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.     

Acute kidney injury in pregnancy—a single center experience

Abstract

Background: Acute kidney injury (AKI) is a serious complication in pregnancy, resulting in significant maternal morbidity/mortality and fetal loss. Although the incidence of pregnancy-related acute kidney injury (PRAKI) has decreased in developed countries, it is still common in developing nations. Methods: A prospective observational study was done between January 2010 and December 2014 to report the incidence, clinical spectrum, maternal and fetal outcome of AKI in pregnancy. Results: Total number of patients: 130; mean age: 25.4?±?4.73 years. The incidence of AKI in pregnancy was 7.8%. Most of the AKI was noted in postpartum period (68%). Etiology of AKI was sepsis (39%), pre-eclampsia (21%), placental abruption (10%), acute diarrheal disease complicating pregnancy (10%), thrombotic microangiopathy (TMA) (9%), postpartum hemorrhage (2%) and glomerular diseases (9%). Renal biopsy (n?=?46) done in these patients showed renal cortical necrosis (16), TMA (11), acute tubular injury (9), acute tubulointerstitial disease (1) and glomerular disease (9). Live births occurred in 42% of patients with vaginal delivery in 34% cases. Thirty-four patients were managed conservatively, while 96 required dialysis. Complete recovery occurred in 56% and about 36% had persistent renal failure at 3 months. Mortality rate observed was 8%. In univariate analysis, low mean platelet count, higher peak serum creatinine, dialysis dependency at presentation and histopathologically presence of cortical necrosis and TMA predicted the progression to chronic kidney disease. Conclusion: AKI in pregnancy was common in postpartum period and sepsis being the commonest cause.     

Incidence and mortality of postoperative acute kidney injury in non-dialysis patients: comparison between the AKIN and KDIGO criteria

Objectives This retrospective study determines whether the kidney disease: improving global outcomes (KDIGO) criteria are superior to acute kidney injury network (AKIN) criteria in detecting non-dialysis AKI events and predicting mortality in chronic kidney disease (CKD) patients after surgery. Methods Surgical patients who were admitted to the intensive care unit were enrolled. Non-dialysis AKI cases were defined using either KDIGO or AKIN creatinine criteria and stratified by CKD stages. The adjusted hazard ratios (AHRs) for in-hospital mortality are compared to those without AKI. The cumulative survival curves and the predictability for mortality are accessed by Kaplan–Meier method and calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve, respectively. Results From a total of 826 postoperative patients, the overall in-hospital mortality rate was 11.6% (96 cases) and that for AKI according to KDIGO and AKIN criteria was 30.0% (248 cases) and 31.0% (256 cases). The cumulative survival curve stratified by CKD and AKI stages were comparable between KDIGO and AKIN criteria. The discriminative power for mortality stratified by CKD stages for KDIGO and AKIN criteria are as followed: all subjects: 0.678 versus 0.670 (both ps?<0.001); non-CKD: 0.800 versus 0.809 (both ps?<0.001); early-stage CKD: 0.676 versus 0.676 (both ps?<0.001); late-stage CKD: 0.674 versus 0.660 (ps were?<0.001 and 0.003). Conclusion The KDIGO criteria are superior to AKIN criteria in predicting mortality after surgery, especially in those with advanced CKD.     

Study of the role of tumor necrosis factor-α (–308 G/A) and interleukin-10 (–1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis

Rational: Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications.

Objective: The aim of the present study was to assess the use of high-resolution melting curve (HRM) analysis in investigating whether the genetic polymorphisms; –308?G/A of tumor necrosis factor-α (TNF-α), and –1082?G?/A of Interleukin-10 (IL-10) genes may predispose patients diagnosed with severe sepsis to the development of AKI.

Methods: One hundred and fifty patients with severe sepsis participated in the present study; only sixty-six developed AKI. Both polymorphisms were studied using HRM analysis.

Main findings: The low producer genotype of both studied polymorphism of TNF-α and IL-10 genes was associated with AKI. Using logistic regression analysis, the low producer genotypes remained an independent risk factor for AKI. A statistically significant difference was detected between both studied groups as regards the low producer genotype in both TNF-α?(–308?G/A) and interleukin-10 (IL-10) (–1082?G/A) polymorphisms being prevalent in patients developing AKI.

