Intermittent Renal Replacement Therapy Research Articles

Sacituzumab-govitecan-induced severe acute tubulointerstitial nephritis requiring hemodialysis

BackgroundSacituzumab govitecan is an antibody-drug conjugate that is FDA approved for refractory metastatic triple-negative breast cancer. It targets the human trophoblastic cell-surface antigen 2 (Trop-2) with SN-38, a topoisomerase I inhibitor, attached to the antibody [1]. SN-38 breaks DNA strands and induces tumor apoptosis [2]. Acute kidney injury (AKI) is one of its adverse effects mainly prerenal due to gastrointestinal toxicity, but it has not been reported to cause acute tubulointerstitial nephritis (ATIN).Case PresentationThis report describes a rare adverse effect of sacituzumab govitecan, the approach to diagnosing the etiology of the patient’s AKI, and the mechanism by which sacituzumab govitecan causes ATIN. A woman with metastatic ER positive, PR positive, HER2 negative breast cancer who was initiated on sacituzumab govitecan presents with vomiting and diarrhea, and findings of nephrotic-range proteinuria, negative anti-PLA2R antibody, and severe AKI requiring hemodialysis. She underwent kidney biopsy and pathology showed ATIN characterized by patchy interstitial inflammation alongside tubular injury without glomerular and vascular involvement. With intermittent renal replacement therapy, furosemide challenge, and a course of prednisone, the patient’s kidney function recovered.ConclusionsSacituzumab has a high affinity for Trop-2 protein which is also expressed within the collecting ducts, and to a lesser extent, the proximal tubule. Individuals, such as this patient, who express a homozygous genotype for UGT1A1*28 allele are at increased risk for AKI from sacituzumab govitecan due to decreased glucuronidation of SN-38.

Achievement of fluid removal targets during intermittent renal replacement therapy in the intensive care unit

ABSTRACT Background In patients with acute kidney injury (AKI), fluid balance management often relies on the prescription and achievement of fluid removal using intermittent renal replacement therapy (IRRT). This study aimed to describe characteristics associated with the failure to achieve target fluid removal (FATFR). Methods This is a retrospective cohort study including IRRT sessions of conventional duration (<5 hours) performed for AKI in the intensive care unit (ICU) from 2017 to 2022 at a tertiary academic center. FATFR-50% was defined as fluid removal of <50% of the prescribed target. Characteristics of patients and sessions, as well as outcomes at 90 days were collected. The causes of FATFR were manually adjudicated. Results A total of 291 patients and 1280 IRRT sessions in the ICU were included. FATFR-50% occurred in 7.3% of sessions and 19.2% of patients had at least one session with FATFR-50% during the first week of IRRT. Sessions with FATFR-50% were characterized by a higher occurrence of intradialytic hypotension (24.2% vs 60.2%, P < .001) and a higher planned fluid removal (6.19 vs 5.27 m/kg/h, P = .02). Multiple episodes of FATFR-50% were associated with a positive cumulative fluid balance (β 3876 (CI 2053–5899) P < .001). At 90-day follow-up, FATFR-50% during the first week after IRRT initiation was independently associated with fewer ICU- and hospital-free days, as well as with a higher risk of mortality (odds ratio 2.01 CI 1.04–3.89, P = .04). Conclusions FATFR occurs in about one out of five critically ill patients within the first week of IRRT and is associated with adverse clinical outcomes.

Successful prolonged intermittent renal replacement therapy in managing isolated coronary artery bypass graft surgery-associated acute kidney injury: A case report

Successful prolonged intermittent renal replacement therapy in managing isolated coronary artery bypass graft surgery-associated acute kidney injury: A case report

Long-Term Mortality and Health-Related Quality of Life After Continuous Versus Intermittent Renal Replacement Therapy in ICU Survivors: A Secondary Analysis of the Quality of Life After ICU Study.

