Development Of AKI Research Articles

Incidence, Clinical Characteristics and Outcomes Associated with Acute Kidney Injury in Patients Hospitalized with COVID-19

Background: Acute kidney Injury associated with Coronavirus disease COVID-19 appeared to negatively influence clinical outcomes and is found to be associated with significant risk of death. This retrospective study aimed to describe the incidence of Acute Kidney Injury, its associations with clinical characteristics and outcomes among COVID-19 patients in Sukraraj Tropical and Infectious Disease Hospital, a tertiary infectious disease hospital in Nepal.Methods: A cross-sectional study was done where. Medical and lab records of reverse transcriptase Polymerase chain reaction positive COVID-19 inpatients, admitted between April 2021 to July 2021 were reviewed. It represented the second wave of wave of coronavirus pandemic caused by the delta strain. Patients aged less than 18 years, pregnant females and patients with known chronic kidney disease were excludedResults: Of 393 admissions, 83 (21.1%) patients developed Acute Kidney Injury. Characteristics found to have significant association with development of AKI was age (p <0.001), multiple co morbidities (2 or more) (p <0.001), use of mechanical ventilation (p <0.001), lymphopenia (p<0.001), Neutrophil to Lymphocyte Ratio (p =0.001) and d-dimer levels (p <0.001). Mortality was found to be significantly higher in COVID-19 patients with AKI compared to COVID-19 patients without AKI ((36.14% vs 15.8%, p value <0.01)). The median duration of hospital stay for patients with AKI was higher than for patients without AKI (10 days vs 6 days,p <0.01).Conclusions: AKI develops in a sizeable percentage of patients with COVID-19 and is significantly associated with increasing age, multiple comorbidities, increased biomarkers, use of mechanical ventilation and is associated with poor outcome in terms of mortality and morbidity.Keywords: AKI; COVID-19; Nepal; outcomes.

Sepsis-Associated Acute Kidney Injury: What's New Regarding Its Diagnostics and Therapeutics?

Sepsis-associated acute kidney injury (SA-AKI) is defined as the development of AKI in the context of a potentially life-threatening organ dysfunction attributed to an abnormal immune response to infection. SA-AKI has been associated with increased mortality when compared to sepsis or AKI alone. Therefore, its early recognition is of the utmost importance in terms of its morbidity and mortality rates. The aim of this review is to shed light on the pathophysiological pathways implicated in SA-AKI as well as its diagnostics and therapeutics. In this review, we will elucidate upon serum and urinary biomarkers, such as creatinine, cystatin, neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin A 119-159, interleukin-6, interleukin-8 and interleukin-18, soluble toll-like receptor 2 (sTLR2), chemokine ligand 2 (CCL2) and chemokine C-C-motif 14 (CCL14). In addition, the role of RNA omics as well as machine learning programs for the timely diagnosis of SA-AKI will be further discussed. Moreover, regarding SA-AKI treatment, we will elaborate upon potential therapeutic agents that are being studied, based on the pathophysiology of SA-AKI, in humans and in animal models.

A Review of Polymyxin-B Dosage for Patients with Renal Impairment

Since polymyxin B has a restricted therapeutic range and increased danger of both neurological damage and kidney damage, it is no longer the first choice for treating emerging gram-negative bacteria with multiple antibiotic resistance. The optimal dose schedule for patients with renal impairment regarding polymyxin B, it is provided as a chemically active formulation and primarily removed via methods other than kidney, is still up for debate. Similar to colistin, polymyxin-B effectively combats gram-negative aerobic bacterium that is resistant to several drugs such as Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli that produces carbapenemase, and Klebsiella pneumoniae. As a result, polymyxins cause cell apoptosis by inducing pan-caspase activation through many routes in a manner that is dependent on time and concentration. One of the most frequent and undesirable side effects of polymyxins is the development of AKI. A great deal of pharmacokinetic studies that have been published to far concur that creatinine clearance affects polymyxin B clearance; nevertheless, there is ongoing debate on the extent of this influence Keywords: Polymyxin-B, kidney damage, gram-negative bacterial infection, creatinine clearance.

