Circulating RNA Profiling in Postreperfusion Plasma From Kidney Transplant Recipients

BackgroundIschemia/reperfusion injury (IRI) is inevitable in kidney transplantation (KT) and may lead to impaired tubular epithelial cell function and reduce graft function and survival. Renal IRI is a complex cellular and molecular event; therefore, investigating the genetic or molecular pathways associated with the early phase of KT would improve our understanding of IRI in KT. MicroRNAs (miRNAs) play a critical role in various pathologic events associated with IRI.MethodsWe compared the expression profile of miRNAs extracted from 2 blood plasma samples, 1 from periphery and the other form gonadal veins immediately after reperfusion, in a total 5 cases of KT.ResultsWe observed that the total RNA yield was higher in postreperfusion plasma and that a subset of miRNAs was upregulated (miR-let-7a-3p, miR-143-3p, and miR-214-3p) or downregulated (let-7d-3p, let-7d-3p, miR-1246, miR-1260b, miR-1290, and miR-130b-3p) in postreperfusion plasma. Gene ontology analyses revealed that these subsets target different biological functions. Twenty-four predicted genes were commonly targeted by the upregulated miRNAs, and gene ontology enrichment and pathway analyses revealed that these were associated with various cellular activities such as signal transduction or with components such as exosomes and membranous organelles.ConclusionWe present 2 subsets of miRNAs that were differentially upregulated or downregulated in postreperfusion plasma. Our findings may enhance our understanding of miRNA-mediated early molecular events related to IRI in KT.     

Deregulated microRNA-22-3p in patients with sepsis-induced acute kidney injury serves as a new biomarker to predict disease occurrence and 28-day survival outcomes

Background

Acute kidney injury (AKI) is a common and serious complication of sepsis. MicroRNA-22-3p (miR-22-3p) has been found to be involved in septic AKI progression. The purpose of this study was to analyze both the serum and urinary expression of miR-22-3p in septic AKI patients, and evaluated the clinical value of miR-22-3p in the diagnosis and prognosis of sepsis-induced AKI.

Methods

Serum and urinary expression of miR-22-3p was examined using qRT-PCR. The risk factors related with septic AKI onset were assessed using logistic analysis. A receiver-operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of miR-22-3p, and the Kaplan–Meier survival curves and Cox regression analysis were used to evaluate the predictive value of miR-22-3p for the 28-day survival of septic AKI patients.

Results

Both serum and urinary miR-22-3p expression was decreased and negatively correlated with kidney injury biomarkers in septic AKI patients. MiR-22-3p expression was a risk factor for AKI onset and had diagnostic accuracy in septic AKI patients. The expression of both serum and urinary miR-22-3p was lower in patients who died, and served as a prognostic biomarker to predict 28-day survival in septic AKI patients.

Conclusion

Serum and urinary miR-22-3p was reduced in sepsis-induced AKI patients, and served as a biomarker to predict AKI occurrence and 28-day survival in sepsis patients.

     

Investigation of Circulating MicroRNA Levels in Antibody-Mediated Rejection After Kidney Transplantation

BackgroundOne of the most important possible complications determining long-term graft survival after kidney transplant is antibody-mediated rejection (ABMR). The criterion standard approach to recognize ABMR is currently the kidney biopsy with histopathologic analysis. However, this test has limitations because of difficulties in timing of sampling, the evaluability of histology because of the questionable representativeness of specimens, and the limited number of this intervention. Hence, new reliable, noninvasive biomarkers are required to detect the development of ABMR in time.MethodsIn this study, we analyzed the clinical data of 45 kidney transplant patients (mean age of 44.51 years, 20 male and 25 female subjects). These participants were recruited into 5 subcohorts based on their clinical status, histologic findings, and level of donor-specific anti-HLA antibodies. Circulating microRNAs (miR-21, miR-181b, miR-146a, miR-223, miR-155, miR-150) in plasma samples were quantified by quantitative polymerase chain reaction and their levels were correlated with the clinical characteristics in different subgroups.ResultsThe relative expression of plasma miR-155 (P = .0003), miR-223 (P = .0316), and miR-21 (P = .0147) were significantly higher in patients who had subsequent histology-approved ABMR with donor-specific anti-HLA antibody positivity (n = 10) than in the “triple negative” group (n = 21), and miR-155 showed the highest sensitivity (90%) and specificity (81%) to indicate ABMR development based on receiver operating characteristic analysis.ConclusionsAccording to our preliminary data, plasma miR-155, miR-21, and miR-223 can indicate the development of ABMR after kidney transplant in correlation with classic clinical parameters. However, future studies with larger number of participants are necessary to further evaluate the diagnostic properties of blood miRNAs in prediction of this life-threatening condition.     

