Persistent acute kidney injury biomarkers: A systematic review and meta-analysis.

BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71-0.79),0.71 (95 % CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.

Intraoperative dexmedetomidine administration and acute kidney injury in patients undergoing unilateral partial nephrectomy: a retrospective study.

Partial nephrectomies are associated with an increased risk of acute kidney injury (AKI), but dexmedetomidine administration may improve renal outcomes. We hypothesized that intraoperative dexmedetomidine administration would be associated with a decrease in AKI development in patients undergoing unilateral partial nephrectomy. In this retrospective study, adult patients who underwent unilateral partial nephrectomy from April 2016 to October 2023 were included. Exclusion criteria were a history of end-stage renal disease, ineligible procedures (i.e., aborted procedure, conversion to radical nephrectomy, surgery on a horseshoe kidney), and reoperation within three days of the initial nephrectomy. Patients were categorized according to whether they received intraoperative dexmedetomidine. The primary outcome was AKI incidence within three days of surgery; AKI was defined according to the Kidney Disease Improving Global Outcomes definition. Propensity score matching (PSM) was conducted to account for potential confounders (age, body mass index, sex, American Society of Anesthesiologists score, final surgical approach, clamping-related ischemia for >15 min). We included 1,632 patients; 214 received dexmedetomidine and 1,418 did not. Before PSM, the AKI rate was 31.2% in patients who received dexmedetomidine and 25.7% in patients who did not (p = 0.081). After PSM, the AKI rate was 31.3% in patients who received dexmedetomidine and 27.6% in those who did not (p = 0.396). The post-PSM odds ratio for AKI following dexmedetomidine administration during unilateral partial nephrectomy was 0.910 (95% CI: 0.585-1.142; p = 0.677). Intraoperative dexmedetomidine was not associated with a reduction in postoperative AKI incidence or severity after unilateral partial nephrectomy.

Association of Acute Kidney Injury with Bronchopulmonary Dysplasia in Preterm Infants.

Objective: Bronchopulmonary dysplasia (BPD) is among the most common complications of prematurity and is associated with high morbidity and mortality rates. Acute kidney injury (AKI) is also commonly observed in premature infants and significantly increases morbidity and mortality. Studies have shown that systemic changes in AKI may also trigger lung damage. Methods: This study aimed to determine the effects of AKI on the development of BPD in preterm infants with a postconceptional age of ≤32 weeks and/or birth weight of ≤1500 grams. The relationship between demographic features and accompanying perinatal and postnatal morbidities among the patients was investigated. Results: The incidence of BPD in infants with AKI was 52.6% (10 of 19 infants) and 38.3% (61 of 140 infants) in infants without AKI. In infants who developed BPD, the rate of AKI did not vary notably between babies born at ≤28 weeks and those born at >28 weeks [n=9, 17.3% (9 of 52 infants) and n= 1, 5.3%, (1 of 19 infants) respectively] of gestation (p>0.05). Conclusions: AKI was associated with a greater need for resuscitation at birth, a greater need for invasive mechanical ventilation, fewer ventilatorfree days, and a higher incidence of sepsis, patent ductus arteriosus, and necrotizing enterocolitis in premature infants. It was also more frequently associated with fluid-electrolyte imbalance, blood pressure, and hemodynamic disorders in the first postnatal week. The rate of BPD development was higher in infants with AKI, but this disparity was not statistically notable (p>0.05).

Iron metabolism indexes as predictors of the incidence of cardiac surgery-associated acute kidney surgery.

BACKGROUND: Acute kidney injury (AKI) is a major complication following cardiac surgery. We explored the clinical utility of iron metabolism indexes for identification of patients at risk for AKI after cardiac surgery. METHODS: This prospective observational study included patients who underwent cardiac surgery between March 2023 and June 2023. Iron metabolism indexes were measured upon admission to the intensive care unit. Multivariable logistic regression analyses were performed to explore the relationship between iron metabolism indexes and cardiac surgery-associated AKI (CSA-AKI). Receiver operating characteristic (ROC) curve was used to assess the predictive ability of iron, APACHE II score and the combination of the two indicators. Restricted cubic splines (RCS) was used to further confirm the linear relationship between iron and CSA-AKI. RESULTS: Among the 112 recruited patients, 38 (33.9%) were diagnosed with AKI. Multivariable logistic regression analysis indicated that APACHE II score (odds ratio [OR], 1.208; 95% confidence interval [CI], 1.003-1.455, P = 0.036) and iron (OR 1.069; 95% CI 1.009-1.133, P = 0.036) could be used as independent risk factors to predict CSA-AKI. ROC curve analysis showed that iron (area under curve [AUC] = 0.669, 95% CI 0.572-0.757), APACHE II score (AUC = 0.655, 95% CI 0.557-0.744) and iron and APACHE II score combination (AUC = 0.726, 95% CI 0.632-0.807) were predictive indicators for CSA-AKI. RCS further confirmed the linear relationship between iron and CSA-AKI. CONCLUSIONS: Elevated iron levels were independently associated with higher risk of CSA-AKI, and there was a linear relationship between iron and CSA-AKI.

