Early Stages Of Acute Kidney Injury Research Articles

Interleuquina-6 como marcador pronóstico en el fracaso renal agudo y su regulación dependiente de klotho

Background and objectiveIn acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI. Materials and methodsPlasma levels of IL-6, klotho and FGF23 were analysed in samples from 28 patients with AKI and related to renal function on hospital admission, and after 24 and 72hours. In addition, the predictive capacity of IL-6 on AKI-associated mortality was analysed at the three study time points. In an experimental nephrotoxic -AKI mouse model, systemic IL-6 and FGF23 values were also analysed 24 and 72hours after induction of kidney damage, as well as in mice overexpressing the anti-ageing protein, klotho. ResultsSystemic IL-6 levels increased in AKI patients, especially in hospital admission time, and decreased in parallel with improving renal function. At the same time as IL-6 values increased, there was an increase in FGF23 and a decrease in klotho levels, with a significant and positive correlation between IL-6 and FGF23 levels. In addition, we obtained that systemic IL-6 levels were a good predictor of mortality in these patients, with an area under the curve equal to one at 72hours after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24hours of kidney damage. Nevertheless, in transgenic mice overexpressing klotho, there was no such increase in any of them. ConclusionsThere is an association between renal damage and increased levels of IL-6 and FGF23 in patients with AKI, especially on hospital admission time. Moreover, IL-6 levels are able to predict mortality in these patients, being a promising prognostic biomarker at any study time with a strong prediction at 72hours after patient admission. Maintaining adequate klotho levels could prevent the IL-6 mediated inflammatory response and therefore also reduce the degree and severity of renal damage after AKI.

CD8 T cells induce the peritubular capillary rarefaction during AKI to CKD transition.

Acute kidney injury (AKI) transformed to chronic kidney disease (CKD) is a critical clinical issue characterized by tubulointerstitial inflammation (TII) and fibrosis. However, the exact mechanism remains largely unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to obtain a high-resolution profile of T cells in AKI to CKD transition with a mice model of unilateral ischemia-reperfusion injury (uIRI). We found that T cells accumulated increasingly with the progression of AKI to CKD, which was categorized into 9 clusters. A notably increased proportion of CD8 T cells via self-proliferation occurred in the early stage of AKI was identified. Further study revealed that the CD8 T cells were recruited through CXCL16-CXCR6 pathway mediated by macrophages. Notably, CD8 T cells induced endothelial cell apoptosis via Fas ligand-Fas signaling. Consistently, increased CD8 T cell infiltration accompanied with peritubular capillaries (PTCs) rarefaction was observed in uIRI mice. More impressively, the loss of PTCs and renal fibrosis was remarkably ameliorated after the elimination of CD8 T cells. In summary, our study provides a novel insight into the role of CD8 T cells in the transition from AKI to CKD via induction of PTCs rarefaction, which could suggest a promising therapeutic target for AKI.

Use of Selective Hemosorption and Hemodiafiltration in a Patient with Toxic Rhabdomyolysis Complicated by Acute Kidney Injury

Rhabdomyolysis ( RM ) is a clinical and laboratory syndrome accompanied by systemic endotoxicosis, a consequence of myocyte destruction and is manifested by acute kidney injury ( AKI ). The use of extracorporeal detoxification in the early stages of AKI is currently not recognized due to the lack of proven effectiveness. The objective: to demonstrate the effectiveness of selective hemoperfusion ( HP ) and hemodiafiltration ( HDF ) in a patient with toxic RM complicated by AKI . Subjects and methods. The article presents a clinical observation of an 1 8-y ea r-o ld patient after the use of 4-m ethylmethcathinone (mephedrone) with development of AKI . Clinical, laboratory, diagnostic, toxicological and instrumental methods of examination were used. HP and HDF were used together with standard intensive therapy. Results. Combined use of HP and HDF was accompanied by regression of markers of endotoxicosis and AKI . A decrease in myoglobin level was noted by 50.3%, 80.3% and 94.1%, respectively, after the 1st and 2nd procedures and by the 5th day. CPK (creatine phosphokinase) decreased by 47.7%, 81.5% and 97.8%, respectively. Cystati n-C went down by 19.3%, 39.9% and 69.9%, respectively. Conclusions. Earlier and justified use of HP and HDF was accompanied by a rapid improvement of clinical and laboratory parameters, which is reflected in the duration of ICU stay, hospital stay and the outcome of the disease in general.