Purpose: We assessed long-term outcomes in intensive care unit (ICU) survivors with acute kidney injury (AKI) submitted to intermittent or continuous renal replacement therapy (RRT) for comparisons between groups. Methods: The multicenter prospective cohort study included 195 adult ICU survivors with an ICU stay >72 h in 10 ICUs that had at least one episode of AKI treated with intermittent RRT (IRRT) or continuous RRT (CRRT) during ICU stay. The main outcomes were mortality and health-related quality of life (HRQoL). Hospital readmissions and physical dependence were also assessed. Results: Regarding RRT, 83 (42.6%) patients received IRRT and 112 (57.4%) received CRRT. Despite the similarity regarding sociodemographic characteristics, pre-ICU state of health and type of admission between groups, the risk of death (23.5% vs 42.7%; P < .001), the prevalence of sepsis (60.7%) and acute respiratory distress syndrome (17%) were higher at ICU admission among CRRT patients. The severity of critical illness was higher among CRRT patients, regarding the need for mechanical ventilation (75.0% vs 50.6%, P = .002) and vasopressors (91.1% vs 63.9%, P < .001). One year after ICU discharge, 67 of 195 ICU survivors died (34.4%) and, after adjustment for confounders, there were no significant differences in mortality when comparing IRRT and CRTT patients (34.9% vs 33.9%; P = .590), on HRQoL in both physical (41.9% vs 42.2%; P = .926) and mental dimensions (57.6% vs 56.6%; P = .340), and on the number of hospital readmissions and physical dependence. Conclusions: Our study suggests that among ICU survivors RRT modality (IRRT vs CRRT) in the ICU does not impact long-term outcomes after ICU discharge.

Incidence of intradialytic hypotension in heart transplant recipients with acute kidney injury treated by acetate-free hemodiafiltration

Introduction. Intradialytic hypotension (IDH) is a common complication of renal replacement therapy (RRT) sessions and may be a particularly detrimental factor in heart recipients. Objective: to investigate the incidence of IDH in heart recipients with acute kidney injury (AKI). Patients and Methods: Two groups of recipients were compared – the study group (SG), n = 313, in which 49 patients required intermittent RRT (IRRT) and in which online hemodiafiltration (OL-HDF) sessions were performed using acetate-free hydrochloric acid-based dialysate fluid; and control group (CG) n = 387, in which 88 patients required IRRT, where standard dialysate with an acetate ion content of 3 mmol/L was used for OL-HDF. Results. There was a significantly lower incidence of IDH in the SG compared to the CG: 10.46% vs 20.47% (p &lt; 0.05). Conclusions. In heart recipients for whom IDH can be considered as a significant adverse factor, the use of acetate-free dialysis fluid can significantly reduce the incidence of this complication.

What is the role of the neutrophil extracellular traps in the cardiovascular disease burden associated with hemodialysis bioincompatibility?

Despite significant progress in dialysis modalities, intermittent renal replacement therapy remains an "unphysiological" treatment that imperfectly corrects uremic disorders and may lead to low-grade chronic inflammation, neutrophil activation, and oxidative stress due to repetitive blood/membrane interactions contributing to the "remaining uremic syndrome" and cardiovascular disease burden of hemodialysis patients. Understanding dialysis bioincompatibility pathways still remains a clinical and biochemical challenge. Indeed, surrogate biomarkers of inflammation including C-reactive protein could not discriminate between all components involved in these complex pathways. A few examples may serve to illustrate the case. Cytokine release during dialysis sessions may be underestimated due to their removal using high-flux dialysis or hemodiafiltration modalities. Complement activation is recognized as a key event of bioincompatibility. However, it appears as an early and transient event with anaphylatoxin level normalization at the end of the dialysis session. Complement activation is generally assumed to trigger leukocyte stimulation leading to proinflammatory mediators' secretion and oxidative burst. In addition to being part of the innate immune response involved in eliminating physically and enzymatically microbes, the formation of Neutrophil Extracellular Traps (NETs), known as NETosis, has been recently identified as a major harmful component in a wide range of pathologies associated with inflammatory processes. NETs result from the neutrophil degranulation induced by reactive oxygen species overproduction via NADPH oxidase and consist of modified chromatin decorated with serine proteases, elastase, bactericidal proteins, and myeloperoxidase (MPO) that produces hypochlorite anion. Currently, NETosis remains poorly investigated as a sensitive and integrated marker of bioincompatibility in dialysis. Only scarce data could be found in the literature. Oxidative burst and NADPH oxidase activation are well-known events in the bioincompatibility phenomenon. NET byproducts such as elastase, MPO, and circulating DNA have been reported to be increased in dialysis patients more specifically during dialysis sessions, and were identified as predictors of poor outcomes. As NETs and MPO could be taken up by endothelium, NETs could be considered as a vascular memory of intermittent bioincompatibility phenomenon. In this working hypothesis article, we summarized the puzzle pieces showing the involvement of NET formation during hemodialysis and postulated that NETosis may act as a disease modifier and may contribute to the comorbid burden associated with dialysis bioincompatibility.

Vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration.

Vancomycin pharmacokinetics are affected by renal replacement therapy and physiologic changes in critically ill patients. Literature regarding vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration (AVVH), a form of prolonged intermittent renal replacement therapy, is limited. To describe the removal and pharmacokinetics of vancomycin during AVVH. Eighteen critically ill adults receiving vancomycin and AVVH were included. Vancomycin serum concentrations were obtained within 4 h before and 2-6 h after the AVVH session. Patients' serum concentrations were plotted against time, and individual pharmacokinetic parameters were determined by a one-compartmental analysis. Continuous data are reported as a median (interquartile range [IQR]) and categorical data as a percentage. The median AVVH effluent rate was 39.3 mL/kg/h (IQR 35.5-48 mL/kg/h) for a duration of 9 h (IQR 8-9.75 h). AVVH decreased vancomycin concentrations by 29.8% (IQR 24.9%-35.9%), at a rate of 3.4% per hour (IQR 3.1%-4.3% per hour) of AVVH. The vancomycin elimination rate constant and half-life were 0.039 h-1 (IQR 0.036-0.053 h-1 ) and 17.6 h (IQR 13.1-18.8 h), respectively. The area under the curve during AVVH was 171.7 mg*h/L (IQR 149.1-190 mg*h/L). The volume of distribution in 10 patients was 1 L/kg (IQR 0.73-1.1 L/kg). After AVVH, vancomycin 1000 mg (IQR 750-1000 mg) was needed to maintain a serum trough concentration ≥15 mg/L. Vancomycin is significantly removed by AVVH, which requires supplemental dosing after completion of the AVVH session to maintain desired serum concentrations. Therapeutic drug monitoring of vancomycin serum concentrations is recommended for patients undergoing AVVH.

Antimicrobial Pharmacokinetics and Dosing in Critically Ill Adults Receiving Prolonged Intermittent Renal Replacement Therapy: A Systematic Review.

Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: 1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, 2) evaluate the quality of evidence supporting this data, and 3) propose dosing recommendations based on the synthesis of this data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction was conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recomendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.

Short-term prognostic models for severe acute kidney injury patients receiving prolonged intermittent renal replacement therapy based on machine learning

BackgroundAs an effective measurement for severe acute kidney injury (AKI), the prolonged intermittent renal replacement therapy (PIRRT) received attention. Also, machine learning has advanced and been applied to medicine. This study aimed to establish short-term prognosis prediction models for severe AKI patients who received PIRRT by machine learning.MethodsThe hospitalized AKI patients who received PIRRT were assigned to this retrospective case-control study. They were grouped based on survival situation and renal recovery status. To screen the correlation, Pearson’s correlation coefficient, partial ETA square, and chi-square test were applied, eight machine learning models were used for training.ResultsAmong 493 subjects, the mortality rate was 51.93% and the kidney recovery rate was 30.43% at 30 days post-discharge, respectively. The indices related to survival were Sodium, Total protein, Lactate dehydrogenase (LDH), Phosphorus, Thrombin time, Liver cirrhosis, chronic kidney disease stage, number of vital organ injuries, and AKI stage, while Sodium, Total protein, LDH, Phosphorus, Thrombin time, Diabetes, peripherally inserted central catheter and AKI stage were selected to predict the 30-day renal recovery. Naive Bayes has a good performance in the prediction model for survival, Random Forest has a good performance in 30-day renal recovery prediction model, while for 90-day renal recovery prediction model, it’s K-Nearest Neighbor.ConclusionsMachine learning can not only screen out indicators influencing prognosis of AKI patients receiving PIRRT, but also establish prediction models to optimize the risk assessment of these people. Moreover, attention should be paid to serum electrolytes to improve prognosis.

