HIPEC-Induced Acute Kidney Injury: A Retrospective Clinical Study and Preclinical Model.
Ontology highlight
ABSTRACT: Background
Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) is the treatment of choice for selected patients with peritoneal malignancies. HIPEC is accompanied by moderate-to-high patient morbidity, including acute kidney injury. The significance of nephrotoxic agents such as cisplatin versus hyperthermia in HIPEC-induced nephrotoxicity has not been defined yet.Patients and methods
A total of 153 patients treated with HIPEC were divided into groups with (AKI+) and without (AKI-) kidney injury. Laboratory parameters and data concerning patient demographics, underlying disease, surgery, complications, and HIPEC were gathered to evaluate risk factors for HIPEC-induced AKI. A preclinical mouse model was applied to assess the significance of cisplatin and hyperthermia in HIPEC-induced AKI, as well as protective effects of the cytoprotective agent amifostine.Results
AKI occurred in 31.8% of patients undergoing HIPEC. Treatment with cisplatin-containing HIPEC regimens represented a major risk factor for HIPEC-related AKI (p < 0.001). Besides, angiotensin receptor blockers and increased preoperative creatinine and urea levels were independent risk factors for AKI after HIPEC. In a preclinical mouse model, intraperitoneal perfusion with cisplatin induced AKI, whereas hyperthermia alone, or in combination with cisplatin, did not induce or enhance renal injury. Amifostine failed to confer nephroprotective effects in a miniaturized HIPEC model.Conclusions
AKI is a frequent complication after HIPEC. The risk of renal injury is particularly high in patients treated with cisplatin-containing HIPEC regimens. Hyperthermic perfusion of the abdomen by itself does not seem to induce or aggravate HIPEC-induced renal injury.
SUBMITTER: Liesenfeld LF
PROVIDER: S-EPMC8677640 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundCisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently applied in selected patients with peritoneal malignancies derived from ovarian cancer, gastric cancer, and primary peritoneal mesothelioma. HIPEC with CDDP increases perioperative morbidity, in particular by inducing acute kidney injury (AKI). Factors contributing to occurrence of AKI after intraperitoneal perfusion with CDDP have not been sufficiently evaluated.Patients and methodsData from 63 patients treated with a CDDP-containing HIPEC regimen were retrospectively analyzed concerning demographics, underlying disease, surgery, and HIPEC details to evaluate risk factors of AKI. A preclinical rat perfusion model was applied to assess the influence of temperature, concentration, perfusate volume, perfusion flow rate, and extent of peritonectomy on drug absorption upon intraperitoneal CDDP perfusion.ResultsAKI occurred in 66.1% of patients undergoing CDDP-containing HIPEC, with total intraoperative fluid influx being a negative and the extent of parietal peritonectomy being a positive independent predictor of postoperative AKI. In a preclinical model, bilateral anterior parietal peritonectomy significantly increased systemic CDDP absorption by 1.6 to 2-fold. CDDP plasma levels in animals were significantly higher after both perfusion with increased CDDP perfusate concentrations and bilateral anterior parietal peritonectomy.ConclusionCDDP-containing HIPEC is associated with relevant morbidity owing to its systemic toxicity. Extent of parietal peritonectomy is an independent predictor of AKI. CDDP dose reduction should be considered in case of extensive parietal peritonectomy. Cytostatic drug concentrations in HIPEC perfusate should be paid more attention to than total dose per body surface area. Further clinical studies are needed to confirm the presented preclinical findings.