The effectiveness of various approaches to the use of renal replacement therapy in the treatment of toxic rhabdomyolysis complicated by acute kidney injury

BACKGROUND. 60 % of cases of acute poisoning are complicated by the occurrence of rhabdomyolysis . The most common and dangerous complication of rhabdomyolysis is acute kidney injury (AKI), which increases mortality by up to 10 %. One of the most promising directions of pathogenetic therapy of rhabdomyolysis complicated by AKI is extracorporeal removal of myoglobin and other factors of endogenous intoxication from the systemic bloodstream . THE AIM: to improve the results of treatment of patients with toxic rhabdomyolysis complicated by acute kidney injury by applying the most effective tactics of renal replacement therapy . PATIENTS AND METHODS. The prospective study included 81 patients with toxic rhabdomyolysis complicated by AKI. In the first group , standard basic intensive therapy was performed ; in the second group , hemodiafiltration was performed at an early stage of AKI, in the third group , early application of hemodiafiltration with selective hemosorption was performed . The analysis of laboratory parameters of rhabdomyolysis , renal damage , as well as the outcomes of treatment of patients in groups was carried out . RESULTS. Early use of renal replacement therapy (RRT) increased the severity of reduction of myoglobin concentrations in blood and KIM-1 in urine during the first week of treatment from 26.3 % to 73.4 % and from 76.1 % to 96.8 %, respectively . The inclusion of RRT with selective hemosorption in the intensive therapy at an early stage of AKI allowed to increase these indicators to 88.0 % and 99.0 %, respectively . The most effective method is the use of a combination of RRT with selective hemosorption , which allows to increase the rate of recovery of kidney function and reduce the duration of the necessary use of RRT from 15 to 6 days , as well as to reduce hospital mortality from 14.3 % to 6.9 %.

In situ detection of alkaline phosphatase in a cisplatin-induced acute kidney injury model with a fluorescent/photoacoustic bimodal molecular probe.

Kidneys play an important part in drug metabolism and excretion. High local concentration of drugs or drug allergies often cause acute kidney injury (AKI). Identification of effective biomarkers of initial stage AKI and constructing activable molecular probes with excellent detection properties for early evaluation of AKI are necessary, yet remain significant challenges. Alkaline phosphatase (ALP), a key hydrolyzing protease, exists in the epithelial cells of the kidney and is discharged into the urine following kidney injury. However, no studies have revealed its level in drug-induced AKI. Existing ALP fluorescent molecular probes are not suitable for testing and imaging of ALP in the AKI model. Drug-induced AKI is accompanied by oxidative stress, and many studies have indicated that a large increase in reactive oxygen species (ROS) occur in the AKI model. Thus, the probe used for imaging of AKI must be chemically stable in the presence of ROS. However, most existing near-infrared fluorescent (NIRF) ALP probes are not stable in the presence of ROS in the AKI model. Hence, we built a chemically stable molecular sensor (CS-ALP) to map ALP level in cisplatin-induced AKI. This novel probe is not destroyed by ROS generated in the AKI model, thus allowing high-fidelity imaging. In the presence of ALP, the CS-ALP probe generates a new absorbance peak at 685nm and a fluorescent emission peak at 716nm that could be used to "turn on" photoacoustic (PA) and NIRF imaging of ALP in AKI. Levels of CS-ALP build up rapidly in the kidney, and CS-ALP has been successfully applied in NIRF/PA bimodal in vivo imaging. Through the NIRF/PA bimodal imaging results, we demonstrate that upregulated expression of ALP occurs in the early stages of AKI and continues with injury progression.