Outcomes of Prolonged Intermittent Renal Replacement Therapy Combined with Hemoperfusion among Patients Aged &lt;18 Years Old with Severe Dengue

Context: Fluid overload is inevitable in severe dengue shock syndrome despite intensive fluid management. Aims: To compare the outcomes of prolonged intermittent renal replacement therapy (PIRRT) with or without hemoperfusion (HP) in treating severe dengue among patients ≤18 years old. Settings and Design: Retrospective cohort study in the hemodialysis unit of a tertiary hospital in the Philippines. Methods: Demographic and clinical data, kidney replacement therapy prescription variables, hemodynamic status, and outcomes were analyzed retrospectively for pediatric patients who underwent PIRRT with or without HP for severe dengue. The primary outcome was 28-day all-cause mortality, whereas secondary outcomes were changes in percent fluid overload, vasopressor index (VI), mean arterial pressure, and vasopressor dependency. Statistical Analysis Used: Mann–Whitney U, Chi-square, Fisher exact, and Student’s t test. Results: Among 357 severe dengue patients, 27 underwent PIRRT with (n = 18) or without (n = 9) HP. Baseline demographic and clinical characteristics differed significantly only with respect to the degree of fluid overload, time to therapy initiation, proportion with obesity and overweight, and duration of treatment during the first session. There were no significant differences between the two groups in 28-day mortality (PIRRT, n = 7 of 9, vs. PIRRT + HP, n = 10; P = 0.40) or secondary outcomes except an increased VI in PIRRT group (mean 38.2 vs. 12.4; P = 0.04). Conclusions: PIRRT combined with HP is feasible in hemodynamically unstable children with severe dengue in a resource-limited setting, but the outcomes of the combination are similar to those with PIRRT alone. Larger prospective studies should examine the efficacy of the combination of PIRRT with HP in terms of the dialysis dose and changes in cytokine levels or other inflammatory markers.

Long-term arteriovenous fistula prognosis for maintenance hemodialysis patients who accepted PIRRT by using arteriovenous fistula.

Maintenance hemodialysis (MHD) patients are often admitted to the hospital for severe morbidities. Prolonged intermittent renal replacement therapy (PIRRT) is required during the hospital staying. There are controversial opinions on the use of arteriovenous fistula (AVF) as vascular access for PIRRT in MHD patients. Patients with AVF who accepted PIRRT in our center between January 2014 and June 2021 were retrospectively screened. AVF dysfunction and patient mortality were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of AVF dysfunction. About 162 patients were included in our present study. Twenty-six experienced AVF dysfunction, of whom 53.8%, 19.2%, and 27.0% had percutaneous transluminal balloon angioplasty, surgical revision, and AVF reconstruction, respectively. The accumulated AVF dysfunction rates were 11.8%, 16.2%, and 21.0% in 1, 2, and 3 years, respectively. Multivariate analysis revealed that smoking (HR 2.750, 95% CI 1.181-6.402, p = 0.019), higher platelet (PLT, HR 1.009, 95% CI 1.000-1.017, p = 0.047), higher prothrombin activity (PTA, HR 1.039, 95% CI 1.012-1.066, p = 0.004), and lower diastolic blood pressure (DBP, HR 0.963, 95% CI 0.932-0.996, p = 0.026) were independent risk factors for AVF dysfunction. During the follow-up period, 37 patients died. Overall, the use of AVF for PIRRT might not dramatically increase the incidence of AVF dysfunction. And, Smoking, lower DBP, higher PLT, and higher PTA were associated with increased AVF dysfunction.

Global Perspectives in Acute Kidney Injury: Spain.

Global Perspectives in Acute Kidney Injury: Spain.

Comparison of hemodynamic indices of dialysis patients in continuous renal replacement therapy and intermittent renal replacement therapy methods with ultrasonic cardiac output monitor in intensive care unit