Principle conclusions: The low producer genotypes of both TNF-α (–308?G/A) and IL-10 (–1082?G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury. Using HRM for genotyping proved to be a highly efficient, simple, cost-effective genotyping technique that is most appropriate for the routine study of large-scale samples.     

Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury

Ischemic acute kidney injury (AKI) triggers an inflammatory response which exacerbates injury that requires increased expression of endothelial adhesion molecules. To study this further, we used in situ hybridization, immunohistology, and isolated endothelial cells, and found increased Toll-like receptor 4 (TLR4) expression on endothelial cells of the vasa rectae of the inner stripe of the outer medulla of the kidney 4?h after reperfusion. This increase was probably due to reactive oxygen species, known to be generated early during ischemic AKI, because the addition of hydrogen peroxide increased TLR4 expression in MS1 microvascular endothelial cells in vitro. Endothelial TLR4 may regulate adhesion molecule (CD54 and CD62E) expression as they were increased on endothelia of wild-type but not TLR4 knockout mice in vivo. Further, the addition of high-mobility group protein B1, a TLR4 ligand released by injured cells, increased adhesion molecule expression on endothelia isolated from wild-type but not TLR4 knockout mice. TLR4 was localized to proximal tubules in the cortex and outer medulla after 24?h of reperfusion. Thus, at least two different cell types express TLR4, each of which contributes to renal injury by temporally different mechanisms during ischemic AKI.     

Epidemiology of acute kidney injury in surgical intensive care at University Hospital in Egypt. A prospective observational study

IntroductionThe acute kidney injury (AKI) incidence in ICU patients varies widely from 3% to 30%, with mortality ranging from 36% to 90%, depending on the type of ICU, study population, the period during which the study is conducted, and the criteria used to define AKI.There have been many studies about the epidemiology and risk factors of AKI in critically ill patients in the different regions of the world. However, little data on the epidemiology of AKI in critically ill patients are available in Egypt.ObjectivesThe aim of this study was to assess the incidence of AKI among critical ill patients using RIFEL [risk (R), injury (I), failure (F), loss (L), and end-stage kidney disease (E)] classification and to determine the risk factors and outcome of patients who developed AKI in our surgical ICU.MethodsWe conducted a 6-month prospective observational study in the surgical ICU. Patients were classified daily using the RIFLE criteria. Patients were considered as having new AKI if they did not have AKI on ICU admission and subsequently reached at least class risk during their follow-up. Deterioration of AKI was diagnosed if the patient had increased in RIFLE class compared to the initial classification.ResultsOne hundred and twelve patients were studied. AKI occurred in 40 (35.7%) of patients. The most common risk factors for AKI are APACHE II score (acute physiology and chronic health evaluation score, version II.) and sepsis. APACHEII was lower in non-AKI group than AKI group (17.3 ± 7.5 versus 22.4 ± 7.4, p = 0.001), and sepsis was more common in AKI patients than non-AKI patients (77.5% versus 49% p = 0.004). Patients with AKI had a mortality rate of 67.5% which was more in patients with failure compared with risk patients. APACHEII, AKI, and needs for mechanical ventilation were independent risks for mortality.     

Incidence and outcomes of acute kidney disease in patients after type A aortic dissection surgery

BackgroundAcute kidney injury (AKI), acute kidney disease (AKD) and CKD (chronic kidney disease) were a continuous process. There has been little discussion of risk factors for AKD in the population undergoing surgery for acute type A aortic dissection (AAAD).ObjectiveThe main objective of this study was to investigate the risk factors for AKD after surgery for acute type A aortic dissection and the impact of AKD on early and late mortality.DesignAKI was to be defined as an increase in serum creatinine to >0.3 mg/dL or 1.5 times above baseline within 7 days. AKD was defined as the kidney damage within 90 days after AKI. Logistic regression models were performed to identify the risk factors of AKD and the association between AKD and early mortality after AAAD surgery.ParticipantsPatients with AKI after AAAD surgery admitted in ICU from March 2009 to September 2021 were included.Key resultsAmong the 328 patients who developed AKI after AAAD surgery, 98 patients (29.9%) progressed to AKD. Multivariable analysis revealed that AKI stage 2 (OR, 3.032) and AKI stage 3 (OR, 4.001) have been shown to be independent risk factors for the development of AKD. AKD (OR, 3.175) proved to be an independent risk factor for early mortality, while no significant difference in late mortality was observed between patients in the AKD and non-AKD groups.ConclusionThe severity of AKI after surgery of AAAD was independently associated with AKD. The occurrence of AKD had a negative impact on early mortality.Clinical trial registrationChiCTR, ChiCTR1900021290. Registered 12 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35795.     