Role of Z-DNA Binding Protein 1 Sensing Mitochondrial Z-DNA and Triggering Necroptosis in Oxalate-Induced Acute Kidney Injury.

Calcium oxalate-induced acute kidney injury is a severe condition in which the kidneys suffer rapid damage due to the deposition of oxalate crystals. Known factors contributing to cell death induced by calcium oxalate include receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein dependent necroptosis, as well as necrosis involving peptidylprolyl isomerase F (PPIF) mediated mitochondrial permeability transition. However, the detailed molecular mechanisms linking mitochondrial dysfunction to RIPK3 activation are not fully understood. Mice with gene knock-out of Zbp1, Ripk3, or Mlkl and mice with mutations in the Z-nucleic acid sensing domain of ZBP1 or deletion of Zα1 were used in an oxalate-induced AKI model. Proximal renal tubule cells were isolated and cultured for further investigation. Human oxalate nephropathy biopsy samples were analyzed. Specific gene deletions of Zbp1, Ripk3, or Mlkl in proximal renal tubules significantly reduced the severity of oxalate-induced AKI by preventing necroptosis and subsequent inflammation. Notably, mice with mutations in the Z-nucleic acid sensing domain of ZBP1 or deletion of Zα1 were protected from AKI. In cultured proximal tubular cells, calcium oxalate damaged mitochondria, accompanied by an increase in Bax and a decrease in BCL2 and TAFM, leading to the release of mitochondrial Z-DNA. ZBP1 sensed this mitochondrial Z-DNA and then recruited RIPK3 via the RIP homotypic interaction motifs (RHIM), which in turn activated MLKL through RIPK3 phosphorylation, leading to necroptosis and contributing to AKI. ZBP1 plays a critical role in sensing mitochondrial Z-DNA and initiating RIPK3/MLKL-mediated necroptosis, contributing to the development of oxalate-induced AKI.

Acute Kidney Injury after Isolated Coronary Bypass Surgery

AbstractAcute kidney injury (AKI) is among the most serious of the common postoperative complications of cardiac surgeries, which can increase the short- and long-term morbidity and mortality of patients. This study aimed to examine possible risk factors that lead to AKI. We sought to compare our AKI rates to national averages in coronary artery bypass grafting (CABG) reported by the Society of Thoracic Surgeons (STS). We reviewed our institution's data for renal failure in CABG procedures performed between January 1, 2020, and June 30, 2023. From the database, we identified 1,068 CABG patients and reviewed demographics, nonmodifiable conditions, and modifiable risk factors. The STS database uses the Risk, Injury, Failure, Loss, and End-stage renal disease definition for renal failure. Of our patient sample, 14 (1.3%) experienced renal failure. The national rate for AKI after isolated CABG was 1.9% in 2023. Chronic lung disease was a risk factor for AKI development. The mean perfusion, cross-clamp, ventilator times, and hospital stay increased in AKI patients. All patients who suffered from AKI had undergone perioperative blood transfusion. Our single-center experience with renal failure is slightly better than the national average. In our population, chronic lung disease and lower preoperative ejection fractions were associated with increased rates of AKI. Modifiable risk factors in our population included perioperative blood transfusion and increased perfusion/cross-clamp times. Lastly, AKI patients spent longer time on ventilators, increased lengths of stay, and increased postoperative mortality.

