Developed Acute Kidney Injury Stage Research Articles

Furosemide stress test to predict acute kidney injury progression in critically ill children.

Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. Children 3months to 18years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7days of admission underwent FST (intravenous furosemide 1mg/kg). Urine output was measured hourly for the next 6h; a value > 2ml/kg within the first 2h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.

Risk factors of acute kidney injury in adult patients under veno-arterial extracorporeal membrane oxygenation support

ObjectiveTo investigate the incidence and risk factors of acute kidney injury (AKI) stage 3 in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. DesignA retrospective case-control study. SettingSingle center, Fuwai hospital. ParticipantsAdult VA-ECMO patients aged 18 years and older, treated from January 2020 to December 2022 were included. InterventionsThe patients were grouped by whether they developed AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 or < 3. Multivariate logistic regression was performed to evaluate risk factors of AKI stage 3. Measurements and main resultsAmong enrolled patients, 40 (53.3%) developed AKI stage 3. The in-hospital mortality of AKI stage 3 patients was significantly higher than that of AKI stage<3 patients (67.5% vs. 34.3%, p = 0.004). Multivariate logistic regression analysis revealed that concomitant hypertension [OR 0.250, 95% CI (0.063, 0.987), p = 0.048), pre-ECMO hemoglobin [OR 0.969, 95% CI (0.947, 0.992), p = 0.009], pre-ECMO lactate [OR 1.173, 95% CI (1.028, 1.339), p = 0.018], and pre-ECMO creatinine [OR 1.014, 95% CI (1.003, 1.025), p = 0.011] were independent risk factors for AKI stage 3. ConclusionThis study found a high incidence (53.3%) of AKI stage 3 in adult patients with VA-ECMO support and was associated with increased in-hospital mortality. Concomitant hypertension, low pre-ECMO hemoglobin, elevated pre-ECMO lactate and pre-ECMO creatinine were independent risk factors for AKI stage 3 in patients receiving VA-ECMO. It is imperative to identify and adjust these risk factors to enhance outcomes for those supported by VA-ECMO.

Acute kidney injury in infants hospitalized for viral bronchiolitis

We investigated prevalence of and factors associated with acute kidney injury (AKI) in a group of patients hospitalized with viral bronchiolitis. We retrospectively enrolled 139 children (mean age = 3.2 ± 2.1 months; males = 58.9%) hospitalized for viral bronchiolitis in a non-pediatric intensive care unit (PICU) setting. The Kidney Disease/Improving Global Outcomes creatinine criterion was used to diagnose AKI. We estimated basal serum creatinine by back-calculating it by Hoste (age) equation assuming that basal eGFR were the median age-based eGFR normative values. Univariate and multivariate logistic regression models were used to explore associations with AKI. Out of 139 patients, AKI was found in 15 (10.8%). AKI was found in 13 out of 74 (17.6%) patients with and in 2 out of 65 (3.1%) without respiratory syncytial virus (RSV) infection (p = 0.006). No patient required renal replacement therapies, while 1 out of 15 (6.7%) developed AKI stage 3, 1 (6.7%) developed AKI stage 2, and 13 (86.6%) developed AKI stage 1. Among the 15 patients with AKI, 13 (86.6%) reached the maximum AKI stage at admission, 1 (6.7%) at 48 h, and 1 (6.7%) at 96 h. At multivariate analysis, birth weight < 10th percentile (odds ratio, OR = 34.1; 95% confidence interval, CI = 3.6–329.4; p = 0.002), preterm birth (OR = 20.3; 95% CI = 3.1–129.5; p = 0.002), RSV infection (OR = 27.0; 95% CI = 2.6–279.9; p = 0.006), and hematocrit levels > 2 standard deviation score (SDS) (OR = 22.4; 95% CI = 2.8–183.6; p = 0.001) were significantly associated with AKI.Conclusion: About 11% of patients hospitalized with viral bronchiolitis in a non-PICU setting develop an AKI (frequently mild in degree). Preterm birth, birth weight < 10th percentile, hematocrit levels > 2SDS, and RSV infection are significantly associated with AKI in the setting of viral bronchiolitis.What is Known:• Viral bronchiolitis affects children in the first months of life and in 7.5% of cases it can be complicated by acute kidney injury (AKI).• No studies investigated associations with AKI in infants hospitalized for viral bronchiolitis.What is New:• About 11% of patients hospitalized with viral bronchiolitis can develop an AKI (frequently mild in degree).• Preterm birth, birth weight <10th percentile, hematocrit levels > 2 standard deviation score, and respiratory syncytial virus infection are associated with AKI development in infants with viral bronchiolitis.