ACE2 Promoted by STAT3 Activation Has a Protective Role in Early-Stage Acute Kidney Injury of Murine Sepsis.

Sepsis-induced AKI (SIAKI) is the most common complication with unacceptable mortality in hospitalized and critically ill patients. The pathophysiology of the development of SIAKI is still poorly understood. Our recent work has demonstrated the role of signal transducer and activator of transcription 3 (STAT3) pathways in regulating inflammation and coagulation in sepsis. We hypothesized that STAT3 activation has a critical role in early-stage SIAKI. The early-stage SIAKI model was established in cecal ligation and puncture (CLP) mice, which recapitulates the clinical and renal pathological features of early-stage AKI patients. Brush border loss (BBL) was the specific pathological feature of acute tubular injury in early-stage AKI. The role of STAT3 signaling and angiotension system in early-stage SIAKI was evaluated. The STAT3 activation (increased pSTAT3) and increased angiotensin-converting enzyme 2 (ACE2) expressions were observed in CLP mice. The low responsive expressions of pSTAT3 and ACE2 to septic inflammation in CLP AKI mice were associated with BBL. Correlation analysis of proteins' expressions showed pSTAT3 expression was significantly positively related to ACE2 expression in CLP mice. Reduced pSTAT3 after S3I201 intervention, which blocked STAT3 phosphorylation, decreased ACE2 expression, and exacerbated tubular injury in early-stage SIAKI. Our data indicate that endogenous increase of ACE2 expression upregulated by STAT3 activation in early-stage SIAKI play protective role against acute tubular injury.

Molecular Visualization of Early-Stage Acute Kidney Injury with a DNA Framework Nanodevice.

DNA nanomachines with artificial intelligence have attracted great interest, which may open a new era of precision medicine. However, their in vivo behavior, including early diagnosis and therapeutic effect are limited by their targeting efficiency. Here, a tetrahedral DNA framework (TDF)‐based nanodevice for in vivo near‐infrared (NIR) diagnosis of early‐stage AKI is developed. This nanodevice comprises three functional modules: a size‐tunable TDF nanostructure as kidney‐targeting vehicle, a binding module for the biomarker kidney injury molecule‐1 (Kim‐1), and a NIR signaling module. The cooperation of these modules allows the nanodevice to be selectively accumulated in injured kidney tissues with high Kim‐1 level, generating strong NIR fluorescence; whereas the nanodevice with the proper size can be rapidly cleared in healthy kidneys to minimize the background. By using this nanodevice, the early diagnosis of AKI onset is demonstrated at least 6 h ahead of Kim‐1 urinalysis, or 12 h ahead of blood detection. It is envisioned that this TDF‐based nanodevice may have implications for the early diagnosis of AKI and other kidney diseases.

The use of combined extracorporeal detoxification in the treatment of toxic rhabdomyolysis complicated by acute kidney injury: single-center prospective randomized trial

INTRODUCTION. Rhabdomyolysis (RM) occurs in 40–60 % of patients with acute poisoning and is accompanied by acute kidney injury (AKI). The most effective method of treatment is the use of extracorporeal detoxification. The most promising is the combined methods of detoxification. OBJECTIVES. Improve outcomes in patients with toxic RM complicated by AKI through early use of selective hemosorption and hemodiafiltration. MATERIALS AND METHODS. The study included 57 patients with toxic genesis RM complicated by AKI. The first group received standard intensive therapy. For the treatment of the second group at the early stage of AKI, hemodiafiltration and selective hemoperfusion were used. We performed a comparative analysis of the dynamics of the main clinical and laboratory parameters, as well as treatment outcomes between groups. RESULTS. The use of selective hemoperfusion and hemodiafiltration at the early stage of AKI allowed to increase the decrease in the level of myoglobin in the blood from 26.3 to 88.0 % and KIM-1 in the urine from 76.1 to 99.0 % during the first week of treatment in the ICU (intensive care unit). Combined detoxification reduced the duration of RRT use from 15 to 6 days, which led to a significant decrease in the level of hospital mortality from 14.3 to 6.9 %, the duration of inpatient treatment from 19.5 to 11 days and the period of stay in the ICU from 11 to 4 days. CONCLUSIONS. Early use of combined extracorporeal detoxification leads to a significant decrease in the level of endogenous intoxication factors, which ultimately made it possible to reduce the duration of treatment in the ICU, hospital and reduce the level of hospital mortality.

