Machine learning derived serum creatinine trajectories in acute kidney injury in critically ill patients with sepsis.

BACKGROUND: Current classification for acute kidney injury (AKI) in critically ill patients with sepsis relies only on its severity-measured by maximum creatinine which overlooks inherent complexities and longitudinal evaluation of this heterogenous syndrome. The role of classification of AKI based on early creatinine trajectories is unclear. METHODS: This retrospective study identified patients with Sepsis-3 who developed AKI within 48-h of intensive care unit admission using Medical Information Mart for Intensive Care-IV database. We used latent class mixed modelling to identify early creatinine trajectory-based classes of AKI in critically ill patients with sepsis. Our primary outcome was development of acute kidney disease (AKD). Secondary outcomes were composite of AKD or all-cause in-hospital mortality by day 7, and AKD or all-cause in-hospital mortality by hospital discharge. We used multivariable regression to assess impact of creatinine trajectory-based classification on outcomes, and eICU database for external validation. RESULTS: Among 4197 patients with AKI in critically ill patients with sepsis, we identified eight creatinine trajectory-based classes with distinct characteristics. Compared to the class with transient AKI, the class that showed severe AKI with mild improvement but persistence had highest adjusted risks for developing AKD (OR 5.16; 95% CI 2.87-9.24) and composite 7-day outcome (HR 4.51; 95% CI 2.69-7.56). The class that demonstrated late mild AKI with persistence and worsening had highest risks for developing composite hospital discharge outcome (HR 2.04; 95% CI 1.41-2.94). These associations were similar on external validation. CONCLUSIONS: These 8 classes of AKI in critically ill patients with sepsis, stratified by early creatinine trajectories, were good predictors for key outcomes in patients with AKI in critically ill patients with sepsis independent of their AKI staging.

Loss of SAV1 in Kidney Proximal Tubule Induces Maladaptive Repair after Ischemia and Reperfusion Injury.

Kidney ischemia and reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI), characterized by tubular injury and kidney dysfunction. Salvador family WW domain containing protein 1 (SAV1) is a key component of the Hippo pathway and plays a crucial role in the regulation of organ size and tissue regeneration. However, whether SAV1 plays a role in kidney IRI is not investigated. In this study, we investigated the role of SAV1 in kidney injury and regeneration following IRI. A proximal tubule-specific knockout of SAV1 in kidneys (SAV1ptKO) was generated, and wild-type and SAV1ptKO mice underwent kidney IRI or sham operation. Plasma creatinine and blood urea nitrogen were measured to assess kidney function. Histological studies, including periodic acid-Schiff staining and immunohistochemistry, were conducted to assess tubular injury, SAV1 expression, and cell proliferation. Western blot analysis was employed to assess the Hippo pathway-related and proliferation-related proteins. SAV1 exhibited faint expression in the proximal tubules and was predominantly expressed in the connecting tubule to the collecting duct. At 48 h after IRI, SAV1ptKO mice continued to exhibit severe kidney dysfunction, compared to attenuated kidney dysfunction in wild-type mice. Consistent with the functional data, severe tubular damage induced by kidney IRI in the cortex was significantly decreased in wild-type mice at 48 h after IRI but not in SAV1ptKO mice. Furthermore, 48 h after IRI, the number of Ki67-positive cells in the cortex was significantly higher in wild-type mice than SAV1ptKO mice. After IRI, activation and expression of Hippo pathway-related proteins were enhanced, with no significant differences observed between wild-type and SAV1ptKO mice. Notably, at 48 h after IRI, protein kinase B activation (AKT) was significantly enhanced in SAV1ptKO mice compared to wild-type mice. This study demonstrates that SAV1 deficiency in the kidney proximal tubule worsens the injury and delays kidney regeneration after IRI, potentially through the overactivation of AKT.

Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury After Massive Burns.

