SOX4 silencing alleviates renal injury in rats with acute renal failure by inhibiting the NF-κB signaling pathway and reducing apoptosis and oxidative stress.

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

To bite the hand that feeds you: A case of thrombotic microangiopathy due to Tiger snake bite.

This report details the case of a 51-year-old man with a Tiger snake bite who developed systemic envenomation, coagulopathy and thrombotic microangiopathy (TMA) requiring renal replacement therapy. He received plasma exchange as additional therapy while awaiting confirmation of the cause of the TMA. We discuss clinical decision making in detection of systemic envenomation and management of the rare complication of TMA, as well as current Australian guidelines around antivenom administration. This is the fourth known documented case of TMA from a Tiger snake bite in Australia.

Comparison of diluted vs concentrated regional citrate anticoagulation in continuous renal replacement therapy: A quasi-experimental study.

BACKGROUND: The incidence of coagulation of continuous renal replacement therapy circuits remains high. To the best of our knowledge, no scholar has published a protocol to avoid management errors when different types of citrates coexist in the same Intensive Care Unit. AIM: To assess the safety and efficacy of the unification of two protocols with different concentrations of citrate solution. STUDY DESING: A prospective, quasi-experimental study was carried out in the intensive care unit of a tertiary referral hospital (in Barcelona, Spain), over 3 years. Consecutive adult patients requiring continuous renal replacement therapy with citrate were included. The sample was divided into two groups, a control group (concentrated citrate) and an intervention group (diluted citrate). The decision to initiate anticoagulation with diluted (18 mmol/L) or concentrated (136 mmol/L) citrate was made based on the machine available and the decision of the doctor responsible for the patient. It was not possible to randomize the sample. Both protocols were matched with a starting citrate dose of 3.5 mmol/L, and a dialysis solution was used. Post-filter replacement was not used, and the citrate solution was the only fluid administered pre-filter. RESULTS: The analysis included 59 circuits in the concentrated citrate group and 40 circuits in the diluted citrate group. An increased need for electrolyte replacement was observed in the diluted group (p < .001). The concentrated citrate group had a longer filter life (p < .05), and there was a slight trend toward alkalosis. CONCLUSION: The diluted citrate group had a higher incidence of electrolyte replacement. The concentrated citrate group had longer circuit lifespan and a trend toward metabolic alkalosis, although this was not statistically significant. If these conclusions are considered, the protocol can be unified. RELEVANCE TO CLINICAL PRACTICE: The present work aims to provide information on the differences in the use of regional anticoagulation with diluted or concentrated citrate. The objective is to pay special attention to aspects that can lead to complications. The unified protocol proposed in this paper could be extrapolated to any machine on the market that uses either of these two types of citrate concentration.

Change in prefilter pressure as a key determinant in the decision to return blood in continuous renal replacement therapy: An observational study.

BACKGROUND: During continuous renal replacement therapy (CRRT), circuit coagulation is an important event that can result in suboptimal outcomes. Nurses must remain alert throughout the treatment and observe machine pressures. Transmembrane pressure (TMP) is commonly used for monitoring but it is sometimes too late to return blood to the patient. AIM: To compare the capacity of prefilter pressure (FP) versus TMP to predict the risk of circuit coagulation in adult patients with acute renal failure on CRRT. STUDY DESIGN: An observational, longitudinal, prospective study. This study was carried out in a tertiary referral hospital over 2 years. Data collected included the following variables: TMP, filter or FP, effluent pressure, venous and arterial pressure, filtration fraction, and ultrafiltration constant of each circuit. Means and their trends over time were collected, for both diffusive and convective therapy and for two membrane types. RESULTS: A total of 151 circuits (24 polysulfone and 127 acrylonitrile) were analysed, from 71 patients (n = 22 [34%] women; mean age, 66.5 [36-84] years). Of the total treatments, 80 were diffusive, and the rest were convective or mixed. In the diffusive circuits, a progressive rise in FP was observed without an increase in TMP and with an increasing trend in effluent pressure. Circuit lifespan was between 2 and 90 h. In 11% (n = 17) of the cases, the blood could not be returned to the patient. CONCLUSION: These findings allowed the creation of graphs that indicate the appropriate point to return blood to the patient. FP was a major determinant in this decision; in most cases, TMP was not a reliable parameter. Our findings are applicable to convective, diffusive, and mixed treatments as well as both types of membranes used in this acute setting. RELEVANCE TO CLINICAL PRACTICE: This study provides two clear reference graphs showing risk scales for the assessment of circuit pressures in CRRT. The graphs proposed here can be used to evaluate any machine on the market and the two types of membranes used in this acute setting. Both convective and diffusive circuits can be assessed, allowing safer evaluation in patients who change treatment.

