretic or piperacillin/tazobactam use, and pre-existing renal dysfunction. A temporarily elevated Cmin (>15-20 mg/L) was not associated with a greater risk of AKI. In patients with risk factors, the cut-off Cmin for AKI and the estimated safe Cmin for reduced AKI risk were 18.8-21.0 mg/L and <11.7-13.5 mg/L, respectively. Patients with known AKI risk factors require a low target Cmin. The presence of several risk factors for AKI may indicate a need for more accurate dose titration using AUC-guided dosing.

Predictive utility of fibrinogen in acute kidney injury in living donor liver transplantation: A propensity score-matching analysis.

BackgroundThis study investigated the association between the fibrinogen level and the risk of acute kidney injury (AKI) in patients who have undergone living donor liver transplantation (LDLT).Patients and methodsA total of 676 patients who underwent LDLT were analyzed retrospectively. Exclusion criteria included a history of severe kidney dysfunction, emergency operation, deceased donor, ABO-incompatible transplantation, and missing data. The study population was divided into low and normal fibrinogen groups. A 1:1 propensity score (PS) matching analysis was used to evaluate the association between a low fibrinogen level (< 160 mg/dL) and postoperative development of AKI.ResultsIn total, 142 patients (23.1%) developed AKI after LDLT. The PS matching analysis showed that the probability of AKI was two-fold higher in the low fibrinogen group than in the normal fibrinogen group. In addition, patients with AKI had poorer postoperative outcomes such as longer hospitalization, longer ICU stay, and higher mortality than patients without AKI.ConclusionsThe preoperative fibrinogen level may be useful for risk stratification of patients undergoing LDLT in terms postoperative development of AKI.

Not All Piggybacks Are Equal: A Retrospective Cohort Analysis of Variation in Anhepatic Transcaval Pressure Gradient and Acute Kidney Injury During Liver Transplant.

Complete inferior vena cava clamping in cavalreplacement during livertransplantis associated with substantial physiological derangement and postoperative morbidity. Partial clamping in the piggyback technique may be relatively protective, but evidence is lacking. Having observed substantial variation in transhepatic inferior vena cava pressure gradient with piggyback, we hypothesized that the causative mechanism is the extent of caval clamping rather than the surgical approach. We used internal jugular and femoral catheters to estimate suprahepatic and infrahepatic inferior vena cava pressures during clamping. Pressure gradients were calculated, and distributions were compared by surgical technique. We estimated adjusted odds ratios for pressure gradient on acute kidney injury at 72 hours. In 115 case records, we observed substantial variation in maximum pressure gradient; median values were 18.0 mm Hg(interquartile range, 8.0-25.0 mm Hg) with the piggyback technique and 24.0 mm Hg (interquartile range, 19.5-27.0 mm Hg) with caval replacement. Incidence of acute kidney injury was 25% (29 patients). Pressure gradient was linearly associated with probability of acute kidney injury (odds ratio, 1.06; 95% CI, 1.01-1.13). We report 2 novel findings. (1) Anhepatic inferior vena cavapressuregradient variedsubstantially in individuals undergoing piggyback, and (2) gradient was positively associatedwith early acute kidney injury. We hypothesize that this (unmeasured) variation explains the conflictingfindings ofprevious studies that compared surgical techniques. Also, we propose that caval pressure gradient could be routinely assessed to optimize real-time piggyback clamp position during livertransplant surgery.

MO411ACUTE KIDNEY INJURY AFTER PARATHYROIDECTOMY FOR PRIMARY HYPERPARATHYROIDISM: PREVALENCE, PREDICTORS AND RISK ASSESSEMENT