Effect of electronic alerts on the care and outcomes in patients with acute kidney injury: a meta-analysis and trial sequential analysis.

BACKGROUND: Although electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients. METHODS: PubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected. RESULTS: Six studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97-1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = - 0.21, 95% CI = - 1.60-1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90-1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05-1.25, P = 0.002; RR = 1.21, 95% CI = 1.01-1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups. CONCLUSIONS: Electronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

Protective effects of silymarin on preventing vancomycin nephrotoxicity in infectious patients: a randomized, double-blinded, placebo-controlled, pilot clinical trial.

Nephrotoxicity is one of the most common complications of vancomycin use in clinical practice. Silymarin has potential to be a renoprotective agent for nephrotoxic drugs due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. The aim of this clinical study is evaluating the potential effects of silymarin on preventing vancomycin nephrotoxicity. A multicenter, randomized, double-blinded, placebo-controlled, clinical trial was conducted on patients with the indication of systemic vancomycin for at least 7 days. Patients were screened daily and those who met the inclusion criteria were selected and randomly assigned into either silymarin or placebo groups. Accordingly, 140 mg silymarin tablet (Livergol®) or placebo was given orally three times daily. Silymarin or placebo were provided in conjunction with vancomycin for at least 7 days. If vancomycin therapy was extended beyond 7 days, the administration of silymarin or placebo was continued until the end of vancomycin treatment. Malondialdehyde, glutathione, and total antioxidant capacity were measured in the serum on days 0 and 7. A trough level of vancomycin was assessed 30 min before the fifth dose of vancomycin. Acute kidney injury (AKI) was monitored in each patient daily during the course of vancomycin treatment. The causality assessment of all identified cases of vancomycin associated AKI was performed by the Naranjo scale. The primary endpoint was vancomycin nephrotoxicity. It was defined based on the KDIGO 2012 criteria for AKI as either an increase of 0.3 units or more in serum creatinine level during 48 h or 50% (1.5-fold) or more during 7 days compared to baseline values. During the study period, 34 patients in the silymarin group and 32 patients in the placebo group completed the clinical trial. Demographic, baseline clinical, and laboratory characteristics were comparable between placebo and silymarin groups. The number of patients with AKI on days 5, 6, 7, 11,12, 13, and 14 in the placebo group was significantly higher than that in the silymarin group (p-value < 0.05). The incidence of acute tubular injury on the day  5 and 7 of vancomycin treatment was significantly lower in the silymarin group (p-value = 0.005 and p-value = 0.032, respectively). Antioxidant indexes including serum total antioxidant capacity and glutathione significantly increased in the silymarin group (p-value < 0.001 for both indexes). In contrast, serum malondialdehyde as an end product of lipid peroxidation pathway significantly decreased in the silymarin group during 7 days (p-value < 0.001). The results of the present pilot, clinical trial suggested that silymarin co-administration may prevent vancomycin nephrotoxicity.

Postoperative Fluid Accumulation is Associated With Underestimation of AKI Severity in Lung Transplant Recipients.

BACKGROUND: Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). METHODS: In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72 h of onset, respectively. RESULTS: AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p = 0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p = 0.005). CONCLUSION: Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039959, NCT03046277.

Heart rate to identify non-febrile children with dehydration and acute kidney injury in emergency department: a prospective validation study.