Gremlin1 and TGF-β1 protect kidney tubular epithelial cells from ischemia-reperfusion injury through different pathways.

Gremlin1 belongs to the superfamily members of transforming growth factor (TGF)-β1, playing a profibrotic role in chronic kidney diseases (CKD) and the transition from the late stage of acute kidney injury (AKI) to CKD, but the effect it plays in the early stage of AKI is unclear. This study aimed to investigate the role of Gremlin1on apoptosis in renal tubular epithelial cells under ischemia-reperfusion (I/R) induction. We detected Gremlin1 and TGF-β1 expression in the kidneys of mice undergoing renal ischemia-reperfusion injury bilaterally. We induced apoptosis through depletion and reperfusion of oxygen and serum in human kidney tubular epithelial cells (HKCs), mimicking I/R injury in vivo, and detected the role and pathways of Gremlin1 and TGF-β1on HKCs injury. Mice undergoing bilateral I/R surgery presented AKI with a significant increase in serum creatinine, obvious renal tubular injuries, and increased macrophage cell and T-cell infiltration in interstitial areas. Gremlin1 expression was significantly increased along with TGF-β1 in the kidneys of AKI mice compared to sham mice. Exogenous Gremlin1 inhibited I/R-induced caspase3 expression in HKCs, which was blocked by a VEGFR2 kinase inhibitor III (SU5416). TGF-β1 also inhibited I/R-induced cell apoptosis in HKCs but had no synergic effect with Gremlin1. The TGF-β1's inhibitory effect could be blocked by the TGF-β1 type I receptor (activin receptor-like kinase 5, and ALK5)-specific inhibitor SB431542. Gremlin1 and TGF- β1 protect kidney tubular epithelial cells from ischemia-reperfusion-induced apoptosis through VEGFR2 and Smad2 signaling pathways.

Early-Phase Urine Output and Severe-Stage Progression of Oliguric Acute Kidney Injury in Critical Care.

Background: The relationship between urine output (UO) and severe-stage progression in the early phase of acute kidney injury (AKI) remains unclear. This study aimed to investigate the relationship between early-phase UO6−12h [UO within 6 h after diagnosis of stage 1 AKI by Kidney Disease: Improving Global Outcomes (KDIGO) UO criteria] and severe-stage progression of AKI and to identify a reference value of early-phase UO6−12h for guiding initial therapy in critical care.Methods: Adult patients with UO < 0.5 ml/kg/h for the first 6 h after intensive care unit (ICU) admission (meeting stage 1 AKI by UO) and UO6−12h ≥ 0.5 ml/kg/h were identified from the Medical Information Mart for Intensive Care (MIMIC) III database. The primary outcome was progression to stage 2/3 AKI by UO. After other variables were adjusted through multivariate analysis, generalized additive model (GAM) was used to visualize the relationship between early-phase UO6−12h and progression to stage 2/3 AKI by UO. A two-piecewise linear regression model was employed to identify the inflection point of early-phase UO6−12h above which progression risk significantly leveled off. Sensitivity and subgroup analyses were performed to assess the robustness of our findings.Results: Of 2,984 individuals, 1,870 (62.7%) with KDIGO stage 1 UO criteria progressed to stage 2/3 AKI. In the multivariate analysis, early-phase UO6−12h showed a significant association with progression to stage 2/3 AKI by UO (odds ratio, 0.40; 95% confidence interval, 0.34–0.46; p < 0.001). There was a non-linear relationship between early-phase UO6−12h and progression of AKI. Early-phase UO6−12h of 1.1 ml/kg/h was identified as the inflection point, above which progression risk significantly leveled off (p = 0.780). Patients with early-phase UO6−12h ≥ 1.1 ml/kg/h had significantly shorter length of ICU stay (3.82 vs. 4.17 days, p < 0.001) and hospital stay (9.28 vs. 10.43 days, p < 0.001) and lower 30-day mortality (11.05 vs. 18.42%, p < 0.001). The robustness of our findings was confirmed by sensitivity and subgroup analyses.Conclusions: Among early-stage AKI patients in critical care, there was a non-linear relationship between early-phase UO6−12h and progression of AKI. Early-phase UO6−12h of 1.1 ml/kg/h was the inflection point above which progression risk significantly leveled off.