Algorithm-based detection of acute kidney injury according to full KDIGO criteria including urine output following cardiac surgery: a descriptive analysis

BackgroundAutomated data analysis and processing has the potential to assist, improve and guide decision making in medical practice. However, by now it has not yet been fully integrated in a clinical setting. Herein we present the first results of applying algorithm-based detection to the diagnosis of postoperative acute kidney injury (AKI) comprising patient data from a cardiac surgical intensive care unit (ICU).MethodsFirst, we generated a well-defined study population of cardiac surgical ICU patients by implementing an application programming interface (API) to extract, clean and select relevant data from the archived digital patient management system. Health records of N = 21,045 adult patients admitted to the ICU following cardiac surgery between 2012 and 2022 were analyzed. Secondly, we developed a software functionality to detect the incidence of AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, including urine output. Incidence, severity, and temporal evolution of AKI were assessed.ResultsWith the use of our automated data analyzing model the overall incidence of postoperative AKI was 65.4% (N = 13,755). Divided by stages, AKI 2 was the most frequent maximum disease stage with 30.5% of patients (stage 1 in 17.6%, stage 3 in 17.2%). We observed considerable temporal divergence between first detections and maximum AKI stages: 51% of patients developed AKI stage 2 or 3 after a previously identified lower stage. Length of ICU stay was significantly prolonged in AKI patients (8.8 vs. 6.6 days, p < 0.001) and increased for higher AKI stages up to 10.1 days on average. In terms of AKI criteria, urine output proved to be most relevant, contributing to detection in 87.3% (N = 12,004) of cases.ConclusionThe incidence of postoperative AKI following cardiac surgery is strikingly high with 65.4% when using full KDIGO-criteria including urine output. Automated data analysis demonstrated reliable early detection of AKI with progressive deterioration of renal function in the majority of patients, therefore allowing for potential earlier therapeutic intervention for preventing or lessening disease progression, reducing the length of ICU stay, and ultimately improving overall patient outcomes.Graphical

Using Postoperative Coagulation Parameters Within 24 h After Liver Transplantation to Predict Incidence of Stage 3 Acute Kidney Injury (AKI).

BackgroundThis study aimed to investigate the relationship between coagulation function and the incidence of acute kidney injury (AKI) stage 3 within 24 h after liver transplantation (LT) and explore the predictive value of coagulation parameters for post-LT stage 3 AKI.Material/MethodsA retrospective study was conducted on 241 patients who underwent LT at the Renji Hospital affiliated with Shanghai Jiao Tong University School of Medicine between February 2021 and February 2022. The coagulation parameters within 24 h after LT and the incidence of post-LT AKI within 7 days were recorded. The correlation between post-LT coagulation function and post-LT stage 3 AKI was determined using binary logistic regression analysis.ResultsPost-LT AKI occurred in 99 cases (41.1%), 28 (28.3%) of which developed AKI stage 3. In univariate logistic regression analysis, multiple coagulation indexes of the AKI stage 3 group were worse than in the AKI stage 0–2 group. In multivariate logistic regression analysis, lower post-LT ADP-induced PLT aggregation rate (cut-off: 15.75%), higher D-dimer level (cut-off: 3.52 ug/ml), and prolonged R-value (cut-off: 7.5 min) within 24 h were independent risk factors for post-LT AKI stage 3. The AUROC value for predicting the incidence of post-LT AKI stage 3 combining the 3 indices was 0.835 (sensitivity: 83.3%, specificity: 76.9%). The decision curve showed that combining D-dimer, R-value, and ADP-induced PLT aggregation rate yielded the highest net benefit for predicting the incidence of stage 3 AKI.ConclusionsPost-LT coagulation function within 24 h correlated with the incidence of post-LT AKI stage 3. Lower ADP-induced PLT aggregation rate, higher D-dimer level, and prolonged R-value from the TEG were independent risk factors for the incidence of post-LT AKI stage 3.

Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report

BackgroundThrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown.Case presentationA 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation.ConclusionsWe suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

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.

MO414ACUTE KIDNEY INJURY AFTER ELECTIVE ENDOCRINE SURGERY: ARE PATIENTS WITH PRIMARY HYPERPARATHYROIDISM AT RISK?

Abstract Background and Aims Development of acute kidney injury (AKI) after elective endocrine surgery is underreported. We aimed to assess the prevalence of AKI among patients underwent surgery for primary hyperparathyroidism (PHPT) and thyroid surgery and compare risk of AKI between these cohorts. Method A retrospective cohort study included 299 patients who underwent successful selective parathyroidectomy (PTx) for PHPT, and 40 patients after thyroid surgery with comparable scope of the intervention (thyroid follicular cells tumor, non-invasive papillary thyroid carcinoma). AKI was defined according to KDIGO-2012 criteria. Results Change of serum creatinine before/after surgery differed significantly between PHPT and thyroid surgery group: type of surgery*time interaction p&amp;lt;0,0001 (repeated measures ANOVA after Box-Cox transformation) – fig.1. 109 patients (36,5%) in the PHPT group and 2 patients (5%) in the thyroid group met AKI criteria after PTx. Most of the patients developed AKI stage 1. Risk of AKI was significantly higher in the PHPT patients: RR=7,3 [2,19; 26,6], OR=10,9 [2,82; 46,6], р&amp;lt;0,0001. Patients in the thyroid surgery group were significantly younger than those in the PHPT group (41,5 [Q1-Q3: 30; 51] years vs 59 [Q1-Q3: 50,8; 67] years, respectively, p&amp;lt;0,0001), had higher mean baseline estimated glomerular filtration rate (eGFR) (91,1 ± 18 vs 78,8 ± 18,6 ml/min/1,73 m2 respectively, p=0,0001) and had less comorbidity index (p&amp;lt;0,0001). Hypertension encountered much more often in PHPT group vs thyroid group (69% and 22,5%, respectively, χ2 p&amp;lt;0,0001). Duration of surgery also differed between groups: 25 min [Q1-Q3: 20; 40] min in PHPT group vs 50 [Q1-Q3: 31; 62,5] min in thyroid group, p&amp;lt;0,0001. We hypothesized that acute decline of parathyroid hormone after PTx increases risk of AKI in the PHPT group. To evaluate whether type of surgery (PTx/thyroid surgery) is independently associated with risk of AKI, we used 1:1 pseudorandomization (Propensity Score Matching, “matchit” package, “nearest” method in R) to balance the baseline characteristics (age, BMI, comorbidity, baseline eGFR, duration of surgery, presence of hypertension). The 40 patients in the thyroid surgery group were matched to 40 patients in the PHPT group according to these confounders. After PSM the prevalence of AKI remained significantly higher in the PHPT group than in the thyroid surgery group (30% vs. 5%, respectively, RR=6 [95%CI: 1,7; 23,1], p=0,006), confirming that PTx is the independent risk factor of AKI. Conclusion We observed higher prevalence of AKI after PTx for PHPT comparing with patients after thyroid surgery. Our data suggests that PTx itself is the main risk factor of AKI development after elective endocrine surgery.

Severe acute kidney injury in critically ill COVID-19 patients.

