Abstract Acute Kidney Injury Research Articles

Autophagy in acute kidney injury and maladaptive kidney repair.

Acute kidney injury (AKI) is a major renal disease characterized by a sudden decrease in kidney function. After AKI, the kidney has the ability to repair, but if the initial injury is severe the repair may be incomplete or maladaptive and result in chronic kidney problems. Autophagy is a highly conserved pathway to deliver intracellular contents to lysosomes for degradation. Autophagy plays an important role in maintaining renal function and is involved in the pathogenesis of renal diseases. Autophagy is activated in various forms of AKI and acts as a defense mechanism against kidney cell injury and death. After AKI, autophagy is maintained at a relatively high level in kidney tubule cells during maladaptive kidney repair but the role of autophagy in maladaptive kidney repair has been controversial. Nonetheless, recent studies have demonstrated that autophagy may contribute to maladaptive kidney repair after AKI by inducing tubular degeneration and promoting a profibrotic phenotype in renal tubule cells. In this review, we analyze the role and regulation of autophagy in kidney injury and repair and discuss the therapeutic strategies by targeting autophagy.

Validation of Neutrophil gelatinase associated lipocalin (NGAL), a urinary biomarker for Acute Kidney Injury and the positive interference from high leukocyturia samples

Abstract Acute kidney injury (AKI) is a sudden and serious kidney damage condition that affects more than 1.2 million people every year. KIDNEY DISEASE IMPROVING GLOBAL OUTCOMES (KDIGO) guidelines currently suggest measuring the increase of serum creatinine as a diagnostic marker for AKI. However, the elevation of serum creatinine levels can take up to seven days or when >50% kidney function is lost. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for tubular injury, which can be detected in the urine of AKI patients in as early as three hours. In the current study, we evaluated the performance of BioPorto’s (Hellerup, Denmark) NGAL assay, which uses particle enhanced turbidimetry immunoassay (PETIA) technology on the Roche (Indianapolis, USA) cobas c502 chemistry analyzer. Linearity was determined using linearity material from BioPorto and also verified by serial dilutions of a high NGAL patient sample. The limit of quantitation was determined by running urine samples with values of 20 ng/mL, 25 ng/mL, and 35 ng/mL, respectively in duplicate for 10 days. Within-run precisions were determined by running urine two samples containing 100 ng/mL and 400 ng/mL NGAL 20 times and between–run precisions were determined by running the same samples 2 times a day for 10 days. To determine the accuracy of the NGAL method on cobas 502, 40 samples were used to compare results with those measured on Siemens Atellica using the BioPorto’s NGAL assay. Reference interval was verified in 40 urine samples collected from healthy donors. A urine dipstick test was performed to confirm the normal urine samples did not contain leukocyte esterase activity. Since NGAL is also present in neutrophils, we evaluated the effect of leukocytes in urine with the NGAL assay. Results showed the sample with 75 leukocytes/µL had an NGAL of 68 ng/mL and the sample with 500 leukocytes/µL has an NGAL of 222 ng/mL. The linearity range was determined to be 0 - 3000 ng/mL with a limit of quantification of 26 ng/mL. The within-run precision mean and CV% are 121 ng/mL, 4.3% for Level 1 and 401 ng/mL, 1.8% for Level 2. Between-run precisions mean and CV% are 106 ng/mL, 4.8% for Level 1 and 399 ng/mL, 2.6% Level 2. Method comparison had a slope of 0.90 and an intercept of 32.9. The reference interval was determined to be <50 ng/mL and Leukocytes in urine did cause false-positive NGAL results.

Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells.