BACKGROUND Acute kidney injury (AKI) is a common and serious complication after massive burn injury. One of the postulated etiologies is destruction of the extracellular matrix of nephrons, caused by a local imbalance between matrix metalloproteinases (MMPs) and specific inhibitors. The aim of this study was to analyze the dynamics of tissue inhibitors of metalloproteinases (TIMPs) during the first 5 days after massive thermal injury and the relationship with the risk of AKI. MATERIAL AND METHODS Thirty-three adults (22 men, 11 women) with severe burns were enrolled in the study. The values of TIMPs 1 to 4 were measured in blood serum and urine using the multiplex Luminex system. The associations between TIMPs and the risk of AKI were analyzed by using the generalized linear mixed models for repeated measurements. RESULTS Significant changes in serum and urine activities of TIMPs were confirmed, especially during the first 2 days after burn injury. Almost half of patients presented renal problems during the study. Significant differences between values of TIMPs in AKI and non-AKI status were also observed. However, a significant relationship between concentration of TIMPs and risk of AKI was confirmed only for urine TIMP-1 and serum TIMP-3. CONCLUSIONS The evaluation of TIMPs in the early stage after burn injury has potential benefits. The important roles of urine TIMP-1 and serum TIMP-3, as novel markers of the risk of AKI development, were confirmed. Other parameters require further analysis.

Hemodynamic Changes in Intrarenal Blood Flow are Associated With Poor Prognosis in Patients With Acute Decompensated Heart Failure.

AIM: To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF). MATERIAL AND METHODS: This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death. RESULTS: According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p<0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p<0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p<0.001) and had a decreased sodium concentration to less than 50 mmol/l (p<0.001) in a spot urine test obtained one hour after the initiation of furosemide administration. CONCLUSION: Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.

Clinical presentation and outcomes of patients with rhabdomyolysis: A tertiary care center experience.

OBJECTIVES: To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. METHODS: Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. RESULTS: Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5 kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. CONCLUSION: This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.

Risk factors and early prediction of cardiorenal syndrome type 3 among acute kidney injury patients: a cohort study.

BACKGROUND: Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram. METHODS: In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort. RESULTS: The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009-1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193-6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012-1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96--0.987; p < 0.001), homocysteine (OR = 1.05; 95%CI = 1.03-1.069; p < 0.001), AKI stage [(stage 1: reference), (stage 2: OR = 5.427; 95%CI = 1.781-16.534; p = 0.003), (stage 3: OR = 5.554; 95%CI = 2.234-13.805; p < 0.001)]. The nomogram exhibited excellent predictive performance with an AUC of 0.907 in the study cohort and 0.892 in the validation cohort. Calibration and decision curve analyses upheld its accuracy and clinical utility. CONCLUSIONS: We developed a nomogram predicting CRS type 3 in AKI patients, incorporating 6 risk factors: age, CVD history, MAP, hemoglobin, homocysteine, and AKI stage, enhancing early risk identification and patient management.

Geriatric nutritional risk index is associated with the occurrence of acute kidney injury in critically ill patients with acute heart failure.

Background: During the acute heart failure (AHF), acute kidney injury (AKI) is highly prevalent in critically ill patients. The occurrence of the latter condition increases the risk of mortality in patients with acute heart failure. The current research on the relationship between nutritional risk and the occurrence of acute kidney injury in patients with acute heart failure is very limited. Methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with AHF who were admitted to the intensive care unit in the study. Results: A total of 1310 critically ill patients with acute heart failure were included. The AUC of geriatric nutritional risk index (GNRI) (0.694) is slightly superior to that of controlling nutritional status (CONUT) (0.656) and prognostic nutritional index (PNI) (0.669). The Log-rank test revealed a higher risk of acute kidney injury in patients with high nutritional risk (p < 0.001). Multivariate COX regression analysis indicated that a high GNRI (adjusted HR 0.62, p < 0.001) was associated with a reduced risk of AKI during hospitalization in AHF patients. The final subgroup analysis demonstrated no significant interaction of GNRI in all subgroups except for diabetes subgroup and ventilation subgroup (P for interaction: 0.057-0.785). Conclusion: Our study findings suggest a correlation between GNRI and the occurrence of acute kidney injury in patients hospitalized with acute heart failure.

Clinical significance of the lactate-to-albumin ratio on prognosis in critically ill patients with acute kidney injury.

OBJECTIVE: To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI). METHODS: A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis. RESULTS: A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients (p < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI (p < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group (p < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone (p < 0.001). CONCLUSION: High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI.

Influence of acute kidney injury and its recovery subtypes on patient-centered outcomes after lung transplantation.

