OBJECTIVES: To investigate the association of serum albumin level after human albumin infusion with 28-day mortality in critically ill patients with acute kidney injury (AKI) and its impact on 90-day outcomes of the patients. METHODS: We conducted a retrospective cohort study based on the MIMIC IV database (2008-2019), including 5918 AKI patients treated with albumin in the ICU. Based on serum albumin levels within 72 h after albumin infusion, the patients were divided into low (<30 g/L), medium (30-35 g/L), and high albumin (>35 g/L) groups. Restricted cubic spline regression and multivariate logistic regression were used to analyze the association of albumin levels with patient mortality, and the results were verified in a external validation cohort consisting of 110 sepsis-induced AKI patients treated in Nanfang Hospital between 2017 and 2022 using survival analysis and multivariate adjustment. RESULTS: In the MIMIC training cohort, multivariate logistic regression showed no significant differences in 28-day mortality of the patients with different albumin levels (P>0.05). However, restricted cubic spline analysis indicated a non-linear dose-response relationship between albumin levels and 28-day mortality (threshold effect: risk increased when albumin levels >3.6 g/dL). Secondary endpoint analysis revealed that the patients with high albumin levels had a shorter duration of mechanical ventilation (P<0.001) but a longer ICU stay (P<0.001). In the validation cohort, albumin levels ≥30 g/L were significantly associated with a reduced 28-day mortality rate (P<0.05). CONCLUSIONS The association between increased serum albumin levels following albumin infusion and 28-day mortality of critically ill patients with AKI exhibits a cohort dependency and can be influenced by multiple factors including disease type and severity, infusion strategies, and statistical methods.
Humans ; Acute Kidney Injury/therapy* ; Critical Illness/mortality* ; Retrospective Studies ; Serum Albumin/analysis* ; Male ; Female ; Intensive Care Units ; Middle Aged ; Logistic Models ; Aged

OBJECTIVE: To investigate the effects of using different filters in continuous renal replacement therapy (CRRT) on the mortality, inflammatory mediator level and hemodynamics in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective study was conducted. The patients with SA-AKI undergoing first CRRT admitted to the critical care medicine department of General Hospital of Ningxia Medical University from August 2022 to October 2023 were enrolled as the study objects, and they were divided into observation group and control group by random number table method. All patients received routine treatment including anti-infection, optimized volume management and organ function support. On this basis, the observation group was treated with oXiris filter for CRRT, while the control group was treated with ordinary filter for CRRT, and the first treatment time was ≥ 36 hours. General data of the two groups were collected and compared. At the same time, the inflammatory indicators [high-sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), interleukin-6 (IL-6)], sequential organ failure assessment (SOFA) score, mean arterial pressure (MAP), blood lactic acid (Lac), noradrenaline dosage and other related indicators were collected before CRRT treatment and 24 hours and 48 hours after treatment, and the 7-day and 28-day mortality of patients were recorded. RESULTS: Finally, 65 patients were enrolled, including 30 in the observation group and 35 in the control group. There were no significant differences in baseline data including age, gender, acute kidney injury (AKI) stage and infection source between the two groups. The 7-day mortality of observation group was significantly lower than that of control group [16.7% (5/30) vs. 42.9% (15/35), P < 0.05]. There was no significant difference in 28-day mortality between the observation group and the control group [36.7% (11/30) vs. 54.3% (19/35), P > 0.05]. There were no significant differences in inflammation indicators, SOFA score, MAP, Lac and norepinephrine dosage before treatment between the two groups. After 24-hour and 48-hour treatment, the hemodynamics of the two groups were stable compared with before treatment, the inflammatory indicators, SOFA score, Lac and norepinephrine dosage were reduced to varying degrees, and MAP was significantly increased. In the observation group, hs-CRP, PCT, IL-6, SOFA score, MAP, and norepinephrine dosage showed statistical significance at 24 hours after treatment as compared with before treatment [hs-CRP (mg/L): 125.0 (105.0, 171.2) vs. 280.5 (213.2, 313.8), PCT (μg/L): 51.0 (20.0, 62.8) vs. 71.0 (10.8, 100.0), IL-6 (ng/L): 1 762.2 (300.8, 4 327.5) vs. 4 447.5 (630.4, 5 000.0), SOFA score: 13.0 (12.0, 14.0) vs. 16.0 (15.0, 17.0), MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 79.00±12.87 vs. 65.20±11.70, norepinephrine dosage (μg×kg^-1×min^-1): 0.82±0.33 vs. 1.63±0.51, all P < 0.05]. In the control group, PCT and MAP showed statistical significance after 48 hours of treatment as compared with before treatment. Compared with the control group, hs-CRP, SOFA score and norepinephrine dosage after 48 hours of treatment in the observation group were significantly decreased [hs-CRP (mg/L): 87.2 (74.2, 126.0) vs. 157.0 (88.0, 200.0), SOFA score: 11.0 (10.0, 12.0) vs. 12.0 (10.0, 14.0), norepinephrine dosage (μg×kg^-1×min^-1): 0.51±0.37 vs. 0.81±0.58, all P < 0.05], MAP was significantly increased (mmHg: 82.00±8.71 vs. 77.77±7.80, P < 0.05). CONCLUSION In the treatment of CRRT, oXiris filter can reduce the short-term mortality of SA-AKI patients, lower inflammatory mediators levels and improve hemodynamics, showing therapeutic advantages over conventional filters.
Humans ; Acute Kidney Injury/etiology* ; Sepsis/therapy* ; Prospective Studies ; Interleukin-6 ; Continuous Renal Replacement Therapy/methods* ; C-Reactive Protein ; Male ; Female ; Middle Aged ; Hemodynamics ; Procalcitonin ; Aged