Sphingosine-1-phosphate reduces hepatic ischaemia/reperfusion-induced acute kidney injury through attenuation of endothelial injury in mice

Aim: Hepatic ischaemia/reperfusion injury (IRI) frequently complicates acute kidney injury (AKI) during the perioperative period. This study was to determine whether hepatic IRI causes AKI and the effect of the sphingosine‐1‐phosphate (S1P) on AKI. Methods: S1P and vehicle were given to mice before ischaemia and mice were subjected to hepatic IRI. Plasma creatinine (PCr), alanine transaminase (ALT), urinary neutrophil gelatinase‐associated lipocalin (NGAL) and renal histological changes were determined. As a marker of endothelial injury, vascular permeability was measured. The effect of VPC 23019, a S1P₁ receptor antagonist, was also assessed. Results: Hepatic IRI resulted in liver injury (increased ALT) and systemic inflammation. Kidneys showed elevated inflammatory cytokines, leucocyte infiltration, increased vascular permeability, tubular cell apoptosis and increased urinary NGAL, although PCr did not increase. Pretreatment with S1P resulted in an attenuation of systemic inflammation and kidney injury without any effect on plasma ALT or peripheral lymphocytes. The protective effect of S1P was partially reversed by VPC 23019, suggesting the important contribution of the S1P/S1P₁ pathway to protect against hepatic IRI‐induced AKI. Conclusion: The study data demonstrate the important contribution of systemic inflammation and endothelial injury to AKI following hepatic IRI. Modulation of the S1P/S1P₁ receptor pathway might have some therapeutic potential in hepatic IRI‐induced kidney injury.     

Loss of matrix metalloproteinase-8 is associated with worsened recovery after ischemic kidney injury

Abstract

Acute kidney injury (AKI) leads to chronic kidney disease. The mechanisms involved with recovery from AKI are poorly understood and molecular mediators responsible for healing and restoration of kidney function are understudied. We previously discovered differential expression of matrix metalloproteinase-8 (MMP-8) mRNA and protein in patients with severe sepsis associated AKI versus sepsis without AKI. Here, we demonstrate the involvement of MMP-8 in purely ischemic AKI. Mice subjected to 30?min of bilateral renal ischemia developed increased plasma creatinine and MMP-8 expression within 24?h versus sham controls. After an initial surge and subsequent return toward baseline, both kidney MMP-8 expression and activity exhibited a late increase (Days 5–7 post-ischemia reperfusion) in mice subjected to AKI. Neutrophil infiltration of the kidney was significantly higher after AKI in wild-type mice than in MMP-8 null mice, starting at 4 days. Additionally, MMP-8 null mice subjected to AKI demonstrated a persistent histopathologic and functional injury and worsened health (greater overall weight loss) versus wild-type cohorts after seven days. Taken together, our findings suggest that MMP-8 is involved with restoration of baseline kidney health after ischemic kidney injury and that a potential mechanism involves the interaction of MMP-8 and neutrophil recruitment to the site of injury.     

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92^endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92^endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92^endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92^endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.     

Serum MicroRNAs as New Diagnostic Biomarkers for Pre– and Post–Kidney Transplantation