| S-EPMC10085927 | biostudies-literature
Project description:Background and objectivesAcute kidney injury is a common comorbidity in patients with intracerebral hemorrhage. Although there are predictive models to determine risk of AKI in patients in critical care or post-surgical scenarios or in general medical floors, there are no models that specifically determine the risk of AKI in patients with ICH.MethodsClinical features and laboratory tests were selected by previous studies and LASSO (least absolute shrinkage and selection operator) regression. We used multivariable logistic regression with a bidirectional stepwise method to construct ICH-AKIM (intracerebral hemorrhage-associated acute kidney injury model). The accuracy of ICH-AKIM was measured by the area under the receiver operating characteristic curve. The outcome was AKI development during hospitalization, defined as KDIGO (Kidney Disease: Improving Global Outcomes) Guidelines.ResultsFrom four independent medical centers, a total of 9649 patients with ICH were available. Overall, five clinical features (sex, systolic blood pressure, diabetes, Glasgow coma scale, mannitol infusion) and four laboratory tests at admission (serum creatinine, albumin, uric acid, neutrophils-to-lymphocyte ratio) were predictive factors and were included in the ICH-AKIM construction. The AUC of ICH-AKIM in the derivation, internal validation, and three external validation cohorts were 0.815, 0.816, 0.776, 0.780, and 0.821, respectively. Compared to the univariate forecast and pre-existing AKI models, ICH-AKIM led to significant improvements in discrimination and reclassification for predicting the incidence of AKI in all cohorts. An online interface of ICH-AKIM is freely available for use.ConclusionICH-AKIM exhibited good discriminative capabilities for the prediction of AKI after ICH and outperforms existing predictive models.
| S-EPMC10472951 | biostudies-literature
Project description:IntroductionAcute kidney injury (AKI) following cardiovascular surgery has been shown to increase costs and overall morbidity and mortality. The incidence, risk factors, and outcomes of AKI following other types of major surgeries have not been as well characterized. We sought to study the incidence of AKI following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) per the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.Materials and methodsPatients undergoing CRS and HIPEC between 2013 and 2015 were included. Demographic and perioperative data were compared between patients who experienced AKI versus controls using appropriate statistical analysis between categorical and continuous variables. AKI was recorded by a Certified Professional in Healthcare Quality (CPHQ) and defined as a rise in serum creatinine by ≥ 0.3 mg/dL within 48 h (KDIGO criteria).ResultsFifty-eight consecutive patients undergoing CRS and HIPEC were included. Twelve (20.7%) patients were recorded to develop AKI. This was the most common complication recorded by the CPHQ member. There was one 30-day mortality secondary to cerebral infarction. AKI patients had a longer hospitalization period (14.2 ± 6.9 vs. 9.5 ± 3.3 days, p = 0.002), and a higher rate of major complications (50.00% vs. 15.21%; p = 0.018). Readmission rate was similar (p = 0.626). Multivariate regression identified excessive blood loss during surgery as a major predictor of AKI occurrence, and pre-existing comorbidities and postoperative AKI as predictors of major morbidities following CRS and HIPEC.ConclusionAKI following CRS and HIPEC appears to be a common complication which is associated with further major morbidities. Current quality improvement programs may be under-reporting this incidence.
| S-EPMC6178214 | biostudies-literature
Project description:BACKGROUND:Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19-associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom. METHODS AND FINDINGS:We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19-negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19-positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19-negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ?85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region. CONCLUSIONS:We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this. TRIAL REGISTRATION:ClinicalTrials.gov NCT04407156.
| S-EPMC7598516 | biostudies-literature
Project description:Postoperative acute kidney injury is associated with high mortality and poor prognosis. Additional investigations into the risk factors for this condition and the outcomes of patients who undergo surgeries under non-general anesthesia (GA) are necessary.This retrospective cohort study included data on all surgeries performed in adult patients from January 2006 to December 2015 at a tertiary hospital in Korea. Patients were divided into those undergoing surgeries with non-GA and those undergoing surgeries with GA. We analyzed the nephrological evaluation patterns, the risk factors for acute kidney injury, and prognoses after acute kidney injury by reviewing mortality, progression to end-stage renal disease, and serum creatinine doubling/estimated glomerular filtration rate halving from baseline.Of 74,524 patients, 20,332 underwent surgery with non-GA. These patients had baseline (adjusted odds ratio [OR], .68, 95% confidence interval [CI], .63-.72; P < .01] and follow-up serum creatinine levels (adjusted OR, .34; 95% CI, .33-.36; P < .01) less frequently measured than those undergoing GA. However, the incidence of acute kidney injury did not differ significantly between the 2 groups. Moreover, postoperative acute kidney injury after non-GA surgery showed a worse clinical prognosis which was similar with that of GA operations.Patients undergoing surgeries under non-GA did not receive sufficient evaluation for their risks of acute kidney injury. As an acute kidney injury in non-GA was associated a worse prognosis as in GA surgeries, more clinical attention should be considered.