Effectiveness of myo-inositol oxygenase in the early diagnosis of experimental acute kidney injury.

The effectiveness of the myo-inositol oxygenase (MIOX) enzyme was investigated in the diagnosis of acute kidney injury (AKI). In total, 40 rats were divided into 5 groups (n = 8, for each group) while left kidney ischemia-reperfusion was implemented in groups 2, 3, 4 and 5. Group 1 was the control group. Group 2 underwent 1‑hour ischemia and 2‑hour reperfusion. Group 3 underwent 1‑hour ischemia and 4‑hour reperfusion. Group 4 underwent 2‑hour ischemia and 2‑hour reperfusion. Group 5 underwent 2‑hour ischemia and 4‑hour reperfusion. Serum creatinine and blood urea nitrogen levels in all ischemia-reperfusion groups were higher than in the control group (p<0.001). Serum MIOX level was higher in groups 2, 3 and 4 than in group 1 (p=0.002). Tissue MIOX level was lower in groups 2, 4, and 5 than in group 1 (p=0.039). Serum and tissue neutrophil gelatinase-associated lipocalin levels were not significantly different between the groups. The injury level in histopathologic examination was as follows: group 1<group 3<group 2=group 4<group 5. The serum MIOX level increases in the early stages of AKI, however, decreases subsequently. Therefore, the serum MIOX may be a potential promising biomarker in the early diagnosis of AKI (Tab. 5, Fig. 6, Ref. 30).

Early Diagnosis and Prognostic Value of Acute Kidney Injury in Critically Ill Patients.

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 h was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39–49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI.

MON-222 URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (nGAL) IN EARLY ACUTE KIDNEY INJURY (AKI) PREDICTS PROGRESSION AND NEED FOR DIALYSIS

Predicting the progression of acute kidney injury (AKI) and need for renal replacement therapy (RRT) in early stages of AKI would be a useful bedside tool for clinicians, especially in resource-limited countries to optimize resource utilisation. We tested the predictive value of urine neutrophil gelatinase-associated lipocalin (NGAL) measured in the AKI stages 1 and 2, to predict progression of AKI and need for RRT. We analysed 288 patients of AKI diagnosed based on KDIGO criteria, who had measurement of urine NGAL (uNGAL) in AKI stages 1 (n=202) and 2 (n=86), admitted to a tertiary care hospital in South India. The progression of AKI was defined as the progression to a higher stage of AKI with a rise of at least 0.5 mg/dl in serum creatinine from the time of measurement of uNGAL or need for RRT. The outcomes studied were progression of AKI, need for RRT and hospital mortality. The mean age was 61.5±13.4 years and 78% were males. Sixty-two patients (21.5%) had progression of AKI, 55(19%) required RRT and hospital mortality was seen in 77(27%). The uNGAL (ng/ml) was 1778±2325 in progressive AKI and 399±1019 in non-progressive AKI patients (p<0.001). Similarly, uNGAL (ng/ml) was 1921±2432 in patients who ultimately received RRT and was 408±1007 in patients who did not receive RRT (p<0.001). The area under the curve (AUC) of receiver operating characteristic curve (ROC) for uNGAL to predict progression of AKI was 0.79 and to predict the need for RRT was 0.78. The cut-off uNGAL value of 1000 ng/ml to predict progression of AKI had sensitivity of 49.2% and specificity of 90.2%, whereas to predict need for RRT, the sensitivity was 52% and specificity was 90%. Strengths: Ours is a large study from a developing country, where AKI demography may be different from developed countries. Limitations: Ours is a single center study and needs validation from other centers in developing countries. Urine NGAL, when measured in early stages of AKI, was a strong predictor of progression of AKI and need for RRT. A cut-off uNGAL value of 1000 ng/ml is a reliable specific marker of progression of AKI and requirement of RRT when measured in AKI stages 1 and 2.