We previously developed and retrospectively validated the estimated percentage of heart rate variation (EHRV) as a predictor of the composite outcome of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile children. The current study aimed to prospectively validate EHRV as a predictor for dehydration or AKI in a different cohort of children attending the Pediatric Emergency Department. From July 2022 to August 2023, 256 pediatric patients aged 0-18 years attending the Pediatric Emergency Department were enrolled. EHRV was calculated as follows: [(HR at admission - 50th percentile of HR for age and sex)/HR at admission] × 100. Dehydration was categorized as < 5% or ≥ 5% fluid deficit. AKI was defined according to KDIGO creatinine criteria. Statistical analyses included receiver-operating characteristic (ROC) curves and logistic regression analysis. Among enrolled patients, 52 had ≥ 5% dehydration, 50 had AKI, and 16 had both conditions. EHRV demonstrated significant predictive ability for both ≥ 5% dehydration (AUROC = 0.71; 95% confidence interval (CI), 0.63-0.78; p < 0.001) and AKI (AUROC = 0.78; 95% CI, 0.71-0.84; p < 0.001). An EHRV > 24.5% was associated with an increased odds ratio (OR), adjusted for confounders, of ≥ 5% dehydration (OR = 3.5; 95% CI, 1.6-8.0; p = 0.003) and AKI (OR = 3.4; 95% CI, 1.6-7.3; p = 0.002). The sensitivity and specificity of this cut-off were 34% and 83% for ≥ 5% dehydration and 36% and 84% for AKI, respectively. CONCLUSIONS: This study prospectively validates the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. An EHRV > 24.5% could serve as a marker for suspecting dehydration or AKI. Further validation across diverse patient populations and settings is needed. WHAT IS KNOWN: • An increased heart rate (HR) is a readily detectable sign of dehydration in children. • In a retrospective validation cohort, an estimated HR variation (EHRV) greater than 24.5% compared to the 50th percentile of HR was predictive of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile patients. WHAT IS NEW: • We prospectively validated the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. • We confirmed that an EHRV greater than 24.5% is associated with increased odds of ≥ 5% dehydration and AKI.

Methods for phenotyping adult patients with acute kidney injury: a systematic review.

BACKGROUND: Acute kidney injury (AKI) is a multifaceted disease characterized by diverse clinical presentations and mechanisms. Advances in artificial intelligence have propelled the identification of AKI subphenotypes, enhancing our capacity to customize treatments and predict disease trajectories. METHODS: We conducted a systematic review of the literature from 2017 to 2022, focusing on studies that utilized machine learning techniques to identify AKI subphenotypes in adult patients. Data were extracted regarding patient demographics, clustering methodologies, discriminators, and validation efforts from selected studies. RESULTS: The review highlights significant variability in subphenotype identification across different populations. All studies utilized clinical data such as comorbidities and laboratory variables to group patients. Two studies incorporated biomarkers of endothelial activation and inflammation into the clinical data to identify subphenotypes. The primary discriminators were comorbidities and laboratory trajectories. The association of AKI subphenotypes with mortality, renal recovery and treatment response was heterogeneous across studies. The use of diverse clustering techniques contributed to variability, complicating the application of findings across different patient populations. CONCLUSIONS: Identifying AKI subphenotypes enables clinicians to better understand and manage individual patient trajectories. Future research should focus on validating these phenotypes in larger, more diverse cohorts to enhance their clinical applicability and support personalized medicine in AKI management.

Renal-Targeted Drug Delivery by Chitosan Oligosaccharide Micelles with HSA-Enriched Protein Corona for the Treatment of Ischemia/Reperfusion-Induced Acute Kidney Injury.

Renal-specific nanoparticulate drug delivery systems have shown great potential in reducing systemic side effects and improving the safety and efficacy of treatments for renal diseases. Here, stearic acid-grafted chitosan oligosaccharide (COS-SA) was synthesized as a renal-targeted carrier due to the high affinity of the 2-glucosamine moiety on COS to the megalin receptor expressed on renal proximal tubular epithelial cells. Specifically, COS-SA/CLT micelles were prepared by encapsulating celastrol (CLT) with COS-SA, and different proportions of human serum albumin (HSA) were then adsorbed onto its surface to explore the interaction between the protein corona and cationic polymeric micelles. Our results showed that a multilayered protein corona, consisting of an inner "hard" corona and an outer "soft" corona, was formed on the surface of COS-SA/CLT@HSA8, which was beneficial in preventing its recognition and phagocytosis by macrophages. The formation of HSA protein corona on COS-SA/CLT micelles also increased its accumulation in the renal tubules. Furthermore, the electropositivity of COS-SA/CLT micelles affected the conformation of adsorbed proteins to various degrees. During the adsorption process, the protein corona on the surface of COS-SA/CLT@HSA1 was partially denatured. Overall, COS-SA/CLT and COS-SA/CLT@HSA micelles demonstrated sufficient safety with renal targeting potential, providing a viable strategy for the management of ischemia/reperfusion-induced acute kidney injury.