| S-EPMC6392954 | biostudies-literature
Project description:BACKGROUND:Injured patients are at risk of developing acute kidney injury (AKI), which is associated with increased morbidity and mortality. The aim of this study is to describe the incidence, timing, and severity of AKI in a large trauma population, identify risk factors for AKI, and report mortality outcomes. METHODS:A prospective observational study of injured adults, who met local criteria for trauma team activation, and were admitted to a UK Major Trauma Centre. AKI was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression and Cox proportional hazard modelling was used to analyse parameters associated with AKI and mortality. RESULTS:Of the 1410 patients enrolled in the study, 178 (12.6%) developed AKI. Age; injury severity score (ISS); admission systolic blood pressure, lactate and serum creatinine; units of Packed Red Blood Cells transfused in first 24 hours and administration of nephrotoxic therapy were identified as independent risk factors for the development of AKI. Patients that developed AKI had significantly higher mortality than those with normal renal function (47/178 [26.4%] versus 128/1232 [10.4%]; OR 3.09 [2.12 to 4.53]; p<0.0001). After adjusting for other clinical prognostic factors, AKI was an independent risk factor for mortality. CONCLUSIONS:AKI is a frequent complication following trauma and is associated with prolonged hospital length of stay and increased mortality. Future research is needed to improve our ability to rapidly identify those at risk of AKI, and develop resuscitation strategies that preserve renal function in trauma patients.
| S-EPMC6347290 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a serious post-surgery complication; however, few preoperative risk models for AKI have been developed for hypertensive patients undergoing general surgery. Thus, in this study involving a large Chinese cohort, we developed and validated a risk model for surgery-related AKI using preoperative risk factors.Methods and findingsThis retrospective cohort study included 24,451 hypertensive patients aged ≥18 years who underwent general surgery between 2007 and 2015. The endpoints for AKI classification utilized by the KDIGO (Kidney Disease: Improving Global Outcomes) system were assessed. The most discriminative predictor was selected using Fisher scores and was subsequently used to construct a stepwise multivariate logistic regression model, whose performance was evaluated via comparisons with models used in other published works using the net reclassification index (NRI) and integrated discrimination improvement (IDI) index.ResultsSurgery-related AKI developed in 1994 hospitalized patients (8.2%). The predictors identified by our Xiang-ya Model were age, gender, eGFR, NLR, pulmonary infection, prothrombin time, thrombin time, hemoglobin, uric acid, serum potassium, serum albumin, total cholesterol, and aspartate amino transferase. The area under the receiver-operating characteristic curve (AUC) for the validation set and cross validation set were 0.87 (95% CI 0.86-0.89) and (0.89; 95% CI 0.88-0.90), respectively, and was therefore similar to the AUC for the training set (0.89; 95% CI 0.88-0.90). The optimal cutoff value was 0.09. Our model outperformed that developed by Kate et al., which exhibited an NRI of 31.38% (95% CI 25.7%-37.1%) and an IDI of 8% (95% CI 5.52%-10.50%) for patients who underwent cardiac surgery (n = 2101).Conclusions/significanceWe developed an AKI risk model based on preoperative risk factors and biomarkers that demonstrated good performance when predicting events in a large cohort of hypertensive patients who underwent general surgery.