Peroxisome proliferator activated receptor-α (PPAR-α) is significantly expressed in various tissues such as the liver, kidney, myocardium, and skeletal muscle, which plays a central role in the development of various diseases by regulating key physiological processes such as energy homeostasis, redox balance, inflammatory response, and ferroptosis. As an important metabolic and excretory organ of the body, renal dysfunction can lead to water and electrolyte imbalance, toxin accumulation, and multiple system complications. The causes of kidney injury are complex and diverse, including acute injury factors (such as ischemia/reperfusion, nephrotoxic drugs, septic shock, and immune glomerulopathy), as well as chronic progressive causes [such as metabolic disease-related nephropathy, hypertensive nephropathy (HN)], and risk factors such as alcohol abuse, obesity, and aging. This review briefly describes the structure, function, and activity regulation mechanism of PPAR-α, systematically elucidates the molecular regulatory network of PPAR-α in the pathological process of kidney injury including acute kidney injury (AKI) such as renal ischemia/reperfusion injury (IRI), drug-induced AKI, sepsis-associated acute kidney injury (SA-AKI), glomerulonephritis, chronic kidney disease (CKD) such as diabetic nephropathy (DN), HN, and other kidney injury, and summarizes the mechanisms related to PPAR-α regulation of kidney injury, including regulation of metabolism, antioxidation, anti-inflammation, anti-fibrosis, and anti-ferroptosis. This review also evaluates PPAR-α's medical value as a novel therapeutic target, and aims to provide theoretical basis for the development of kidney protection strategies based on PPAR-α targeted intervention.
Humans ; PPAR alpha/metabolism* ; Acute Kidney Injury/therapy* ; Animals ; Kidney/metabolism*

Acute kidney injury (AKI) is one of the most common complications in critically ill patients, and sepsis is the main cause of AKI in the intensive care unit (ICU), which can lead to a poor prognosis in severe cases. For patients with sepsis-associated acute kidney injury (SA-AKI) for whom urgent dialysis is indicated, it is now clear that renal replacement therapy (RRT) can be initiated immediately to control disease progression. However, the optimal timing to initiate RRT in patients whose disease is not severe enough to warrant urgent dialysis remains controversial. Some previous studies were small and heterogeneous, and there was a lack of effective reference indicators for guiding RRT in SA-AKI patients. Therefore, this article reviews the relevant experimental studies on the treatment of critically ill patients with AKI in recent years, and reviews the latest research progress on the optimal timing of RRT initiation, in order to provide an effective reference for clinical practice.
Humans ; Acute Kidney Injury/etiology* ; Renal Replacement Therapy/methods* ; Sepsis/therapy* ; Time Factors ; Intensive Care Units