El catéter como elemento fundamental en las terapias de depuración renal / The catheter as a fundamental element in renal cleansing therapies

El término “catéter” es muy conocido para las enfermeras, sin embargo, el manejo de las vías para los pacientes con fallo renal es un tema que ofrece cierta dificultad.Las facetas específicas con relación a este tipo de catéteres y el tratamiento depurativo renal son el objetivo de este capítulo. Se analiza cómo hacer el cálculo del flujo de sangre, cómo elegir un buen catéter según su morfología, cuál es la técnica mejor para conservarlo y de qué forma sellarlo cuando se deje en reposo, sin tratamiento depurativo.Estos y otros conocimientos fundamentales se describirán, a partir de la evidencia hallada en la literatura. (AU)

The word catheter is well known to nurses, however, its management for patients with renal failure is a subject that offers some difficulty.The problems with this specific catheter and the renal purifying treatment are the objective of this paper. It analyses how to calculate the blood flow, how to choose a good catheter according to its morphology, what is the best technique to preserve it and how to lock it when it is left at rest, without any purifying treatment.These and other fundamental knowledge will be described, based on the evidence founded in the literature. (AU)

Intensive Care Unit-Acquired Weakness in Patients With Acute Kidney Injury: A Contemporary Review.

Acute kidney injury (AKI) and intensive care unit-acquired weakness (ICU-AW) are 2 frequent complications of critical illness that, until recently, have been considered unrelated processes. The adverse impact of AKI on ICU mortality is clear, but its relationship with muscle weakness-a major source of ICU morbidity-has not been fully elucidated. Furthermore, improving ICU survival rates have refocused the field of intensive care toward improving long-term functional outcomes of ICU survivors. We begin our review with the epidemiology of AKI in the ICU and of ICU-AW, highlighting emerging data suggesting that AKI and AKI treated with kidney replacement therapy (AKI-KRT) may independently contribute to the development of ICU-AW. We then delve into human and animal data exploring the pathophysiologic mechanisms linking AKI and acute KRT to muscle wasting, including altered amino acid and protein metabolism, inflammatory signaling, and deleterious removal of micronutrients by KRT. We next discuss the currently available interventions that may mitigate the risk of ICU-AW in patients with AKI and AKI-KRT. We conclude that additional studies are needed to better characterize the epidemiologic and pathophysiologic relationship between AKI, AKI-KRT, and ICU-AW and to prospectively test interventions to improve the long-term functional status and quality of life of AKI survivors.

Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.

Outcomes Among Patients Hospitalized With COVID-19 and Acute Kidney Injury.

RATIONALE & OBJECTIVE: Outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) are not well understood. The goal of this study was to investigate the survival and kidney outcomes of these patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients (aged≥18 years) hospitalized with COVID-19 at 13 hospitals in metropolitan New York between March 1, 2020, and April 27, 2020, followed up until hospital discharge. EXPOSURE: AKI. OUTCOMES: Primary outcome: in-hospital death. SECONDARY OUTCOMES: requiring dialysis at discharge, recovery of kidney function. ANALYTICAL APPROACH: Univariable and multivariable time-to-event analysis and logistic regression. RESULTS: Among 9,657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1,000 patient-days. Incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1-3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. Taking those without AKI as the reference group, we observed greater risks for in-hospital death for patients with AKI 1-3 and AKI 3D (HRs of 5.6 [95% CI, 5.0-6.3] and 11.3 [95% CI, 9.6-13.1], respectively). After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI 1-3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI 3D (adjusted HR, 6.4 [95% CI, 5.5-7.6]) compared with those without AKI. Among patients with AKI 1-3 who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI 3D who survived, 30.6% remained on dialysis at discharge, and prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (adjusted OR, 9.3 [95% CI, 2.3-37.8]). LIMITATIONS: Observational retrospective study, limited to the NY metropolitan area during the peak of the COVID-19 pandemic. CONCLUSIONS: AKI in hospitalized patients with COVID-19 was associated with significant risk for death.