Furosemide stress test, a novel assessment tool for tubular function in critically ill patients with acute kidney injury: potential therapeutic and prognostic values

Introduction Acute kidney injury (AKI) is well recognized for its effect on the outcome of patients admitted to ICU. The pursuit of improved biomarkers for the early diagnosis of AKI and its outcomes is an area of intense contemporary research; studies demonstrated the utility of furosemide stress test (FST) for predicting the severity of AKI, and a possibility of administration as a treatment for acute kidney injury network (AKIN) I and II.Patients and methods A total of 80 patients in ICU of Nasser Institute Hospital (July 2014–2015) were recruited, including 40 patients who received FST and 40 patients who received standard management. Patients included were those who developed AKI grades Ι–Π according to AKIN criteria. They were assessed clinically and followed through the duration of the study by hourly central venous pressure measurement (CVP) and urine output for 6 h, besides daily kidney function tests and estimated glomerular filtration rate for 3 days.Results In the first 6 h, there was a significant increase in urine output in group I after first and second hours (P=0.026, 0.008, respectively), as well as cumulative UOP over 6 h (P=0.003), as compared with group II. The cutoff point regarding UOP for detection of progress to AKIN III and dialysis was found to be 325 ml in both groups, with sensitivity of 86.7% and specificity of 68% in group I and sensitivity of 95% and specificity of 95% in group II. There was a highly significant difference between the two groups concerning hypotension, which occurred in 11 patients in group I versus none in group II, with P value of 0.001, whereas there was no significant difference between both the groups concerning progression to AKIN III and dialysis, with P value of 0.260; ICU stay, with P value of 0.621; and mortality, with P value of 0.201. Our results in group I patients who did not show worsening of AKIN class had significantly higher urine output as compared with those whose AKIN class worsened, with P value of 0.001.Conclusion FST is a good predictor of severity of tubular damage in early stages of AKI, with no additional privilege over standard management in the treatment of AKI. Moreover, it carries more risk of hemodynamic compromise.

Early-Stage Acute Kidney Injury Adversely Affects Thoracoabdominal Aortic Aneurysm Repair Outcomes