BackgroundAcute kidney injury (AKI) is frequent in Coronavirus Infection Disease 2019 (COVID-19) patients. Factors associated with AKI in COVID-19 intensive care unit (ICU) patients and their outcomes have not been previously explored.MethodsProspective observational study of COVID-19 patients admitted to the ICUs of the Hospital Clínic of Barcelona (Spain), from March 25th to April 21st, 2020, who developed AKI stage 2 or higher (AKIN classification). The primary goal was to describe the characteristics of moderate-severe AKI of COVID-19 patients in an ICU context. As a secondary goal, we aimed to find independent predictors of AKI progression, Renal Replacement Therapy (RRT) requirement and mortality among these patients.ResultsDuring the study period, 52 out of 237 ICU patients, developed AKIN stage 2 or higher and were included in the study. A Sequential Organ Failure Assessment (SOFA) score at AKI diagnosis of 8 or higher was associated with RRT, OR 5.2, p 0.032. At the time of AKI diagnosis, patients had a worse liver profile and higher inflammation markers than at admission. Fifty per cent of the patients presented AKI progression from AKIN 2 to 3 and 28.85% required RRT. The use of corticosteroids in 69.2% of patients was associated with a reduced requirement of RRT, OR 0.13 (CI 95% 0.02–0.89), p 0.037. AKI was associated with high mortality (50%) and a longer hospital stay, median 35 vs 18 days (p 0.024).ConclusionsThe prevalence of moderate/severe AKI in COVID-19 patients admitted to the ICU is high and has a strong correlation with mortality and length of hospital stay.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40620-020-00918-7.

Prevalence of Acute Kidney Injury in Pediatric Patients with Congenital Heart Disease Following Open Heart Surgery

Background: Acute kidney injury (AKI) occurs in approximately 40% of children undergoing cardiac surgery and is a risk factor for morbidity and mortality. Such injury leads to several complications, including fluid and electrolyte disturbances. Objective: To determine prevalence of acute kidney injury in pediatric patients with congenital heart disease following open heart surgery. Patients and Methods: We conducted a case control study on 20 patients with congenital heart disease (10 males and 10 females) with mean age of 3.39 ± 1.17 years old, and a range from 1 to 5 years old. They were recruited from Pediatric Cardiothoracic Unit, Zagazig University Hospital and 20 sex and age matched healthy children worked as control group. Results: The mean age of our patients was 3.39 ± 1.17 years old with a range from 1 to 5 years. 50% were males and 50 % were females with no statistically significant difference between both groups regarding age and sex. about 1/3 of the studied group had ASD (30 %), while 1/4 of them had Fallot tetralogy (25 %), and only 15% of them had VSD, subaortic membrane and PM + VSD. The mean serum creatinine level was 0.8 ± 0.15mg/dl, with a range from 0.22 - 0.9 mg/dl. 70% of the patients had no acute kidney injury, 15% developed AKI stage 1 and 15% developed stage 2 AKI. In addition, all patients with AKI needed dialysis. Conclusion: Present study identified that high percentage of pediatric patients with congenital heart disease following open-heart surgery developed acute kidney injury.

Mild AKI is associated with mortality of patients who underwent cardiopulmonary bypass surgery.

Acute kidney injury (AKI) stage I is the most common stage of AKI observed among patients who underwent cardiac surgery with cardiopulmonary bypass (CPB). The relationship between AKI stage I and mortality requires further investigation. Patients aged 18 years or older who underwent cardiac surgery with CPB between July 1, 2013 and May 31, 2014, were reviewed in the present study. Patients were dichotomized into: i) The AKI stage I group, and ii) the non-AKI group. The primary measured characteristic in the present study was the relationship between AKI and mortality. Kaplan-Meier survival analyses were taken to obtain survival curves. A total of 1,846 patients were included in this present study. The mean age was 51.76±13.56 years. A total of 1,508 patients did not develop AKI and 338 developed AKI stage I. The mean follow-up period among survivors was 9.95±3.45 months. Kaplan-Meier survival analyses showed that patients with AKI stage I were at an increased mortality risk (P<0.0001). In multivariate Cox regression analysis, AKI stage I remained independently associated with a reduced survival. Using a subgroup analysis, patients with non-recovery AKI (defined as non-recovery AKI if the serum level does not return before surgery) had a higher mortality rate than patients with recovery AKI (P<0.0001). AKI stage I is the most common form of AKI and it is independently related to all-cause mortality in patients who underwent cardiovascular surgery with cardiopulmonary bypass.