Estimating Shortages in Capacity to Deliver Continuous Kidney Replacement Therapy During the COVID-19 Pandemic in the United States.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, New York encountered shortages in continuous kidney replacement therapy (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis. To inform planning for current and future crises, we estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. STUDY DESIGN: We developed mathematical models to project nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation model, the Harvard Global Health Institute model, and published literature. SETTING & POPULATION: US patients hospitalized during the initial wave of the COVID-19 pandemic (February 6, 2020, to August 4, 2020). INTERVENTION: CKRT. OUTCOMES: CKRT demand and capacity at peak resource use; number of states projected to encounter CKRT shortages. MODEL, PERSPECTIVE, & TIMEFRAME: Health sector perspective with a 6-month time horizon. RESULTS: Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval, 910-1,568) machines, and shortages in 6 states at peak resource use. In sensitivity analyses, varying assumptions around: (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of acute kidney injury stage 3 requiring dialysis requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3 to 8 states (933-1,282 machines) and 4 to 8 states (945-1,723 machines), respectively. In the best- and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines). LIMITATIONS: Parameter estimates are influenced by assumptions made in the absence of published data for CKRT capacity and by the Institute for Health Metrics and Evaluation model's limitations. CONCLUSIONS: Several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. These findings, although based on limited data for CKRT demand and capacity, suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.

Urgent Peritoneal Dialysis in Patients With COVID-19 and Acute Kidney Injury: A Single-Center Experience in a Time of Crisis in the United States.

At Montefiore Medical Center in The Bronx, NY, the first case of coronavirus disease 2019 (COVID-19) was admitted on March 11, 2020. At the height of the pandemic, there were 855 patients with COVID-19 admitted on April 13, 2020. Due to high demand for dialysis and shortages of staff and supplies, we started an urgent peritoneal dialysis (PD) program. From April 1 to April 22, a total of 30 patients were started on PD. Of those 30 patients, 14 died during their hospitalization, 8 were discharged, and 8 were still hospitalized as of May 14, 2020. Although the PD program was successful in its ability to provide much-needed kidney replacement therapy when hemodialysis was not available, challenges to delivering adequate PD dosage included difficulties providing nurse training and availability of supplies. Providing adequate clearance and ultrafiltration for patients in intensive care units was especially difficult due to the high prevalence of a hypercatabolic state, volume overload, and prone positioning. PD was more easily performed in non-critically ill patients outside the intensive care unit. Despite these challenges, we demonstrate that urgent PD is a feasible alternative to hemodialysis in situations with critical resource shortages.

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report.

We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/glucose cotransporter 2 (SGLT2). The patient presented with hematuria, non-nephrotic-range proteinuria, and serum creatinine level of 6.8 (baseline, 1.1-1.3) mg/dL. There was no recent use of radiocontrast agents or exposure to other nephrotoxins. The patient subsequently required hemodialysis. Due to recent antibiotic use (ampicillin-sulbactam), acute interstitial nephritis was considered in the differential diagnosis. Kidney biopsy was performed, which showed the presence of osmotic nephropathy. The patient's kidney function returned to baseline after 2 weeks of hemodialysis. This case provides evidence of an association of osmotic nephropathy with the use of canagliflozin and discusses potential mechanisms. We recommend kidney biopsy for cases of severe AKI associated with SGLT2 inhibitors to better understand the relationship of this complication with the use of this class of medications.

