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Current advances in cancer chemotherapeutics have remarkably helped in rapid and definitive treatment options. However, these potent chemotherapeutics have been associated with severe renal toxicities that later impact treatment options. Acute kidney injury is common in patients with cancer. In hospitalized patients with cancer, acute kidney injury is associated with increased morbidity, mortality, length of stay, and costs. This article provides an overview of acute kidney injury caused by cancer or its treatment, including prerenal, tubular, glomerular diseases, infiltrative disease, tumor lysis syndrome, anticancer drug nephrotoxicity, hematopoietic stem cell transplantation-related acute kidney injury, and cancer-associated thrombotic microangiopathy., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Recognition and clinical diagnosis of acute kidney injury (AKI) after trauma is difficult. The majority of trauma patients do not have a known true baseline creatinine, which makes application of the guidelines set forth by the international guidelines difficult to apply. Use of alternative biomarkers of renal dysfunction in trauma patients may be beneficial. We hypothesized that urinary tissue inhibitor of metalloprotease 2 (TIMP-2) × insulin-like growth factor binding protein 7 (IGFBP-7) would accurately predict AKI development in severely injured trauma patients., Methods: A prospective observational study of adult (≥16 years old) trauma intensive care unit (ICU) patients was performed between September 2018 to March 2019. Urine was collected on ICU admission and was measured for TIMP-2 × IGFBP-7. Univariate, multivariable, and receiver operating characteristic curve analyses were performed using the optimal threshold generated by a Youden index., Main Results: Of 88 included patients, 75% were male, with a median injury severity score was 27 (interquartile range [IQR], 17-34), and age of 40 years (IQR, 28-54 years). Early AKI developed in 39 patients (44%), and of those, 7 (8%) required dialysis within 48 hours. Patients without early AKI had a TIMP-2 × IGFBP-7 of 0.17 U (IQR, 0.1-0.3 U), while patients with early AKI had a TIMP-2 × IGFBP-7 of 0.46 U (IQR, 0.17-1.29 U; p < 0.001). On multivariable analyses, TIMP-2 × IGFBP-7 was associated with AKI development (p = 0.02) and need for dialysis (p = 0.03). Using the optimal threshold 0.33 U to predict AKI, the area under the receiver operating characteristic curve was 0.731, with an accuracy of 0.75, sensitivity of 0.72, and specificity of 0.78., Conclusion: Urinary TIMP-2 × IGFBP-7 measured on ICU admission accurately predicted 48-hour AKI and was independently associated with AKI and dialysis requirement after trauma and is a promising screening tool for treatment., Level of Evidence: Prognostic, prospective, observational study, level III.