Acute Kidney Injury in Pediatric Patients Treated with Vancomycin and Piperacillin-Tazobactam Versus Vancomycin and Cefotaxime: A Single-center Study.

BackgroundPrevious literature showed a higher incidence of acute kidney injury (AKI) in pediatric patients using vancomycin + piperacillin-tazobactam compared to cefepime + vancomycin. Our aim was to compare the incidence of developing AKI during the use of vancomycin + cefotaxime with that during the use of vancomycin + piperacillin-tazobactam in pediatric patients.MethodsThis was a retrospective, matched cohort study that used electronic records from May 1, 2015 through April 30, 2018 for all patients aged less than 16 years who received intravenous (IV) vancomycin + piperacillin-tazobactam or cefotaxime + vancomycin for at least 72 hours. AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Each patient from the vancomycin + piperacillin-tazobactam group was matched 1:1 with those in the vancomycin + cefotaxime group according to their age, chronic disease, gender, and the number of concomitant nephrotoxic agents. A total of 64 cases were included. Statistical analysis was performed using descriptive statistics and binary logistic regression.ResultsAKI developed in 10 of 32 patients (31.25%) who were using vancomycin + piperacillin-tazobactam. On the other hand, 13 of 32 patients (40.62%) were using cefotaxime + vancomycin (p = 0.047). Of the 10 patients who were on vancomycin + piperacillin-tazobactam regimen, 80% developed AKI Stage I. Of the 13 patients who were using cefotaxime + vancomycin, 46% developed AKI Stage II, although no statistical significance was noted in all stages. ConclusionOur study showed that patients treated with cefotaxime and vancomycin showed a higher incidence of AKI than patients treated with vancomycin and piperacillin-tazobactam, although the study showed no statistical significance.

Correlation between urinary biomarker and organ failure in patients with sepsis and patients after esophagectomy: a prospective observational study

BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is a diagnostic marker for acute kidney injury (AKI). NGAL expression is highly induced not only in kidney injury but also in bacterial infection, inflammation, and cancer. The factors regulating NGAL expression are proinflammatory cytokines, and plasma NGAL levels have been increased in septic shock. However, there are no reports of urine neutrophil gelatinase-associated lipocalin (uNGAL) levels after open esophagectomy.MethodsWe prospectively enrolled critically ill patients, including patients with sepsis (n = 45) and patients who underwent open esophagectomy (n = 40). We compared vital signs, PaO2/FIO2, serum C-reactive protein (CRP) levels, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and uNGAL levels between the sepsis group and the esophagectomy group. Then, we investigated whether uNGAL is associated with the severity of illness and organ failure, and whether uNGAL is a reliable screening test for AKI.ResultsThe median uNGAL levels, APACHE II score, SOFA score, and serum CRP levels were significantly (p < 0.001) higher in the sepsis group than in the esophagectomy group on ICU day 1. In the sepsis group, uNGAL levels were significantly (p < 0.05) correlated with APACHE II score and SOFA score on intensive care unit (ICU) day 1, 2, and 3. In the esophagectomy group, uNGAL levels were significantly (p < 0.05) correlated with SOFA score on ICU day 3 and 4. In the sepsis group, 1 patient developed AKI stage 2 and 6 patients developed AKI stage 3. No patients developed AKI in the esophagectomy group. In a total of 85 patients of this study, 80 patients had an abnormal value of uNGAL and only 7 patients (8.7%) of those 80 patients developed AKI.ConclusionsuNGAL levels were correlated with the severity of illness and organ failure in critically ill patients. The value of uNGAL increases under the surgical and inflammatory responses, thereby losing a significance of a screening test of AKI in critically ill patients.