Acute Kidney Injury Events in Patients With Type 2 Diabetes Using SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease and prevent heart failure events. However, SGLT2 inhibitors may increase the risk for acute kidney injury (AKI). Our objective was to assess whether SGLT2 inhibitor use, compared with all other glucose-lowering drugs (oGLDs), is associated with increased rates of AKI. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba, Canada, with type 2 diabetes mellitus followed up from June 2014 until March 2017. EXPOSURES: Initial SGLT2 inhibitor or oGLD use ascertained through a province-wide outpatient prescription database. OUTCOME: The primary outcome was incident AKI, identified either by an increase in serum creatinine level and/or hospital discharge codes for AKI while taking glucose-lowering drugs (on-treatment approach). ANALYTICAL APPROACH: A propensity score analysis was used to assemble groups of incident users of SGLT2 inhibitors and a 1:1 matched set of oGLD users. The rate of AKI was compared across matched groups using cause-specific hazards models. Sensitivity analyses considered exposure to be constant throughout follow-up after initiation of the drug treatment (intention-to-treat approach) or incorporated recurrent exposures (new user design). RESULTS: Comparing 4,778 incident users of SGLT2 inhibitors with 4,778 incident users of oGLDs, there were no differences observed in the primary outcome (HR, 0.64; 95% CI, 0.40-1.03; P = 0.06) using an on-treatment approach. In neither set of sensitivity analyses were SGLT2 inhibitors associated with increased risk for AKI. LIMITATIONS: Drug choice may have been related to AKI risk, laboratory data were obtained from clinical care, and changes in adverse event reporting may have followed the US Food and Drug Administration warning. There were insufficient data to compare individual SGLT2 inhibitors. CONCLUSIONS: Compared with oGLDs, SGLT2 inhibitors were not observed to be associated with increased risk for AKI in a clinical population-based cohort.

AKI-A Relevant Safety End Point?

Acute kidney injury (AKI) is a common outcome evaluated in clinical studies, often as a safety end point in a variety of cardiovascular, kidney disease, and other clinical trials. AKI end points that include modest increases in serum creatinine levels from baseline may not associate with patient-centered outcomes such as initiation of dialysis, sustained decline in kidney function, or death. Surprisingly, data from several randomized controlled trials have suggested that in certain settings, the development of AKI may be associated with favorable outcomes. AKI safety end points that are nonspecific and may not associate with patient-centered outcomes could result in beneficial therapies being inappropriately withheld or never developed for commercial use. We review several issues related to commonly used AKI definitions and suggest that future work in AKI use more patient-centered AKI end points such as major adverse kidney events at 30 days or other later time points.

Interstitial Nephritis Secondary to Vedolizumab Treatment in Crohn Disease and Safe Rechallenge Using Steroids: A Case Report.

Vedolizumab is a gut-selective humanized monoclonal antibody that binds selectively to the α4 ß7 integrin and acts as a lymphocyte-homing antagonist. It is indicated in ulcerative colitis and Crohn disease. We report a case of acute interstitial nephritis following vedolizumab infusion in a 55-year-old white woman treated for severe Crohn disease resistant to several therapies. Other kidney disease causes were ruled out. Glucocorticoids were administrated, leading to full renal recovery. In the absence of other therapeutic options, vedolizumab was re-administered along with transient corticosteroids; this treatment was well tolerated. Fewer than 10 cases of immunoallergic acute interstitial nephritis following treatment with monoclonal antibody have previously been reported in the literature. The pathophysiology of delayed-type hypersensitivity secondary to monoclonal antibody therapeutics is discussed in this case report.

Effect of sustained low efficient dialysis versus continuous renal replacement therapy on renal recovery after acute kidney injury in the intensive care unit: A systematic review and meta-analysis.

Critically ill adults with acute kidney injury (AKI) experience considerable morbidity and mortality. Controversy remains regarding the optimal renal replacement intervention for these patients. Our systematic review aimed to determine the effect(s) of sustained low-efficiency dialysis (SLED) compared with continuous renal replacement (CRRT) therapy on relevant patient outcomes. A systematic search of Medline, Embase, CINAHL and the Cochrane Library was conducted. Identified citations were screened independently in duplicate for relevance, and the methodological quality of included studies was evaluated. Data were extracted on study, patient and intervention characteristics and relevant clinical outcomes. Results were pooled using inverse variance fixed and random effects meta-analysis. A total of 1564 patients from 18 studies were included. Meta-analysis results indicated no statistically significant difference in our primary outcome, overall proportion of renal recovery (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.63-1.20, I2 = 66%). No significant difference was observed for the secondary outcome of time to renal recovery (mean difference 1.33, 95% CI 0.23-2.88, I2 = 0%). Statistically, SLED was marginally favoured over CRRT for the secondary outcome of mortality (RR 1.21, 95% CI 1.02-1.43, I2 = 47%); however, this diminished when sensitivity analysis of only randomized controlled trials was conducted (RR 1.25, 95% CI 1.00-1.57, I2 = 0%). There appears to be no clear for advantage continuous renal replacement in the hemodynamically unstable patient. Currently, both modalities are safe and effective means of treating AKI in the critically ill adult.