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation.

Hepcidin, in contrast to heparin binding protein, does not portend acute kidney injury in patients with community acquired septic shock.

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication in patients treated at an Intensive Care Unit (ICU). The pathogenesis of AKI has been reported to involve hypoperfusion, diminished oxygenation, systemic inflammation, and damage by increased intracellular iron concentration. Hepcidin, a regulator of iron metabolism, has been shown to be associated with sepsis and septic shock, conditions that can result in AKI. Heparin binding protein (HBP) has been reported to be associated with sepsis and AKI. The aim of the present study was to compare serum hepcidin and heparin binding protein (HBP) levels in relation to AKI in patients admitted to the ICU. METHODS: One hundred and forty patients with community acquired illness admitted to the ICU within 24 hours after first arrival to the hospital were included in the study. Eighty five of these patients were diagnosed with sepsis and 55 with other severe non-septic conditions. Logistic and linear regression models were created to evaluate possible correlations between circulating hepcidin and heparin-binding protein (HBP), stage 2-3 AKI, peak serum creatinine levels, and the need for renal replacement therapy (RRT). RESULTS: During the 7-day study period, 52% of the 85 sepsis and 33% of the 55 non-sepsis patients had been diagnosed with AKI stage 2-3 already at inclusion. The need for RRT was 20% and 15%, respectively, in the groups. Hepcidin levels at admission were significantly higher in the sepsis group compared to the non-sepsis group but these levels did not significantly correlate to the development of stage 2-3 AKI in the sepsis group (p = 0.189) nor in the non-sepsis group (p = 0.910). No significant correlation between hepcidin and peak creatinine levels, nor with the need for RRT was observed. Stage 2-3 AKI correlated, as expected, significantly with HBP levels at admission in both groups (Odds Ratio 1.008 (CI 1.003-1.014, p = 0.005), the need for RRT, as well as with peak creatinine in septic patients. CONCLUSION: Initial serum hepcidin, and HBP levels in patients admitted to the ICU are biomarkers for septic shock but in contrast to HBP, hepcidin does not portend progression of disease into AKI or a later need for RRT. Since hepcidin is a key regulator of iron metabolism our present data do not support a decisive role of initial iron levels in the progression of septic shock into AKI.

Risk Factors and Prognosis of Acute Kidney Injury in Hospitalised Sepsis Patients.

OBJECT: This study aimed to analyse the risk factors and prognosis of sepsis complicated with acute kidney injury (AKI). METHODS: The clinical data of 324 patients with sepsis in the nephrology department of our hospital from January 2022 to January 2023 were collected. A total of 188 patients with AKI were the occurrence group, and 136 patients without AKI were the non-occurrence group. The influencing factors and prognosis of sepsis complicated with AKI were analysed. RESULTS: We observed significant differences in Acute Physiology and Chronic Health Evaluation II (APACHE II), total length of hospital stay, Intensive Care Unit (ICU) stay, mechanical ventilation support, diabetes mellitus and urine volume >1500 mL between the two groups (p < 0.05). After a follow-up period of 1 month, 125 (66.49%) of 188 patients with sepsis complicated with AKI died, and 63 (33.51%) survived. The results of logistic regression analysis showed that Sequential Organ Failure Assessment (SOFA), APACHE II, mechanical ventilation support, diabetes, urine volume >1500 mL and serum creatinine were independent risk factors of sepsis complicated with AKI (p < 0.05). Moreover, SOFA, APACHE II, ICU admission days, mechanical ventilation support, serum creatinine and non-continuous renal replacement therapy were independent risk factors of death in patients with sepsis complicated with AKI (p < 0.05). CONCLUSIONS: SOFA, APACHE II, ICU admission days, mechanical ventilation support, serum creatinine and non-continuous renal replacement therapy may be the influencing factors leading to death in patients with sepsis complicated with AKI. Early clinical intervention should be performed.

[Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy].

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) µmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

Impact of severe acute kidney injury on short-term mortality in urosepsis.

PURPOSE: To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis. METHODS: This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development. RESULTS: The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development. CONCLUSIONS: Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.

Septic acute kidney injury and gut microbiome: Should we change our approach?