Urinary [TIMP-2] \xd7 [IGFBP-7] for predicting acute kidney injury in patients undergoing orthotopic liver transplantation

BackgroundThe product of the concentrations of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (urinary [TIMP-2] × [IGFBP-7]) has been suggested as biomarker for early detection of acute kidney injury (AKI) in various clinical settings. However, the performance of urinary [TIMP-2] × [IGFBP-7] to predict AKI has never been assessed in patients undergoing orthotopic liver transplantation (OLT). Thus, the aim of this study was to assess the early predictive value of urinary [TIMP-2] × [IGFBP-7] for the development of AKI after OLT.MethodsIn this observational study, urinary [TIMP-2] × [IGFBP-7] was measured in samples from adult OLT patients. AKI was diagnosed and classified according to KDIGO criteria. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of urinary [TIMP-2] × [IGFBP-7] for the development of AKI.ResultsForty patients (mean age 55 ± 8 years) were included. Twenty-eight patients (70%) developed AKI stage 1, 2, or 3 within 48 h after OLT. Urinary [TIMP-2] × [IGFBP-7] was not predictive for AKI at the end of OLT (AUC: 0.54, CI [0.32–0.75], P = 0.72), at day 1 (AUC: 0.60, CI [0.41–0.79], P = 0.31), or day 2 after OLT (AUC: 0.63, CI [0.46–0.8], P = 0.18).ConclusionBased on our results, routine clinical use of urinary [TIMP-2] × [IGFBP-7] cannot be recommended for risk assessment of AKI in patients undergoing OLT.

Radioisotopic Evaluation Glomerular Filtration Rate (GFR) before and after Kidney Donation

Background Because of the decrease of the nephron mass following nephrectomy, kidney donors (KD) develop a partial loss of renal function defined as Acute Kidney Injury (AKI) according to KDIGO criteria (Clinical Practice Guideline, 2012). The recovery of renal function following AKI is mainly ascribed to the concept of renal functional reserve (RFR), defined as the capacity of the kidney to increase glomerular filtration rate (GFR). However, only few studies correlated RFR in KD with long term functional outcomes. Aim of the Study The aim of the present study was to analyse 30 KD renal function before nephrectomy, in the immediate postoperative period and 1 year after the surgical procedure, developing the concept of estimated RFR (eRFR) for the long term follow-up of renal function in KD. Results KD mean age at the time of donation was 54.4 years (min-max, 30-78), mean serum creatinine 0.73 mg/dL (0.5-0.96), eGFR (CKD-EPI) 99 mL/min/1.73m2 (69-119) and radioisotope (51Cr-EDTA) GFR 101.4 mL/min (78-129). The split function was evaluated by concomitant scintigraphy using 99mTc-MAG: the mean percentage of renal function of right kidney was 48% (43-56) and left 52% (44-57), respectively. As expected, immediately after nephrectomy all KD worsened renal function: the mean percentage increase of serum creatinine was 79% (50-112.2%) within 72 hours post-surgery; most of KD (25/30) developed AKI stage 1, and 5 KD AKI stage 2 according to KDIGO criteria. Seven days after surgery, renal recovery was observed in all cases: the mean percentage increase of serum creatinine (50.6%) was significantly lower than the zenith of serum creatinine. These results suggest a potential gain of about 30% in comparison to the starting value of the right kidney. One year after nephrectomy (all KD were subjected to left nephrectomies), we studied KD renal function (GFR) by radioisotopic evaluation using 51Cr-EDTA and we then compared it with the split radioisotope (51Cr-EDTA) GFR of the right kidney at the first scintigraphic evaluation. Mean GFR was 68.8 mL/min (50-87) vs. 48.6 mL/min (39.7-60.4) before donation with an average GFR increase of 20 mL/min (0.8-45.6) and a percentage increase of the right renal function up to 110% (mean 42%, min 1.4%). Conclusions The results of this study show that radioisotopic evaluation is feasible and allows an estimated determination of RFR at different time points after nephrectomy in KD. We observed a compensatory hypertrophy due to RFR in all the 30 KD included in the study, independently from age and co-morbidities such as elevated BMI and hypertension. The limitation of this study is the evaluation of RFR only after the decrease of the nephron mass due to donation: we have now started a kidney stress test with a protein load to estimate RFR of KD before surgery with the aim of finding a correlation with radioisotpic GFR after nephrectomy.