Abstract Background and Aims Surgery is the most effective and the only definitive treatment of primary hyperparathyroidism (PHPT). We aimed to assess the prevalence of acute kidney injury (AKI) among patients underwent surgery for PHPT, to determine the possible risk factors. Method A retrospective cohort study included 290 patients who underwent successful selective parathyroidectomy (PTx) for PHPT. We did not include patients who underwent re-operative surgeries. AKI was defined according to KDIGO-2012 criteria. Results In our cohort, 106 patients (36,6%) met AKI criteria after PTx. Most of the patients developed AKI stage 1. In univariate analysis preoperative serum PTH level (р=0,0004) aa well as degree of its decrease before/after PTx (р&amp;lt;0,0001), preoperative serum total calcium level (р=0,0158), size of the parathyroid adenoma (р=0,0184), presence of proteinuria (RR=1,9 [95%CI: 1,19; 3,54], р=0,0061), hypertension (р=0,019) and anemia (р=0,0313), older age (RR=1,32 [95%CI: 1,03; 1,72], р=0,0265) were significant risk factors of AKI development. In multivariate analysis age (OR 1,05 [95%CI: 1,02; 1,08] per a year, р=0,002), body-mass index (OR 1,07 [95%CI: 1,02; 1,13] per each kg/m2, р=0,005), anemia (yes/no OR 3,38 [95%CI: 1,38; 8,2], р=0,008), preoperative PTH (OR 1,03 [95%CI: 1,01; 1,05] per each pmol/l, р=0,002), proteinuria (yes/no OR 3,45 [95%CI: 1,34; 8,93], р=0,011), use of ACE inhibitors/ARBs (yes/no OR 2,84 [95%CI: 1,58; 5,12], р=0,001) were discovered as independent predictors of AKI. Considering the most significant risk factors we developed two regression models for AKI risk assessment: the model 1 for patients with preserved kidney function (estimated glomerular filtration rate (eGFR ≥60 ml/min/1,73 m2) and the model 2 for those with decreased kidney function (eGFR less than 60 ml/min/1,73 m2) – tab. 1 and 2. Both models were statistically significant: χ2=25,39, df=5, р&amp;lt;0,001, RN2=0,341 for the model 1, χ2=19,355, df=3, р&amp;lt;0,001, RN2=0,428 for the model 2. The proposed models had good discrimination to predict AKI with area under the receiver operating characteristic curves (AUC-ROC) of 0,792 [95%CI: 0,691; 0,894], р&amp;lt;0,001 for the model 1 (normal kidney function) and 0,84 [95%CI: 0,73; 0,951], р&amp;lt;0,001 for the model 2 (decreased kidney function). Optimal cut-off values for predicted probability of AKI to define high-risk individuals were &amp;gt; 0,57 (Youden’s index 0,525) for the model 1 and &amp;gt; 0,439 (Youden’s index 0,589) for the model 2. Conclusion We observed high prevalence of AKI in patients after PTx for primary HPT. Developed risk models predict AKI with adequate accuracy. Risk factors of AKI should be considered when planning PTx, special attention should be paid to modifiable ones.

Predictive Utility of Antithrombin III in Acute Kidney Injury in Living-Donor Liver Transplantation: A Retrospective Observational Cohort Study

IntroductionThis study was performed to determine the association between the serum level of antithrombin III (ATIII) level and the risk of acute kidney injury (AKI) in patients undergoing living-donor liver transplantation (LDLT). Patients and methodsA total of 591 patients undergoing LDLT were retrospectively investigated and 14 patients were excluded because of a history of kidney dysfunction or missing data; 577 patients were finally enrolled in the study. The study population was divided into normal and low ATIII groups. Data on all laboratory variables, including ATIII, were collected on the day before surgery. ResultsAfter LDLT, 143 patients developed AKI (24.8%). A lower ATIII was independently associated with postoperative AKI along with preoperative (diabetes mellitus) and intraoperative (mean heart rate, hourly urine output) factors. Based on the standard cutoff for normal ATIII (<70%), the probability of AKI was 2.8-fold higher in the low ATIII group than in the normal ATIII group. In addition, patients with low ATIII received blood transfusion products during the operation and underwent longer duration mechanical ventilation. ConclusionsPreoperative ATIII measurement will help improve risk stratification for postoperative AKI development in patients undergoing LDLT.

Toward Individualized Approaches to Partial Nephrectomy: Assessing the Correlation Between Ischemia Time and Patient Health Status (RECORD2 Project)