Acute kidney injury (AKI) represents a prevailing complication of sepsis, and its onset involves ferroptosis. Ginsenoside Rg1 exerts a positive effect on kidney diseases. This study explored the action of ginsenoside Rg1 in sepsis-induced AKI (SI-AKI) by regulating ferroptosis in renal tubular epithelial cells (TECs). Sepsis rat models were established using cecal ligation and puncture (CLP) and cell models were established by treating human renal TECs (HK-2) with LPS to induce ferroptosis. Serum creatinine (SCr) and blood urea nitrogen (BUN) and urine KIM1 contents in rats were determined by ELISA kits. Kidney tissues were subjected to immunohistochemical and H&E stainings. Iron concentration, malondialdehyde (MDA), glutathione (GSH), and ferroptosis-related protein (ferritin light chain [FTL], ferritin heavy chain [FTH], GSH peroxidase 4 [GPX4], and Ferroptosis suppressor protein 1 [FSP1]) levels in kidney tissues and HK-2 cells were measured using ELISA kits and Western blotting. HK-2 cell viability was detected by cell counting kit-8, and cell death was observed via propidium iodide staining. Reactive oxygen species accumulation in cells was detected using C11 BODIPY 581/591 as a molecular probe. In CLP rats, ginsenoside Rg1 reduced SCr, BUN, KIM1, and NGAL levels, thus palliating SI-AKI. Additionally, ginsenoside Rg1 decreased iron content, FTL, FTH, and MDA levels, and elevated GPX4, FSP1, and GSH levels, thereby inhibiting lipid peroxidation and ferroptosis. Moreover, FSP1 knockdown annulled the inhibition of ginsenoside Rg1 on ferroptosis. In vitro experiments, ginsenoside Rg1 raised HK-2 cell viability and lowered iron accumulation and lipid peroxidation during ferroptosis, and its antiferroptosis activity was dependent on FSP1. Ginsenoside Rg1 alleviates SI-AKI, possibly resulting from inhibition of ferroptosis in renal TECs through FSP1.

Acute kidney injury secondary to urinary tract infection in kidney transplant recipients

Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with urosepsis, 100 KTRs with UTI, and 100 KTRs without history of UTI or sepsis. The incidences of AKI in the urosepsis and UTI groups were 75.2% and 41%, respectively. The urosepsis group has also presented with a significantly higher prevalence of AKI stage 2 and 3 than the UTI group. The rates of recovery from AKI stages 1, 2 and 3, were 75,6%, 55% and 26.1%, respectively. Factors independently associated with renal recovery from AKI were: AKI severity grade (AKI stage 2 with OR = 0.25 and AKI stage 3 with OR = 0.1), transfusion of red blood cells (RBC) (OR = 0.22), and the use of steroid bolus in the acute phase of treatment (OR = 4). The septic status (urosepsis vs UTI) did not influence the rates of renal recovery from AKI after adjustment for the remaining variables. The dominant cause of RBC transfusions in the whole population was upper GI-bleeding. In multivariable analyses, the occurrence of AKI was also independently associated with a greater decline of eGFR at 1-year post-discharge and with a greater risk of graft loss. In KTRs with both urosepsis and UTI, the occurrence of AKI portends poor transplantation outcomes. The local transfusion policy, modulation of immunosuppression and stress ulcer prophylaxis (which is not routinely administered in KTRs) in the acute setting may be modifiable factors that significantly impact long-term transplantation outcomes.

"Acute Kidney Injury predictive models: advanced yet far from application in resource-constrained settings."

Acute kidney injury (AKI) remains a major cause of morbidity and mortality in hospitalized patients, particularly critically ill patients. It poses a public health challenge in resource-constrained settings due to high administrative costs. AKI is commonly misdiagnosed due to its painless onset and late disruption of serum creatinine, which is the gold standard biomarker for AKI diagnosis. There is increasing research into the use of early biomarkers and the development of predictive models for early AKI diagnosis using clinical, laboratory, and imaging data. This field note provides insight into the challenges of using available AKI prediction models in resource-constrained environments, as well as perspectives that practitioners in these settings may find useful.

