Features Of Acute Kidney Injury Research Articles

Acute kidney injury, an underrecognized feature of VEXAS syndrome.

VEXAS syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome. Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first acute kidney injury (AKI) event. For patients with a kidney biopsy, histopathologic findings were reviewed. Eighty-one patients were included, all white men, with a mean age of 66.3±8.6 years. Median (IQR) follow up was 3.5 (2.1-5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80-11.3%), 16.7% (7.5-25.0%) and 27.9% (14.9-38.9%), respectively. Age and baseline C-reactive protein were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1), and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering. AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding.

DY131 activates ERRγ/TFAM axis to protect against metabolic disorders and acute kidney injury.

Renal tubular injury is considered as the main pathological feature of acute kidney injury (AKI), and mitochondrial dysfunction in renal tubular cells is implicated in the pathogenesis of AKI. The estrogen-related receptor γ (ERRγ) is a member of orphan nuclear receptors which plays a regulatory role in mitochondrial biosynthesis, energy metabolism and many metabolic pathways. Online datasets showed a dominant expression of ERRγ in renal tubules, but the role of ERRγ in AKI is still unknown. In the present study, we investigated the role of ERRγ in the pathogenesis of AKI and the therapeutic efficacy of ERRγ agonist DY131 in several murine models of AKI. ERRγ expression was reduced in kidneys of AKI patients and AKI murine models along with a negative correlation to the severity of AKI. Consistently, silencing ERRγ in vitro enhanced cisplatin-induced tubular cells apoptosis, while ERRγ overexpression in vivo utilizing hydrodynamic-based tail vein plasmid delivery approach alleviated cisplatin-induced AKI. ERRγ agonist DY131 could enhance the transcriptional activity of ERRγ and ameliorate AKI in various murine models. Moreover, DY131 attenuated the mitochondrial dysfunction of renal tubular cells and metabolic disorders of kidneys in AKI, and promoted the expression of the mitochondrial transcriptional factor A (TFAM). Further investigation showed that TFAM could be a target gene of ERRγ and DY131 might ameliorate AKI by enhancing ERRγ-mediated TFAM expression protecting mitochondria. These findings highlighted the protective effect of DY131 on AKI, thus providing a promising therapeutic strategy for AKI.

The inhibitory impact of Schisandrin on inflammation and oxidative stress alleviates LPS-induced acute kidney injury.

Inflammation and oxidative stress (OS) are the major pathogenic characteristics of acute kidney injury (AKI). Studies have shown that Schisandrin (Sch) could regulate inflammatory disease. However, the function and mechanism of Sch in AKI progression are still unknown. Here, we investigated Sch's potential effects and mechanism on mice's renal damage and macrophages induced by lipopolysaccharide (LPS). Sch decreased LPS-induced inflammatory factor production while increasing the activity of related antioxidant enzymes in macrophages and mouse kidney tissues. Hematoxylin and eosin staining revealed that Sch may have the ability to profoundly inhibit inflammatory cell invasion and tissue damage caused by LPS in renal tissue. Furthermore, Western blot and immunohistochemical studies showed that Sch exerted its effects mainly through up-regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibition of Toll-like receptor 4‒mitogen-activated protein kinases/nuclear factor-kappa B pathways. Collectively, this study illustrates that Sch suppresses LPS-stimulated AKI by descending inflammation and OS, illuminating prospective AKI treatment options.

