scholarly journals Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0249760
Author(s):  
Johanna Schneider ◽  
Bernd Jaenigen ◽  
Dirk Wagner ◽  
Siegbert Rieg ◽  
Daniel Hornuss ◽  
...  

Background Acute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25–29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known. Methods We retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients. Results In non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597). Conclusion Triple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.

2020 ◽  
Vol 86 (8) ◽  
pp. 950-954
Author(s):  
Andrew L. Drahos ◽  
Anthony M. Scott ◽  
Tracy J. Johns ◽  
Dennis W. Ashley

Background There is an opioid epidemic in the United States. With the increased concern of over-prescribing opioids, physicians are seeking alternative pain management strategies. The purpose of this study is to review the impact of instituting a multimodal analgesia (MMA) guideline on decreasing opioid use in trauma patients at a Level 1 trauma center. Methods In 2017, an MMA guideline was developed and included anti-inflammatories, muscle relaxants, neuropathic agents, and local analgesics in addition to opioids. Staff were educated and the guideline was implemented. A retrospective review of medications prescribed to patients admitted from 2016 through 2018 was performed. Patients admitted in 2016 served as the control group (before MMA). In 2018, all patients received multimodal pain therapy as standard practice, and served as the comparison group. Results A total of 10 340 patients were admitted to the trauma service from 2016 through 2018. There were 3013 and 3249 patients for review in 2016 and 2018, respectively. Total morphine milligram equivalents were 2 402 329 and 1 975 935 in 2016 and 2018, respectively, a 17.7% decrease ( P < .001). Concurrently, there was a statistically significant increase in the use of multimodal pain medications. A secondary endpoint was studied to evaluate for changes in acute kidney injury; there was not a statistically significant increase (0.56% versus 0.68%, P = .55). Discussion Implementation of an MMA guideline significantly reduced opioid use in trauma patients. The use of nonopioid MMA medications increased without an increased incidence of acute kidney injury.


2019 ◽  
Vol 49 (3) ◽  
pp. 175-185 ◽  
Author(s):  
Thorir E. Long ◽  
Solveig Helgadottir ◽  
Dadi Helgason ◽  
Gisli H. Sigurdsson ◽  
Tomas Gudbjartsson ◽  
...  

Background: The aim of this study was to examine different definitions of renal recovery following postoperative acute kidney injury (AKI) and how these definitions associate with survival and the development and progression of chronic kidney disease (CKD). Methods: This was a retrospective study of all patients who underwent abdominal, cardiothoracic, vascular, or orthopedic surgery at a single university hospital between 1998 and 2015. Recovery of renal function following postoperative AKI was assessed comparing 4 different definitions: serum creatinine (SCr) (i) < 1.1 × baseline, (ii) 1.1–1.25 × baseline, (iii) 1.25–1.5 × baseline, and (iv) > 1.5 × baseline. One-year survival and the development or progression of CKD within 5 years was compared with a propensity score-matched control groups. Results: In total, 2,520 AKI patients were evaluated for renal recovery. Risk of incident and progressive CKD within 5 years was significantly increased if patients did not achieve a reduction in SCr to < 1.5 × baseline (hazard ratio [HR] 1.50; 95% CI 1.29–1.75) and if renal recovery was limited to a fall in SCr to 1.25–1.5 × baseline (HR 1.32; 95% CI 1.12–1.57) within 30 days. The definition of renal recovery that best predicted survival was a reduction in SCr to < 1.5 × baseline within 30 days. One-year survival of patients whose SCr decreased to < 1.5 × baseline within 30 days was significantly better than that of a propensity score-matched control group that did not achieve renal recovery (85 vs. 71%, p < 0.001). Conclusions: These findings should be considered when a consensus definition of renal recovery after AKI is established.


2021 ◽  
Vol 10 (11) ◽  
pp. 2288
Author(s):  
Matthias Diebold ◽  
Tobias Zimmermann ◽  
Michael Dickenmann ◽  
Stefan Schaub ◽  
Stefano Bassetti ◽  
...  