BackgroundIn the present study, we compared the expression levels of 3 microRNAs (miRNAs) between patients who had undergone kidney transplantation and healthy individuals in a search for a new diagnostic biomarker after kidney transplantation.MethodsWe used real-time quantitative polymerase chain reaction to investigate the expression levels of miR-181a, miR-483-5p, and miR-557 in the serum of 15 kidney transplantation patients before transplantation on the first, third, and seventh days after transplantation. The study was performed in the Guilin 181st Hospital between 2010 and 2012. The results of this study may assist with early diagnosis and treatment and contribute to our understanding of the pathological parameters. Receiver operating characteristic (ROC) analysis was performed to determine the area under the curve of each equation to predict evolution to rejection.ResultsROC curves were performed to explore miRNAs to predict rejection occurrence after transplantation showed pre-transplantation expression levels of miR-181a to be a potential factor with a significant area under the curve (AUC = 0.985, P < .05). The expression of miR-181a before kidney transplantation was also significantly different on days 1 and 3 after kidney transplantation, the area under the curve (AUC) was, respectively, 0.980 (P < .05) and 0.830 (P < .05). Predictors on days 1, 3, and 7 show that miR-483-5p and miR-557 are also predictive factors for rejection. Predictors for miR-483-5p and miR-557 were significantly under the area ROC, respectively (AUC = 0.920, P < .05), and (AUC = 0.990, P < .005) on day 1 (AUC = 0.920, P < .05) and (AUC = 0.960, P < .005) on day 3, (AUC = 0.845, P < .05) and (AUC = 0.889, P < .05) on day 7.ConclusionsThis study of miRNAs was unrelated to age, sex, histological classification, and metastasis (all P > .05). Serum miR-181a, miR-483-5p, and miR-557 could serve as circulating biomarkers for the early diagnosis of active situations of before and after kidney transplantation.     

Atrial natriuretic peptide attenuates kidney–lung crosstalk in kidney injury

Background

Renal ischemia–reperfusion injury (IRI) is a common cause of acute kidney injury after cardiovascular surgery, which in turn deteriorates oxygenation. Atrial natriuretic peptide (ANP) has natriuretic, diuretic, and anti-inflammatory effects. To elucidate whether renal IRI induces inflammation in the kidney and lung and ANP attenuates kidney–lung crosstalk.

Materials and methods

The rats were anesthetized, tracheostomized, mechanically ventilated, and randomized to four groups: saline + IRI (n = 12), ANP + IRI (n = 12), ANP + sham (n = 6), and saline + sham (n = 6). Saline (6 mL/kg/h) or ANP (0.2 μg/kg/min) at the rate of 6 mL/kg/h was started 5 min before clamping, respectively. Renal IRI was induced by clamping the left renal pedicle for 30 min. The hemodynamics, arterial blood gases, and plasma concentrations of creatinine and lactate were measured at baseline and 1, 2, and 3 h after declamping. Lung wet-to-dry ratio was measured. The mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL) 1β, and IL-6 and histologic localization of TNF-α in the kidney and lung were measured.

Results

Renal IRI induced metabolic acidosis, pulmonary edema, increases in plasma concentrations of creatinine and lactate, and augmentation of the cytokine mRNA expression and histologic localization of TNF-α in the kidney and Renal IRI induced lung. ANP prevented IRI-induced metabolic acidosis, pulmonary edema, increases in creatinine, lactate, and the cytokine mRNA expression, attenuated histologic localization of TNF-α in the kidney and lung, and increased oxygenation.

Conclusions

ANP has renoprotective and anti-inflammatory effects on the kidney and lung in a rat model of renal IRI, suggesting that ANP attenuates kidney–lung crosstalk.     

Prediction of early acute kidney injury after trauma using prehospital systolic blood pressure and lactate levels: A prospective validation study

BackgroundAcute kidney injury (AKI) after trauma is a major complication independently associated with a prolonged hospital stay and increased mortality. We previously reported that the prehospital systolic blood pressure (SBP) and early hospital arterial lactate level, along with specific cut-off values, show good performance in the early prediction of AKI using AUC-ROC [1]. The purpose of this study was to prospectively validate whether or not these parameters are predictive of newly occurring AKI after trauma.MethodsThis was a prospective review of trauma patients who were admitted to a single trauma center from January to December 2019. Patients who were <16 years old, who had burns, and who had chronic kidney disease were excluded. AKI was defined according to the Risk, Injury, Failure, Loss of the kidney function, and End-stage kidney disease (RIFLE) classification based on serum creatinine alone. Patients with a low prehospital SBP (≤126 mmHg) and high lactate levels (≥2.5 mmol/L) were defined as the high-risk group, and other patients were defined as the low-risk group.ResultsA total of 489 trauma patients were admitted to our center, of whom 403 were eligible for the study. The high-risk group consisted of 38 patients, and the low-risk group consisted of 365 patients. The incidence of severe AKI in Stage Injury and Failure was significantly higher in the high-risk group (5 patients, 13.2%) than in the low-risk group (7 patients, 1.9%), with an odds ratio of 7.75 and 95% confidence interval of 2.33–25.77.ConclusionsThese predictors showed good performance in the early prediction of severe AKI after trauma. Early prediction of the high-risk groups for severe AKI after trauma prompting early treatment may help improve the prognosis of trauma patients.     