#1256 Comparison of clinical characteristics of acute kidney injury between glufosinate and glyphosate poisoning

Abstract Background and Aims There are few studies comparing the clinical characteristics of acute kidney injury (AKI) between glufosinate and glyphosate poisoning. In this study, we investigated the clinical characteristics of AKI in patients with glufosinate and glyphosate poisoning, and compared the clinical features of AKI between two groups. Method This study performed between 2008 and 2021 included 76 patients with glufosinate poisoning and 184 patients with glyphosate poisoning. This study included 76 patients with glufosinate poisoning and 184 patients with glyphosate poisoning in the period from 2008 to 2021. Based on Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease classification, we investigated the incidence, clinical characteristics, and severity of AKI between two groups [(glufosinate-induced AKI (Glu-AKI, n=54) and glyphosate-induced AKI (Gly-AKI, n=82)]. Results The incidence of AKI in patients with glufosinate poisoning is higher than that of glyphosate poisoning (57.5% vs 44.5%, P<0.05). However, there is no difference of AKI severity between two groups (Glu-AKI; Risk 56.2%, Injury 36.9%, Failure 6.9% vs Gly-AKI; Risk 56.2%, Injury 14.6%, Failure 29.2%, P=NS). Comparing two groups, there is also no difference in age (62.6 ± 14.2 years vs. 63.3 ± 16.2 years, P=NS) and renal function on admission (63.9 ± 25.2 mL/min/1.73 m2 vs. 62.2 ± 22.9 mL/min/1.73 m2, P=NS). The length of hospitalization was longer (17.2 ± 17.2 days vs. 10.7 ± 12.1 days, P<0.05) in Glu-AKI group than that of Gly-AKI group. The mortality rate was higher in the Gly-AKI group than Glu-AKI (11.1% vs. 18.3%, P=NS). Multivariate logistic regression analysis showed that serum bicarbonate concentration on admission was a significant predictors of AKI in patients with AKI after glyphosate and glufosinate intoxication. Conclusion Although there is a higher incidence of AKI in glufosinate poisoning, there is no difference in clinical characteristics between the two types of intoxication.

#1304 Clinical characteristics of acute kidney injury caused by Phytolaccaceae ingestion

Abstract Background and Aims Phytolaccaceae is a poisonous plant that is associated with cardiac and gastrointestinal toxicity. However, there are limited data about acute kidney injury (AKI) in patients with Phytolaccaceae ingestion. We conducted this study to investigate the clinical characteristics of AKI by Phytolaccaceae overdose. Method From 2010 to 2022, 15 patients with Phytolaccaceae ingestion were enrolled in this study. The incidence, clinical characteristics, and severity of AKI were compared between AKI (N=8) and non-AKI (N=7) groups according to the RIFLE classification. Results Of the 15 patients, 8 patients experienced AKI during hospitalization period. There is no difference in age (54.3 ± 7.2 years vs. 67.1 ± 13.5 years, P=0.057) and comorbidities such as hypertension and diabetes (37.5% vs 28.5%, P=0.563) between two groups. In addition, there is also no difference in total leukocyte count (10.8 × 103/mL vs. 11.4 × 103/mL, P=0.84) and serum albumin level (4.5 ± 2.6 vs 4.3 ± 0.5, P=0.498). Compared to patients without AKI, the estimated glomerular filtration rate was lower in the AKI group (57 ± 12 ml/min/1.73 m2 vs. 77 ± 24 ml/min/1.73 m2, p<0.05) on admission. The AKI group had a significantly longer hospital stay (9.7 ± 6.2 vs 6.1 ± 3.1 days, p<0.001). The overall AKI incidence was 61.5%, of which 46.1% and 15.4% cases were classified as risk and injury, respectively. All patients recovered baseline renal function without renal replacement therapy following antibiotics therapy and supportive care. Conclusion The incidence of AKI in patient with Phytolaccaceae ingestion is 61.5%. Most patients with AKI had a mild type of AKI during admission period. In cases of AKI patients with Phytolaccaceae ingestion, aggressive supportive care including hydration is very important.