Preoperative Fasting Time Is Not Associated with Development of AKI after Cardiac Surgery

Preoperative Fasting Time Is Not Associated with Development of AKI after Cardiac Surgery

Chloride Variation as an Independent Risk Factor for AKI Development and In-Hospital Mortality in Patients with Rhabdomyolysis

Chloride Variation as an Independent Risk Factor for AKI Development and In-Hospital Mortality in Patients with Rhabdomyolysis

Association of corticosteroid therapy with reduced acute kidney injury and lower NET markers in severe COVID-19: an observational study

BackgroundAcute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19.ResultsTwo hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p < 0.001). Fewer patients demonstrated detectable concentrations of extracellular histones in plasma when treated with corticosteroids (8.7% vs 43.1%; p < 0.001). Extracellular histones and in particular non-proteolyzed histones were observed more frequently with increasing AKI severity (p < 0.001). MPO-DNA was found in lower concentrations in patients that received corticosteroids before established renal dysfunction (p = 0.03) and was found in higher concentrations in patients with AKI stage 3 (p = 0.03). Corticosteroids did not ameliorate established AKI during the first week of treatment.ConclusionCorticosteroid treatment in severe COVID-19 is associated with a lower incidence of AKI and reduced concentrations of NET markers in plasma.

Clinical implications of admission and follow-up urea-to-creatinine ratio in patients with acute decompensated heart failure

PurposeAcute decompensated heart failure (ADHF) patients with a poor renal function have a worse prognosis. The urea-to-creatinine ratio (UCR) may be a valuable tool for assessing kidney function and stratifying patients with ADHF. We evaluated the value of an admission and follow-up UCR in predicting AKI, 28-day mortality, and rehospitalization in patients with ADHF.MethodsThis prospective research comprised sixty patients with ADHF. Based on the mean admission UCR, patients are classified into two groups: the high UCR group (UCR ≥ 42.33) and the low UCR group (UCR < 42.33). On the third day, they are categorized into high UCR and low UCR groups according to the same mean of UCR (42.33). A 28-day follow-up was implemented.ResultsThirty patients (50%) developed AKI, and nine (15%) died during follow-up. In the high UCR group, the development of AKI was considerably more significant than in the low UCR group on the 3rd day (69.2% vs. 35.2%, respectively, p = 0.010). Furthermore, the high UCR group experienced a higher death rate than the low UCR group on the 3rd day (26.9% vs. 5.8%, respectively, p = 0.024). A considerable statistical correlation was reported between UCR and eGFR on the 3rd day (p = 0.025). According to ROC, UCR on the 3rd day was a significant predictor of AKI and 28-day mortality in these patients ((AUC = 0.736 and 0.718, respectively). In contrast, UCR on admission was not a predictor of AKI or 28-day mortality (p = 0.578 and 0.305, respectively). Also, neither admission nor 3rd day UCR could predict HF readmission (p = 0.108 and 0.298, respectively). By the Kaplan–Meier curve, survival rates were highest when UCR ≤ 34.85 and reduced when UCR > 34.85 (p < 0.001).ConclusionThe follow-up UCR is a good predictor of AKI development and elevated 28-day mortality in ADHF patients. Considering its simplicity, this biomarker should be used more systematically in clinical practice.

Circ_001653 alleviates sepsis associated-acute kidney injury by recruiting BUD13 to regulate KEAP1/NRF2/HO-1 signaling pathway