Blocking Fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury

Inflammation contributes to the pathogenesis of ischemic acute kidney injury (AKI), and T cells mediate the early phase of ischemia-reperfusion injury (IRI). The Fas/Fas ligand (FasL) pathway modulates the balance of T cell subsets in the peripheral circulation as well as multiple inflammatory responses, suggesting that FasL may mediate ischemic AKI. Here, we induced bilateral renal IRI in mice bearing a loss-of-function mutation of FasL (the gld mutation) and in wild-type mice. Compared with wild-type mice, serum creatinine was lower in gld mice (1.4 ± 0.9 mg/dl versus 2.6 ± 0.4) at 24 hours after IRI (P<0.05). In addition, gld mice had fewer TNF-α-producing T lymphocytes in the kidneys and renal lymph nodes. Furthermore, pharmacologic blockade of FasL protected the kidneys of wild-type mice from IRI. Analysis of bone marrow chimeric mice suggested that the pathogenic effect of FasL involves leukocytes; reconstitution of wild-type mice with gld splenocytes attenuated IRI. In contrast, reconstitution of gld mice with wild-type splenocytes enhanced IRI. These data demonstrate that FasL, particularly on leukocytes, mediates ischemic AKI.     

The attributable mortality of sepsis for acute kidney injury: a propensity-matched analysis based on multicenter prospective cohort study

BackgroundBoth sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI).MethodsA propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3–5. The primary outcome was hospital death of AKI patients.ResultsA total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8–13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3–20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1–5.9%, p = 0.825).ConclusionsThe attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis.Registration for the multicenter prospective cohort studyregistration number ChiCTR-ECH-13003934     

Evaluation of serum cysteine-rich protein 61 and cystatin C levels for assessment of acute kidney injury after cardiac surgery

Objective The occurrence of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) can lead to morbidity and mortality. We hypothesized that cysteine-rich protein 61 (CYR61) and cystatin C (CysC) may be potential novel biomarkers of AKI after cardiopulmonary bypass. Methods Patients were classified into AKI and non-AKI group depending on serum creatinine. Levels of creatinine, CysC, and CYR61 were measured at five time-points before and within 48?h after the surgery. Results Fifty patients were included in the study. Serum creatinine pre-operative values were 74.0?±?43.3?μmol/L in AKI group vs. 64.8?±?17.9?μmol/L in non-AKI group. During 48?h, the values increased to 124.6?±?67.2?μmol/L in AKI group (p?<?0.001) but in non-AKI group they did not change significantly. Serum CysC values were significantly increased already 2?h after CBP in AKI group (949?±?557?μg/L, p?<?0.05) compared to non-AKI group (700?±?170?μg/L). Pre-operative serum CYR61 tended to be lower in AKI group (12.4?μg/L) than in non-AKI group (20.3?μg/L), but 24?h after the surgery, the levels in AKI group tended to be higher than non-AKI group. Conclusion Serum CYR61 does not seem to be an early predictor of AKI in patients after cardiac surgery with CPB, but it might possibly identify patients at risk of developing more severe kidney injury. Serum CysC could be a promising biomarker of AKI, differentiating patients at risk of developing AKI after cardiac surgery as early as 2?h after surgery.     