Dysregulated microRNAs involved in contrast-induced acute kidney injury in rat and human

Abstract

Background: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. Methods: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. Results: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. Conclusions: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.     

Recurrent acute kidney injury in elderly patients is common and associated with 1-year mortality

Background

Acute kidney injury (AKI) is common among elderly patients after a first hospitalized AKI. Patients who recover are at risk for recurrence, but recurrent geriatric AKI is not well-studied.

Methods

This was a retrospective, 12-month cohort study using data from the National Clinical Research Center for Geriatric Diseases. Recurrent AKI was defined as a new spontaneous rise of?≥?0.3 mg/dl (≥?26.5 µmol/L) within 48 h or a 50% increase in serum creatinine (Scr) from the baseline within 7 days after the previous AKI episode. The outcome measured was 12-month mortality.

Results

Among 1711 study patients, 652 developed AKI. Of the 429 AKI survivors in whom recovery could be assessed, 314 patients recovered to their baseline renal function, and 115 patients developed chronic kidney disease (CKD). Of the group that recovered renal function, 90 patients (28.7%) subsequently developed recurrent AKI, while 224 (71.3%) did not. Of the 429 survivors with AKI, 103 patients (24.0%) died within 12 months. Multivariate logistic regression analysis revealed that recurrent AKI was significantly associated with coronary disease (odds ratio [OR?=?2.008; 95% confidence interval [CI] 1.024–3.938; P?=?0.042), a need for mechanical ventilation (OR?=?2.265; 95% CI 1.267–4.051; P?=?0.006) and high blood urea nitrogen levels (OR?=?1.036; 95% CI 1.002–1.072; P?=?0.040) at the first AKI event. Kaplan–Meier curves showed the 12-month survival of patients with non-recurrent AKI was better than that of patients with CKD, and survival of patients with recurrent AKI was worse than that of patients with CKD (log rank P?<?0.001). In the multivariate Cox regression analysis, mortality at 12 month was higher in the patient with recurrent AKI as compared with those with a single episode (HR?=?3.375; 95% CI 2.241–5.083; P?<?0.001).

Conclusion

Recurrent AKI is common among elderly patients who recovered their renal function post-AKI and is associated with significantly higher 12-month mortality compared with CKD patients.

     

Downregulation of miR-574-5p inhibits HK-2 cell viability and predicts the onset of acute kidney injury in sepsis patients

BackgroundIncreased levels of microRNA-574-5p (miR-574-5p) have been found to be associated with increased survival of septic patients, indicating the potential role of miR-574-5p in protecting against septic progression and complications. Acute kidney injury (AKI) is one of the most common and serious complications of sepsis. Therefore, the aim of this study was to test these hypotheses: (1) in a renal cell culture line (HK-2), upregulated expression of miR-574-5p increases, and downregulated expression of miR-574-5p decreases cell viability, and (2) serum levels of miR-574-5p from patients with sepsis and AKI are lower than those of patients with sepsis but no AKI.MethodsThe expression of miR-574-5p was regulated by cell transfection in HK-2 cells, and HK-2 cell viability was measured using the Cell Counting Kit-8. Serum miR-574-5p expression was analyzed using qRT-PCR. The predictive value of miR-574-5p for AKI onset was evaluated using the receiver operating characteristic curve and logistic regression analysis.ResultsThe overexpression of miR-574-5p promoted HK-2 cell viability. Fifty-eight sepsis patients developed AKI, who had significantly lower miR-574-5p expression. miR-574-5p expression was decreased with AKI stage increase and correlated with kidney injury biomarker and had relatively high accuracy to predict AKI occurrence from sepsis patients.ConclusionOverexpression of miR-574-5p in cultured HK-2 cells increases cell viability and knocked-down expression of miR-574-5p decreases cell viability. Consistently, septic patients with AKI were found to have less upregulation of miR-574-5p expression compared to septic patients without AKI. Thus, serum miR-574-5p may provide a novel biomarker for septic AKI.     