Background: Acute kidney injury (AKI) is common in severely injured trauma patients and is associated with poor outcomes. A positive fluid balance is associated with AKI and poor long-term renal outcomes among general ICU and cardiac surgery patients. Currently, the optimal endpoint of resuscitation of severely injured trauma patients is unknown, which may result in excess fluid administration. We hypothesized that positive fluid balance is common after severe trauma and is associated with increased AKI development., Study Design: A cohort study of adult (≥16 years old) trauma patients requiring ICU admission from January 2017 to June of 2017 was conducted. Patients were excluded for early death, rhabdomyolysis, or previous history of end-stage renal disease or congestive heart failure. Acute kidney injury within 7 days of admission was defined according to Kidney Disease Improving Global Outcomes creatinine-based criteria. Univariate and multivariable analyses were performed., Results: Of 364 patients, 74% were male. The median age was 41 years (interquartile range [IQR] 27 to 59 years), and the median Injury Severity Score (ISS) was 18 (IQR 10 to 29). Positive fluid balance (>2 L) was observed in 49% of patients. Acute kidney injury was diagnosed in 105 (29%) patients. After adjustment, there was an increased risk of AKI with a positive fluid balance >2 L (relative risk [RR] 1.98 [95% CI 1.24 to 3.17]). Additionally, the risk of AKI incrementally increased by 1.22 with each liter fluid positive above a zero balance (95% CI 1.11 to 1.34)., Conclusions: Positive fluid balance in excess of 2 L at 48 hours occurs in half of severely injured trauma patients, and fluid positivity is independently and incrementally associated with AKI development. Fluid responsiveness should be investigated as an end point of post-traumatic resuscitation to prevent unnecessary fluid administration and subsequent AKI., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) after trauma is associated with poor outcomes. According to current guidelines, a diagnosis of AKI should be made based on an increase in serum creatinine from a reference value. However, a true reference is often unknown in patients presenting with traumatic injury. The aim of this study was to determine the optimal reference creatinine estimate for post-traumatic AKI diagnosis and staging. The optimal reference estimate was defined by a high incidence, strong prognostic ability, and incrementality at each stage., Study Design: This was a cohort study of adult trauma patients (older than 16 years) requiring ICU admission between 2009 and 2018 (n = 8,026) at a single Level I trauma center. AKI was determined using the following 4 reference creatinine estimates: Modified Diet of Renal Diseases (MDRD), Trauma MDRD, admission creatinine, and the first-day creatinine nadir. Inclusivity was assessed by incidence of AKI diagnosed with different reference creatinine estimates; prognostic ability was assessed by multivariable modified Poisson regression; and incrementality was assessed by correlation of mortality risk by AKI stage., Results: There was a wide range of AKI incidence, from 21% when using admission creatinine to 76% using the Trauma MDRD. The MDRD reference creatinine estimate resulted in an AKI incidence of 41% and a diagnosis that was both prognostic of mortality and incremental with each AKI stage. All other reference estimates resulted in AKI diagnoses that were either not prognostic or not incremental., Conclusions: Reference creatinine estimate determines the clinical importance of AKI diagnoses. In this study, the MDRD reference resulted in optimal AKI diagnoses., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate risk predictors of acute kidney injury (AKI) after contrast-media procedures in a broader cohort of patients than previously reported., Data Sources: Comprehensive medical and pharmacy commercial claims data from 2012 to 2014., Data Collection and Extraction Methods: Claims associated with contrast-media procedures for 2,737,020 persons between January 1, 2012 and November 30, 2014, were reviewed., Principal Findings: The overall incidence of AKI after a contrast-media procedure was 0.85%. AKI occurred in 26% of cases that had two or more contrast procedures within 30 days, compared with 9% of non-AKI cases. Although the incidence of postcontrast AKI was low, 10% of patients who developed AKI had a recent previous episode of AKI. In cases when AKI had occurred within 180 days of contrast administration, the odds of subsequent kidney injury was 9.39., Conclusions: Overall, there is a low risk (0.85%) of developing an AKI after a procedure with contrast-media consistent with several recent studies. However, in adults with a recent history of AKI, physicians must consider this history as a risk factor for subsequent AKI., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Nearly 50% of patients with multiple myeloma develop renal disease; acute kidney injury (AKI) from cast nephropathy, or "myeloma kidney" is the most common type. Development of AKI is associated with worse 1-year survival and reduces the therapeutic options available to patients. Therefore, there is a great need to develop more effective therapies. Cast nephropathy is due to the interaction and aggregation of filtered free light chains (FLCs) and Tamm- Horsfall protein (THP) causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of FLCs as this correlates with renal recovery. Newer chemotherapy agents lower FLCs and have been referred to as "renoprotective". However there remains great interest in using various extracorporeal therapies to remove serum FLCs. Initially, therapeutic plasma exchange (TPE) was thought to improve renal outcomes in cast nephropathy based on small trials. The largest randomized trial of TPE, however, failed to show any benefit. A newer technique is extended high cut-off hemodialysis (HCO-HD). This modality uses a high molecular weight cut-off filter to remove FLCs. To date, trials with HCO-HD in patients with cast nephropathy have been encouraging. However, there are no randomized trials demonstrating the benefit of HCOHD when used in addition to newer chemotherapeutic regimens. Until these studies are available, HCO-HD cannot be recommended as standard of care.