Overexpression of toll-like receptor 2 in glomerular endothelial cells and podocytes in septic acute kidney injury mouse model

Abstract

Acute kidney injury (AKI) is one of the most common complications in patients with severe sepsis. The development of septic AKI increases patients’ mobility and even mortality. Toll-like receptor 2 (TLR2), as a membrane surface receptor for bacterial, fungal, viral and certain endogenous substances, has been described to contribute to the development of septic AKI; however, the renal cell types associating TLR2 overactivation in septic AKI has not been described. In the current study, we investigated the TLR2 activation patterns in the kidney of lipopolysaccharide-induced septic AKI mice. Our results demonstrated that mRNA level of TLR2 significantly increased in the kidney of lipopolysaccharide-treated mice. Immunohistochemistry revealed the overactivation of TLR2 in the glomeruli. Double immunofluorescence analysis shows the precise distribution of TLR2 by showing the colocalization of TLR2 in glomeruli with synaptopodin, a podocyte marker, and Tie2, an endothelial marker. In addition, proapoptotic molecules Bax and Caspase-3 were increased in the glomeruli of lipopolysaccharide-treated mice. Together, the current study indicates that TLR2 is overactivated in the glomerular endothelial cells and podocytes in septic AKI mice, while the abundance of Bax and Caspase-3 were increased in the glomeruli of these mice, it may supply a clue that TLR2 induced these cell apoptosis in AKI. This finding provides an alternative mechanism to understand AKI development and potential targets for treatment.     

Incidence,characteristics and prognosis of acute kidney injury in Cameroon: a prospective study at the Douala General Hospital

Objective: There are limited data on AKI in sub-Saharan Africa. We aim to determine the incidence, characteristics and prognosis of AKI in Cameroon.

Patients and methods: A prospective study including all consenting acute admissions in the internal medicine and the ICU of a tertiary referral hospital in Cameroon from January 2015 to June 2016. Serum creatinine assay was done on admission, days 2 and 7 to diagnose AKI. For patients with AKI, serum creatinine was done on discharge, days 30, 60 and 90. AKI was defined according to the modified KDIGO 2012 criteria as an increase or decrease in serum creatinine of 3?mg/l or greater, or an increase of 50% or more from the reference value obtained at admission or the known baseline value. AKI severity was graded using KDIGO2012 criteria. Outcome measures were renal recovery, mortality and causes of death. Renal recovery was complete if serum creatinine between the first 90?days was less than baseline or reference, partial if less than diagnosis but not baseline or reference, no-recovery if creatinine did not decrease or if the patient remained on dialysis.

Results: Of the 2402 patients included, 536 developed AKI giving a global incidence of 22.3% and annual incidence of 15 per 100 patients-years. Of the 536 patients with AKI, 43.3% were at stage 3, 54.7% were males, median age was 56?years. Pre-renal AKI (61.4%) and acute tubular necrosis (28.9%) were the most frequent forms. Main etiologies were sepsis (50.4%) and volume depletion (31.6%). Renal outcome was unknown in 34% of patients. Of the 354 patients with known renal function at 3?months, 84.2% recovered completely, 14.7% partially and 1.1% progressed to CKD. Global mortality rate was 36.9% mainly due to sepsis.

Conclusions: AKI is frequent in our setting, mainly due to sepsis and hypovolemia. It carries a poor prognosis.     

Monitor lizard bite-induced acute kidney injury – a case report

Envenomations by venomous lizards are rare. Monitor lizard bite-induced acute kidney injury (AKI) is a previously unreported complication in humans. A 55-year-old female was bitten on her right leg during farming activity by a monitor lizard (Varanus bengalensis). The patient experienced severe local pain and bleeding from the wound, coagulopathy, hemolysis, rhabdomyolysis, sepsis, and AKI. Patient was treated with supportive care and peritoneal dialysis but succumbed to a sudden cardiac arrest. Post mortem kidney biopsy revealed pigment induced-acute tubular injury. AKI after monitor lizard envenomation is caused by acute tubular injury in the setting of intravascular hemolysis, rhabdomyolysis and sepsis. Coagulopathy and direct nephrotoxicity may be the other contributory factors in causing AKI.     