#2727 Acute kidney in patients with ANCA associated vasculitis

Abstract Background and Aims Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is considered an emergency situation. Early diagnosis and treatment significantly improve prognosis. The aim of this study was to investigate the characteristics of acute kidney injury (AKI) in ANCA-associated vasculitis and assess its developmental aspects. Method Our study, conducted in the Internal Medicine Department A of Charles Nicole Hospital over a four-year period (January 2018-August 2022), was retrospective and descriptive. The diagnosis of ANCA vasculitis was made based on the ACR 1990 and/or EULAR 2012 criteria. The severity of AKI was categorized according to the KDIGO AKI classification. Results Seventeen patients were included, with a mean age of 51 ± 17.42 years and a sex ratio of 0.42. The primary clinical presentation of AKI was rapidly progressive glomerulonephritis (n=11), followed by acute nephritic syndrome (n=4). Pneumo-renal syndrome was observed in 4 patients. Proteinuria and hematuria were present in all 17 patients, with 4 being oligoanuric on dipstick. The mean creatinine level was 584 μmol/L, ranging from 125 to 1151 μmol/L. Thirteen patients had KDIGO stage 3 AKI on admission. The predominant histological lesion was extracapillary crescentic glomerulonephritis, based on the Berden classification (n=6). Hemodialysis was initiated immediately in 12 cases, and plasma exchange was performed in 10 cases. The average follow-up time was 24 months, ranging from 3 months to 4 years. Evolution was marked by partial remission in 7 cases, with a mean creatinine of 173 μmol/L. Progression to end-stage renal disease (ESRD) occurred in 10 cases. Relapses, presenting as pneumo-renal syndrome, were observed in 4 patients. Seven patients succumbed, with vasculitis being the cause of death in 3 cases. In univariate analysis, age >70 years was associated with progression to ESRD (p=0.03). No factor studied emerged as a prognostic factor for overall survival. Conclusion The presence and severity of AKI in ANCA-associated vasculitis are linked to a poorer prognosis, affecting both patient and renal survival.

Clinical and histopathological characteristics of acute kidney injury in a cohort of brain death donors with procurement biopsies.

Kidney biopsies are routinely used for diagnostic and prognostic purposes but their utility in the intensive care unit (ICU) setting is limited. We investigated the associations of clinical and histopathological risk factors with ICU-acute kidney injury (AKI) in donors with brain death (DBD) with kidneys of lower quality and procurement biopsies. Overall,221 donors with brain death, 239 biopsies and 197 recipients were included. The biopsies were reread and scored according to the Banff recommendations. Clinical and histopathological data were compared between donors with and without AKI defined by serum creatinine and by urine output. Logistic regression analysis was applied to identify independent clinical and histopathological risk factors for both phenotypes. Lastly, the impact of each AKI phenotype on outcome was explored.AKI was diagnosedbased on the RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease)AKIN (Acute Kidney Injury Network) orKDIGO (Kidney Disease Improving Global Outcomes) criteria. Acute kidney injury occurred in 65% of donorsbased both uponserum creatinine and by urine output. Serum creatinine was able to better discriminate AKI. Multiorgan failure and severe AKI were captured by serum creatinine, and hemodynamic instability by urine output. Donors with serum creatinine-AKI showed lower chronic macrovascular scores, while donors with urine output-AKI had higher chronic microvascular and tubulointerstitial scores. Tubular injury was similar between the subgroups. Except for delayed graft function and one-year death-censored graft survival, the other short-term recipient outcomes were similar for both AKI phenotypes. Serum creatinine is more suitable than urine output for defining AKI in donors with brain death. There are distinct clinical risk factors for each AKI-ICU phenotype. Donor AKI phenotype does not predict the recipient´s prognosis. Kidney biopsies do not seem to confer any tangible benefit in defining AKI indonors with brain death.

Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway

BackgroundPyroptosis of the renal tubular epithelial cells (RTECs) and interstitial inflammation are central pathological characteristics of acute kidney injury (AKI). Pyroptosis acts as a pro-inflammatory form of programmed cell death and is mainly dependent on activation of the NLRP3 inflammasome. Previous studies revealed that acetyl-CoA synthetase 2 (ACSS2) promotes inflammation during metabolic stress suggesting that ACSS2 might regulate pyroptosis and inflammatory responses of RTECs in AKI.Methods and resultsThe expression of ACSS2 was found to be significantly increased in the renal epithelial cells of mice with lipopolysaccharide (LPS)-induced AKI. Pharmacological and genetic strategies demonstrated that ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the stimulation of the KLF5/NF-κB pathway in RTECs. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model, and ACSS2-deficient mice displayed impaired NLRP3 activation-mediated pyroptosis and decreased IL-1β production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and pyroptosis through the downregulation of the KLF5/NF-κB pathway. The KLF5 inhibitor ML264 suppressed NF-κB activity and NLRP3-mediated caspase-1 activation, thus protecting HK-2 cells from LPS-induced pyroptosis.ConclusionOur results suggested that ACSS2 regulates activation of the NLRP3 inflammasome and pyroptosis by inducing the KLF5/NF-κB pathway in RTECs. These results identified ACSS2 as a potential therapeutic target in AKI.Graphical We found that the expression of ACSS2 was significantly increased in RTECs in septic AKI. ACSS2-deficient mice displayed resistance to renal damage in this model. ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the KLF5/NF-κB pathway in RTECs. Pharmacological inhibition of KLF5 suppressed NLRP3 activation and caspase-1 cleavage by downregulating of NF-κB. Our results suggest that ACSS2 is a pro-pathogenic mediator of cell pyroptosis of RTECs and renal inflammation in sepsis-induced AKI.

Characteristics of acute kidney injury and mortality in patients with sepsis and septic shock

Background and Objective: Acute kidney injury (AKI) is a life-threatening disease and a global health burden, with an increasing incidence in both developed and developing countries. 40 - 50% of AKI cases are caused by sepsis and septic shock. Mortality increases respectively with disease severity. Therefore, we conduct this research with the objective of determining the incidence of sepsis-associated and septic shock-associated AKI and mortality in these patients. Methods: This cross sectional study was conducted on 65 patients with sepsis or septic shock in the Department of ICU - Hue Central Hospital - Vietnam, from February 2022 to March 2023. Results: Of the 65 patients admitted with sepsis and septic shock, 38 (58.5%) developed AKI, the rates of KDIGO stage 1, 2, 3 were 44.7%, 38.8%, and 18.5%, respectively. The rate of patients receiving RRT was 39.5%. The rate of patients with positive blood cultures was 12.6%. The average SOFA score, APACHE II score at admission were respectively 7.63 ± 5.8; 19.18 ± 9.2. The average serum levels of lactate and PCT in patients with sepsis and septic shock were respectively 3.9 ± 3.23 mmol/l; 33.13 ± 38.49 ng/ml. The average ICU length of stay was 9.03 ± 5.23 days, the rate of requiring mechanical ventilation was 36.9%, in-28-day mortality was 32.3%. Mortality was statistically significantly higher in the AKI groups compared to non-AKI group (p < 0.05). Conclusion: Patients with sepsis and septic shock have high rates of AKI and mortality, increased length of hospital stay. Key words: acute kidney injury, sepsis, septic shock.

