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 evaluate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute kidney injury induced by acute liver failure and unravel the underlying mechanism, so as to provide insights into the clinical therapy of acute kidney injury. METHODS: Twenty-four male C57BL/6J mice at ages of 6 to 8 weeks were randomly divided into the normal control group, rSj-Cys control group, lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) model group and LPS/D-GaIN + rSj-Cys treatment group, of 6 mice each group. Mice in the LPS/D-GaIN group and LPS/D-GaIN + rSj-Cys group were intraperitoneally injected with LPS (10 μg/kg) and D-GaIN (700 mg/kg), and mice in the LPS/D-GaIN + rSj-Cys group were additionally administered with rSj-Cys (1.25 mg/kg) by intraperitoneal injection 30 min post-modeling, while mice in the rSj-Cys group were intraperitoneally injected with rSj-Cys (1.25 mg/kg), and mice in the normal control group were injected with the normal volume of PBS. All mice were sacrificed 6 h post-modeling, and mouse serum and kidney samples were collected. Serum creatinine (Cr) and urea nitrogen (BUN) levels were measured, and the pathological changes of mouse kidney specimens were examined using hematoxylin-eosin (HE) staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were detected using enzyme-linked immunosorbent assay (ELISA), and the expression of inflammatory factors and pyroptosis-related proteins was quantified in mouse kidney specimens using immunohistochemistry. In addition, the expression of pyroptosis-related proteins and nuclear factor-kappa B (NF-κB) signaling pathway-associated proteins was determined in mouse kidney specimens using Western blotting assay. RESULTS: HE staining showed no remarkable abnormality in the mouse kidney structure in the normal control group and the rSj-Cys control group, and renal tubular injury was found in LPS/D-GaIN group, while the renal tubular injury was alleviated in LPS/D-GaIN+rSj-Cys treatment group. There were significant differences in serum levels of Cr (F = 46.33, P < 0.001), BUN (F = 128.60, P < 0.001), TNF-α (F = 102.00, P < 0.001) and IL-6 (F = 202.10, P < 0.001) among the four groups, and lower serum Cr [(85.35 ± 32.05) μmol/L], BUN [(11.90 ± 2.76) mmol/L], TNF-α [(158.27 ± 15.83) pg/mL] and IL-6 levels [(56.72 ± 4.37) pg/mL] were detected in the in LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (all P values < 0.01). Immunohistochemical staining detected significant differences in TNF-α (F = 24.16, P < 0.001) and IL-10 (F = 15.07, P < 0.01) expression among the four groups, and lower TNF-α [(106.50 ± 16.57)%] and higher IL-10 expression [(91.83 ± 5.23)%] was detected in the LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (both P values < 0.01). Western blotting and immunohistochemistry detected significant differences in the protein expression of pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3 (NLRP3) (F = 24.57 and 30.72, both P values < 0.001), IL-1β (F = 19.24 and 22.59, both P values < 0.001) and IL-18 (F = 16.60 and 19.30, both P values < 0.001) in kidney samples among the four groups, and lower NLRP3, IL-1β and IL-18 expression was quantified in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (P values < 0.05). In addition, there were significant differences in the protein expression of NF-κB signaling pathway-associated proteins p-NF-κB p-P65/NF-κB p65 (F = 71.88, P < 0.001), Toll-like receptor (TLR)-4 (F = 45.49, P < 0.001) and p-IκB/IκB (F = 60.87, P < 0.001) in mouse kidney samples among the four groups, and lower expression of three NF-κB signaling pathway-associated proteins was determined in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (all P values < 0.01). CONCLUSIONS rSj-Cys may present a protective effect against acute kidney injury caused by acute liver failure through inhibiting inflammation and pyroptosis and downregulating the NF-κB signaling pathway.
Mice ; Male ; Animals ; Interleukin-10 ; Tumor Necrosis Factor-alpha/genetics* ; NF-kappa B/therapeutic use* ; Interleukin-18/therapeutic use* ; Schistosoma japonicum/metabolism* ; Interleukin-6/therapeutic use* ; Lipopolysaccharides/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice, Inbred C57BL ; Acute Kidney Injury/drug therapy* ; Liver Failure, Acute ; Cystatins/therapeutic use*

Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Acute Kidney Injury

Humans ; Adult ; Renal Replacement Therapy ; Retrospective Studies ; Acute Kidney Injury/therapy* ; Critical Illness/therapy*