Deletion of Myeloid Interferon Regulatory Factor 4 (Irf4) in Mouse Model Protects against Kidney Fibrosis after Ischemic Injury by Decreased Macrophage Recruitment and Activation

BackgroundAKI is characterized by abrupt and reversible kidney dysfunction, and incomplete recovery leads to chronic kidney injury. Previous studies by us and others have indicated that macrophage infiltration and polarization play key roles in recovery from AKI. The role in AKI recovery played by IFN regulatory factor 4 (IRF4), a mediator of polarization of macrophages to the M2 phenotype, is unclear.MethodsWe used mice with myeloid or macrophage cell–specific deletion of Irf4 (MΦ Irf4 ^−/−) to evaluate Irf4’s role in renal macrophage polarization and development of fibrosis after severe AKI.ResultsSurprisingly, although macrophage Irf4 deletion had a minimal effect on early renal functional recovery from AKI, it resulted in decreased renal fibrosis 4 weeks after severe AKI, in association with less-activated macrophages. Macrophage Irf4 deletion also protected against renal fibrosis in unilateral ureteral obstruction. Bone marrow–derived monocytes (BMDMs) from MΦ Irf4 ^−/− mice had diminished chemotactic responses to macrophage chemoattractants, with decreased activation of AKT and PI3 kinase and increased PTEN expression. PI3K and AKT inhibitors markedly decreased chemotaxis in wild-type BMDMs, and in a cultured macrophage cell line. There was significant inhibition of homing of labeled Irf4 ^−/− BMDMs to postischemic kidneys. Renal macrophage infiltration in response to AKI was markedly decreased in MΦ Irf4 ^−/− mice or in wild-type mice with inhibition of AKT activity.ConclusionsDeletion of Irf4 from myeloid cells protected against development of tubulointerstitial fibrosis after severe ischemic renal injury in mice, due primarily to inhibition of AKT-mediated monocyte recruitment to the injured kidney and reduced activation and subsequent polarization into a profibrotic M2 phenotype.     

Effects of acute kidney injury on clinical outcomes in patients with upper gastrointestinal bleeding

Aim Upper gastrointestinal bleeding (UGIB) is a very frequently encountered condition that has a high morbidity and which increases treatment costs. Duration of hospital stay and mortality increases in patients with UGIB complicated by acute kidney injury (AKI). The aim of this study was to reveal risk factors in patients with UGIB developing AKI and to compare clinical outcomes and hospital costs between patients with UGIB developing AKI and those with UGIB not developing AKI.

Material and methods This retrospective study included 245 patients admitted to the emergency unit and the intensive care unit for internal diseases at Ankara Numune Education and Research Hospital, Turkey. Results The difference in mortality rates between the patients with AKI and those without AKI was significant (p?0.001). The mean duration of intensive care unit stay was 0.2?±?1.1 days in the patients without AKI (n?=?143) and 2.5?±?5.6 days in the patients with AKI. It was significantly higher in the patients with AKI (p?0.001). Hospital stay was significantly longer in the patients with AKI than those without AKI, and as severity of AKI increased, hospital stay became considerably longer (p?0.001). Hospital costs were significantly higher in the patients with AKI than those without AKI, and as severity of AKI increased, hospital costs considerably rose (p?0.001). Conclusion AKI is a condition that lengthens hospital stay, increases hospital costs and creates a burden on health care systems. Detect kidney injury earlier and administering an appropriate treatment can improve clinical outcomes in patients with UGIB developing AKI.     

Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA receptor antagonism in rats

Objective: The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.

Methods: Rats were subjected to bilateral renal I/R (40?min I, 24?hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin &; eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60?mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200?mg/kg), and spermidine (20?mg/kg) were administered prior to curcumin treatment in rats followed by AKI.

Results: I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.

Conclusion: It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.     

Risk of Acute Kidney Injury after Exposure to Gadolinium-Based Contrast in Patients with Renal Impairment

Objectives: Gadolinium-based contrast media (Gd-CM) are reported to induce acute kidney injury (AKI) in a high-risk population group at the usual dose for magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) examinations. We assessed gadolinium-induced nephropathy in patients with renal impairment who underwent MRI or MRA examinations, and evaluated the risk factors. Materials and methods: In this retrospective study, 238 patients with baseline renal impairment, who received MRI or MRA examinations with Gd-CM, were recruited. After all other AKI causes—liver decompensation, severe heart failure, all kinds of shock, and severe sepsis—and patients on dialysis were excluded, 158 patients were enrolled. AKI was defined as a decrease in glomerular filtration rate (GFR) >10% of baseline data within 3 days after administration of Gd-CM. Regression analysis was used to find independent risk factors for gadolinium-induced AKI (Gd-AKI). Results: Twenty-six of the 158 patients (16.5%) developed Gd-AKI. There were no significant differences in gender, age, or baseline GFR between those who did and who did not develop AKI. Comorbid coronary artery disease, liver cirrhosis, diabetes mellitus, and hypertension were not significantly associated with the development of Gd-AKI. However, sepsis was an independent risk factor for Gd-AKI after multivariate regression analysis (adjusted odds ratio: 4.417; 95% confidence interval: 1.671–11.676, p = 0.03). Conclusions: It is potential AKI after administration of Gd-CM under sepsis condition at the dose for MRI and MRA examinations in patients with renal impairment. It is important to identify high-risk patients and closely monitor renal function after administration of Gd-CM.     