Introduction: Acute kidney injury (AKI) is a common complication in the intensive care unit (ICU) and is independently associated with end-stage renal disease and higher mortality in the ICU. There are different methods to supporting kidney function in critically ill patients. The renal replacement therapy (RRT) can be conducted continuously, intermittently, or in combination. Objectives: The purpose of our study is to investigate the hemodynamic indices of dialysis patients in the ICU by two methods high flow continuous renal replacement therapy (CRRT) and intermittently renal replacement therapy (IRRT) of ultrasonic cardiac output monitor (USCOM). Patients and Methods: In this study conducted at Sina hospital, patients requiring dialysis hospitalized to the ICU were studied. Around 48 patients benefited from rapid CRRT or IRRT in the opinion of a specialist. Basic patient information was recorded. To check hemodynamic parameters during dialysis, USCOM was carried out to check corrected flow time value (FTc) parameters, systemic vascular resistance (SVR) and cardiac output. Results were compared between the IRRT and CRRT groups. Results: This study was conducted on 48 patients who were candidates for dialysis. Patients were divided into high flow CRRT and IRRT groups based on clinical indications. In CRRT group, 19 patients (79.2%) and in the IRRT group, 20 patients (83.3%) were male (P=0.712). Their mean age was 68.70 ± 8.25 years in the CRRT group and 68.58 ± 7.19 years in the IRRT group. All patients had cardiac output monitored using USCOM or ultrasound. The mean Sequential Organ Failure Assessment (SOFA) score in the CRRT group was 7 and in the IRRT group was 6, with no significant difference among them. FTc value variable or modified flow time in the carotid artery, cardiac output, cardiac index, SVR variable and mean arterial pressure in in the two groups at four evaluated times (before dialysis, 15 minutes later, one hour later and end of dialysis) from the study the difference were not statistically significant. Conclusion: Although previos studies have recommended CRRT, our study showed significant difference may not be existed between IRRT and CRRT.

Results of the 2018 Japan Society for Blood Purification in Critical Care survey: current status and outcomes

BackgroundThe Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018.MethodsWe analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores.ResultsBPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality.ConclusionThis large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration: UMIN000027678.

The Role of Sustained Low-Efficiency Dialysis (SLED) in the Intensive Care Unit

Renal replacement therapies are frequently used in the intensive care unit, most often in patients with severe acute kidney injury, a common complication in this setting. The choice of a prolonged intermittent renal replacement therapy (PIRRT) has grown in its popularity. Nevertheless, not all clinicians are familiar with it. The most frequently performed PIRRT is sustained low-efficiency dialysis. The aim of this article is to review the sustained low-efficiency dialysis technique, namely the necessary machinery, the prescription specificities, its complications and the particularities related to intoxications and drug dosing. Lastly, when to start sustained low-efficiency dialysis and its advantages and disadvantages over intermittent hemodialysis and continuous renal replacement therapies is discussed.

Online Hemodiafiltration Compared to Conventional Hemodialysis in Critically Ill Patients

Online hemodiafiltration (HDF) has been increasingly used for improved clearance of middle molecular weight toxins. The impact of this mode of clearance is unknown in critically ill patients. We aimed to determine whether the use of HDF in acute kidney injury (AKI) is associated with lower mortality and improved kidney recovery up to 90 days after initiation of therapy. Single-center retrospective cohort study using data from 2017 to 2020 of adults with AKI who initiated intermittent renal replacement therapy (IRRT) in the intensive care unit (ICU), using either hemodialysis (HD) or HDF depending on the maintenance status of the water system without regards for patient characteristics. We assessed association with patient-events and session-events using time-dependent Cox models and general estimating equations models, respectively. We included 182 adults with AKI for whom 848 IRRT sessions were performed in the ICU. The 90-day mortality rate was 43 of 182 (24.6%). There was no significant association with the use of HDF and mortality (adjusted hazard ratio [aHR]: 0.85 (0.43; 1.67) P= 0.64), kidney recovery (aHR: 1.18 (0.76; 1.84) P=0.47), or intradialytic hypotension (adjusted odds ratio [aOR]: 0.91 confidence interval [CI]: 0.64-1.28 P= 0.58). HDF treatment was associated with a lower rate of subsequent vasopressor use (aOR: 0.60 CI: 0.36-0.99 P= 0.047) and a greater reduction of the neutrophil-to-lymphocyte ratio (NLR) following the first session (-15.0% vs.+5.1%, P= 0.047) but was also associated with increased risk of filter thrombosis during treatment (aOR: 2.42 CI: 1.67-3.50 P< 0.001). The use of HDF in the setting of AKI was not associated with a differential risk of mortality or kidney recovery.

