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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.)

The Healthcare Effectiveness Data and Information Set (HEDIS) is used by health plans to measure and report on quality and performance. This study evaluated the appropriateness of the prescription drug compliance step for the Medical Attention for Nephropathy quality measure for patients with diabetes. Data from national commercial claims for 28,348,363 persons were reviewed. The study applied the standard HEDIS specifications for compliance in medical attention for nephropathy for diabetic patients. Evaluation of the third and final process (evidence of angiotensin-converting enzyme [ACE] inhibitors or angiotensin II receptor blockers [ARBs]) found that the addition of this step contributed 14% to 16% of the numerator, bringing the final rate to the >80% range. Yet, presence of a prescription for an ACE inhibitor or ARB did not confirm microalbuminuria. Only 1% of the persons satisfying Step 3 had evidence of microalbuminuria in years prior and none in the reporting year. Use of these medications does not obviate the need for a nephropathy screening in diabetics. Inclusion of these medications as numerator compliance leads to overreporting and may contribute to underscreening of a population at risk.

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy., Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial., Setting: ICUs., Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively)., Interventions: IV angiotensin II or placebo., Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively., Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Objective: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II., Data Sources: PubMed, Medline, Scopus, and Cochrane., Study Selection: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed., Data Extraction: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events., Data Synthesis: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis., Conclusion: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.

Nearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm-Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high-cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high-cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care., (Copyright © 2016 by the American Society of Nephrology.)

Paraproteins are monoclonal Igs or their components (light or heavy chains) that are produced by a clonal population of mature B cells, most commonly plasma cells. These paraproteins or monoclonal proteins are secreted into the blood and subsequently filtered by the glomerulus before entering into urine, where they can cause various types of kidney disease, including both glomerular and tubulointerstitial injuries. Furthermore, a monoclonal protein that causes a specific glomerular or tubulointerstitial lesion in a human can reproducibly cause the same pathology when injected into an animal, supporting unique paraprotein characteristics. This Moving Points in Nephrology will provide an update for the Clinical Journal of the American Society of Nephrology readership on some of the clinically relevant kidney lesions associated with monoclonal paraprotein production and the pathophysiology underlying these kidney lesions., (Copyright © 2016 by the American Society of Nephrology.)