Clinical practice guidelines are intended to standardize the diagnosis and treatment of diseases in order to improve both patient outcomes and resource utilization, using evidence-based criteria. As recently as a decade ago, there was no agreed upon definition of acute kidney injury (AKI), making it difficult to conduct proper clinical studies on the epidemiology and treatment of the disorder. Following the advent of the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria for defining AKI, several guidelines for the diagnosis and management of AKI have been developed. In our review, we present a narrative description and comparison of the major published guidelines. Overall, there has been significant agreement among the various guidelines, and each seems well-reasoned and clinically useful. Perhaps the most striking conclusion upon review of the various guidelines is the limited scope of knowledge about optimal management of patients with AKI.

Objective: To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria., Design: A retrospective cohort study of severely injured trauma patients admitted to the shock trauma intensive care unit., Setting: Texas Trauma Institute, a state designated level I trauma unit certified by the American College of Surgeons Committee on Trauma., Patients: 901 severely injured trauma patients admitted over a 15 month period to the shock trauma intensive care unit., Interventions: Retrospective analysis of prospectively collected data abstracted from an electronic trauma database., Measurements and Main Results: Of 901 eligible patients admitted to the shock trauma intensive care unit after traumatic injury, 54 patients (6%) developed acute kidney injury, of whom 10 (19%) required renal replacement therapy. The 30-day mortality rate for the entire cohort was 83/901 (9.2%). Patients with early acute kidney injury had a mortality rate of 16/54 (29.6%). When corrected for multiple covariates including injury severity scores, the development of early acute kidney injury was associated with a significantly higher risk of death at 30 days with an OR of 3.4 (95% CI 1.6-7.4)., Conclusions: Applying the Acute Kidney Injury Network creatinine criteria in severely injured trauma patients, the incidence of early acute kidney injury was 6%. After correction for injury severity, development of early acute kidney injury was independently associated with significantly higher 30-day mortality.

Acute kidney injury (AKI) is characterized by deterioration in kidney function resulting in multisystem abnormalities. Much of the morbidity and mortality associated with AKI result from a systemic inflammatory response syndrome (SIRS). This study described herein is a prospective, single-arm, multicenter US study designed to evaluate the safety and efficacy of the Selective Cytopheretic Device (SCD) treatment on AKI requiring continuous renal replacement therapy (CRRT) in the ICU. The study enrolled 35 subjects. The mean age was 56.3±15. With regard to race, 71.4% of the subjects were Caucasian, 22.9% were Black, and 5.7% were Hispanic. Average SOFA score was 11.3±3.6. Death from any cause at Day 60 was 31.4%. Renal recovery, defined as dialysis independence, was observed in all of the surviving subjects at Day 60. The results of this pilot study indicate the potential for a substantial improvement in patient outcomes over standard of care therapy, which is associated with a greater than 50% 60-day mortality in the literature. The SCD warrants further study in scientifically sound, pivotal trial to demonstrate reasonable assurance of safety and effectiveness., (© 2012 Wiley Periodicals, Inc.)

Background: Rhabdomyolysis can cause acute kidney injury (AKI). It remains controversial whether or not myoglobin can be removed from the circulation with extracorporeal therapy and decrease the incidence of AKI. Therefore, we examined myoglobin removal in a series of 11 patients with oliguric AKI treated with high-volume hemofiltration., Methods: Patients received prefilter hemofiltration using a polysulphone filter with a molecular size cutoff of 65 kDa and a surface area of 1.7 m(2). Sieving coefficients and myoglobin clearances were calculated at 6, 12, and 24 h after the start of hemofiltration., Results: The mean sieving coefficient was 0.158, and the mean myoglobin clearance was 8.7 ml/min., Conclusion: Despite the use of high-volume hemofiltration, the removal of myoglobin was negligible. In patients with normal renal function, the anticipated amount of extracorporeal removal would not significantly impact renal exposure to myoglobin., (© 2013 S. Karger AG, Basel.)

Acute kidney injury (AKI) is a common clinical syndrome in hospitalized patients associated with high morbidity and mortality rates. Despite several years of improvement in the medical care of the severely ill, there has been little improvement in outcome. Furthermore, effective means of preventing and treating AKI have remained elusive. Although dialysis has been the mainstay of treating AKI for > 40 years, several questions regarding its application remain unsettled, including method (continuous vs intermittent), timing, and dose. The purpose of this review is to summarize recent advances in the epidemiology and treatment of AKI in hospitalized patients.