BackgroundThe kidney is exceptionally vulnerable during sepsis, often resulting in sepsis-associated acute kidney injury (SA-AKI), a condition that not only escalates morbidity but also significantly raises sepsis-related mortality rates. Circular RNA circ_001653 has been previously reported to be upregulated in the serum of SA-AKI patients, while the role and underlying mechanism of circ_001653 in SA-AKI remains unknown. In this study, we aimed to explore the functional role and the molecular mechanism of circ_001653 in the pathogenesis of SA-AKI.MethodsLPS-stimulated HK-2 cells and ligation and perforation of cecum (CLP)-induced rats were used as in vitro and in vivo models of SA-AKI. The target gene expression levels were measured using qRT-PCR and western blot. Renal function (BUN, sCr, uNGAL, and uKIM-1), and renal pathological changes were detected in septic mice. TUNEL and EdU assays were conducted to measure apoptosis and proliferation rates in vitro. DCFH-DA staining was used to detect ROS levels in vitro and in vivo. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), and inflammation markers (IL-1β, IL-6, and TNF-α) were determined using commercial kits both in vitro and in vivo. Additionally, gain-and-loss-of-function assays and mechanistic experiments were conducted to explore the regulatory role of circ_001653 in SA-AKI pathogenesis.ResultsData showed that circ_001653 expression was high in LPS-stimulated HK-2 cells and CLP-induced rat renal tissue and was mainly localized in the cytoplasm. Notably, circ_001653 silencing alleviated SA-AKI by reducing apoptosis and alleviating oxidative stress and inflammation in HK-2 cells and renal tissue of rats. Mechanistically, it was found that circ_001653 alleviated SA-AKI by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway.ConclusionsTo summarize, our study is the first to reveal elevated expression of circ_001653 in sepsis-associated AKI, and its downregulation effectively attenuates AKI by reducing apoptosis, inflammation, and oxidative stress. Mechanistically, circ_001653 exerts its effects by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway. These findings suggest circ_001653 as a potential therapeutic target for the drug development of sepsis-associated AKI.

113: Thrombocytopenia as a predictor of persistent AKI development in ECMO patients.

113: Thrombocytopenia as a predictor of persistent AKI development in ECMO patients.

Predictive value of perioperative NT-proBNP levels for acute kidney injury in patients with compromised renal function undergoing cardiac surgery: a case control study

BackgroundAcute kidney injury (AKI) significantly increases morbidity and mortality following cardiac surgery, especially in patients with pre-existing renal impairments. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and dysfunction, conditions often exacerbated during cardiac surgery and prevalent in chronic kidney disease (CKD) patients. Elevated NT-proBNP levels can indicate underlying cardiac strain, hemodynamic instability and volume overload. This study evaluated the association between perioperative changes in NT-proBNP levels and the incidence of AKI in this particular patient group.MethodsThis retrospective study involved patients with impaired renal function (eGFR 15–60 ml/min/1.73 m²) who underwent cardiac surgery from July to December 2022. It analyzed the association between the ratio of preoperative and ICU admittance post-surgery NT-proBNP levels and the development of AKI and AKI stage 2–3, based on KDIGO criteria, using multivariate logistic regression models. Restricted cubic spline analysis assessed non-linear associations between NT-proBNP and endpoints. Subgroup analysis was performed to assess the heterogeneity of the association between NT-proBNP and endpoints in subgroups.ResultsAmong the 199 participants, 116 developed postoperative AKI and 16 required renal replacement therapy. Patients with AKI showed significantly higher postoperative NT-proBNP levels compared to those without AKI. Decreased baseline eGFR and increased post/preoperative NT-proBNP ratios were associated with higher AKI risk. Specifically, the highest quantile post/preoperative NT-proBNP ratio indicated an approximately seven-fold increase in AKI risk and a ninefold increase in AKI stage 2–3 risk compared to the lowest quantile. The area under the receiver operating characteristic curve for predicting AKI and AKI stage 2–3 using NT-proBNP were 0.63 and 0.71, respectively, demonstrating moderate accuracy. Subgroup analysis demonstrated that the positive association between endpoints and logarithmic transformed post/preoperative NT-proBNP levels was consistently robust in subgroup analyses stratified by age, sex, surgery, CPB application, hypertension, diabetes status and fluid balance.ConclusionPerioperative NT-proBNP level changes are predictive of postoperative AKI in patients with pre-existing renal deficiencies undergoing cardiac surgery, aiding in risk assessment and patient management.