Acute Kidney Injury After Cardiac Transplantation: Foe or Common Innocent Bystander?

BackgroundHeart transplantation (HT) is regarded as the treatment of choice for end-stage heart failure (ESHF) patients. Severe acute kidney injury (AKI) after HT is a frequent clinical problem with devastating consequences for HT recipients. MethodsData from 112 ESHF patients undergoing HT in 2010–2015 were retrospectively reviewed. The primary end point was the development of AKI stage III, and secondary outcomes were in-hospital and 1-year mortality according to Kidney Disease Improving Global Outcomes criteria. ResultsIn total, 81 patients (72.3%) developed AKI, of which 33 (29.4%) developed AKI stage I, 18 (16%) stage II, and 30 (26.7%) stage III; within this group, 27 recipients (24%) required renal replacement therapy (RRT). Overall hospital mortality was 14%. However, when stratifying by AKI stage, hospital mortality increased from 0% to 46% comparing recipients without AKI and those with AKI stage III, respectively (P = .001). In the same way, 1-year mortality increased from 6% to 53% for recipients without AKI compared with those who developed AKI stage III (log-rank test for trend: P = .001). Recipients that required RRT had a 1-year mortality of 59.2% compared with 5.8% in those without RRT requirement. ConclusionsThe findings indicate that AKI stage III is common after HT and adversely affects early and late mortality. Clinical variables together with perioperative hemodynamic assessment could add more powerful prognostic information to predict severe AKI before HT and therefore evaluate potential heart-kidney recipients.

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels

BackgroundFurosemide responsiveness (FR) is determined by urine output after furosemide administration and has recently been evaluated as a furosemide stress test (FST) for predicting severe acute kidney injury (AKI) progression. Although a standardized furosemide dose is required for FST, variable dosing is typically employed based on illness severity, including renal dysfunction in the clinical setting. This study aimed to evaluate whether FR with different furosemide doses can predict AKI progression. We further evaluated the combination of an AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for predicting AKI progression.ResultsWe retrospectively analyzed 95 patients who were treated with bolus furosemide in our medical–surgical intensive care unit. Patients who had already developed AKI stage 3 were excluded. A total of 18 patients developed AKI stage 3 within 1 week. Receiver operating curve analysis revealed that the area under the curve (AUC) values of FR and plasma NGAL were 0.87 (0.73–0.94) and 0.80 (0.67–0.88) for AKI progression, respectively. When plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI, indicating that plasma NGAL measurements were sufficient to predict AKI progression. We further evaluated the performance of FR in 51 patients with plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67–0.94) for AKI progression in this population with high NGAL levels.ConclusionsAlthough different variable doses of furosemide were administered, FR revealed favorable efficacy for predicting AKI progression even in patients with high plasma NGAL levels. This suggests that a combination of FR and biomarkers can stratify the risk of AKI progression in a clinical setting.

Renal function at 1year after cardiac transplantation rather than acute kidney injury is highly associated with long-term patient survival and loss of renal function - a retrospective cohort study.