Urine Microscopy Score and Neutrophil Lymphocyte Ratio at Presentation are Good Biomarkers of Acute Kidney Injury in Patients with Upper Urinary Tract Infection when Assessed in Correlation with Virulence Factors of Escherichia coli and Blood Group Secretor Status

Acute kidney injury (AKI) is a leading cause of morbidity in urinary tract infection (UTI). We aimed to identify simple biomarkers and bacterial virulence factors associated with AKI in a setting of upper UTI due to uropathogenic Escherichia coli (UPEC). We designed a cross-sectional study to analyse biomarkers of AKI in upper UTI patients. A total of 2758 patients presenting to a tertiary care center with symptoms of upper UTI were assessed for the presence of diabetes mellitus, AKI, blood group non-secretors, urine microscopy and hemogram. 300 patients with UPEC in bacterial culture were studied for bacterial virulence factors by phenotypic and genotypic methods and the patients were followed up for a minimum period of two weeks. Patients with diabetes mellitus, non-secretors, Urine microscopy (UM) score > 2 and higher (> 3.9) neutrophil-lymphocyte ratio (NLR) at initial presentation, were found to be significantly associated with AKI at presentation and predicted AKI at 7th and 14th day follow up. They were also significantly associated with need and increased duration of hospitalization. There was no association of virulence factors of UPEC with diabetes mellitus, AKI or need for hospitalization. However, virulence factors had a significant association (p<0.001)with non-secretors. UM score and NLR are simple tools to identify AKI at presentation and predict AKI during follow-up and the need for hospitalization. Patients with diabetes mellitus and non-secretors are also at higher risk of AKI. Non-secretors are significantly associated with both phenotypic and genotypic expression of virulence factors of UPEC.

An evaluation of patient's knowledge about acute kidney injury pre- and post-follow-up clinic

Acute kidney injury (AKI) is a common occurrence among hospital patients, with patients being cared for by a wide range of health care specialties, rather than purely under the care of nephrologists. Patients with severe AKI are known to have poorer outcomes if they do not receive appropriate follow-up and medication reviews. Following the successful implementation of a nurse-led AKI follow-up clinic, a service evaluation was undertaken to assess whether there had been any impact on patients' knowledge of AKI. Patients were asked to assess their perceived knowledge about AKI before and after attending an AKI nurse-led clinic appointment. The results found that patients were more knowledgeable following attendance at clinic and felt reasonably confident in preventing future AKI.

Development and validation of an interpretable clinical score for early identification of acute kidney injury at the emergency department

Acute kidney injury (AKI) in hospitalised patients is a common syndrome associated with poorer patient outcomes. Clinical risk scores can be used for the early identification of patients at risk of AKI. We conducted a retrospective study using electronic health records of Singapore General Hospital emergency department patients who were admitted from 2008 to 2016. The primary outcome was inpatient AKI of any stage within 7 days of admission based on the Kidney Disease Improving Global Outcome (KDIGO) 2012 guidelines. A machine learning-based framework AutoScore was used to generate clinical scores from the study sample which was randomly divided into training, validation and testing cohorts. Model performance was evaluated using area under the curve (AUC). Among the 119,468 admissions, 10,693 (9.0%) developed AKI. 8491 were stage 1 (79.4%), 906 stage 2 (8.5%) and 1296 stage 3 (12.1%). The AKI Risk Score (AKI-RiSc) was a summation of the integer scores of 6 variables: serum creatinine, serum bicarbonate, pulse, systolic blood pressure, diastolic blood pressure, and age. AUC of AKI-RiSc was 0.730 (95% CI 0.714–0.747), outperforming an existing AKI Prediction Score model which achieved AUC of 0.665 (95% CI 0.646–0.679) on the testing cohort. At a cut-off of 4 points, AKI-RiSc had a sensitivity of 82.6% and specificity of 46.7%. AKI-RiSc is a simple clinical score that can be easily implemented on the ground for early identification of AKI and potentially be applied in international settings.