Unravelling the Histomorphological Features of Kidney: An Autopsy-based Study

Introduction: Renal failure and End-stage Renal Disease (ESRD) are one of the leading causes of mortality. The presence of co-morbidities like Diabetes Mellitus (DM), Hypertension (HT), pregnancy, liver diseases, and various infections accelerates renal failure. Understanding the pathophysiology of Acute Renal Failure (ARF) is necessary to interpret and correlate the spectrum of morphologic changes associated with it. Aim: To study the aetiopathological causes of renal failure and evaluate the histopathological features associated with them. Materials and Methods: A cross-sectional autopsy-based study was performed in the Department of Pathology, Topiwala National Medical College, Mumbai, Maharashtra, India over three consecutive years. A total of 650 adult autopsies were studied. Clinical and laboratory details were obtained from hospital records. Gross and histopathological examinations were performed with a special focus on the kidneys. Special stains were performed wherever required to highlight any characteristic features. Results: It was found that males (n=460) were more affected than females (n=190). The age range was 13-90 years. The majority of autopsies were performed within 24 hours of hospital stay. Acute febrile illness was found to be the most common cause of ARF. Maximum number of cases were from medical units (n=520, 80%), followed by surgical (n=94, 14.5%) and gynaecological units (n=36, 5.5%). Features of Acute Kidney Injury (AKI) were seen in (n=374) 57.6% of cases, while Advanced Renal Disease (ARD) was noted in 10.9% of cases. Incidental findings at autopsy included two cases of renal cortical adenoma, one case each of renal cell carcinoma and medullary fibroma. Conclusion: Acute febrile illness does not just a reflect ion of co-existent pathologies but also directly contributes to mortality, possibly due to the risk of non renal complications like bleeding and sepsis. In the present study, the majority of cases were from medical units, in a young age group with a male predominance. Maximum cases had a short hospital stay. Several characteristic histopathological features in the kidney were identified in different clinical settings, aiding in pinpointing the cause of death. Autopsy findings of the kidney are indeed a treasure untouched and needs to be explored and warrants meticulous investigation.

Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment

Mitochondrial oxidative stress and inflammation are the main pathological features of acute kidney injury (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment of AKI. Here, the lipid micelle nanosystem modified with l-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified curcumin (Cur-TPP) and quercetin (Que). In the cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved renal function. Compared to mono-targeted group, the mitochondrial ROS content of renal tubular epithelial cells acting in the dual-target group decreased about 1.66-fold in vitro, serum creatinine (Scr) and urea nitrogen (BUN) levels were reduced by 1.5 and 1.2 mmol/L in vivo, respectively. Mechanistic studies indicated that the nanosystem inhibited the inflammatory response by interfering with the NF-κB and Nrf2 pathways. This study provides an efficient and low-toxicity strategy for AKI therapy.

Characteristics of acute kidney injury in patients with acute decompensation of heart failure

Introduction. Acute decompensation of heart failure (AHF) can cause acute kidney injury (AKI), hyponatremia, episodes of oliguria and polyuria in the treatment of furosemide. These complications lengthen the time of hospitalization, increase the economic costs of treatment and worsen the prognosis. Currently, the relationship of these manifestations in patients with CHF has not been studied.Objective. To evaluate the effect of AKI on the rate of diuresis and the level of plasma sodium during the complex therapy of AHF.Materials and methods. Kidney function was assessed in 125 patients receiving complex therapy for AHF. The glomerular filtration rate (GFR) was determined in two ways: by the level of creatinine and cystatin C in blood serum. The number of AKI, hyponatremia, episodes of oliguria and polyuria were studied. An analysis of the relationship between these events was carried out.Results. At the time of admission to the hospital, the study of GFR by the level of cystatin C showed 2.6 times more AKI than by the level of creatinine. In total, AKI was found in 22.4% of cases, hyponatremia in 24.8%, episodes of oliguria in 18.4%, episodes of polyuria in 24.8%. The analysis showed that there is a connection of violations of the rate of diuresis and hyponatremia with AKI.Conclusions. Сases of impaired urinary excretion and hyponatremia during AHF therapy are more common in patients with AKI.

Clinical and Laboratory Characteristics of Acute Kidney Injury in Critically Ill Children: A Single Center Study

Clinical and Laboratory Characteristics of Acute Kidney Injury in Critically Ill Children: A Single Center Study

Acute kidney injury in children with moderate-severe COVID-19 and multisystem inflammatory syndrome in children: a referral center experience.

