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A Single-Center Retrospective Study of Acute Kidney Injury Incidence in Patients With Advanced Malignancies Treated With Antimitochondrial Targeted Drug.

ABSTRACT: Introduction:Mitochondrial dysfunction plays an important role in the pathophysiology of kidney disease. Inhibitors of mitochondrial metabolism are being developed for the treatment of solid organ and hematologic malignancies. We describe the incidence and clinical features of acute kidney injury (AKI) in patients treated with the antimitochondrial drug CPI-613. Methods:We identified 33 patients with relapsed or refractory malignancy, previously enrolled in 3 open-label phase II studies, who received single-agent CPI-613 chemotherapy. AKI was defined by the Kidney Disease Improving Global Outcomes serum creatinine criteria. Participants were followed for a median (25th-75th percentile) of 120.0 (74.0-301.0) days. Risk factors for AKI were assessed by proportional hazards regression using univariate and multivariate analyses. Results:Participants had baseline mean (SD) age of 63.8 (11.6) years and serum creatinine 0.9 (0.3) mg/dl. AKI developed in 9 (27%) patients; chart review failed to identify a potential cause of AKI other than CPI-613 administration in 5 (15%) patients, of whom 1 had AKI stage 1, 1 had AKI stage 2, and 3 experienced AKI stage 3. Time from initiation of CPI-613 treatment to AKI was 51.0 (16.0-58.0) days. Age, per 5-year increase, was associated with higher risk of AKI (adjusted hazard ratio 2.01, 95% confidence interval 1.06-3.79, P = 0.03). Follow-up serum creatinine was available in 4 participants 174.8 (139.6) days after the episode of AKI; 3 patients had complete recovery in kidney function and 1 had partial recovery. Conclusion:AKI is a possible complication during treatment with mitochondria-targeted chemotherapy.

SUBMITTER: Anderson EM

PROVIDER: S-EPMC6365364 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A Single-Center Retrospective Study of Acute Kidney Injury Incidence in Patients With Advanced Malignancies Treated With Antimitochondrial Targeted Drug.

Anderson Elizabeth M EM Zhang Jin J Russell Greg G Bowline Isai G IG Thyagarajan Braghadheeswar B Li DengFeng D Ma Lijun L Anderson Erica R ER Murea Mariana M

Kidney international reports 20181029 2

<h4>Introduction</h4>Mitochondrial dysfunction plays an important role in the pathophysiology of kidney disease. Inhibitors of mitochondrial metabolism are being developed for the treatment of solid organ and hematologic malignancies. We describe the incidence and clinical features of acute kidney injury (AKI) in patients treated with the antimitochondrial drug CPI-613.<h4>Methods</h4>We identified 33 patients with relapsed or refractory malignancy, previously enrolled in 3 open-label phase II s ...[more]

PMID: 30775628

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Project description:Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria.Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P ⟨ 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74-2.39; aOR, 2.31; 95% CI, 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.In this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy. Journal of Hospital Medicine 2017;12:77-82.

Project description:BackgroundPregnancy-related acute kidney injury (Pr-AKI) is associated with maternal and fetal morbidity and mortality. There are few studies focusing on Pr-AKI at high altitude in the literature.Objectivesto investigate the incidence, etiology, clinical features and maternal-fetal outcomes of Pr-AKI in women living at high altitude.Methods6,512 pregnant women attending the Department of Obstetrics & Gynecology at local hospital from January 2015 to December 2018 were screened for Pr-AKI. Patients with serum creatinine above normal range(> 70umol/L) then underwent assessment to confirm the diagnosis of Pr-AKI. AKI was diagnosed and staged based on Kidney Disease Improving Global Outcomes(KDIGO) guideline. Individuals meeting the Pr-AKI criteria were recruited. Their clinical data were recorded and retrospectively analyzed.ResultsPr-AKI was identified in 136/6512(2.09 %) patients. Hypertensive disorders of pregnancy(HDP) was the leading cause of Pr-AKI(35.3 %). 4(2.9 %) women died and the majority(86.1 %) had recovered renal function before discharge. Fetal outcomes were confirmed in 109 deliveries with gestational age ≥ 20 weeks. Pre-term delivery occurred in 30(27.3 %) cases and perinatal deaths in 17(15.5 %). The rate of low birth weight infant(LBWI) and intrauterine growth restriction(IUGR) was 22.0 and 10.9 % respectively. 16(14.5 %) infants were admitted to NICU after birth. Patients with HDP had a higher cesarean rate(56.3 %). More IUGR(25.0 %) and LBWI(37.8 %) were observed in their infants with a higher risk of admission to NICU(22.0 %). High altitude might have an adverse impact on HDP-related Pr-AKI patients with earlier terminated pregnancy and more stillbirth/neonatal death. Logistic regression models indicated that uncontrolled blood pressure, high altitude and advanced AKI were associated with adverse fetal outcomes in HDP-related Pr-AKI patients.ConclusionsPr-AKI was not rare in high-altitude regions and caused severe fetal morbidities and mortalities. Uncontrolled blood pressure, high altitude and advanced AKI were all risk factors for adverse fetal outcomes in Pr-AKI patients, especially for those with hypertensive disorders of pregnancy.

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A Single-Center Retrospective Study of Acute Kidney Injury Incidence in Patients With Advanced Malignancies Treated With Antimitochondrial Targeted Drug.

Publications

A Single-Center Retrospective Study of Acute Kidney Injury Incidence in Patients With Advanced Malignancies Treated With Antimitochondrial Targeted Drug.

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