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Background: Renal injury is a common perioperative complication. The adoption of renal endpoints, standardised and valid for use in perioperative clinical trials, would enhance the quality of perioperative clinical research. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive standardised endpoints for use in perioperative clinical trials., Methods: A systematic review was conducted to identify renal endpoints currently reported in perioperative clinical trials. In parallel, an initial list of candidate endpoints was developed based on renal theme group expertise. A multi-round Delphi consensus process was used to refine this list and produce a suite of recommended perioperative renal outcome measures., Results: Based on our systematic review, 63 studies were included for analysis. Marked heterogeneity and imprecision of endpoint definitions were observed. Our initial list of candidate endpoints included 10 endpoints for consideration. The response rates for Delphi rounds 1, 2, and 3 were 89% (n=16), 90% (n=75), and 100% (n=6), respectively. A final list of four renal endpoints was identified: acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria, acute kidney disease defined by ≥30% decline in estimated glomerular filtration rate from baseline at 30 days after operation in patients meeting the acute-kidney-injury criteria within 7 days of surgery, the composite of death or renal replacement therapy, and the Major Adverse Kidney Events (MAKE) composite., Conclusions: We identified four key renal outcome measures that should be considered for use in perioperative clinical trials. Using standardised definitions to capture and report these endpoints will facilitate improved benchmarking and meta-analysis of future trials., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Intravenous fluid therapy is the most commonly prescribed inpatient medication in hospitals around the world. Intravenous fluids are drugs and have an indication, a dose, and expected and unintended effects. The type and amount of fluid given to patients are both important, and can either hasten or slow recovery depending on how they are administered. This narrative review provides a brief summary of the effect of intravenous fluid administration on kidney function and on renal outcome measures of relevance to both patients and clinicians. Several large clinical trials of fluid therapy are currently underway, the results of which are likely to change clinical practice., (Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) occurs frequently in critically ill patients with sepsis, in whom it doubles the mortality rate and half of the survivors suffer permanent kidney damage or chronic kidney disease. Failure in the development of viable therapies has prompted studies to better elucidate the cellular and molecular etiologies of AKI, which have generated novel theories and paradigms for the mechanisms of this disease. These studies have shown multifaceted origins and elements of AKI that, in addition to/in lieu of ischemia, include the generation of damage-associated molecular patterns and pathogen-associated molecular patterns, the inflammatory response, humoral and cellular immune activation, perturbation of microvascular flow and oxidative stress, bioenergetic alterations, cell-cycle alterations, and cellular de-differentiation/re-differentiation. It is becoming clear that a major etiologic effector of all these inputs is the renal tubule epithelial cell (RTEC). This review discusses these elements and their effects on RTECs, and reviews the current hypotheses of how these effects may determine the fate of RTECs during sepsis-induced AKI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Objectives: AKI is associated with major adverse kidney events (MAKE): death, new dialysis, and worsened renal function. CKD (arising from worsened renal function) is associated with a higher risk of major adverse cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure. Therefore, the study hypothesis was that veterans who develop AKI during hospitalization for an MI would be at higher risk of subsequent MACE and MAKE., Design, Setting, Participants, & Measurements: Patients in the Veterans Affairs (VA) database who had a discharge diagnosis with International Classification of Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted to a VA facility from October 1999 through December 2005 were selected for analysis. Three groups of patients were created on the basis of the index admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI. Patients with mean baseline estimated GFR<45 ml/min per 1.73 m(2) were excluded. The primary outcomes assessed were mortality, MAKE, and MACE during the study period (maximum of 6 years). The combination of MAKE and MACE-major adverse renocardiovascular events (MARCE)-was also assessed., Results: A total of 36,980 patients were available for analysis. Mean age±SD was 66.8±11.4 years. The most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred in patients with an uncomplicated MI admission. In both the unadjusted and adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95% confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively)., Conclusions: Veterans who develop AKI in the setting of MI have worse long-term outcomes than those with AKI or MI alone. Veterans with AKI alone have worse outcomes than those diagnosed with an MI in the absence of AKI.

Objective: The purpose of our study was to assess the effect of IV contrast medium administered at CT on serum creatinine in an oncologic ICU population and to determine which of the variables before CT are most associated with renal function after administration of contrast material., Materials and Methods: We retrospectively reviewed 3,848 patient admissions to an oncology ICU. The following matched comparisons were undertaken: contrast-enhanced CT versus unenhanced CT and CT (with or without contrast medium) versus no CT. Matching criteria included age, sex, baseline serum creatinine, and severity of illness (modified sequential organ failure assessment [mSOFA] score). No patients with creatinine > 2.0 mg/dL received contrast material. Groups were compared using a rank sum test. Factors influencing creatinine after administration of contrast material were evaluated by multiple regression analysis. Parallel analyses using estimated glomerular filtration rate (eGFR) also were performed., Results: No significant difference was found in absolute change in creatinine between matched contrast-enhanced CT and unenhanced CT groups (n = 81), with mean (95% CI) creatinine rises after CT of 0.25 (0.04-0.46) and 0.11 (0.04-0.18) mg/dL, respectively. Similarly, for matched CT versus non-CT groups (n = 152), mean creatinine rises were 0.15 (0.05-0.25) and 0.12 (0.08-0.16) mg/dL, respectively. Parallel analyses using eGFR yielded similar results. Creatinine after administration of contrast material was associated with sex and mSOFA (p = 0.04 and 0.02, respectively) but not baseline creatinine. eGFR after administration of contrast material was associated with baseline eGFR (p < 0.0001)., Conclusion: Administration of IV contrast medium in oncologic ICU patients with relatively normal creatinine is associated with an increase in creatinine but not beyond that of simply undergoing CT or of a matched non-CT group in ICU. The eGFR, which includes sex in its derivation, may be a better predictor of contrast-enhanced renal function than creatinine.