Previous studies have indicated an association between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) but lacked a control group. The prospective observational COronaVIrus-surviVAl (COVIVA) study performed at the University Hospital, Basel, Switzerland consecutively enrolled patients with symptoms suggestive of COVID-19. We compared patients who tested positive for SARS-CoV-2 with patients who tested negative but with an adjudicated diagnosis of a respiratory tract infection, including pneumonia. The primary outcome measure was death at 30 days, and the secondary outcomes were AKI incidence and a composite endpoint of death, intensive care treatment or rehospitalization at 30 days. Five hundred and seven patients were diagnosed with respiratory tract infections, and of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. The incidence of AKI was higher in patients with COVID-19 (30% versus 12%, p < 0.001), more severe (KDIGO stage 3, 22% versus 13%, p = 0.009) and more often required renal replacement therapy (4.4% versus 0.93%; p = 0.03). The risk of 30-day mortality and a composite endpoint was higher in patients with COVID-19-associated AKI (adjusted hazard ratio (aHR) mortality 3.98, 95% confidence interval (CI) 1.10–14.46, p = 0.036; composite endpoint aHR 1.84, 95% CI 1.02–3.31, p = 0.042). The mortality risk was attenuated when adjusting for disease severity (aHR 3.60, 95% CI 0.93–13.96, p = 0.062). AKI occurs more frequently and with a higher severity in patients with COVID-19 and is associated with worse outcomes.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Heyman Luckraz ◽  
Ramesh Giri ◽  
Benjamin Wrigley ◽  
Kumaresan Nagarajan ◽  
Eshan Senanayake ◽  
...  

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). Methods Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20–60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. Results Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14–4.27, p = 0.02). Conclusions Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946.


2018 ◽  
Vol 103 (7-8) ◽  
pp. 386-395
Author(s):  
Tadataka Takagi ◽  
Masayuki Sho ◽  
Satoshi Nishiwada ◽  
Takahiro Akahori ◽  
Minako Nagai ◽  
...  

Objective: The study objective is to investigate the impact of unilateral nephrectomy on the complications after pancreatoduodenectomy (PD). Summary of background data: Preoperative renal insufficiency is a risk factor for postoperative complications and mortality after various types of surgery. However, the specific postoperative risks in uninephrectomized (UN) patients are largely unknown. Methods: Between January 2010 and June 2014, a total of 177 patients underwent PD at the Department of Surgery, Nara Medical University. Among them, 7 patients (4.0%) were UN. We retrospectively evaluated the influence of the UN status on the postoperative complications. Results: The rate of acute kidney injury in the UN group was significantly higher than that in the control group (28.6% versus 1.2%; P = 0.017). In addition, the rates of surgical site infection of the organ/space (57.1% versus 9.0%; P = 0.006) and sepsis (42.9% versus 3.5%; P = 0.003) in UN group were significantly higher. Even on a reanalysis of only patients with soft pancreas, the significance remained. Conclusions: The UN status has a significant impact on the rate of morbidities, such as acute kidney injury and various infectious complications, including surgical site infections of organ/space, sepsis, and cholangitis after PD. Appropriate intervention should be implemented to decrease the morbidity rate for UN patients.


2021 ◽  
Author(s):  
Abdel Mumin SidAhmed ◽  
Nusaiba Hassan Mohamed Eltahir

Abstract Background: acute kidney injury is a common complication in critically ill patients and it is commonly associated with high mortality and morbidity with adverse short and long term outcome. bjectives: The main objective of this study was to determine the frequency of acute kidney injury in ICU patients in Omdurman teaching hospital. And to assess the risk factors associated with the development of acute kidney injury (AKI) in a critically ill patient. We also intended to correlate acute kidney injury with the primary disease required admitting to ICU and find out the impact of acute kidney injury in ICU outcomes. Methods: In this descriptive prospective, cohort hospital-based study, 211 patients were studied and followed up during admission in ICU using standardized questionnaire to collect clinical data and investigation Results: a total of 61 patients has been included in the study developed renal impairment during their stay in ICU 39 (64%) patients were males and 22 ( 36%) were female mean age was 41 ± 5 renal impairment developed after mean of 5 days of admission and the most common cause was decreased level of consciousness and severe hypotension. sepsis accounting for 40% of the admission. The outcome in ICU showed that the mortality rate was high up to 41% in kidney injury patients Sepsis account for over 96 % (24 patients) who have passed away. Conclusions: development of AKI in ICU is an important risk factor for poor outcomes in critically setting. Prevention is the best method for avoiding AKI, with the early identification and recognition of high-risk patients.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S251-S251
Author(s):  
Shannon NovosadShannon NovosadLeah Gilbert ◽  
Ibironke W Apata ◽  
Rahsaan Overton ◽  
Shikha Garg ◽  
Lindsey Kim ◽  
...  