This study aimed to assess the association between acute kidney injury (AKI), renal function 1year after transplantation, and long-term adverse outcomes after cardiac transplantation. A retrospective cohort study was performed including 471 adult cardiac transplantation recipients that survived the first postoperative year between 1984 and 2012. Primary outcome variables were long-term overall and renal survival. During the first postoperative week, 40% (n=188) of the recipients developed AKI stage I, 22% (n=104) stage II, and 13% (n=63) stage III, and 4% (n=17) required temporary renal replacement therapy (RRT). No crude association was found between the development of AKI and long-term mortality (P=0.50) or chronic RRT dependence (P=0.27). In multivariable analysis, only AKI requiring RRT was associated with an increased risk for mortality (HR=2.59, 95% CI=1.17-5.73) and chronic RRT dependence (HR= 13.14, 95% CI=3.26-52.92). While less severe episodes of AKI did not affect the recipient's long-term prognosis, renal function 1year after transplantation had a strong association with long-term outcome. An eGFR <30ml/min/1.73 was independently associated with mortality (HR=2.69, 95% CI=1.68-4.32) and an eGFR <60ml/min/1.73 with chronic RRT dependence (eGFR 30-59: HR=3.57, 95% CI=1.41-9.01; eGFR <30: HR=16.53, 95% CI=5.72-47.78). In conslusion, besides AKI requiring RRT, less severe episodes of AKI have limited implications for the recipient's prognosis and long-term outcome after cardiac transplantation is strongly determined by the degree of renal impairment 1year after transplantation.

Urinary [TIMP-2] × [IGFBP7] for risk prediction of acute kidney injury in decompensated heart failure.

In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP-2] × [IGFBP7], a new US Food and Drug Administration-cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients. In patients with ADHF, urinary [TIMP-2] × [IGFBP7] is associated with moderate to severe AKI and related to increased mortality. We enrolled 400 patients in the emergency department at Robert-Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP-2] × [IGFBP7] (units: [ng/mL]2 /1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0. Forty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2-3 within 7 days. Urinary [TIMP-2] × [IGFBP7] discriminated for AKI stage 2-3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72-0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65-0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2-3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP-2] × [IGFBP7] >2.0 and AKI 2-3. Urinary [TIMP-2] × [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.

Plasma Levels of Receptor Interacting Protein Kinase-3 (RIP3), an Essential Mediator of Necroptosis, are Associated with Acute Kidney Injury in Critically Ill Trauma Patients.

Receptor interacting protein kinase-3 (RIP3) is a key mediator of necroptosis, a form of regulated cell death recently implicated in murine models of renal ischemia-reperfusion injury and transfusion-associated endothelial injury. The importance of necroptosis in human AKI is unknown. We hypothesized that plasma RIP3 concentrations would be associated with acute kidney injury (AKI) after severe trauma. We performed a case-control study nested in a prospective cohort of critically ill trauma patients. AKI was defined by AKI Network creatinine criteria within 6 days of presentation. Of 158 cohort subjects, we selected 13 who developed AKI stage 2 or 3, 27 with AKI stage 1, and 40 without AKI. We compared plasma RIP3 concentrations across these groups at presentation and 48 h. Since red blood cell (RBC) transfusion is an AKI risk factor, we also tested the association of RBCs transfused during resuscitation with RIP3 levels. Median plasma RIP3 concentration rose more than 10-fold from presentation (15.6 (interquartile range 15.6-41.3) pg/mL) to 48 h (164.7 (66.9-300.6) pg/mL; P <0.001). RIP3 concentrations at 48 h were associated with AKI stage (no AKI: 144.8 (58.6-234.9) pg/mL; AKI stage 1: 165.8 (43.0-310.9) pg/mL; AKI stage 2-3: 365.5 (155.1-727.5) pg/mL; P = 0.010) whereas this association was not seen at presentation (P = 0.324). RBC transfusions were also associated with 48-h plasma RIP3 (no RBCs: 99.4 (15.6-166.1) pg/mL; 1-5 units: 182.6 (98.5-274.1) pg/mL; >5 units: 341.8 (150.1-423.8) pg/mL; P <0.001). In critically ill trauma patients, plasma levels of the necroptosis mediator RIP3 at 48 h were associated with AKI stage and RBC transfusions.