Background: Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Anesthetic agents have been shown to modulate apoptotic signal transduction in various tissues. We examined the effects of 6 h of different general anesthetic techniques on renal cell apoptosis in rat kidneys., Methods: Twenty-one male Sprague-Dawley rats were randomly allocated into four groups: (i) control, non-anesthetized rats (n= 3) and rats anesthetized with (ii) inhaled isoflurane (n= 6), (iii) intraperitoneal pentobarbital (n= 6), and (iv) intraperitoneal urethane (n= 6). Animals were sacrificed 6 h after the induction of anesthesia., Results: Apoptosis was assessed by terminal deoxynucleotidyl transferase-fluorescein end-labeling analysis. RNA was extracted from the left kidney to probe cDNA microarrays. Gene expression was measured as a percentage of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequently confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the control (no anesthesia), urethane significantly (P < 0.001) induced apoptosis in both the renal cortex and medulla. Isoflurane significantly (P < 0.001) inhibited apoptosis in the medulla. Microarray analysis revealed that urethane up-regulated more (74) genes than pentobarbital (16) and isoflurane (10). Isoflurane down-regulated more genes (85) than pentobarbital (74) and urethane (12). These anesthetic-induced modulations were significant (P < 0.05) for 60 isoflurane-, 30 pentobarbital- and 4 urethane-modulated genes., Conclusion: Our results suggest that general anesthetic drugs have an effect on renal cell apoptosis and apoptotic signal transduction, and thus may potentially affect the risk of subsequent acute renal failure.

Objective: Vasoactive compounds are known to modulate gene transcription, including nuclear factor kappa B (NF-kappaB), in renal tissues, but the molecular effects of fenoldopam in this setting are not known. The authors used a rat model of surgical acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates ischemia/reperfusion (I/R)-induced NF-kappaB-mediated inflammation., Design: Prospective, single-blind, randomized, controlled animal study., Setting: Academic Department of Anesthesiology laboratory., Subjects: Twenty-four male Sprague-Dawley rats., Interventions: Rats were anesthetized by intraperitoneal administration of 50 mg/kg of urethane and randomly allocated into 4 groups (n = 6 each): sham operation, sham operation with infusion of 0.1 microg/kg/min of fenoldopam, unilateral renal ischemia (1 hour, left renal artery cross-clamping) followed by 4 hours of reperfusion, and unilateral renal I/R with fenoldopam infusion., Measurements and Main Results: Kidney samples were used to measure NF-kappaB DNA-binding activity with an electrophoretic mobility shift assay. NF-kappaB signaling-dependent gene transcription was assessed with microarray analysis, and validated with reverse transcriptase polymerase chain reaction (RT-PCR). Expression of insulin-like growth factor-1 and nitric oxide synthetase-3 messenger RNA (not included in the array) was studied with RT-PCR. NF-kappaB DNA binding activity was significantly higher (p < 0.001) after I/R injury. Of the 96 genes analyzed, 75 were induced and another 8 were suppressed completely (2-fold or greater change v control) after I/R. Treatment with fenoldopam prevented activation of NF-kappaB DNA binding activity (p < 0.001) and attenuated 72 of 75 I/R-induced genes and 3 of 8 I/R-suppressed genes., Conclusion: Data from this rat model of renal I/R suggest that the mechanism by which fenoldopam attenuates I/R-induced inflammation appears to involve inhibition of NF-kappaB translocation and signal transduction.

Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NFkappaB mediated pro-inflammatory signal transduction. However, the effect of fenoldopam on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates I/R-induced apoptosis. Sprague-Dawley rats were anesthetized by intraperitoneal administration of 50 mg/kg urethane and randomly allocated into 4 groups (n=6 each): (1) sham-operated, (2) sham operation with infusion of 0.1 microg/kg/min fenoldopam, (3) unilateral renal ischemia followed by 4 h of reperfusion, and (4) I/R with fenoldopam infusion. Kidney samples were fixed and paraffin-embedded to measure apoptosis. Data were compared between groups using ANOVA with Bonferroni correction. RNA was extracted from each left kidney to probe cDNA microarray and measure gene expression as percent of positive control. Compared to the control group, I/R significantly (P < 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that IR induced 73 apoptosis-related genes. Treatment with fenoldopam significantly reduced (P < 0.001) I/R-induced apoptosis both in the cortex and medulla and attenuated all 73 I/R-induced apoptosis-related genes. Data from this rat model of ischemic nephropathy suggest that fenoldopam may attenuate I/R-induced apoptosis and apoptosis-related gene transcription.