Prolonged Intermittent Renal Replacement Therapy Combined with Hemoperfusion Can Improve Early Recovery of Moderate and Severe Acute Pancreatitis, Especially in Patients with Acute Kidney Injury

Introduction: The aim of this study was to investigate the efficacy of prolonged intermittent renal replacement therapy (PIRRT) plus hemoperfusion (HP) in treating moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). Methods: A total of 105 MSAP and SAP patients were enrolled. Sixty of them received routine internal medical therapy (control group), and 45 received PIRRT and HP in addition to routine internal medical therapy (PIRRT + HP group). The vital signs, laboratory results, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared between the two groups before treatment and on the 3rd and 7th days of treatment. Results: No deaths or treatment-related serious adverse reactions occurred in both groups. After 3 and 7 days of treatment, the APACHE II score decreased more significantly in the PIRRT + HP group than in the control group (3 days: 5.47 [±3.30] vs. 7.53 [±3.89], p = 0.005. 7 days: 4.82 [±3.49] vs. 6.87 [±3.54], p = 0.004). After 3 days of treatment, the inflammatory combination parameters systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in the PIRRT + HP group decreased more significantly than those in the control group (SII: 1,239.00 [737.80–1,769.00] vs. 2,013.00 [1,260.00–3,167.00], p = 0.001. NLR: 8.78 [±4.52] vs. 11.88 [±7.30], p = 0.009). After 7 days of treatment, SII, NLR, and hypersensitive C-reactive protein decreased significantly compared with baseline, but no statistical differences between the two groups were observed. AST in both groups remained stable with treatment. There was no significant difference in baseline creatinine between the two groups of AKI patients, but after 3 and 7 days of treatment, the proportion of acute kidney injury (AKI) patients in the PIRRT + HP group whose creatinine decreased by 50% from baseline or fell to the normal range was significantly higher than that in the control group (p < 0.05). Conclusion: PIRRT + HP therapy could not only improve the general conditions, as measured by APACHE II score, but also reduce the inflammatory cascade of patients with acute pancreatitis. For MSAP and SAP patients complicated with AKI, this therapy may accelerate the recovery of renal function.

Comparison of hemodynamic instability among continuous, intermittent and hybrid renal replacement therapy in acute kidney injury: A systematic review of randomized clinical trials.

To compare hemodynamic instability during continuous, intermittent and hybrid renal replacement therapy (RRT) in critically ill patients, and its association with renal recovery and mortality. The search was conducted in accordance with the PRISMA guidelines which was registered at the PROSPERO Database (CRD42018086504). Randomized clinical trials (RCTs) involving critically ill patients with acute kidney injury (AKI) treated with continuous, intermittent or hybrid RRT were included. The search was performed using PubMed, Embase and Cochrane databases. Out of 3442 citations retrieved, 12 RCTs were included in the systematic analysis, representing 1419 patients. Most studies (n = 8) did not report differences in hemodynamic parameters across different RTT modalities. The incidence of hypotensive episodes varied from 5 to 60% among the studies. Punctual differences on heart rate and blood pressure were observed among studies. However, studies presented high heterogeneity in terms of outcome definitions and measurement, thus making the conduction of meta-analysis impossible. There is very few information available regarding hemodynamic tolerance of renal replacement therapy methods. A better standardization of hemodynamic tolerance and further reports are needed before conclusions can be drawn.

Hidden risks associated with conventional short intermittent hemodialysis: A call for action to mitigate cardiovascular risk and morbidity.

The development of maintenance hemodialysis (HD) for end stage kidney disease patients is a success story that continues to save many lives. Nevertheless, intermittent renal replacement therapy is also a source of recurrent stress for patients. Conventional thrice weekly short HD is an imperfect treatment that only partially corrects uremic abnormalities, increases cardiovascular risk, and exacerbates disease burden. Altering cycles of fluid loading associated with cardiac stretching (interdialytic phase) and then fluid unloading (intradialytic phase) likely contribute to cardiac and vascular damage. This unphysiologic treatment profile combined with cyclic disturbances including osmotic and electrolytic shifts may contribute to morbidity in dialysis patients and augment the health burden of treatment. As such, HD patients are exposed to multiple stressors including cardiocirculatory, inflammatory, biologic, hypoxemic, and nutritional. This cascade of events can be termed the dialysis stress storm and sickness syndrome. Mitigating cardiovascular risk and morbidity associated with conventional intermittent HD appears to be a priority for improving patient experience and reducing disease burden. In this in-depth review, we summarize the hidden effects of intermittent HD therapy, and call for action to improve delivered HD and develop treatment schedules that are better tolerated and associated with fewer adverse effects.

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review.

Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). Continuous renal replacement may alter the pharmacokinetics (PK) and the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluate drug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment (TA) in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM. Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD TA. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines. In total, 2383 reports were retrieved. After excluding nonrelevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD TA for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and TA rates were highly variable. TDM seems to be necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes. Highly variable antibiotic exposure and TA have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.