Continuous renal replacement therapy (CRRT) is commonly used in critically ill patients with acute kidney injury. Many studies show that compared with intermittent hemodialysis, continuous therapy has superior hemodynamic stability, metabolic clearance, and volume control. Despite these benefits, no survival advantage can be demonstrated with its use. Although study design explains much of this paradox, it is also quite plausible that the complications associated with CRRT negate its potential benefits in the critically ill patient. We summarize the common complications associated with the use of CRRT.

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.

Objective: To report a case of acute renal failure in a patient with severe aplastic anemia after administration of antithymocyte globulin (ATG)., Case Summary: A 41-year-old man diagnosed with severe aplastic anemia was treated with ATG and cyclosporine. After one dose of ATG (3012 mg, 40 mg/kg), the patient developed anuric acute renal failure, with serum creatinine 3.4 mg/dL (1.2 mg/dL at baseline) and blood urea nitrogen (BUN) 29 mg/dL (13 mg/dL at baseline), which required intermittent hemodialysis. Renal failure resolved with cessation of the drug, serum creatinine and BUN returned to baseline levels, and the patient no longer required hemodialysis., Discussion: ATG is a purified and concentrated gamma globulin, primarily a monomeric immunoglobulin G from hyperimmune serum of horses. It is widely used to treat severe aplastic anemia and to manage acute transplant rejection. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment using the Naranjo probability scale suggested that ATG was the probable cause of the acute renal failure. Primary glomerular disease was not excluded, as a renal biopsy was not performed., Conclusions: The association between renal injury and administration of ATG remains unclear; therefore, we recommend that renal function be assessed and carefully monitored prior to and after administration of ATG.

Objective: To report a case of acute renal failure associated with the administration of imatinib mesylate., Case Summary: A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate., Discussion: Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy., Conclusions: Imatinib mesylate-induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy.

Background: Sustained low efficiency dialysis (SLED) is a hybrid therapy that uses a conventional hemodialysis machine to deliver lower solute clearance over prolonged periods of time, typically 8 to 12 hours per treatment, and utilizes the same sodium and bicarbonate concentrations as intermittent hemodialysis. The therapy has been shown to be an effective dialysis mode for the critically ill patient with acute renal failure and hemodynamic instability. At our institution, critically ill patients requiring renal replacement therapy receive SLED on a continuous, 24-hour schedule (C-SLED). The higher dialysis dose with C-SLED compared to continuous venovenous hemodiafiltration (CVVHDF) or traditional SLED would likely alter the prescription needed to provide regional citrate anticoagulation and the incidence of hypernatremia and metabolic alkalosis., Objective: To evaluate the safety of utilizing regional citrate anticoagulation with continuous SLED in critically ill patients who frequently clot the hemofilter and have contraindications to systemic anticoagulation with heparin. We hypothesized that the higher dialysis dose with C-SLED would affect the prescription of citrate anticoagulation and the development of hypernatremia and metabolic alkalosis., Design: We prospectively followed the first 20 patients who received regional citrate anticoagulation on C-SLED for acute renal failure in the intensive care unit. Important outcomes measured included serum sodium, bicarbonate, ionized calcium concentration, serum pH, and PCO2. The number of clotting episodes for each patient while on regional citrate anticoagulation was recorded. Setting. Surgical and medical intensive care units at The University of Texas MD Anderson Cancer Center., Results: In over 2200 hours of continuous dialysis with citrate anticoagulation none of the 20 patients had derangements in the serum sodium or acid base status requiring cessation of regional citrate anticoagulation. In 14 patients, no clotting occurred during 1500 hours of SLED with the citrate infusion. There were eight episodes of hemofilter clotting in six patients during 750 hours of C-SLED., Conclusion: Regional citrate anticoagulation is a safe method of anticoagulation in critically ill patients on continuous SLED.