Acute Kidney Injury in Hospitalized Patients With Exertional Rhabdomyolysis

An association between serum creatine kinase (CK) levels and the risk of kidney failure in patients with exertional rhabdomyolysis (ERM) has been suggested. However, the actual incidence of AKI in hospitalized patients with ERM along with the contributing cofactors that may increase the risk of AKI have rarely been investigated. To examine the incidence of kidney injury in hospitalized patients with ERM and to identify additional cofactors that might contribute to the development of kidney injury in patients with ERM. This retrospective cohort study was conducted in a diverse community population of patients 18 years or older with ERM who were hospitalized across Kaiser Permanente Northern California between January 1, 2009, and December 31, 2019. Patients were initially identified through electronic screening for all-cause rhabdomyolysis admissions, followed by manual medical record reviews to verify their eligibility for the study. The diagnosis of AKI and chronic kidney disease (CKD) was determined using KDIGO (Kidney Disease Improving Global Outcomes) criteria and confirmed by medical record review. Data analysis was performed from October 1, 2023, to January 31, 2024. History of strenuous physical exercise before hospitalization for ERM. Development of AKI, CKD, and compartment syndrome and number of deaths. Among 3790 patients hospitalized for rhabdomyolysis between 2009 and 2019 in Kaiser Permanente Northern California, 200 (mean [SD] age, 30.5 [8.5] years; 145 [72.5%] male) were confirmed to have ERM via medical record review. Seventeen patients (8.5%) developed AKI, none developed CKD, 1 (0.5%) developed compartment syndrome, and there were no fatalities. There was no association between serum CK levels and the risk of AKI. However, the risk of AKI was significantly higher in patients with ERM who used nonsteroidal anti-inflammatory drugs (NSAIDs) before admission (11 of 17 with AKI [64.7%] vs 40 of 183 without AKI [21.9%], P < .001) or experienced dehydration (9 of 183 without AKI [52.9%] vs 9 of 17 with AKI [4.9%], P < .001). This analysis suggests that eliminating preadmission NSAID use and dehydration could reduce the risk of potential AKI in patients with ERM by 92.6% (95% CI, 85.7%-96.1%) in this population. The findings of this cohort study of hospitalized patients with ERM suggest that serum CK elevation alone is insufficient as an indicator of AKI in patients with ERM. Concurrent risk factors, such as NSAID use or dehydration, may be associated with AKI development in patients with ERM.

To Evaluate the Role of Comorbidities in the Development of Acute Kidney Injury in Intensive Care Patients at a Tertiary Care Hospital in Bangladesh

Background: Indeed, AKI is a common complication in ICU patients, and it is associated with an increase in morbidity and mortality as well as healthcare costs. Recognizing AKI risk factors in LMIC settings is important for intervention approaches. Objectives: The objectives of this study are as follows: To determine the incidence of AKI based on RIFLE criteria among the critically ill patients in a tertiary care hospital in Bangladesh and to analyze the impact of the presence of comorbidities on the development of AKI in these patients. Methods: This prospective observational study was carried out at the ICU of Community Based Medical College in Bangladesh from January to December 2023. The target subjects were adult patients who were admitted to the ICU for a period of 24 to 48 hours. Patients with AKI were categorized using RIFLE criteria based on serum creatinine and urine output. For the univariate and multivariate logistic regression, demographic data, comorbidities, and clinical characteristics were collected. Results: In the present study of 22 patients with a mean age of 42.16 years and 63.6% of male patients, 86.4 percent of the patients had AKI according to both serum creatinine and urine output criteria. Sepsis/septic shock ([OR] 2. 2, [CI] 0. 8–5. 8) and cardiac etiology ([OR] 2. 7, [CI] 1. 0–7.1) were significant predictors of AKI. The study revealed that respiratory disease [OR. = 3.56, 95% confidence interval (CI): 0.33–38.78] and hematologic malignancy [OR. = 4.20, 95% CI: 0.40–43.82] were the comorbid conditions most closely associated with AKI. Conclusions: This research shows a very high prevalence rate of AKI among the clients in critical conditions in Bangladesh. Sepsis, cardiac dysfunction, respiratory disease, and hematologic malignancies emerged as significant factors. The results are therefore informative for programs aimed at improving AKI awareness, early detection activities, and prevention efforts in low-resource settings.