Abstract Background Acute kidney injury (AKI) is a complication that has been described among severely ill patients with COVID-19 and may be more common in those with underlying chronic kidney disease (CKD). Some patients with AKI require renal replacement therapy (RRT), including continuous RRT (CRRT). During the COVID-19 pandemic, some US areas experienced CRRT supply shortages. We sought to describe the percent of hospitalized COVID-19 patients who developed AKI or needed RRT to inform patient care and resource planning. Methods We searched for studies in the literature and public health investigations that described CKD, AKI, and/or RRT in COVID-19 patients from January 2020 onward. Studies were excluded if no CKD, AKI, or RRT information was provided. We abstracted counts of hospitalized COVID-19 patients, including those admitted to intensive care units (ICU) who developed AKI, underwent RRT, and/or had CKD. Data were pooled across cohorts by geographic region with available data (US, China, or United Kingdom [UK]). We compared proportions using Chi-square tests. Results A total of 311 studies were identified; 23 studies (US n=11; China n=11; UK n=1) that described kidney disease and/or kidney-related outcomes in hospitalized COVID-19 patients were included. Underlying CKD prevalence was higher in US cohorts (10.3%) compared with China (2.5%) or UK (1.5%) (p&lt; 0.0001). AKI was markedly higher among hospitalized (31.3% vs. 6.4%; p &lt; 0 .001) and ICU patients (55.4% vs. 18.2%; p&lt; 0.0001) in the US compared to China. The percent of ICU patients requiring RRT in the US (16.8%) was significantly different from that reported in China (12.5%) and the UK (23.9%) (p&lt; 0.0001). Limitations include differences in CKD and RRT definitions across studies. Conclusion AKI is a frequent outcome among US COVID-19 patients, affecting almost one third of hospitalized and more than half of ICU patients. AKI was reported more frequently in the US than China. The percent of ICU patients who received RRT was higher in the US and UK than in China. Understanding the occurrence of kidney-related outcomes among patients with COVID-19 including the impact of underlying CKD and regional practice variations is essential for healthcare systems to successfully plan for RRT needs during the pandemic. Disclosures All Authors: No reported disclosures


2021 ◽  
Author(s):  
Heyman Luckraz ◽  
Ramesh Giri ◽  
Benjamin Wrigley ◽  
Kumaresan Nagarajan ◽  
Eshan Senanayake ◽  
...  

Abstract BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-hour post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB).MethodsPatients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20–60 ml/min/1.73m2, Logistic EuroScore > 5, anticipated CPB time > 120 minutes. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-hour post CPB NGAL levels were the primary and secondary end-points.ResultsPre & intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-hour post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14–4.27, p = 0.02).ConclusionsOverall, the 6-hour post-CPB plasma NGAL levels were significantly higher in patients who developed AKI.Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury.Clinical Registration NumberClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946


Author(s):  
Andrew M Vekstein ◽  
Babtunde A Yerokun ◽  
Oliver K Jawitz ◽  
Julie W Doberne ◽  
Jatin Anand ◽  
...  

Abstract OBJECTIVES The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS A total of 85% (n = 645) of patients underwent deep hypothermia (14.1–20.0°C), 11% (n = 83) low-moderate hypothermia (20.1–24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1–28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1–34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P &gt; 0.05). CONCLUSIONS In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiong-Fang Wu ◽  
Hao Kong ◽  
Zhen-Zhen Xu ◽  
Huai-Jin Li ◽  
Dong-Liang Mu ◽  
...  

Abstract Background The incidence of acute kidney injury (AKI) remains high after partial nephrectomy. Ischemia-reperfusion injury produced by renal hilum clamping during surgery might have contributed to the development of AKI. In this study we tested the hypothesis that goal-directed fluid and blood pressure management may reduce AKI in patients following partial nephrectomy. Methods This was a pilot randomized controlled trial. Adult patients who were scheduled to undergo partial nephrectomy were randomized into two groups. In the intervention group, goal-directed hemodynamic management was performed from renal hilum clamping until end of surgery; the target was to maintain stroke volume variation < 6%, cardiac index 3.0–4.0 L/min/m2 and mean arterial pressure > 95 mmHg with crystalloid fluids and infusion of dobutamine and/or norepinephrine. In the control group, hemodynamic management was performed according to routine practice. The primary outcome was the incidence of AKI within the first 3 postoperative days. Results From June 2016 to January 2017, 144 patients were enrolled and randomized (intervention group, n = 72; control group, n = 72). AKI developed in 12.5% of patients in the intervention group and in 20.8% of patients in the control group; the relative reduction of AKI was 39.9% in the intervention group but the difference was not statistically significant (relative risk 0.60, 95% confidence interval [CI] 0.28–1.28; P = 0.180). No significant differences were found regarding AKI classification, change of estimated glomerular filtration rate over time, incidence of postoperative 30-day complications, postoperative length of hospital stay, as well as 30-day and 6-month mortality between the two groups. Conclusion For patients undergoing partial nephrectomy, goal-directed circulatory management during surgery reduced postoperative AKI by about 40%, although not significantly so. The trial was underpowered. Large sample size randomized trials are needed to confirm our results. Trial registration Clinicaltrials.gov identifier: NCT02803372. Date of registration: June 6, 2016.


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