TRPA1 protects against contrast-induced renal tubular injury by preserving mitochondrial dynamics via the AMPK/DRP1 pathway.

Mitochondrial dysfunction and oxidative stress are involved in the development of contrast-induced acute kidney injury (CI-AKI). The present study aimed to reveal the role of transient receptor potential ankyrin 1 (TRPA1), an oxidative sensor, in CI-AKI. Trpa1PT-/- mice with Trpa1 conditionally knocked out in renal proximal tubular (PT) cells, Trpa1 overexpression mice (Trpa1-OE), and TRPA1 agonists and antagonists were used to study its function in a mouse model of iohexol-induced CI-AKI. We found that TRPA1 was functionally expressed in PT cells. Activation of TRPA1 with cinnamaldehyde or overexpression of Trpa1 remarkably ameliorated renal tubular injury and dysfunction in a mouse model of CI-AKI, while CI-AKI was significantly exacerbated in Trpa1PT-/- mice. Proteomics demonstrated that mouse kidneys with CI-AKI had downregulated proteins involved in mitochondrial dynamics and upregulated mitophagy-associated proteins. The beneficial effects of TRPA1 activation/overexpression on CI-AKI were associated with improved mitochondrial function, decreased mitochondrial fission and oxidative stress, enhanced mitophagy, and less apoptosis of renal tubular cells. TRPA1-induced decreases in mitochondrial fission were linked to upregulated fusion-related proteins (mitofusin 1, mitofusin 2 and optic atrophy 1) and downregulated fission mediator, phosphorylated dynamin-related protein 1 (Drp1). Importantly, inhibition of Drp1 with mitochondrial division inhibitor 1 improved CI-AKI. In addition, the decreased mitochondrial fission was also mediated by inactivation of AMP-activated protein kinase which mediates mitochondrial biogenesis. The findings suggest that TRPA1 plays a protective role in CI-AKI through regulating mitochondrial fission/fusion, biogenesis, and dysfunction. Activating TRPA1 may become novel therapeutic strategies for the prevention of CI-AKI.

Assessment of renal pathophysiological processes and protective effect of quercetin on contrast-induced acute kidney injury in type 1 diabetic mice using diffusion tensor imaging.

Purpose: To investigate the renal pathophysiological processes and protective effect of quercetin on contrast-induced acute kidney injury (CI-AKI) in mice with type 1 diabetic mellitus(DM) using diffusion tensor imaging(DTI).Methods: Mice with DM were divided into two groups. In the diabetic + contrast medium(DCA) group, the changes of the mice kidneys were monitored at 1, 24, 48, and 72 h after the injection of iodixanol(4gI/kg). The mice in the diabetic + contrast medium + quercetin(DCA + QE) group were orally given different concentrations of quercetin for seven days before injection of iodixanol. In vitro experiments, renal tubular epithelial (HK-2) cells exposed to high glucose conditions were treated with various quercetin concentrations before treatment with iodixanol(250 mgI/mL).Results: DTI-derived mean diffusivity(MD) and fractional anisotropy(FA) values can be used to evaluate CI-AKI effectively. Quercetin significantly increased the expression of Sirt 1 and reduced oxidative stress by increasing Nrf 2/HO-1/SOD1. The antiapoptotic effect of quercetin on CI-AKI was revealed by decreasing proteins level and by reducing the number of apoptosis-positive cells. In addition, flow cytometry indicated quercetin-mediated inhibition of M1 macrophage polarization in the CI-AKI.Conclusions: DTI will be an effective noninvasive tool in diagnosing CI-AKI. Quercetin attenuates CI-AKI on the basis of DM through anti-oxidative stress, apoptosis, and inflammation.

Evaluation of the methanol extract of BaiYangJie: Toxicology and protective effect against acute kidney injury.

BaiYangJie (BYJ) is a terrestrial perennial plant commonly used as a Dai medicine and has therapeutic effects on liver and kidney diseases. Cisplatin (CP), a chemotherapy drug, has good therapeutic effects but causes many side effects, including nephrotoxicity. This article investigated the toxicology of the methanol extract of BYJ (ME-BYJ) and its protective effect on CP-induced acute kidney injury (AKI) through pharmacological experiments. The results showed that the treated mice had no toxicological symptoms and no anatomical, physiological, or histological abnormalities. The BYJ-high-dose group showed significantly attenuated CP-induced AKI. It is concluded that ME-BYJ has the most significant protective effect on AKI at a dose of 8 g/kg and BYJ was not toxic.