Incidence of acute kidney injury (AKI) remained relatively stable over the last decade and the adjusted risks for it and mortality are similar across different continents and regions. Also, the mortality of septic-AKI can reach 70% in critically-ill patients. These sole facts can give rise to a question: is there something we do not understand yet? Currently, there are no specific therapies for septic AKI and the treatment aims only to maintain the mean arterial pressure over 65mmHg by ensuring a good fluid resuscitation and by using vasopressors, along with antibiotics. On the other hand, there is an increased concern about the different hemodynamic changes in septic AKI versus other forms and the link between the gut microbiome and the severity of septic AKI. Fortunately, progress has been made in the form of administration of pre- and probiotics, short chain fatty acids (SCFA), especially acetate, and also broad-spectrum antibiotics or selective decontaminants of the digestive tract in a successful attempt to modulate the microbial flora and to decrease both the severity of AKI and mortality. In conclusion, septic-AKI is a severe form of kidney injury, with particular hemodynamic changes and with a strong link between the kidney and the gut microbiome. By modulating the immune response we could not only treat but also prevent severe forms. The most difficult part is to categorize patients and to better understand the key mechanisms of inflammation and cellular adaptation to the injury, as these mechanisms can serve in the future as target therapies.

Predictive performance of two types of urinary biomarkers for renal non-recovery in sepsis-associated acute kidney injury: a prospective observational study.

BACKGROUND AND PURPOSE: Renal non-recovery is known to have negative prognostic implications in patients suffering from acute kidney injury (AKI). Nevertheless, the identification of biomarkers for predicting renal non-recovery in sepsis-associated AKI (SA-AKI) within clinical settings remains unresolved. This study aims to evaluate and compare the predictive ability for renal non-recovery, use of kidney replacement therapy (KRT) in the Intensive Care Unit (ICU), and 30-day mortality after SA-AKI by two urinary biomarkers, namely C-C motif chemokine ligand 14 (CCL14) and [TIMP-2]•[IGFBP7]. METHODS: We prospectively screened adult patients who met the criteria for AKI stage 2-3 and Sepsis-3.0 in two ICUs from January 2019 to May 2022. Patients who developed new-onset SA-AKI after ICU admission were enrolled and urinary biomarkers including [TIMP-2]•[IGFBP7] and CCL14 were detected at the time of SA-AKI diagnosis. The primary endpoint was non-recovery from SA-AKI within 7 days. The secondary endpoints were the use of KRT in the ICU and 30-day mortality after SA-AKI. The individual discriminative ability of [TIMP-2]•[IGFBP7] and CCL14 to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). RESULTS: 141 patients with stage 2-3 SA-AKI were finally included, among whom 54 (38.3%) experienced renal non-recovery. Urinary CCL14 exhibited a higher predictive capability for renal non-recovery compared to [TIMP-2]•[IGFBP7], with CCL14 showing an AUC of 0.901, versus an AUC of 0.730 for [TIMP-2]•[IGFBP7] (P = 0.001). Urinary CCL14 and [TIMP-2]•[IGFBP7] demonstrated a moderate predictive value for the need for KRT in ICU, with AUC values of 0.794 and 0.725, respectively; The AUC of [TIMP-2]•[IGFBP7] combined with CCL14 reached up to 0.816. Urinary CCL14 and [TIMP-2]•[IGFBP7] exhibited poor predictive power for 30-day mortality, with respective AUC values of 0.623 and 0.593. CONCLUSION: Urinary CCL14 had excellent predictive value for renal non-recovery in SA-AKI patients. For predicting the use of KRT in the ICU, the predictive capability of urinary [TIMP-2]•[IGFBP7] or CCL14 was fair. However, a combination of [TIMP-2]•[IGFBP7] and CCL14 showed good predictive ability for the use of KRT.

Urinary L-FABP as an Early Biomarker for Pediatric Acute Kidney Injury Following Cardiac Surgery with Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.

Innovative insights: ITLN1 modulates renal injury in response to radiation.