The elevated lactate dehydrogenase to albumin ratio is a risk factor for developing sepsis-associated acute kidney injury: a single-center retrospective study

BackgroundThere is no evidence to determine the association between the lactate dehydrogenase to albumin ratio (LAR) and the development of sepsis-associated acute kidney injury (SAKI). We aimed to investigate the predictive impact of LAR for SAKI in patients with sepsis.MethodsA total of 4,087 patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC IV) database were included. Logistic regression analysis was used to identify the association between LAR and the risk of developing SAKI, and the relationship was visualized using restricted cubic spline (RCS). The clinical predictive value of LAR was evaluated by ROC curve analysis. Subgroup analysis was used to search for interactive factors.ResultsThe LAR level was markedly increased in the SAKI group (p < 0.001). There was a positive linear association between LAR and the risk of developing SAKI (p for nonlinearity = 0.867). Logistic regression analysis showed an independent predictive value of LAR for developing SAKI. The LAR had moderate clinical value, with an AUC of 0.644. Chronic kidney disease (CKD) was identified as an independent interactive factor. The predictive value of LAR for the development of SAKI disappeared in those with a history of CKD but remained in those without CKD.ConclusionsElevated LAR 12 h before and after the diagnosis of sepsis is an independent risk factor for the development of SAKI in patients with sepsis. Chronic comorbidities, especially the history of CKD, should be taken into account when using LAR to predict the development of AKI in patients with sepsis.

Acute kidney injury development is associated with mortality in Japanese patients with cirrhosis: impact of amino acid imbalance

BackgroundAcute kidney injury (AKI) is a serious complication of cirrhosis. This study analyzed the prognostic effect of AKI in patients with cirrhosis and its risk factors, particularly in relation to amino acid imbalance.MethodsThis retrospective study reviewed 808 inpatients with cirrhosis at two institutes in Gifu, Japan. AKI was diagnosed according to the recommendations of the International Club of Ascites. Amino acid imbalance was assessed by measuring serum branched-chain amino acid (BCAA) levels, tyrosine levels, and the BCAA-to-tyrosine ratio (BTR). Factors associated with mortality and AKI development were assessed using the Cox proportional hazards regression model with AKI as a time-dependent covariate and the Fine–Gray competing risk regression model, respectively.ResultsOf the 567 eligible patients without AKI at baseline, 27% developed AKI and 25% died during a median follow-up period of 4.7 years. Using a time-dependent covariate, AKI development (hazard ratio [HR], 6.25; 95% confidence interval [CI], 3.98–9.80; p < 0.001) was associated with mortality in patients with cirrhosis independent of potential covariates. In addition, alcohol-associated/-related liver disease, metabolic dysfunction-associated steatohepatitis, Child–Pugh score, and BTR (subdistribution HR 0.78; 95% CI 0.63–0.96; p = 0.022) were independently associated with AKI development in patients with cirrhosis. Similar results were obtained in the multivariate model that included BCAA and tyrosine levels instead of BTR.ConclusionsAKI is common and associated with mortality in Japanese patients with cirrhosis. An amino acid imbalance is strongly associated with the development of AKI in patients with cirrhosis.

