Influence of Polymyxin B Dose on Development and Recovery of Acute Kidney Injury

Abstract Background Nephrotoxicity is a common adverse effect of polymyxin B (PMB) with reported acute kidney injury (AKI) rates of 20% to >60%. Data on PMB dosing to optimize efficacy while minimizing toxicity are limited. Previous studies suggest higher doses improve outcomes but are also associated with more AKI. Data are needed to evaluate optimal dosing and contributing factors to minimize AKI and to evaluate renal recovery. Methods Retrospective study evaluating PMB in adults at NewYork-Presbyterian Hospital from 2012 to 2016. Patients who received PMB dosed twice daily for ≥2 days were included. Patients on renal replacement therapy within 48 hours prior to PMB or with AKI at time of PMB initiation were excluded. A classification and regression tree (CART) analysis was performed to identify the PMB dose most predictive of AKI which defined the breakpoint for high- vs. low-dose PMB cohorts for all subsequent comparisons. The primary outcome was to determine whether high-dose PMB independently predicted AKI. Secondary outcomes included in-hospital mortality, time to AKI, and recovery of renal function. Results 246 patients were included: majority were male (59%) with median age 41 years. Median PMB dose was 2.9 mg/kg/day or 180 mg/day for a median duration of 10 days. AKI occurred in 64% and 38% had recovery of renal function by hospital discharge. The breakpoint for high-dose PMB determined by CART was 160 mg/day, putting 104 in low-dose and 142 in high-dose groups. High-dose PMB was associated with AKI compared with low-dose PMB on univariable (75% vs.. 49%, P < 0.001) and multivariable (OR 3.43; 95% CI 1.68,6.99; P = 0.001) analyses. Concomitant vancomycin (OR 3.34; 95% CI 1.74,6.41;P < 0.001), history of transplant (OR 4.96; 95% CI 2.14,11.48;P < 0.001), and previous PMB exposure (OR 2.37; 95% CI 1.23,4.57; P = 0.01) were also identified as independent predictors of AKI. No significant differences were found for in-hospital mortality (28% vs. 21%, P = 0.326), renal recovery (37% vs. 41%, P = 0.723), time to AKI (median 5 vs. 6 days, P = 0.125) between groups. Conclusion High-dose PMB (>160 mg/day) was independently associated with AKI as well as concomitant vancomycin, history of transplant, and previous PMB exposure. High-dose PMB did not have a significant impact on in-hospital mortality, recovery of renal function, or time to development of AKI. Disclosures M. Yin, Gilead Sciences: Consultant, Consulting fee.

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High-dose versus low-dose haemofiltration for the treatment of critically ill patients with acute kidney injury: an updated systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2016-014171 ◽

2017 ◽

Vol 7 (10) ◽

pp. e014171 ◽

Cited By ~ 7

Author(s):

Peng Li ◽

Li-ping Qu ◽

Dong Qi ◽

Bo Shen ◽

Yi-mei Wang ◽

...

Keyword(s):

Systematic Review ◽

Acute Kidney Injury ◽

Hospital Mortality ◽

Hospital Stay ◽

Critically Ill ◽

Critically Ill Patients ◽

Low Dose ◽

Meta Analysis ◽

Kidney Injury ◽

High Dose

ObjectiveThe purpose of this study was to perform a systematic review and meta-analysis to evaluate the effect of high-dose versus low-dose haemofiltration on the survival of critically ill patients with acute kidney injury (AKI). We hypothesised that high-dose treatments are not associated with a higher risk of mortality.DesignMeta-analysis.SettingRandomised controlled trials and two-arm prospective and retrospective studies were included.ParticipantsCritically ill patients with AKI.InterventionsContinuous renal replacement therapy.Primary and secondary outcome measuresPrimary outcomes: 90-day mortality, intensive care unit (ICU) mortality, hospital mortality; secondary outcomes: length of ICU and hospital stay.ResultEight studies including 2970 patients were included in the analysis. Pooled results showed no significant difference in the 90-mortality rate between patients treated with high-dose or low-dose haemofiltration (pooled OR=0.90, 95% CI 0.73 to 1.11, p=0.32). Findings were similar for ICU (pooled OR=1.12, 95% CI 0.94 to 1.34, p=0.21) and hospital mortality (pooled OR=1.03, 95% CI 0.81 to 1.30, p=0.84). Length of ICU and hospital stay were similar between high-dose and low-dose groups. Pooled results are not overly influenced by any one study, different cut-off points of prescribed dose or different cut-off points of delivered dose. Meta-regression analysis indicated that the results were not affected by the percentage of patients with sepsis or septic shock.ConclusionHigh-dose and low-dose haemofiltration produce similar outcomes with respect to mortality and length of ICU and hospital stay in critically ill patients with AKI.This study was not registered at the time the data were collected and analysed. It has since been registered on 17 February 2017 athttp://www.researchregistry.com/, registration number: reviewregistry211.