BackgroundIschemia time during partial nephrectomy (PN) is among the greatest determinants of acute kidney injury (AKI). Whether this association is affected by the preoperative risk of AKI has never been investigated. ObjectiveTo assess the effect of the interaction between the preoperative risk of AKI and ischemia time on the probability of AKI during PN. Design, setting, and participantsData of 944 patients treated with on-clamp PN for cT1 renal tumors were extracted from the Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease (RECORD2) database, a prospective multicenter project. Outcome measurements and statistical analysisWe estimated the preoperative risk of AKI (defined according to the risk/injury/failure/loss/end-stage [RIFLE] criteria) according to age, baseline renal function, clinical stage, preoperative aspects and dimensions used for an anatomical (PADUA) score, and surgical approach. Classification and regression tree (CART) analysis identified patients at “high” and “low” risk of AKI. Finally, we plotted the probability of AKI over ischemia time stratified by the preoperative risk of AKI. Results and limitationsOverall, 235 (25%) patients experienced AKI after surgery. At multivariable analysis, older patients, those with more complex tumors, those with higher baseline function, and those treated with open surgery had an increased risk of AKI (all p ≤ 0.011). According to the first split at CART analysis, patients were categorized as those with “high” and “low” risk of AKI having a probability of >40% or <40%. For low-risk patients, the probability of AKI in case of <10 versus >20 min of ischemia was 13% versus 28% (absolute risk increase 15%). The risk of AKI for high-risk patients who had <10 versus >20 min of ischemia was 31% versus 77%. This corresponds to an absolute risk increase of 45%. Limitations include retrospective data analyses and lack of surgeons’ prior experience. ConclusionsIschemia time during PN has different implications for patients with different health status. Clamp time seems less clinically relevant for patients in good conditions who may endure prolonged ischemia with a mild increase in the risk of AKI, whereas frail patients seem to be more vulnerable to ischemic damage even for short clamp time. For individualized intra- and postoperative management, duration of ischemia needs to be questioned in the context of the individual health status. Patient summaryFunctional sequelae related to ischemia time during partial nephrectomy depend on baseline health status. The correlation between the duration of ischemia and baseline health status should be taken into account toward individualized intra- and postoperative management.

P0578QUININE EXPOSURE AND THE RISK OF ACUTE KIDNEY INJURY: A POPULATION BASED OBSERVATIONAL STUDY OF OLDER PEOPLE

Abstract Background and Aims Quinine can precipitate Acute Kidney Injury (AKI) by immune-mediated reactions. Cramps, for which quinine is traditionally prescribed, may be a symptom of conditions that are risk factors for AKI. The relationship between quinine and AKI at a population level is unclear. The aim of this study was to establish and quantify any observable association between the exposure to community prescriptions for quinine and AKI events in a population of older adults. Method We performed two observational studies of older adults (60+ years) who received quinine prescriptions in Tayside, Scotland, between January 2004 and December 2015. The first study was a retrospective longitudinal cohort study with the primary outcome AKI. Creatinine measurements less than seven days apart were grouped as episodes of care. Multivariable logistic regression was used to calculate odds ratios (OR) for AKI comparing between episodes with and without recent quinine exposure after adjustment for demographics, comorbidities and concomitant medications. A self-controlled case series (SCCS) was then conducted with follow-up divided into periods “on” and “off” quinine for the same individual, calculating incidence rate ratios (IRR) for AKI adjusting for age. Results The first study included 12,744 individuals who experienced 13,616 AKI events during cohort follow-up (crude incidence 12.5 per 100 person-years). Exposure to quinine before an episode of care was significantly associated with an increased probability of AKI (adjusted OR=1.27, 95% CI 1.21-1.33). The SCCS cohort included 5,907 people with quinine exposure with ≥1 AKI event. Exposure to quinine was associated with an increased relative incidence of AKI compared to unexposed periods (IRR=1.20, 95% CI 1.15-1.26), with the greatest risk observed within 30 days of quinine initiation (IRR=1.48, 95% CI 1.35-1.61). Conclusion Exposure to quinine in patients aged 60 years and over was associated with an increased risk of AKI, the incidence of which is unlikely to simply be explained be immune-mediated reactions only. Further research is required to determine exact reasons for the increased risk of AKI.