Acute kidney injury (AKI) necessitating renal replacement therapy adversely affects outcomes after thoracoabdominal aortic aneurysm (TAAA) repair. The effects of earlier stages of AKI are less known. We hypothesized that earlier stages of AKI would reduce early survival after TAAA repair. We analyzed prospectively collected data from 1,056 consecutive TAAA repairs from our institution (2006 to 2016). We excluded patients less than 18 years of age, those with preexisting renal disease, and three patients who died intraoperatively, resulting in 873 patients. The Kidney Disease Improving Global Outcomes criteria grouped patients into three AKI stages; stage 3 necessitated initiation of renal replacement therapy. Multivariable modeling identified operative mortality predictors. Kaplan-Meier analysis assessed 1-year survival. Of 873 patients, 642 (73.5%) had no AKI and 231 (26.5%) had postoperative AKI (mild/stage 1, n= 92 [10.5%]; moderate/stage 2, n= 44 [5%]; severe/stage 3, n= 95 [10.9%]). Operative death occurred in 65 patients (7.4%): 14 (2.2%) with no AKI, 5 (5.4%) with mild AKI (p= 0.07 versus no AKI), 8 (18.2%) with moderate AKI (p= 0.02 versus mild), and 38 (40%) with severe AKI (p= 0.01 versus moderate). In multivariable analysis, moderate AKI independently predicted death (relative risk ratio: 9.4, 95% confidence interval: 3.4 to 25.9). Kaplan-Meier 1-year survival was 91.1% ± 1.2% for no AKI, 84.6% ± 3.9% for mild AKI (p= 0.07 versus no AKI), 67.4% ± 7.6% for moderate AKI (p= 0.01 versus mild), and 46.6% ± 5.3% for severe AKI (p= 0.02 versus moderate; p < 0.0001 across all groups). Moderate/stage 2 AKI reduced early survival after TAAA repair. Prevention, earlier detection, and optimal medical management of AKI may improve survival.

Study of neutrophil gelatinase-associated lipocalin in patients with cardiovascular shock

Introduction: Acute kidney injury (AKI) makes a reversible accumulation of nitrogen products. This waste product is partly determined by serum creatinine level but it is not reliable during hypotension. However, neutrophil gelatinase-associated lipocalin (NGAL), as a new biomarker, shows an obvious increase even at hypotensive status. Objectives: The presented study was designed to evaluate NGAL as a right biomarker for AKI early diagnosis and consequent appropriate therapies. Patients and Methods: In this study, 25 healthy individuals and 47 cases out of 60 primarily admitted patients with low blood pressure were evaluated for NGAL level using blood samplings, health documents as well as analysis of questionnaires data. The group’s sizes were determined based on AKI and hypotension risk rates. Exclusion and inclusion criteria were firmly considered to avoid major confounding factors. Results: AKI was found in 20 cases out of 47 hypotensive patients. NGAL levels were about 243.35 ± 105.74 ng/dL (Mean ± SD) in AKI and 192.32 ± 64.31 ng/dL (Mean ± SD) in non-AKI hypotensive patients that showed a significant difference (P=0.037) at the first 6 hours. There was no significant difference between hospitalization duration and NGAL level (P=0.616). Conclusion: NGAL is important diagnostic protein in the early stages of AKI while there was no creatinine increasing. On the other hand, NGAL level during early 6 hours of hypotension introduces it as an indicative biomarker of AKI based on provided literature and our presented results.

Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion.

Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats). Saline was infused in place of PTX or/and MP depending on the group. Renal function (diuresis, serum creatinine, creatinine clearance, sodium and potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival analysis (CKD model). More evidently at early stages of AKI or CKD, treated animals showed higher glomerular filtration and diminished tubular loss of electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (μmol/L) at 48 h of AKI: 60.9 ± 19.1 vs. 131.1 ± 94.4 vs. 233.4 ± 137.0, respectively, vs. 451.5 ± 114.4 in controls, all p < 0.05; and at 4 weeks of CKD: 89.0 ± 31.9 vs. 118.1 ± 64.5 vs. 156.9 ± 72.6, respectively, vs. 222.9 ± 91.4 in controls, p < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP). Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; p < 0.05). PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in rats. This calls for clinical investigations, especially in kidney transplantation.

Serum Cystatin C for Evaluation of Acute Kidney Injury in Adults Treated with Colistin.