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P0602CLINICAL PATTERN, RENAL RECOVERY AND PATIENT OUTCOMES AFTER ACUTE KIDNEY INJURY IN ADULTS IN AN EMERGING COUNTRY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0602 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Arunkumar Subbiah ◽

Sanjay Kumar Agarwal

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Hospital Mortality ◽

Kidney Injury ◽

Hospitalized Patients ◽

Renal Recovery ◽

Common Source ◽

Partial Recovery

Abstract Background and Aims Acute Kidney Injury (AKI) is an important determinant of outcome in hospitalized patients. Further, there is a risk for development of Chronic Kidney Disease (CKD) in the future. Though the long-term impact of AKI has been studied in developed countries, there is a paucity of data in this area from the Indian subcontinent. This single-centre study aimed to assess the pattern, clinical spectrum, short-term and long-term outcomes of AKI. Method In this prospective observational cohort study, detailed demographic and clinical data at presentation, during hospital stay and follow-up at 1, 3, 6 and 12 months after discharge were obtained prospectively for a cohort of patients with AKI. Both community (CAAKI) and hospital acquired AKI (HAAKI) were included. Patient with pre-existing CKD were excluded. Outcome variables examined were in-hospital mortality, renal function at discharge and on follow-up after discharge from hospital. Results In our study cohort with 476 patients, majority of the cases were CAAKI (395, 83%). The mean age at presentation was 44.8 ± 18.7 years. Medical causes (84%) contributed to the majority of AKI while the remaining were due to surgical (10%) and obstetrical (6%) causes. Sepsis (176/476; 36.9%) was the most common cause of AKI. The most common source for sepsis was respiratory (41%) followed by urological source (18.7%). The in-hospital mortality rate for patients with AKI was 38%. Age >60 years (HR = 1.51; 95% CI, 1.11 – 2.07), oliguria (HR = 1.48; 95% CI, 1.05 – 2.10), need for ventilator (HR = 2.45; 95% CI, 1.36 – 4.41) and/or inotropes (HR = 14.4; 95% CI, 6.28 – 33.05) were predictors of mortality. At discharge, 146 (30.7%) patients had complete renal recovery, while 149 (31.3%) had partial renal recovery. Oliguria (p < 0.001), hypoalbuminemia (p = 0.001) and need for renal replacement therapy (RRT) (p = 0.01) were significantly associated with partial recovery. Of the 295 patients on follow-up at discharge, 211 (71.5%) patients had normal renal function, 4 (1.4%) died and 33 (11.2%) were lost to follow up; 47(15.9%) patients developed CKD of which 6 (2%) were dialysis dependent. Elderly patients, higher AKIN stage with oliguria and those requiring RRT were more likely to develop CKD. Among these, the need for in-hospital RRT was the single most important factor predicting the risk of CKD (OR 1.77, 95% CI, 1.12-2.78). Conclusion In conclusion, our data shows that AKI in hospitalized patients still has high mortality in emerging countries like India. Though a fairly good percentage of cases recovered, there is a definite risk of CKD development, especially in patients who required RRT during hospitalization.

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Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy

Journal of Clinical Oncology ◽

10.1200/jco.20.00298 ◽

2020 ◽

Vol 38 (23) ◽

pp. 2647-2657 ◽

Cited By ~ 1

Author(s):

Frank Bridoux ◽

Bertrand Arnulf ◽

Lionel Karlin ◽

Nicolas Blin ◽

Nolwenn Rabot ◽

...

Keyword(s):

Acute Kidney Injury ◽

Controlled Trial ◽

Randomized Study ◽

Kidney Injury ◽

Renal Recovery ◽

High Dose ◽

Serious Adverse Events ◽

Group V ◽

High Dose Dexamethasone ◽

Cast Nephropathy

PURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.

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Impact of polymyxin-B-associated acute kidney injury in 1-year mortality and renal function recovery

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2018.02.016 ◽

2018 ◽

Vol 52 (1) ◽

pp. 86-89 ◽

Cited By ~ 4

Author(s):

Eduardo C. Gomes ◽

Diego R. Falci ◽

Pedro Bergo ◽

Alexandre P. Zavascki ◽

Maria Helena Rigatto

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Kidney Injury ◽

Polymyxin B ◽

Renal Function Recovery ◽

Function Recovery

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Recently published papers: Renal support in acute kidney injury - is low dose the new high dose?