Assessing the prevalence and severity of cisplatin-induced nephrotoxicity in a minority- low socioeconomic population in the Bronx, New York

Studies evaluating Cisplatin-induced nephrotoxicity in minorities are limited. We conducted a retrospective review of adult patients receiving cisplatin from 2019 to 2023 at an inner-city hospital. Renal indices were obtained at baseline and after cycles 1, 2, and 3 of Cisplatin. A total of 93 patients were included, 46% were male. Median age was 57 years. About 40% were Black, 13% White, and 42% Hispanic. About 54% were uninsured. About 16% of the patients developed AKI after cycle 1 of cisplatin, 5% after cycle 2%, and 17% after cycle 3. There was no statistically significant correlation between race, sex, BMI and development of cisplatin-induced AKI. Repeated measures ANOVA test indicated a statistically significant and cumulative rise in creatinine level following cisplatin therapy [Wilks’ Lambda = 0.003, F(1,26)=13.7, η2 = 0.44]. Our study in a minority, low socioeconomic population highlights the progressive kidney injury following each cycle of cisplatin therapy. Further studies targeting this specific population are warranted to develop tailored interventions.

The development of AKI, need for RRT as well as 30-day mortality among Covid-19 patients In King Fahad Armed Hospital, Jeddah, Saudi Arabia - retrospective cohort study

The development of AKI, need for RRT as well as 30-day mortality among Covid-19 patients In King Fahad Armed Hospital, Jeddah, Saudi Arabia - retrospective cohort study

#1408 Dehydration cannot substitute for any of the triple whammy drugs to cause acute kidney injury

Abstract Background and Aims Polymedication in patients with chronic diseases, such as hypertension, can lead to undesired drug interactions. The combination of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) with diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) can cause triple whammy (TW)-induced acute kidney injury (TW-AKI). Up to 9% of hypertensive patients used NSAIDs in combination with ACEIs / ARBs and diuretics. AKI has a mortality rate of 40% and TW increases the risk of AKI by 30% compared to the combination of only two drugs. In addition, TW-AKI is associated with other risk factors such as dehydration, which may exacerbate the injury. Consequently, the aim of our study was to determine whether dehydration combined with two of the TW drugs could induce AKI in an in vivo experimental model. Method Three months old male Spontaneously Hypertensive Rats (SHR) were divided into four experimental groups: control group (CT); TW group (TW), which received four days of double therapy with trandolapril and furosemide, followed by a triple therapy for two days with trandolapril, furosemide and ibuprofen; trandolapril and ibuprofen group (T+I), which received four days of trandolapril followed by two days of trandolapril and ibuprofen; furosemide and ibuprofen group (F+I), which received four days of furosemide followed by two days of furosemide and ibuprofen; and trandolapril and furosemide group (T+F), which received six days of trandolapril and furosemide. All groups were subjected to a 60-70% water restriction of basal intake (i.e. 15 mL/day) to generate mild dehydration. Blood and urine samples were collected at baseline (B), day 4 and day 6. Blood pressure was measured at baseline and day 4. Renal function was assessed by plasma creatinine, plasma urea and creatinine clearance, and hydration status was determined by plasma osmolarity and water balance (i.e. water intake minus urine flow). Results Under basal conditions, all rats were hypertensive. The combination of trandolapril and furosemide significantly reduced the mean blood pressure on day 4 (p = 0.0066), while trandolapril or furosemide alone did not achieve these decreases. After four days of water restriction to 15 mL/day, all groups showed mild dehydration with a decrease in water balance and an increase in plasma osmolarity by. Plasma creatinine and plasma urea values were only increased on day 6 in the TW group (p = 0.0009 and p = 0.02, respectively). Creatinine clearance was also clearly reduced in the TW group (p = 0.0004). F+I and T+F groups showed slight decreases in creatinine clearance at day 6, as well as slight increases in plasma urea. However, these changes were not as pronounced as those observed in the TW group. Conclusion In our in vivo model of TW-AKI, mild dehydration cannot replace any of the TW drugs, although it appears that combination of F+I and T+F in dehydrated rats slightly alter plasma urea and creatinine clearance values at day 6, suggesting that this condition maintained over time might lead to the development of AKI. Funding This research was funded by grants from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación (PI21/01226 and PI21/00548 co-funded by the European Union; and RICORS2040, RD21/0005/0004, co-funded by the European Union—NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)) and from Consejería de Educación, Junta de Castilla y León (IES160P20), co-funded by FEDER funds. Noelia Diaz-Morales is recipient of a Juan de la Cierva-Formación postdoctoral contract (FJC2020-043205-I) funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU/PRTR”. Eva M. Baranda-Alonso is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

#2527 Hemofiltrate reinfusion supra (HFR-S) during sepsis associated AKI: a new perspective to treat inflammation and improving patients outcome?