Data on the characteristics of acute kidney injury (AKI) in pediatric COVID-19 and MIS-C are limited. We aimed to define the frequency, associated factors and early outcome of AKI in moderate, severe or critical COVID-19 and MIS-C; and to present a tertiary referral center experience from Türkiye. Hospitalized patients ≤ 18years of age with confirmed COVID-19 or MIS-C at İhsan Doğramacı Children's Hospital, Hacettepe University, between March 2020-December 2021 were enrolled. The characteristics of AKI in the COVID-19 group were investigated in moderate, severe and critically ill patients; patients with mild COVID-19 were excluded. The median (Q1-Q3) age in theCOVID-19 (n = 66) and MIS-C (n = 111) groups was 10.7years (3.9-15.2) and 8.7years (4.5-12.7), respectively. The frequency of AKI was 22.7% (15/66) in COVID-19 and 15.3% (17/111) in MIS-C; all MIS-C patients with AKI and 73.3% (11/15) of COVID-19 patients with AKI had AKI at the time of admission. Multivariate analyses revealed need for vasoactive/inotropic agents [Odds ratio (OR) 19.233, p = 0.002] and presence of vomiting and/or diarrhea (OR 4.465, p = 0.036) as independent risk factors of AKI in COVID-19 patients; and need for vasoactive/inotropic agents (OR 22.542, p = 0.020), procalcitonin and ferritin levels as independent risk factors of AKI in theMIS-C group. Age was correlated with lymphocyte count (r = -0.513, p < 0.001) and troponin level (r = 0.518, p < 0.001) in MIS-C patients. Length of hospital stay was significantly longer in both groups with AKI, compared to those without AKI. Mortality was 9.1% in theCOVID-19 group; and was associated with AKI (p = 0.021). There was no mortality in MIS-C patients. AKI recovery at discharge was 63.6% in COVID-19 survivors and 100% in MIS-C patients. Independent risk factors for AKI were need for vasoactive/inotropic agents and vomiting/diarrhea in moderate, severe or critical COVID-19 patients; and need for vasoactive/inotropic agents and severe inflammation in MIS-C patients. Our findings suggest that inflammation and cardiac dysfunction are associated with AKI in MIS-C patients; and the association with age in this group merits further studies in larger groups. Early outcome is favorable; long-term follow-up for kidney functions is needed.

Clinical and pathological characteristics of acute kidney injury caused by diquat poisoning

Introduction: Diquat poisoning leads to kidney injury, hepatotoxicity, rhabdomyolysis, gastrointestinal hemorrhage, and respiratory failure. Diquat has high mortality and no specific antidote. The pathology of acute kidney injury caused by diquat poisoning has been mainly investigated in animal studies and autopsies, and typically shows renal tubular necrosis. To our knowledge, antemortem renal biopsy has not been reported in humans. Case reports: Two males and one female presented following deliberate diquat self-poisoning. Their main clinical manifestations were abdominal pain, nausea, and emesis. All developed acute kidney injury. Kidney biopsy was performed in two cases which showed acute tubular necrosis with renal interstitial edema and multifocal inflammatory cell infiltration. Treatments given included gastric lavage, catharsis, early hemoperfusion combined with continuous kidney replacement therapy or hemodialysis, administration of glucocorticoids, and antioxidant therapy. All patients survived. Discussion: Despite potentially lethal ingestions three patients survived oral diquat poisoning with intensive supportive care. No clear relationship can be made between any of the therapies given and patient outcome. Conclusions: Kidney biopsy in these patients confirmed proximal renal tubular injury was the major pathological finding although interstitial injury was also present. The role of therapies that address renal pathology requires further study.

LRRK2 aggravates kidney injury through promoting MFN2 degradation and abnormal mitochondrial integrity

Mitochondrial dysfunction is one of the key features of acute kidney injury (AKI) and associated fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in kidneys and regulates mitochondrial homeostasis. How it functions in AKI is unclear. Herein we reported that LRRK2 was dramatically downregulated in AKI kidneys. Lrrk2−/− mice exhibited less severity of AKI when compared to wild-type counterparts with less mitochondrial fragmentation and decreased reactive oxygen species (ROS) production in proximal renal tubular cells (PTCs) due to mitofusin 2 (MFN2) accumulation. Overexpression of LRRK2 in human PTC cell lines promoted LRRK2-MKK4/JNK-dependent phosphorylation of MFN2Ser27 and subsequently ubiquitination-mediated MFN2 degradation, which in turn exaggerated mitochondrial damage upon ischemia/reperfusion (I/R) mimicry treatment. Lrrk2 deficiency also alleviated AKI-to-chronic kidney disease (CKD) transition with less fibrosis. In vivo pretreatment of LRRK2 inhibitors attenuated the severity of AKI as well as CKD, potentiating LRRK2 as a novel target to alleviate AKI and fibrosis.