Critical Care ◽

10.1186/cc8180 ◽

2009 ◽

Vol 13 (6) ◽

pp. 1014

Author(s):

Yadullah Syed ◽

James AP Tomlinson ◽

Lui G Forni

Keyword(s):

Acute Kidney Injury ◽

Low Dose ◽

Kidney Injury ◽

High Dose ◽

Renal Support

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The impact of diabetes on outcomes, length of stay and costs in acute kidney injury patients: a cross-sectional multicenter study in China

10.21203/rs.3.rs-16071/v1 ◽

2020 ◽

Author(s):

Lishan Tan ◽

Li Chen ◽

Lingyan Li ◽

Jinwei Wang ◽

Xiaoyan Huang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Length Of Stay ◽

Hospital Mortality ◽

Hospital Stay ◽

Kidney Injury ◽

Renal Recovery ◽

Cross Sectional ◽

Patients With Diabetes ◽

The Impact ◽

Physician Diagnosis

Abstract Background : With the increasing worldwide prevalence and disease burden of diabetic mellitus, data on the impact of diabetes on acute kidney injury (AKI) patients in China are limited.Methods: A nationwide cross-sectional and retrospective study was conducted in China, which included 2,223,230 hospitalized adult patients and covered 82% of the country’s population. Diabetes was identified according to blood glucose, hemoglobin A1c levels, physician diagnosis and drug use. In total, 7604 AKI patients were identified, and 1404 and 6200 cases were defined as diabetic and non-diabetic respectively. Clinical characteristics, outcome, in-hospital stay, and costs of AKI patients with and without diabetes were compared. Multivariable logistic and linear regression analyses were conducted to evaluate the association of diabetes with mortality and renal recovery in the admitted AKI patients.Results: In this survey, AKI patients with diabetes were older, male-dominated (61.9%), with more comorbidities, and higher serum creatinine levels. Compared to patients without diabetes, a significant upswing in all-cause in-hospital mortality, hospital stay, and costs were found in those with diabetes ( p <0.05). After adjusted for relevant covariables, diabetes was independently associated with failed renal recovery (OR=1.13, p =0.04), rather than all-cause in-hospital mortality (OR=1.09, p =0.39). Also, diabetic status was positively associated with length of stay ( β =0.04, p =0.04) and costs ( β =0.09, p <0.01) in hospital after adjusted for possible confounders. Conclusions: Failed renal recovery, rather than all-cause in-hospital mortality, is independently associated with diabetes in hospitalized AKI patients. Moreover, diabetes is significantly correlated with in-hospital stay and expenditures in AKI.

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MO359ASSOCIATIONS BETWEEN RENAL FUNCTION TRAJECTORIES AFTER 3 MONTHS ACUTE KIDNEY INJURY AND LONG-TERM RENAL OUTCOMES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab082.0013 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Chien-Ning Hsu ◽

You-Lin Tain

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Kidney Injury ◽

Chronic Dialysis ◽

Dialysis Initiation ◽

Renal Recovery ◽

Post Discharge ◽

Renal Function Recovery ◽

Increased Risk ◽

Function Recovery

Abstract Background and Aims Renal function recovery after acute kidney injury (AKI) is associated with patient outcomes. The study objectives were to assess the patterns of AKI recovery within 6 months following discharge for AKI and subsequent incidence of chronic dialysis. Method A retrospective cohort of 234,867 hospitalized adult patients was examined for AKI between January 1, 2010, and December 31, 2017 in the largest healthcare delivery system in Taiwan. Renal function recovery at 3- and 6-month post discharge, incident chronic kidney disease and chronic dialysis initiation were analyzed over 7 years of follow-up. Renal recovery was defined by < 1.5× baseline SCr (prior to the hospitalization). Independent associations between renal function recovery patterns and renal outcomes was assessed by Cox proportional hazard model controlling for potential confounders, and subdistribution hazard ratio (SHR) with [95% CI] was analysed for competing risk of early death. Results Among 3 months AKI survivors (n=24,132), 14.28% (n=3,430) did not recovery back to baseline, and 16% of recovery did not sustain. Three distinct renal function recovery continuums at 6 months post hospital discharge were: persistent non-recovery (10.18%), non-recovery (14.33%), and recovery (75.5%). Comparing to survivors without AKI (n=50,387), the impact of renal recovery continuum on chronic dialysis initiation varied by patient’s baseline renal disease (SHR was 2.82 [95%CI, 2.42-3.28] in CKD, and 0.8 [95%CI, 0.27-2.38] for non-CKD. Persistent non-recovery was significantly associated with a greater increased risk of chronic dialysis than non-recovery in any patients with AKI. Comparing to patients with sustained AKI recovery, risk of CKD onset increased 5-fold in persistent non-recovery and 3-fold risk in non-recovery. Conclusion The continuum of AKI recovery post 6 months is associated with increased risk of chronic dialysis, particularly in patients with baseline CKD. These study results suggested that patients ever with AKI should receive close renal function monitoring for post-discharge management.