Abstract Background and Aims Sepsis is life-threatening organ dysfunction caused by dysregulated body response to an infection. Mortality rate ranging over 60% for septic shock. AKI is final common pathway of this immune dysregulation leading to systemic inflammation (SI) due to uncontrolled circulating levels of pro-inflammatory mediators and cytokine induced direct organ damage. Kidney replacement therapy (KRT) is often required in Sepsis Associated AKI (SA-AKI) and could improve SI removing pathogens and inflammatory factors. Various blood purification techniques have been used: HCO/MCO membranes, hemoperfusion, plasma filtration/adsorption and, anecdotal, Hemo Filtrate Reinfusion Supra (HFR-S): endogenous reinfusion HDF based on adsorbing resin cartridge that remove cytokines and pro-inflammatory mediators, whose full spectrum is not yet know, and myoglobin also. Aim of this study is to test HFR on outcome of SA-AKI in critically ill pts. Method In a retrospective observational study, we evaluated development of AKI requiring KRT in 12 consecutive SA-AKI patients (pts) admitted in the ICU of our two hospitals from December 2022. ESKD pts in chronic dialysis are excluded. SA-AKI were treated with daily IRRT: HFR-S. Given the laboratory operating standards they were daily assessed: urea, creatinine, C-reactive protein (CRP), procalcitonin (PCT), WBC, platelets (PLT), myoglobin, albumin. Mean arterial pressure (MAP), need for vasopressor, and outcome are also evaluated. The values have been reported as mean ± SD or median and interquartile range (IQR). AKI was defined according to KDIGO. Statistical analyzes were performed with the Wilcoxon Signed Rank Test Results Among the 12 pts 9 had AKI III stage. The mean age was 74 ± 8.2 years, 7 were male. 90% were hypertensive, some with heart disease, 50% with CKD (70% G3-KDIGO, 30% G2) 30% were obese or with diabetes, 40% with COPD. All received mechanical ventilation and several antibiotics, 80% received amines. They underwent IRRT by HFR-S with an average of 7 ± 4.9 treatments (range 2-17 sessions); Qb = 235 ± 19.6 ml/m, TT 225.7 ± 28.5 m. UF 407 ± 120 ml/h. HFR-S confirm an expected reduction for urea and creatinin, significant abatement of CRP, PCT and Myoglobin. Albumin remain stable. Neutral is the effect on WBC and PLT whose progress reflects the trend of sepsis. Cardiovascular instability decreased significantly with the treatments allowing the suspension of vasoactive amines as shown by the significant increase in MAP at the end of treatment (Tab. 1) None of those undergoing HFR had poor intradialytic compliance. Four patients did not survive (three had surgical, one pulmonary, complications), 6 patients had renal recovery, 2 patients had chronic dialysis. Conclusion Our experience with HFR may promote a new strategy to decrease SI and support renal recovery in SA-AKI pts even in the not survived. The adsorbing resin is able to efficacy remove proinflammatory cytokines and many other unknow mediators, that lead to improved MAPs and lower critical illness scores, and allow to eliminate myoglobin too. Indeed there is no study on the use of HFR in SA-AKI and very few experience on his use to hypermyoglobinemia. Finally HFR-Supra is safe and is the cheapest technique for SA-AKI in comparison to the other techniques available (e.g. CRRT, HCO, Cytosorb) by excellent cost-effectiveness-sustainability ratio regarding treatment times and staff-sparing. Larger studies could confirm our evidence but, in the meantime, our cases could help to build a new scientific evidence.