A Rare Case of Severe Preeclampsia and HELLP (Hemolysis, Increased Liver Enzymes, Low Platelets) Syndrome With Complex Clinical Presentation.

Severe preeclampsia is a disorder of pregnancy, characterized by increased blood pressure (>140/90 mmHg) and proteinuria (≥ 300 mg/24 hours) at later than 20 weeks of gestation. Particularly in underdeveloped nations, severe preeclampsia and eclampsia have a significant negative impact on the health of expectant mothers, fetuses, and newborns. The HELLP (hemolysis, increased liver enzymes, low platelets) syndrome is thought to be a subset of preeclampsia, a group of hypertensive disorders of pregnancy that also includes eclampsia. Compared to preeclampsia alone, maternal and fetal problems are more severe in HELLP. There can be a diagnostic dilemma that arises when attempting to differentiate HELLP from its numerous imitators to determine the appropriate course of treatment. Here, we present a rare case of a pregnant woman presenting with preeclampsia complicated by manifestations and investigations suggestive of HELLP syndrome with acute kidney injury (AKI), retinal detachment, and symptoms of DIC (disseminated intravascular coagulation), which can be grievous to the mother as well as the fetus.

Kidney Biopsy Findings After Lung Transplantation.

Introduction: The early diagnosis of histological kidney damage after lung transplantation (LT) is of paramount importance given the negative prognostic implications of kidney disease. Methods: Three pathologists analyzed all kidney biopsies (KBs) (N = 100) performed from 2010 to 2021 on lung transplant patients in 4 Paris transplantation centers. Results: The main indication for biopsy was chronic renal dysfunction (72% of patients). Biopsies were performed at a median of 26.3 months after transplantation and 15 months after a decline in estimated glomerular filtration rate (eGFR) or the onset of proteinuria. Biopsies revealed a wide spectrum of chronic lesions involving the glomerular, vascular, and tubulointerstitial compartments. The 4 most frequent final diagnoses, observed in 18% to 49% of biopsies, were arteriosclerosis, acute calcineurin inhibitor (CNI) toxicity, thrombotic microangiopathy (TMA) and acute tubular necrosis (ATN). TMA was significantly associated with a combination of mTOR inhibitors (mTORi) or CNIs with biological signs present in only 50% of patients. The eGFR was poorly correlated with most lesions, particularly percent glomerulosclerosis, and with the risk of end-stage renal disease (ESRD). Thirty-four patients progressed to ESRD at an average of 20.1 months after biopsy. Three factors were independently associated with the risk of ESRD: postoperative dialysis, proteinuria >3 g/g and percent glomerulosclerosis >4%. Conclusion: Given the great diversity of renal lesions observed in lung transplant recipients, early referral to nephrologists for KB should be considered for these patients when they present with signs of kidney disease.

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

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

Combined strategy of device-based contrast minimization and urine flow rate-guided hydration to prevent acute kidney injury in high-risk patients undergoing coronary interventional procedures.

BACKGROUND AND AIMS: Contrast-associated acute kidney injury (CA-AKI) is a major complication following coronary procedures. We aimed to evaluate the effectiveness of a combination of urine flow rate-(UFR) guided hydration (RenalGuardTM) and device-based contrast media (CM) reduction (DyeVertTM) in CA-AKI prevention. METHODS: Stable high-risk patients undergoing coronary procedures with the use of DyeVertTM and RenalGuardTM were prospectively included (Combined group) and matched with a similar cohort of patients treated only with RenalGuardTM in whom CM volume was controlled by operator-dependent strategies (Control group). CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL at 48 h. RESULTS: Overall, 55 patients were enrolled and matched with comparable controls. Patients in the Combined group were exposed to a lower CM dose (Control: 55 [30-90] mL vs. Combined: 42.1 [24.9-59.4] mL; p = 0.024). A significant interaction was found between treatment allocation and serum creatinine changes (p = 0.048). CA-AKI occurred in five (9.1%) patients in the Combined group and in 14 (25.4%) patients in the Control group (OR 0.29, 95% CI [0.09-0.88]). CONCLUSIONS: A combined strategy of device-based CM reduction plus UFR-guided hydration is superior to operator-dependent CM sparing strategies plus UFR-guided hydration in preventing CA-AKI in high-risk patient.