Anemonin inhibits sepsis-induced acute kidney injury via mitigating inflammation and oxidative stress.

Elevated inflammation and oxidative stress (OS) are the main pathologic features of acute kidney injury (AKI)-caused by sepsis. Here, we made an investigation into the protective effects of the natural compound Anemonin (ANE) on sepsis-induced AKI both in vitro and in vivo. Lipopolysaccharide (LPS) was applied to construct an in vitro AKI model in renal tubular epithelial cells, and the septic C57BL/6J mouse model was constructed via cecal ligation and puncture (CLP). Cell viability and apoptosis were detected. The levels of p53, Bax, Bcl2, Caspase3, Caspase8, Caspase9, AMP-activated protein kinase (AMPK), Sirt-1, and forkhead box O3 were determined by Western Blot or RT-PCR. The reactive oxygen species level and OS markers were measured. Furthermore, the pathological changes of kidneys were evaluated by hematoxylin-eosin staining and immunohistochemistry. As per the information presented, ANE improved LPS-elicited apoptosis, inflammatory response, and OS in a dose-dependent pattern in renal tubular epithelial cells. Besides, ANE activated the AMPK/Sirt-1 pathway, and the AMPK inhibitor (Compound C) and Sirt-1 inhibitor (EX-527) significantly attenuated ANE-mediated protection on renal tubular epithelial cells. In vivo, ANE mitigated the levels of serum creatinine and urea nitrogen in the CLP-induced mouse sepsis model, reduced the renal tissue injury score, and attenuated OS, inflammation, and apoptosis levels in the kidney. Taken together, this study suggested that ANE has protective effects in sepsis-triggered AKI through repressing inflammation, OS, and cell apoptosis by activating the AMPK/Sirt-1 pathway.

#2572 CLINICAL CHARACTERISTICS OF ACUTE KIDNEY INJURY IN PATIENTS WITH GLUFOSINATE POISONING

Abstract Background and Aims Glufosinate-containing herbicide is widely used in agriculture. According to previous reports, glufosinate poisoning causes various complications, but there are few reports of nephrotoxicity. In this study, we investigated the incidence and clinical characteristics of acute kidney injury (AKI) in patients with glufosinate poisoning. Method This study performed between 2008 and 2021 included 76 patients categorized into the AKI and the non-AKI groups. The incidence, clinical characteristics, and severity of AKI were compared between the AKI (n=54) and the non-AKI (n=22) groups, based on the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease classification. Results The incidence of AKI was 71.1%, of which 40.9%, 26.3%, and 3.9% patients were classified into the Risk, Injury, and Failure categories, respectively. Patients in the AKI group were older (62.6±14.2 years vs. 54.9±16.2 years, P=0.045) and poorer renal function (73.9±25.2 mL/min/1.73 m² vs. 94.5±35.5 mL/min/1.73 m², P=0.006) on admission. The length of hospitalization was longer (17.2±17.2 days vs. 7.6±7.6 days, P=0.014) in AKI group, and the mean amount of glufosinate ingested was higher in AKI group than that in non-AKI group (250±172 mL vs. 152±121 mL, P=0.032). In addition, the serum bicarbonate level was lower in AKI group than in non-AKI group (19.9±4.7 vs. 23.0±3.3, P=0.006). Notably, intensive care unit admissions (81.5% vs. 40.9%, P=0.001) and mechanical ventilator support (68.5% vs. 22.7%, P&amp;lt;0.001) were more frequently required in the AKI group. Multivariate logistic regression analysis showed that serum bicarbonate concentration on admission remained significant predictors of AKI in patient with glufosinate poisoning. Conclusion Serum bicarbonate is helpful to predict the development of patients with glufosinate poisoning.