Objective:Recent studies have shown that serum cystatin C (Cys C) is a better marker for measuring the glomerular filtration rate and may rise more quickly with acute kidney injury (AKI). The purpose of this study was to evaluate the clinical application of serum Cys C to predict colistin-induced nephrotoxicity in comparison with serum creatinine (SCr).Methods:Thirty-two adult patients with no history of acute or chronic kidney injury having been planned to receive intravenous colistin for an anticipated duration of at least 1 week for any indication were recruited. At baseline and 5 days after colistin treatment, serum Cys C as well as creatinine levels were measured. The incidence of colistin-induced acute renal failure was defined according to the AKIN criteria for SCr. Rise in concentration of Cys C by more than 10% from baseline considered as AKI.Findings:Colistin-induced nephrotoxicity (defined as SCr ≥0.3 mg/dl) occurred in 6 patients (18.8%). A Cys C increase concentration ≥10% after 5 days of colistin treatment was detected in 15 patients (46.9%). There was a poor agreement between the presence and absence of any SCr-AKI and Cys C-AKI (κ = 0.28, P = 0.04).Conclusion:Serum Cys C is a better marker of renal function in early stages of AKI and predictive of persistent AKI on colistin treatment.

Experimental MRI Monitoring of Renal Blood Volume Fraction Variations En Route to Renal Magnetic Resonance Oximetry.

Diagnosis of early-stage acute kidney injury (AKI) will benefit from a timely identification of local tissue hypoxia. Renal tissue hypoxia is an early feature in AKI pathophysiology, and renal oxygenation is increasingly being assessed through T2*-weighted magnetic resonance imaging (MRI). However, changes in renal blood volume fraction (BVf) confound renal T2*. The aim of this study was to assess the feasibility of intravascular contrast-enhanced MRI for monitoring renal BVf during physiological interventions that are concomitant with variations in BVf and to explore the possibility of correcting renal T2* for BVf variations. A dose-dependent study of the contrast agent ferumoxytol was performed in rats. BVf was monitored throughout short-term occlusion of the renal vein, which is known to markedly change renal blood partial pressure of O2 and BVf. BVf calculated from MRI measurements was used to estimate oxygen saturation of hemoglobin (SO2). BVf and SO2 were benchmarked against cortical data derived from near-infrared spectroscopy. As estimated from magnetic resonance parametric maps of T2 and T2*, BVf was shown to increase, whereas SO2 was shown to decline during venous occlusion (VO). This observation could be quantitatively reproduced in test–retest scenarios. Changes in BVf and SO2 were in good agreement with data obtained from near-infrared spectroscopy. Our findings provide motivation to advance multiparametric MRI for studying AKIs, with the ultimate goal of translating MRI-based renal BVf mapping into clinical practice en route noninvasive renal magnetic resonance oximetry as a method of assessing AKI and progression to chronic damage.

Retrospective analysis of inferior vena cava collapsibility with point of care ultrasound and urine sodium and FENa in patients with early stage acute kidney injury

ABSTRACTEarly stage acute kidney injury (AKI) is an independent risk factor for an increase in mortality. Accurate assessment of volume status is a major challenge during the early stages of acute renal injury. Determining volume status based on the history and physical exam lacks accuracy. Urine sodium and free excretion of sodium (FENa) provide objective evidence of intravascular volume status when interpreted carefully and is helpful to delineate prerenal from intrinsic renal failure. In recent years point of care ultrasound has been used to assess volume status. Our team conducted a retrospective chart review to assess the association of inferior vena cava collapsibility by point of care ultrasound (POCUS) and urine electrolytes (urine sodium, fractional excretion of sodium) during early stage AKI (Stage 1–2 of KDIGO guidelines). We reviewed 150 cases based on the provisional diagnosis. 36 patients met the criteria for further review. Using bivariate analysis, we found a strong association between >50% IVC collapsibility with FENa < 0.4% with an odds ratio 5.3 (CI 1.1–24.5, p = 0.04), and urine sodium <20 meq/dl with an odds ratio of 6.7 (Cl 1.5–30, p = 0.02). Subsequently, multivariate analysis and Spearman correlation showed an inverse relation between IVC collapsibility and fractional excretion of sodium FENa (β = −0.4, p = 0.001) and (r = −0.44, p = 0.01). These findings suggest the role of POCUS and urinary markers in determining the intravascular volume status in AKI. POCUS is also valuable to assess volume status in cases of renal failure where urine studies are difficult to interpret.