Application of group LASSO regression based Bayesian networks in risk factors exploration and disease prediction for acute kidney injury in hospitalized patients with hematologic malignancies

BackgroundPatients who were diagnosed with hematologic malignancies (HM) had a higher risk of acute kidney injury (AKI). This study applies the Bayesian networks (BNs) to investigate the interrelationships between AKI and its risk factors among HM patients, and to evaluate the predictive and inferential ability of BNs model in different clinical settings.MethodsDuring 2014 and 2015, a total of 2501 inpatients with HM were recruited in this retrospective study conducted in a tertiary hospital, Shanghai of China. Patients’ demographics, medical history, clinical and laboratory records on admission were extracted from the electronic medical records. Candidate predictors of AKI were screened in the group-LASSO (gLASSO) regression, and then they were incorporated into BNs analysis for further interrelationship modeling and disease prediction.ResultsOf 2395 eligible patients with HM, 370 episodes were diagnosed with AKI (15.4%). Patients with multiple myeloma (24.1%) and leukemia (23.9%) had higher incidences of AKI, followed by lymphoma (13.4%). Screened by the gLASSO regression, variables as age, gender, diabetes, HM category, anti-tumor treatment, hemoglobin, serum creatinine (SCr), the estimated glomerular filtration rate (eGFR), serum uric acid, serum sodium and potassium level were found with significant associations with the occurrence of AKI. Through BNs analysis, age, hemoglobin, eGFR, serum sodium and potassium had directed connections with AKI. HM category and anti-tumor treatment were indirectly linked to AKI via hemoglobin and eGFR, and diabetes was connected with AKI by affecting eGFR level. BNs inferences concluded that when poor eGFR, anemia and hyponatremia occurred simultaneously, the patients’ probability of AKI was up to 78.5%. The area under the receiver operating characteristic curve (AUC) of BNs model was 0.835, higher than that in the logistic score model (0.763). It also showed a robust performance in 10-fold cross-validation (AUC: 0.812).ConclusionBayesian networks can provide a novel perspective to reveal the intrinsic connections between AKI and its risk factors in HM patients. The BNs predictive model could help us to calculate the probability of AKI at the individual level, and follow the tide of e-alert and big-data realize the early detection of AKI.

Fluid Therapy With Gelatin May Have Deleterious Effects on Kidney Function: An Observational Trial

To explore the effects of fluid therapy with the synthetic colloids hydroxyethyl starch (HES) and gelatin (GEL) on the incidence of acute kidney injury (AKI) and need for renal replacement therapy (RRT) in patients undergoing cardiac surgery. Secondary analysis of a prospective observational study in cardiac surgical patients. University hospital. The study included 584 elective patients (excluding patients on preoperative dialysis). Anamnestic and surgical core data, hemodynamics, and hemodynamic treatments were recorded intraoperatively and postoperatively. Postoperative kidney dysfunction was graded according to the Acute Kidney Injury Network criteria from perioperative changes in plasma creatinine and urine flow. Statistical analyses were performed descriptively, by logistic and probit regression, omitting inotropic and vasoactive medications as established renal risk factors. The incidence of AKI and new renal replacement therapy was 28.6% and 7.5%, respectively. Patients with AKI were older, had a higher additive Euroscore, lower preoperative glomerular filtration rates and hemoglobin level, and presented with a longer duration of cardiopulmonary bypass and surgery and higher postoperative drainage loss. HES (1 [0-2] units of 500 mL) and GEL (3 [2-5] units of 500 mL) were used in 317 and 563 patients, respectively. Crystalloids were used in all patients (4,560 [4,080-5,042] mL). Patients presenting with AKI or new RRT were treated with significantly higher amounts of GEL. The use of HES and crystalloids did not differ between these groups. Probit regression showed significant dose-response relationships between the amount of infused gelatin and the probability of AKI and new RRT. Probit regression showed significant (p = 0.0001 and 0.0003, respectively) dose-response relationships between the total units of gelatin polysuccinate infused and the probability of AKI and new RRT (Fig 1). Logistic regression revealed a statistically significant odds ratio (OR) of 1.9741 (95% CI: 1.3104-2.9740; p = 0.0011) for an association between the number of gelatin units infused and AKI (grade 1-3) but no direct association between the number of gelatin units administered and new RRT. No association between a decrease in kidney function and the application of HES was observed. Taking into account the limitations of the small sample size and a low event rate, the nonconsideration of established renal risk factors such as inotropes and vasopressors, and potentially unmeasured confounders, these findings suggested that gelatin solutions may have deleterious effects on renal function in cardiac surgical patients. The adverse clinical effects of HES on kidney function observed in other studies may have been blunted by the restrictive use of this synthetic colloid.