Risk Factors and Clinical Characteristics of Acute Kidney Injury in Patients with COVID-19: A Systematic Review and Meta-Analysis.

Acute kidney injury (AKI) is associated with a worse prognosis in coronavirus disease 2019 (COVID-19) patients. Identification of AKI, particularly in COVID-19 patients, is important for improving patients' management. The study aims to assess risk factors and comorbidities of AKI in COVID-19 patients. We systematically searched PubMed and DOAJ databases for relevant studies involving confirmed COVID-19 patients with data on risk factors and comorbidities of AKI. The risk factors and comorbidities were compared between AKI and non-AKI patients. A total of 30 studies involving 22385 confirmed COVID-19 patients were included. Male (OR: 1.74 (1.47, 2.05)), diabetes (OR: 1.65 (1.54, 1.76)), hypertension (OR: 1.82 (1.12, 2.95)), ischemic cardiac disease (OR: 1.70 (1.48, 1.95)), heart failure (OR: 2.29 (2.01, 2.59)), chronic kidney disease (CKD) (OR: 3.24 (2.20, 4.79)), chronic obstructive pulmonary disease (COPD) (OR: 1.86 (1.35, 2.57)), peripheral vascular disease (OR: 2.34 (1.20, 4.56)), and history of nonsteroidal anti-inflammatory drugs (NSAID) (OR: 1.59 (1.29, 1.98)) were independent risk factors associated with COVID-19 patients with AKI. Patients with AKI presented with proteinuria (OR: 3.31 (2.59, 4.23)), hematuria (OR: 3.25 (2.59, 4.08)), and invasive mechanical ventilation (OR: 13.88 (8.23, 23.40)). For COVID-19 patients, male gender, diabetes, hypertension, ischemic cardiac disease, heart failure, CKD, COPD, peripheral vascular disease, and history of use of NSAIDs are associated with a higher risk of AKI.

Clinical characteristics of acute kidney injury in patients with glyphosate surfactant herbicide poisoning.

In this study, we investigated the clinical characteristics of acute kidney injury (AKI) in patients with glyphosate surfactant herbicide (GSH) poisoning. This study was performed between 2008 and 2021 and included 184 patients categorized into the AKI (n = 82) and nonAKI (n = 102) groups. The incidence, clinical characteristics, and severity of AKI were compared between the groups based on the Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease (RIFLE) classification. The incidence of AKI was 44.5%, of which 25.0%, 6.5%, and 13.0% of patients were classified into the Risk, Injury, and Failure categories, respectively. Patients in the AKI group were older (63.3 ± 16.2 years vs. 57.4 ± 17.5 years, p = 0.02) than those in the non-AKI group. The length of hospitalization was longer (10.7 ± 12.1 days vs. 6.5 ± 8.1 days, p = 0.004) and hypotensive episodes occurred more frequently in the AKI group (45.1% vs. 8.8%, p &lt; 0.001). Electrocardiographic (ECG) abnormalities on admission were more frequently observed in the AKI group than in the non-AKI group (80.5% vs. 47.1%, p &lt; 0.001). Patients in the AKI group had poorer renal function (estimated glomerular filtration rate at the time of admission, 62.2 ± 22.9 mL/min/1.73 m2 vs. 88.9 ± 26.1 mL/min/1.73 m2 , p &lt; 0.001) on admission. The mortality rate was higher in the AKI group than in the non-AKI group (18.3% vs. 1.0%, p &lt; 0.001). Multiple logistic regression analysis showed that hypotension and ECG abnormalities upon admission were significant predictors of AKI in patients with GSH poisoning. The presence of hypotension on admission may be a useful predictor of AKI in patients with GSH intoxication.