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

Introduction: Since the breakout of COVID-19 in December 2019, the virus has already affected and taken millions of lives over the past year. There is still much to learn about this disease. It has been postulated that the human kidney is a potential pathway for COVID-19 due to the presence of the ACE2 receptors found in the surfaces of kidney cells. Some studies that demonstrated acute tubular necrosis and lymphocyte infiltration among post mortem COVID-19 patients, concluding that the virus could directly damage the kidney, increasing the risk of the development of Acute Kidney Injury (AKI) among patients with COVID-19. This study investigated the incidence and severity of AKI among hospitalized COVID-19 patients and the association of the degree of AKI with regards to the severity and outcomes of COVID-19 patients. Methods: This was a single-center cross-sectional study retrospective chart review of COVID-19 patients who developed AKI. Descriptive statistics were used to summarize the general and clinical characteristics of the patients. Frequency and proportion were used for categorical variables. Shapiro-Wilk test was used to determine the normality distribution of continuous variables. Continuous quantitative data that met the normality assumption was described using mean and standard deviation, while those that did not were described using median and range. Continuous variables which are normally distributed were compared using the One-way ANOVA, while those variables that are not normally distributed were compared using the Kruskal-Wallis H test. For categorical variables, the Chi-square test was used to compare the outcomes. If the expected percentages in the cells are less than 5%, Fisher's Exact Test was used instead. Results: A total of 1441 COVID-19 in-patients from March 1, 2020 to March 1, 2021 were reviewed, 59 of whom were excluded. Among the adults with COVID-19 who developed AKI, 60% were in stage I, 10% in stage II, and 30% in stage III. The incidence of AKI among COVID-19 in-patients at Makati Medical Center was 13.10% (95% CI 11.36% - 14.99%). Among the 181 patients, 79 (43.65%, 95% CI 36.30 - 51.20) had died. The mortality rate is 22.02% for Stage I, 50% for Stage II, and 85.19% for Stage III. The median length of hospital stay was 12 days, ranging from 1 day up to 181 days. Full renal recovery on discharge was observed only in one-third of the patients. It was observed in 44.95% of those in Stage I, 27.78% of those in Stage II, and 5.56% of those in Stage III. Conclusion The study demonstrated that the incidence of AKI in hospitalized COVID-19 patients was 13.1% (95% CI 11.36% - 14.99%), which was lower than previously reported. This could be attributed to the longer study period wherein, to date, we have a better understanding of the disease and had already established a standard of care for treatment for the disease attributing to the decreased incidence of AKI among COVID-19 patients than what was initially reported. The development of AKI has a direct correlation with the degree of infection. Among patients who developed AKI, 20% required renal replacement therapy. Overall development of AKI increases the risk of mortality among hospitalized COVID-19 patients. The stage of AKI has a direct correlation with regards to mortality and has an indirect relationship with regards to renal recovery.
Acute Kidney Injury ; COVID-19 ; Renal Replacement Therapy ; Mortality

OBJECTIVE: To explore the influencing factors of prognosis in patients with sepsis-induced acute kidney injury undergoing continuous renal replacement therapy (CRRT), and to construct a mortality risk prediction model. METHODS: A retrospective research method was adopted, patients with sepsis-induced acute kidney injury who received CRRT at Fuyang People's Hospital from February 2021 to September 2023 were included in this study. Collect general information, comorbidities, vital signs, laboratory indicators, disease severity scores, treatment status, length of stay in the intensive care unit (ICU), and 28-day prognosis were collected within 24 hours of patient enrollment. The Cox regression model was used to identify the factors influencing prognosis in patients with sepsis-induced acute kidney injury, and a nomogram model was developed to predict mortality in these patients. Receiver operator characteristic curve (ROC curve), calibration curve, and Hosmer-Lemeshow test were used to validate the predictive performance of the nomogram model. RESULTS: A total of 146 patients with sepsis-induced acute kidney injury were included, of which 98 survived and 48 died (with a mortality of 32.88%) after 28 days of treatment. The blood lactic acid, interleukin-6 (IL-6), serum cystatin C, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and proportion of mechanical ventilation in the death group were significantly higher than those in the survival group. The ICU stay was significantly longer than that in the survival group, and the glomerular filtration rate was significantly lower than that in the survival group. Cox regression analysis showed that blood lactic acid [odds ratio (OR) = 2.992, 95% confidence interval (95%CI) was 1.023-8.754], IL-6 (OR = 3.522, 95%CI was 1.039-11.929), serum cystatin C (OR = 3.999, 95%CI was 1.367-11.699), mechanical ventilation (OR = 4.133, 95%CI was 1.413-12.092), APACHE II score (OR = 5.013, 95%CI was 1.713-14.667), SOFA score (OR = 3.404, 95%CI was 1.634-9.959) were risk factors for mortality in patients with sepsis-induced acute kidney injury (all P < 0.05), glomerular filtration rate (OR = 0.294, 95%CI was 0.101-0.860) was a protective factor for mortality in patients with sepsis-induced acute kidney injury (P < 0.05). The ROC curve showed that the column chart model has a sensitivity of 80.0% (95%CI was 69.1%-89.2%) and a specificity of 89.3% (95%CI was 83.1%-95.2%) in predicting 28-day mortality in patients with acute kidney injury caused by sepsis. CONCLUSIONS Blood lactic acid, IL-6, mechanical ventilation, APACHEII score, SOFA score, glomerular filtration rate, and serum cystatin C are associated with the risk of death in patients with sepsis-induced acute kidney injury. The nomogram model could help early identification of mortality risk in these patients.
Humans ; Acute Kidney Injury/diagnosis* ; Sepsis/therapy* ; Retrospective Studies ; Prognosis ; Continuous Renal Replacement Therapy/methods* ; Nomograms ; Intensive Care Units ; ROC Curve ; Interleukin-6/blood* ; Proportional Hazards Models ; Female ; Male ; Cystatin C/blood* ; Middle Aged ; Risk Factors ; Lactic Acid/blood*