Determining whether dexmedetomidine provides a reno-protective effect in patients receiving laparoscopic radical prostatectomy: a pilot study

Purpose

This study aims to determine whether perioperative treatment with dexmedetomidine (DEX) during laparoscopic radical prostatectomy (LRP) can provide a reno-protective effect.

Methods

This pilot study enrolled 89 patients between 60 and 79 years old, who underwent LRP. These patients were randomly allocated into two groups: group D (n?=?44) and group C (n?=?45). For patients in group D, 1 µg/kg of DEX was intravenously administered within 10 min, followed by 0.5 µg/kg/h of DEX infusion during the operation. This was stopped at 30 min before the end of surgery. For patients in group C, saline was administered at the same doses. The primary outcome was the incidence of acute kidney injury (AKI), and secondary outcomes included other postoperative variables.

Results

The incidence of AKI in group D and C was 4.5% and 13.3%, respectively (P?>?0.05). Compared with group C, patients in group D had significantly lower urea nitrogen levels at 6 h after surgery, lower creatinine levels at 6 and 48 h after surgery, and significantly lower CysC levels at 48 h after surgery. A significant decrease in VAS scores for pain and postoperative nausea and vomiting (PONV) at the second and third day after surgery was observed in patients in group D when compared to patients in group C.

Conclusion

Intraoperative DEX does not reduce the incidence of AKI, but provides a potential reno-protective effect, and alleviates postoperative pain and PONV in patients undergoing LRP.

     

The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation

Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06–4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.     

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.     

Smooth muscle actin as a novel serologic marker of severe intestinal damage in rat intestinal ischemia–reperfusion and human necrotising enterocolitis

Background

Despite emergence of markers of intestinal mucosal damage such as intestinal fatty-acid binding protein (i-FABP), there are no specific markers of damage extending into the muscle layers. We hypothesized that smooth muscle actin (SMA) released from the intestinal muscularis would be detectable in plasma after severe intestinal injury.

Materials and methods

Serial blood samples were collected from rats (n = 10) undergoing intestinal ischemia–reperfusion injury (IRI) and controls (n = 5). Additionally, admission and/or preoperative plasma samples were collected from twelve neonates with necrotizing enterocolitis (NEC), and five age- and weight-matched controls. Plasma ileal fatty-acid binding protein (rat) or i-FABP (human) were measured by enzyme-linked immunosorbent assay, and plasma SMA was detected by western blotting.

Results

Plasma ileal fatty-acid binding protein was low in both the control group and IRI at baseline, but became rapidly elevated in the IRI group even during ischemia. SMA was detected in reperfusion plasma samples of all IRI rats, but in none of the control samples. Plasma i-FABP was higher in infants with NEC than age- and weight-matched controls. Although i-FABP was higher in infants with severe surgical disease compared with focal disease, there was no difference between the operative and nonoperative groups. SMA was detected in the plasma of all four neonates with severe surgical NEC, but not in those with focal disease or those who were successfully conservatively managed.

Conclusions

SMA is detectable in plasma after severe intestinal injury and maybe a clinically useful maker of intestinal muscle damage.     

Acute kidney injury following SGLT2 inhibitors among diabetic patients: a pharmacovigilance study

Purpose

The sodium–glucose cotransporter-2 (SGLT2) inhibitors have changed the treatment of type 2 diabetes mellitus. Several studies evaluated SGLT2 inhibitor-related acute kidney injury (AKI), but pharmacoepidemiology studies are needed to compare the adverse events in different SGLT2 inhibitors (SGLT2i).

Methods

We used disproportionality analysis and Bayesian analysis in data mining to screen the AKI cases after initiating different SGLT2i among diabetic patients, based on the FDA’s Adverse Event Reporting System (FAERS) updated to December 2020. We also investigated the onset time and fatality rates of SGLT2i-associated AKI, which was based on preferred terms (PTs) coded for the renal adverse events in the structure of the FARES database.