Hepcidin Mitigates Renal Ischemia-Reperfusion Injury by Modulating Systemic Iron Homeostasis

Iron-mediated oxidative stress is implicated in the pathogenesis of renal ischemia–reperfusion injury. Hepcidin is an endogenous acute phase hepatic hormone that prevents iron export from cells by inducing degradation of the only known iron export protein, ferroportin. In this study, we used a mouse model to investigate the effect of renal ischemia–reperfusion injury on systemic iron homeostasis and determine if dynamic modulation of iron homeostasis with hepcidin has therapeutic benefit in the treatment of AKI. Renal ischemia–reperfusion injury induced hepatosplenic iron export through increased ferroportin expression, which resulted in hepatosplenic iron depletion and an increase in serum and kidney nonheme iron levels. Exogenous hepcidin treatment prevented renal ischemia-reperfusion–induced changes in iron homeostasis. Hepcidin also decreased kidney ferroportin expression and increased the expression of cytoprotective H-ferritin. Hepcidin-induced restoration of iron homeostasis was accompanied by a significant reduction in ischemia-reperfusion–induced tubular injury, apoptosis, renal oxidative stress, and inflammatory cell infiltration. Hepcidin–deficient mice demonstrated increased susceptibility to ischemia-reperfusion injury compared with wild-type mice. Reconstituting hepcidin-deficient mice with exogenous hepcidin induced hepatic iron sequestration, attenuated the reduction in renal H-ferritin and reduced renal oxidative stress, apoptosis, inflammation, and tubular injury. Hepcidin-mediated protection was associated with reduced serum IL-6 levels. In summary, renal ischemia–reperfusion injury results in profound alterations in systemic iron homeostasis. Hepcidin treatment restores iron homeostasis and reduces inflammation to mediate protection in renal ischemia–reperfusion injury, suggesting that hepcidin-ferroportin pathway holds promise as a novel therapeutic target in the treatment of AKI.     

Long-term renal and overall survival of critically ill patients with acute renal injury who received continuous renal replacement therapy

Background: Acute kidney injury (AKI) is associated with the increased short-term mortality of critically ill patients on continuous renal replacement therapy (CRRT). The aim of this research was to evaluate the association of kidney function at discharge with the long-term renal and overall survival of critically ill patients with AKI who were on CRRT in an intensive care unit (ICU).

Methods: We retrospectively collected data for critically ill patients with AKI who were admitted to ICU on CRRT at a tertiary metropolitan hospital in China between 2008 and 2013. The patients were followed up to their death or to 30 September 2016 by telephone.

Results: A total of 403 patients were enrolled in this study. The 1-, 3- and 5-year patient survival rates were 64.3?±?2.4, 55.8?±?2.5 and 46.3?±?2.7%, respectively. In multivariate analysis, age, sepsis, decreased renal perfusion (including volume contraction, congestive heart failure, hypotension and cardiac arrest), preexisting kidney disease, Apache II score, Saps II score, vasopressors and eGFR <45?mL/min/1.73?m² at discharge were independent factors for worse long-term patient survival. And age, preexisting kidney disease, Apache II score, mechanical ventilation (MV) and eGFR <45?mL/min/1.73?m² at discharge were also associated with worse renal survival.

Conclusions: This study showed that impaired kidney function at discharge was shown to be an important risk factor affecting the long-term renal survival rates of critically ill patients with AKI. An eGFR <45?mL/min/1.73?m² was an independent risk factor for decreased overall survival and renal survival.