Role of thrombocytopenia in risk stratification for acute kidney injury after living donor liver transplantation

The aim of our study was to investigate pre and intraoperative clinical factors, including platelet count, which could inform risk stratification of early acute kidney injury (AKI) after living donor liver transplantation (LDLT). Additionally, the impact of severe thrombocytopenia on AKI risk was assessed using a propensity score (PS)-matched analysis. In total, 591 adult patients who underwent LDLT between January 2009 and December 2018 at our hospital were retrospectively analyzed. Early postoperative AKI was determined based on the KDIGO criteria, and 149 patients (25.2%) developed AKI immediately after surgery. In a multivariate analysis, a lower preoperative platelet count was significantly associated with early postoperative AKI, together with diabetes mellitus, lower hourly urine output, and longer graft ischemic time; furthermore, a decrease in platelet count was correlated with AKI severity. After adjusting for the PS, the probability of AKI was significantly (1.9-fold) higher in patients with severe thrombocytopenia than in those without severe thrombocytopenia. Patients with thrombocytopenia showed a higher postoperative incidence of AKI and a higher requirement for dialysis than those without thrombocytopenia. The platelet count can easily be obtained via regular blood analysis of patients scheduled for LDLT and can be used to identify patients at risk for AKI.

Revising Pediatric Vancomycin Dosing Accounting for Nephrotoxicity in a Pharmacokinetic-Pharmacodynamic Model.

This study aimed to suggest an initial pediatric vancomycin dose regimen through population pharmacokinetic-pharmacodynamic modeling. A population pharmacokinetic approach was used to analyze vancomycin concentration-time data from a large pediatric cohort. Pharmacokinetic target attainment for patients with bloodstream isolates was compared with clinical outcome using logistic regression and classification and regression trees. Change in serum creatinine during treatment was used as an indicator of acute nephrotoxicity. Probability of acute kidney injury (50% increase from baseline) or kidney failure (75% increase from baseline) was evaluated using logistic regression. An initial dosing regimen was derived, personalized by age, weight, and serum creatinine, using stochastic simulations. Data from 785 hospitalized pediatric patients (1 day to 21 years of age) with suspected Gram-positive infections were collected. Estimated (relative standard error) typical clearance, volume of distribution 1, intercompartmental clearance, and volume of distribution 2 were (standardized to 70 kg) 4.84 (2.38) liters/h, 39.9 (8.15) liters, 3.85 (17.3) liters/h, and 37.8 (10.2) liters, respectively. While cumulative vancomycin exposure correlated positively with the development of nephrotoxicity (713 patients), no clear relationship between vancomycin area under the plasma concentration-time curve and efficacy was found (102 patients). Predicted probability of acute kidney injury and kidney failure with the optimized dosing regimen at day 5 was 10 to 15% and 5 to 10%, increasing by approximately 50% on day 7 and roughly 100% on day 10 across all age groups. This study presents the first data-driven pediatric dose selection to date accounting for nephrotoxicity, and it indicates that cumulative vancomycin exposure best describes risk of acute kidney injury and acute kidney failure.

Dosing vancomycin in the super obese: less is more.

Vancomycin remains the mainstay of empirical therapy directed against MRSA. National guidelines recommend empirical dosing based on total body weight with trough-level therapeutic drug monitoring (TDM), which may not be optimal in obese and super obese patients. Furthermore, nomograms for empirical vancomycin dosing by estimated kidney function pre-date standardization of creatinine assays. To determine an empirical vancomycin dosing strategy for obese and super obese adults that is consistent with the AUC monitoring paradigm. We conducted a population pharmacokinetic study using data obtained from routine peak and trough TDM of vancomycin in obese and super obese adults. An empirical dosing nomogram was developed using Monte Carlo simulation to identify vancomycin doses that optimize the probability of efficacy and minimize the probability of acute kidney injury based on AUC. A total of 346 patients were included encompassing a wide range of body weight (69.6-293.6 kg) and BMI (30.1-85.7 kg/m2) values. In the final model, vancomycin clearance (CLV) was described using a linear combination of age, serum creatinine, sex and allometrically scaled body weight. Monte Carlo simulation demonstrated that maintenance doses >4500 mg/day were not required to achieve pharmacodynamic AUC targets in obese and super obese patients at clinically relevant values of CLV. Empirical vancomycin dosing informed by common clinical variables, including standardized creatinine, with subsequent individualization using AUC-targeted TDM can optimize therapy in obese and super obese adults.