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High dose intravenous vitamin C treatment in Sepsis: associations with acute kidney injury and mortality

BMC Nephrology ◽

10.1186/s12882-021-02599-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thomas R. McCune ◽

Angela J. Toepp ◽

Brynn E. Sheehan ◽

Muhammad Shaheer K. Sherani ◽

Stephen T. Petr ◽

...

Keyword(s):

Acute Kidney Injury ◽

Vitamin C ◽

Hospital Mortality ◽

Significant Risk ◽

Kidney Injury ◽

Significant Risk Factor ◽

High Dose ◽

Clinical Covariates ◽

Observational Cohort ◽

Intravenous Vitamin

Abstract Background The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients. Methods Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU. Results Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46–2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003–2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09–2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48–1.31]). Conclusion Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.

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High Dose Intravenous Vitamin C Treatment in Sepsis: Associations with Acute Kidney Injury and Mortality Running Title Vitamin C associated AKI and mortality

10.21203/rs.3.rs-672093/v1 ◽

2021 ◽

Author(s):

Thomas McCune ◽

Brynn E Sheehan ◽

Muhammad Shaheer K Sherani ◽

Stephan T Petr ◽

Angela J Toepp ◽

...

Keyword(s):

Acute Kidney Injury ◽

Vitamin C ◽

Hospital Mortality ◽

Significant Risk ◽

Kidney Injury ◽

Significant Risk Factor ◽

High Dose ◽

Clinical Covariates ◽

Observational Cohort ◽

Intravenous Vitamin

Abstract The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients. Participants were 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5g IV vitamin C, n = 1178). Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU. Results revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46–2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003–2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09–2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48–1.31]). Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.

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Incidence of Acute Kidney Injury in Intermittent Versus Continuous Infusion of Polymyxin B in Hospitalized Patients

Annals of Pharmacotherapy ◽

10.1177/1060028019841898 ◽

2019 ◽

Vol 53 (9) ◽

pp. 886-893 ◽

Cited By ~ 3

Author(s):

Yarelis Alvarado Reyes ◽

Raquel Cruz ◽

Julia Gonzalez ◽

Yeiry Perez ◽

William R. Wolowich

Keyword(s):

Acute Kidney Injury ◽

Hospital Mortality ◽

Continuous Infusion ◽

Kidney Injury ◽

Polymyxin B ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Baseline Serum ◽

Increased Risk ◽

Dosing Strategies

Background: Studies evaluating the risk of developing acute kidney injury (AKI) with different dosing strategies of polymyxin B are limited. Objectives: To compare the incidence of AKI in patients treated with intermittent versus continuous polymyxin B therapy. Secondary objectives included time to onset of AKI, hospital length of stay (LOS), and all-cause hospital mortality. Variables associated with an increased risk of AKI were evaluated. Methods: A retrospective record review was conducted at a single center in Puerto Rico. Adult patients (≥18 years old) treated with polymyxin B (first course) for at least 48 hours from 2013-2015 were evaluated. Patients with a creatinine clearance <10 mL/min and/or on renal replacement were excluded. Results: A total of 69 patients were included: 42 in the continuous infusion and 27 in the intermittent dosing group. Incidence of AKI was not significantly different between the groups (intermittent 41% vs continuous 31%, P = 0.4). No difference was found in the onset of nephrotoxicity, hospital LOS, or all-cause hospital mortality. Variables associated with increased risk of AKI were baseline serum creatinine, age, and intensive care unit admission. Patients with a body mass index (BMI) >25 kg/m2 on polymyxin B via continuous infusion had a significantly higher cumulative incidence of AKI ( P = 0.016). Conclusion and Relevance: No difference in the risk of polymyxin B nephrotoxicity was found between intermittent and continuous infusion administration. Administration of polymyxin B via a continuous infusion may result in a higher risk of AKI in patients with a BMI >25 kg/m2.

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