End Points for Clinical Trials in Acute Kidney Injury.

Acute kidney injury (AKI) is an increasingly common and feared complication in hospitalized patients. The selection of appropriate primary and secondary end points is critical to the design and eventual success of clinical trials aimed at preventing and treating AKI. In this article, we provide an overview of AKI definitions and suggestions on the rational selection of end points for clinical trials in various settings, including the prevention of contrast-induced AKI, prevention of cardiac surgery-associated AKI, treatment of established AKI, and treatment of dialysis-requiring AKI.

Acute Kidney Injury Incidence in Noncritically Ill Hospitalized Children, Adolescents, and Young Adults: A Retrospective Observational Study.

BACKGROUND: Acute kidney injury (AKI) has been characterized in high-risk pediatric hospital inpatients, in whom AKI is frequent and associated with increased mortality, morbidity, and length of stay. The incidence of AKI among patients not requiring intensive care is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 13,914 noncritical admissions during 2011 and 2012 at our tertiary referral pediatric hospital were evaluated. Patients younger than 28 days or older than 21 years of age or with chronic kidney disease (CKD) were excluded. Admissions with 2 or more serum creatinine measurements were evaluated. FACTORS: Demographic features, laboratory measurements, medication exposures, and length of stay. OUTCOME: AKI defined as increased serum creatinine level in accordance with KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Based on time of admission, time interval requirements were met in 97% of cases, but KDIGO time window criteria were not strictly enforced to allow implementation using clinically obtained data. RESULTS: 2 or more creatinine measurements (one baseline before or during admission and a second during admission) in 2,374 of 13,914 (17%) patients allowed for AKI evaluation. A serum creatinine difference ≥0.3mg/dL or ≥1.5 times baseline was seen in 722 of 2,374 (30%) patients. A minimum of 5% of all noncritical inpatients without CKD in pediatric wards have an episode of AKI during routine hospital admission. LIMITATIONS: Urine output, glomerular filtration rate, and time interval criteria for AKI were not applied secondary to study design and available data. The evaluated cohort was restricted to patients with 2 or more clinically obtained serum creatinine measurements, and baseline creatinine level may have been measured after the AKI episode. CONCLUSIONS: AKI occurs in at least 5% of all noncritically ill hospitalized children, adolescents, and young adults without known CKD. Physicians should increase their awareness of AKI and improve surveillance strategies with serum creatinine measurements in this population so that exacerbating factors such as nephrotoxic medication exposures may be modified as indicated.

Incidence and risk factors of acute kidney injury following transcatheter aortic valve replacement.

AIM: This study aimed to determine the incidence and risk factors of acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR). METHODS: We included all adult patients undergoing TAVR for aortic stenosis from 1 January 2008 to 30 June 2014 at a tertiary referral hospital. AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. We performed a multivariate logistic regression to identify factors associated with post-procedural AKI occurrence. RESULTS: Three hundred eighty-six patients met the inclusion criteria, of which 106 (28%) developed AKI. In multivariate analysis, AKI development was independently associated with a transapical approach (odds ratio (OR), 2.81; 95% confidence interval (CI), 1.72-4.65 compared with transfemoral approach) and the need for an intra-aortic balloon pump (OR, 9.11; 95% CI, 1.77-68.29). Higher baseline renal function (OR, 0.78 per 10 mL/min per 1.73 m2 increment in glomerular filtration rate; 95% CI, 0.68-0.87) was significantly associated with a decreased risk of AKI. After adjustment for the Society of Thoracic Surgeons' risk score, post-procedural AKI development remained significantly associated with an increased in-hospital (OR, 4.74; 95% CI, 1.39-18.48) and 6-month mortality (OR, 4.66; 95% CI, 2.32-9.63). CONCLUSION: In a cohort of patients undergoing TAVR for aortic stenosis, AKI commonly occurred and was significantly associated with increased mortality. Baseline renal function, procedure approach and the need for circulatory support were important predictive factors for post-procedural AKI occurrence.