| S-EPMC5089779 | biostudies-literature
Project description:BackgroundAn alarming number of COVID-19 patients, especially in severe cases, have developed acute kidney injury (AKI).AimThe study aimed to assess the frequency, risk factors, and impact of AKI on mortality in critically ill COVID-19 patients.MethodsThe study was a retrospective observational study conducted in the MICU. Univariate and multivariate analyses were performed to identify risk factors for AKI and clinical outcomes.ResultsDuring the study period, 465 consecutive COVID-19 patients were admitted to the MICU. The patients' characteristics were median age, 64 [54-71] years; median SAPSII, 31 [24-38]; and invasive mechanical ventilation (IMV), 244 (52.5%). The overall ICU mortality rate was 49%. Two hundred twenty-nine (49.2%) patients developed AKI. The factors independently associated with AKI were positive fluid balance (OR, 2.78; 95%CI [1.88-4.11]; p < 0.001), right heart failure (OR, 2.15; 95%CI [1.25-3.67]; p = 0.005), and IMV use (OR, 1.55; 95%CI [1.01-2.40]; p = 0.044). Among the AKI patients, multivariate analysis identified the following factors as independently associated with ICU mortality: age (OR, 1.05; 95%CI [1.02-1.09]; p = 0.012), IMV use (OR, 48.23; 95%CI [18.05-128.89]; p < 0.001), and septic shock (OR, 3.65; 95%CI [1.32-10.10]; p = 0.012).ConclusionThe present study revealed a high proportion of AKI among critically ill COVID-19 patients. This complication seems to be linked to a severe cardiopulmonary interaction and fluid balance management, thus accounting for a poor outcome.
| S-EPMC10419665 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a clinically important condition that has attracted a great deal of interest from the biomedical research community. However, acute kidney injury AKI research findings have yet to be translated into significant changes in clinical practice.ObjectiveThis article reviews many of the preclinical innovations in acute kidney injury AKI treatment, and explores challenges and opportunities to translate these finding into clinical practice.Sources of informationMEDLINE, ISI Web of Science.FindingsThis paper details areas in biomedical research where translation of pre-clinical findings into clinical trials is ongoing, or nearing a point where trial design is warranted. Further, the paper examines ways that best practice in the management of AKI can reach a broader proportion of the patient population experiencing this condition.LimitationsThis review highlights pertinent literature from the perspective of the research interests of the authors for new translational work in AKI. As such, it does not represent a systematic review of all of the AKI literature.ImplicationsTranslation of findings from biomedical research into AKI therapy presents several challenges. These may be partly overcome by targeting populations for interventional trials where the likelihood of AKI is very high, and readily predictable. Further, specific clinics to follow-up with patients after AKI events hold promise to provide best practice in care, and to translate therapies into treatment for the broadest possible patient populations.
| S-EPMC4556308 | biostudies-literature
Project description:Background: Patients with severe acute kidney injury (AKI) require continuous renal replacement therapy (CRRT) when hemodynamically unstable. We aimed to identify prognostic factors and develop a nomogram that could predict mortality in patients with AKI undergoing CRRT. Methods: Data were extracted from the Dryad Digital Repository. We enrolled 1,002 participants and grouped them randomly into training (n = 670) and verification (n = 332) datasets based on a 2:1 proportion. Based on Cox proportional modeling of the training set, we created a web-based dynamic nomogram to estimate all-cause mortality. Results: The model incorporated phosphate, Charlson comorbidity index, body mass index, mean arterial pressure, levels of creatinine and albumin, and sequential organ failure assessment scores as independent predictive indicators. Model calibration and discrimination were satisfactory. In the training dataset, the area under the curves (AUCs) for estimating the 28-, 56-, and 84-day all-cause mortality were 0.779, 0.780, and 0.787, respectively. The model exhibited excellent calibration and discrimination in the validation dataset, with AUC values of 0.791, 0.778, and 0.806 for estimating 28-, 56-, and 84-day all-cause mortality, respectively. The calibration curves exhibited the consistency of the model between the two cohorts. To visualize the results, we created a web-based calculator. Conclusion: We created a web-based calculator for assessing fatality risk in patients with AKI receiving CRRT, which may help rationalize clinical decision-making and personalized therapy.
| S-EPMC9679412 | biostudies-literature