OBJECTIVE: To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI). METHODS: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- β and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. RESULTS: The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01). CONCLUSION CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.
Rats ; Male ; Animals ; AMP-Activated Protein Kinases/metabolism* ; Cordyceps/metabolism* ; Rats, Sprague-Dawley ; Kidney/pathology* ; Acute Kidney Injury/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Reperfusion Injury/metabolism* ; Cytokines/metabolism* ; Acute Lung Injury/drug therapy* ; Mammals/metabolism*

OBJECTIVE: To explore the risk factors for poor prognosis in sepsis-associated acute kidney injury (SA-AKI) and establish a nomogram predictive model. METHODS: The clinical data of patients with SA-AKI admitted to the department of critical care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2019 to September 2022 were retrospectively analyzed, including demographic information, worst values of blood cell counts and biochemical indicators within 24 hours of SA-AKI diagnosis, whether the patient received renal replacement therapy (RRT), mechanical ventilation, vasopressor therapy during hospitalization, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), fibrinogen-to-albumin ratio (FAR) within 24 hours of diagnosis, acute kidney injury (AKI) staging, total length of hospital stay, length of intensive care unit (ICU) stay, and others. According to the 28-day outcome, the patients were divided into survival group and death group, and the indicators between the two groups were compared. Univariate and multivariate Logistic regression analyses were used to screen for risk factors associated with mortality in SA-AKI patients. A nomogram predictive model for SA-AKI prognosis was constructed based on the identified risk factors. Receiver operator characteristic curve (ROC curve) and calibration plots were generated to evaluate the predictive value of the nomogram model for SA-AKI prognosis. RESULTS: A total of 113 SA-AKI patients were included, with 67 in the survival group and 46 in the death group. The 28-day mortality among SA-AKI patients was 40.7%. The comparison between the two groups showed that there were statistically significant differences in age ≥ 65 years, AKI stage, mechanical ventilation, vasopressors, RRT, length of ICU stay, and laboratory indicators cystatin C (Cys C), fibrinogen (Fib), and FAR. Multivariate Logistic regression analysis showed that age ≥ 65 years [odds ratio (OR) = 7.967, 95% confidence interval (95%CI) was 1.803-35.203, P = 0.006], cystatin C (OR = 7.202, 95%CI was 1.756-29.534, P = 0.006), FAR (OR = 2.444, 95%CI was 1.506-3.968, P < 0.001), and RRT (OR = 7.639, 95%CI was 1.391-41.951, P = 0.019) were independent risk factors for mortality in SA-AKI patients. ROC curve analysis showed that the area under the ROC curve (AUC) for age ≥ 65 years, cystatin C, FAR, and RRT in predicting SA-AKI patient mortality were 0.713, 0.856, 0.911, and 0.701, respectively. A nomogram predictive model for SA-AKI patient prognosis was constructed based on age ≥ 65 years, cystatin C, FAR, and RRT, with an AUC of 0.967 (95%CI was 0.932-1.000) according to ROC curve analysis. The calibration plot indicated good consistency between predicted and actual probabilities. CONCLUSIONS Age ≥ 65 years, cystatin C, FAR, and RRT are independent risk factors for mortality in SA-AKI patients. The nomogram predictive model based on these four factors can accurately predict SA-AKI patient prognosis, helping physicians adjust treatment strategies in a timely manner and improve patient outcomes.
Humans ; Aged ; Cystatin C ; Retrospective Studies ; Intensive Care Units ; Sepsis/diagnosis* ; Acute Kidney Injury/therapy* ; Prognosis ; ROC Curve ; Fibrinogen

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.
Animals ; Kidney ; Acute Kidney Injury/chemically induced* ; Ischemia ; Reperfusion Injury/drug therapy* ; Autophagy ; Reperfusion