Urine Biomarkers and Perioperative Acute Kidney Injury: The Impact of Preoperative Estimated GFR.

BACKGROUND: The interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear. STUDY DESIGN: Post hoc analysis of prospective cohort study. SETTING & PARTICIPANTS: The 1,219 TRIBE-AKI Consortium adult cardiac surgery cohort participants. PREDICTOR: Unadjusted postoperative urinary biomarkers of AKI measured within 6 hours of surgery. OUTCOME: AKI was defined as AKI Network stage 1 (any AKI) or higher, as well as a doubling of serum creatinine level from the preoperative value or the need for post-operative dialysis (severe AKI). MEASUREMENTS: Stratified analyses by preoperative estimated glomerular filtration rate (eGFR) ≤ 60 versus > 60mL/min/1.73m(2). RESULTS: 180 (42%) patients with preoperative eGFRs≤60mL/min/1.73m(2) developed clinical AKI compared with 246 (31%) of those with eGFRs>60mL/min/1.73m(2) (P<0.001). For log2-transformed biomarker concentrations, there was a significant interaction between any AKI and baseline eGFR for interleukin 18 (P=0.007) and borderline significance for liver-type fatty acid binding protein (P=0.06). For all biomarkers, the adjusted relative risk (RR) point estimates for the risk for any AKI were higher in those with elevated baseline eGFRs compared with those with eGFRs≤60mL/min/1.73m(2). However, the difference in magnitude of these risks was low (adjusted RRs were 1.04 [95% CI, 0.99-1.09] and 1.11 [95% CI, 1.07-1.15] for those with preoperative eGFRs≤60mL/min/1.73m(2) and those with higher eGFRs, respectively). Although no biomarker displayed an interaction for baseline eGFR and severe AKI, log2-transformed interleukin 18 and kidney injury molecule 1 had significant adjusted RRs for severe AKI in those with and without baseline eGFRs≤60mL/min/1.73m(2). LIMITATIONS: Limited numbers of patients with severe AKI and post-operative dialysis. CONCLUSIONS: The association between early postoperative AKI urinary biomarkers and AKI is modified by preoperative eGFR. The degree of this modification and its impact on the biomarker-AKI association is small across biomarkers. Our findings suggest that distinct biomarker cutoffs for those with and without a preoperative eGFR≤60mL/min/1.73m(2) is not necessary.

Optimum methodology for estimating baseline serum creatinine for the acute kidney injury classification.

AIM: This study aimed to investigate how varied methods of determining baseline serum creatinine (SCr) would affect acute kidney injury (AKI) diagnosis and prediction of 60 day mortality in critically ill patients following an episode of AKI. METHODS: This is a single-centre retrospective study conducted at a tertiary referral hospital. All adult intensive care unit (ICU) patients between January and December 2011, who had at least one SCr values measured between 7 days and 180 days before hospital admission and during ICU stay, were analyzed. The baseline SCr was calculated using either the most recent (SCrmost recent ) or the minimum (SCrmin ) value of SCr measurement over the specified assessment period before hospital admission. AKI was defined based on KDIGO SCr definition. The primary outcome was 60 day mortality after ICU admission. RESULTS: A total of 4020 patients were included in the analysis. AKI was detected in 1204 (30.0%) using the SCrmin and 945 (23.5%) using the SCrmost recent (P < 0.001). Compared with patients without AKI regardless of baseline SCr methodology, the 60 day mortality risk of patients who developed AKI using the SCrmin and SCrmost recent was significantly increased (odds ratio (OR) = 3.74; 95% confidence interval (CI) 2.98-4.70). Similarly, the risk of 60 day mortality in patients who met AKI criteria using the SCrmin but not the SCrmost recent was significant higher than in patients without AKI (OR = 2.04; 95% CI 1.36-3.00). CONCLUSION: Using the minimum value of preadmission SCr as a baseline kidney function not only can detect more AKI cases, but also provides the better predictive ability for 60 day mortality.