Results

We identified 2483 cases of AKI following SGLT2i regimens among diabetic patients. Most of them were 45–64 years old (58.46%) and?>?65 years old (28.67%). Canagliflozin generated the largest number of AKI reports (n?=?1650, 66.45%) in our study. Canagliflozin showed the strongest association among SGLT2i, evidenced by the highest reporting odds ratio (ROR?=?3.70, two-sided 95% CI 3.51–3.91), proportional reporting ratio (PRR?=?3.39, χ²?=?2635.06), and empirical Bayes geometric mean (EBGM?=?3.18, one-sided 95% CI 3.04). The median onset time to AKI was 72.0 (interquartile range [IQR] 21.0–266.0) days after SGLT2i initiation. The general hospitalization rate of SGLT2i-associated AKI was 63.50%, and the fatality rate was 1.59%. The deceased patients (62.94?±?10.69 years) were significantly older than the survived ones (57.82?±?11.84 years) (P?=?0.011).

Conclusion

We compared AKI events in the real-world practice of various SGLT2i among diabetic cases from the FAERS database. It is essential to monitor kidney function during the early administration of SGLT2i. Concern should be paid for AKI in patients older than 65 taking SGLT2i.

     

Predictive value of lactate dehydrogenase combined with the abbreviated burn severity index for acute kidney injury and mortality in severe burn patients

BackgroundExtensive burns are devastating trauma. This study aimed to explore the predictive value of early lactate dehydrogenase (LDH) level, the abbreviated burn severity index (ABSI) and their combination on acute kidney injury (AKI) and mortality after severe burns.Methods and results194 severe burn patients (TBSA ≥ 30%) were included. After multivariate analyses, early LDH value (first 24 h after admission) was an independent risk factor for early AKI (OR=1.095, CI,1.025–1.169,p = 0.007) and AKI (OR=1.452, CI,1.131–1.864, p = 0.003) in severe burn patients and was still a significant risk factor for mortality (OR=1.059, CI,1.006–1.115,p = 0.03). In ROC analysis, after combining LDH and ABSI, the AUC values were 0.925 for AKI, 0.926 for stage 3 AKI, and 0.904 for mortality. Based on cut-off values, patients were divided into different risk groups. The cumulative incidence of AKI (within 5 days, 30 days) and survival rate (within 60 days) were analyzed by the Kaplan-Meier method. The mortality, AKI incidence, and AKI staging showed a significant upward trend with the increasing risk level (P < 0.001).ConclusionEarly LDH level is an independent risk factor for early AKI and AKI. LDH combined with ABSI can better predict mortality and AKI than single indicators.     

The effect of renal artery-only or renal artery–vein clamping during partial nephrectomy on short and long-term functional results: Is clamping technique important?

Purpose

To evaluate the effect of artery-only (AO) and artery–vein (AV) clamping during partial nephrectomy (PN) on short- and long-term renal function outcome.

Methods

Medical records of 154 patients in the AO group and 192 patients in the AV group who underwent open and minimally invasive (laparoscopic/robotic) PN between January 2011 and January 2018 were retrospectively assessed. Preoperative patient and tumor-specific characteristics in addition to perioperative factors and renal function outcomes were compared. The change in the estimated glomerular filtration rate (eGFR) from postoperative 1–3 days, 12 and 24 months after surgery was calculated. Acute kidney injury (AKI) was defined a as a?>?25% reduction in eGFR.

Results

There were no statistically significant differences between the clamping techniques in terms of postoperative 1–3 days, 12 and 24 months eGFR change percentage and risk of progression to chronic kidney disease (CKD). No significant difference in short- and long-term renal functions was found between the minimally invasive or open AO and AV clamping subgroups at any time point. In multivariate analysis, the R.E.N.A.L score (AO group p?=?0.026, AV group p?<?0.001) and preoperative eGFR (AO group p?<?0.001, AV group p?=?0.010) were strong predictors of the acute kidney injury in both groups. Older age (AO group p?=?0.045, AV group p?=?0.010) and preoperative eGFR (AO group p?=?0.008, AV group p?=?0.002) were significantly associated with CKD progression at 2-year follow-up in both groups.

Conclusion

AV clamping does not adversely affect postoperative renal function compared to AO clamping. Preoperative patient- and tumor-related factors are more important for renal function regardless of the clamping technique.