Radiation-induced kidney injury is a common side effect of radiotherapy, as the pelvic region is in close proximity to the kidneys, posing a risk of inducing radiation-induced kidney injury when treating any pelvic malignancies with radiotherapy. This type of injury typically manifests as chronic kidney disease a few months after radiotherapy, with the potential to progress to end-stage renal disease. Radiation-induced damage involves various components of the kidney, including glomeruli, tubules, interstitium, and extracellular matrix. Therefore, investigating its molecular mechanisms is crucial. In this study, we extensively searched literature databases, selecting recent transcriptomic studies related to acute kidney injury (AKI) published in the past decade. We downloaded the raw RNA sequencing datasets GSE30718 and GSE66494 related to AKI from the GEO database and identified that intestinal-type lectin ITLN1 plays a significant role in regulating radiation-induced kidney injury in rats. Differential gene analysis was performed using chip data from the GEO database, and further bioinformatics analysis identified 13 genes that may be involved in regulating kidney injury, with ITLN1 being the most relevant to kidney damage, thus selected as the target gene for this study. Subsequently, a rat model of radiation-induced kidney injury was established for experimental validation, assessing kidney tissue morphology and injury extent through staining observation and immunohistochemical staining. The protective effect of ITLN1 on kidney function was evaluated by measuring changes in rat body weight and blood pressure, serum kidney injury markers, and kidney structure. The experimental results indicate that overexpression of ITLN1 can improve kidney function in rats with radiation-induced kidney injury by activating the Akt/GSK-3ß/Nrf2 signaling pathway, suppressing oxidative stress, cell apoptosis, inflammation, cellular senescence, and fibrosis. This study highlights the significant role of ITLN1 in regulating kidney injury, providing a novel target for future treatments of radiation-induced kidney injury.

Anti-GBM disease in pregnancy.

We present the case of a pregnant woman in her 20s who presented in her second trimester with severe pulmonary haemorrhage and dialysis-dependent acute kidney failure due to antiglomerular basement membrane (GBM) disease. Responding to therapy, she recovered kidney function and delivered a baby. During her pregnancy, she developed cytomegalovirus viraemia, gestational diabetes and pre-eclampsia. Here, we report the first combined use of cyclophosphamide, rituximab and intensified plasma exchange in anti-GBM disease in pregnancy, allowing minimal exposure to cytotoxic medication, resulting in live birth and dialysis independence.

Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI).

INTRODUCTION: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI. METHODS AND ANALYSIS: Blind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis. TRIAL REGISTRATION NUMBER: NCT05900284.

Dehydroandrographolide facilitates M2 macrophage polarization by downregulating DUSP3 to inhibit sepsis-associated acute kidney injury.

BACKGROUND: Sepsis is perceived as lethal tissue damage and significantly increases mortality in combination with acute kidney injury (AKI). M2 macrophages play important roles in the secretion of anti-inflammatory and tissue repair mediators. We aimed to study the role of Dehydroandrographolide (Deh) in sepsis-associated AKI in vitro and in vivo through lipopolysaccharide (LPS)-induced macrophages model and cecal ligation and puncture-induced AKI mice model, and to reveal the mechanism related to M2 macrophage polarization. METHODS: Enzyme-linked immunosorbent assay kits were used to assess the levels of inflammatory factors. Expression of markers related to M1 macrophages and M2 macrophages were analyzed. Additionally, dual specificity phosphatase 3 (DUSP3) expression was tested. Cell apoptosis was evaluated by flow cytometry analysis and terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Moreover, renal histological assessment was performed by using hematoxylin and eosin staining. RESULTS: Deh reduced inflammation of THP-1-derived macrophages exposed to LPS. Besides, Deh induced the polarization of M1 macrophages to M2 and downregulated DUSP3 expression in THP-1-derived macrophages under LPS conditions. Further, DUSP3 overexpression reversed the impacts of Deh on the inflammation and M2 macrophages polarization of THP-1-derived macrophages stimulated by LPS. Additionally, human proximal tubular epithelial cells (HK-2) in the condition medium from DUSP3-overexpressed THP-1-derived macrophages treated with LPS and Deh displayed decreased viability and increased apoptosis and inflammation. The in vivo results suggested that Deh improved the renal function, ameliorated pathological injury, induced the polarization of M1 macrophages to M2, suppressed inflammation and apoptosis, and downregulated DUSP3 expression in sepsis-induced mice. CONCLUSION: Deh facilitated M2 macrophage polarization by downregulating DUSP3 to inhibit septic AKI.