Spatial transcriptomics and single cell sequencing identifies a unique injury associated resident macrophage subpopulation and reveals differential response to injury

Abstract Acute kidney injury (AKI) is a growing concern in the U.S. and globally. Despite recovery of kidney function, patients remain at increased risk for developing chronic kidney disease (CKD). The cause of this increased risk is unknown and biomarkers to determine kidney injury are severely lacking. A potential candidate is the network of kidney resident macrophages interwoven throughout the tissue, and specifically a subpopulation of kidney injury associated macrophages (KIA) we first identified to appear after AKI and lack MHC II expression. KIA cells were localized within the tissue using Visium Spatial Transcriptomics and flow cytometry. Comparison of KIA cell kinetics between AKI and CKD indicated a correlation between the presence of KIA cells and the persistence of injury. Additionally, KIA cells have localized to the sight of greatest injury following an ischemic event. As kidney function recovers, KIA cells decrease in number and return to quiescent levels by 14 days post injury. In contrast, in the severe CKD model, KIA cells persist for up to six weeks, composing approximately 20% of the total kidney resident macrophage population. A less severe version of CKD results in fewer KIA cells but similar persistence, indicating appearance of KIA cells directly correlates with injury severity. Targeting KIA cells to either enhance or negate their function is a possible therapeutic target to reduce the risk of developing CKD following AKI. As we have identified KIA cells in multiple models of kidney injury, in the future they should be investigated as a potential injury biomarker. We hypothesize that KIA cells are uniquely involved in the pathogenesis of injury and may be a key to an AKI to CKD transition. Supported by grants from the American Heart Association: (AHA 827257)

TLR2/caspase-5/Panx1 pathway mediates necrosis-induced NLRP3 inflammasome activation in macrophages during acute kidney injury

Acute kidney injury (AKI) is characterized by necroinflammation formed by necrotic tubular epithelial cells (TECs) and interstitial inflammation. In necroinflammation, macrophages are key inflammatory cells and can be activated and polarized into proinflammatory macrophages. Membranous Toll-like receptors (TLRs) can cooperate with intracellular NOD-like receptor protein 3 (NLRP3) to recognize danger signals from necrotic TECs and activate proinflammatory macrophages by assembling NLRP3 inflammasome. However, the cooperation between TLRs and NLRP3 is still unclear. Using conditioned medium from necrotic TECs, we confirmed that necrotic TECs could release danger signals to activate NLRP3 inflammasome in macrophages. We further identified that necrotic TECs-induced NLRP3 inflammasome activation was dependent on ATP secretion via Pannexin-1 (Panx1) channel in macrophages. Next, we verified that TLR2 was required for the activation of Panx1 and NLRP3 in macrophages. Mechanistically, we indicated that caspase-5 mediated TLR2-induced Panx1 activation. In addition, we showed that necrotic TECs-induced activation of TLR2/caspase-5/Panx1 axis could be decreased in macrophages when TECs was protected by N-acetylcysteine (NAC). Overall, we demonstrate that danger signals from necrotic TECs could activate NLRP3 inflammasome in macrophages via TLR2/caspase-5/Panx1 axis during AKI.

Review Article: Acute Kidney Injury

Acute kidney injury (AKI) is described as a loss of excretory renal function that occurs suddenly. AKI is one of a group of diseases and disorders known as acute kidney diseases and disorders (AKD), in which a gradual loss of kidney function or persistent renal dysfunction is linked to the irreversible loss of kidney cells and nephrons, which can lead to chronic kidney disease (CKD). New biomarkers are currently being explored in the clinic to detect damage before function loss. People all throughout the world are affected by AKI and AKD. Infections and hypovolaemic shock are the most common causes of AKI in low- and middle-income nations. Infections, drugs, or invasive procedures cause AKI, which is more common in elderly hospitalized patients in high-income countries. Infections are widespread in all areas, as are AKI and AKD caused by trauma. The large range of symptoms associated with AKI suggests a number of pathophysiological reasons. In critical care settings, AKI management can be difficult, especially when it comes to volume control, nephrotoxic medication management, and when it comes to the timing and kind of renal support. Conclusion: AKI is a significant medical disorder that has been linked to poor clinical outcomes in individuals who are hospitalized. Significant progress has been made in refining the definition of this syndrome and establishing the underlying pathophysiologic processes of the many clinical manifestations. It is self-evident that no single pathophysiologic mechanism can account for all clinical symptoms of AKI.

Emodin-Mediated Treatment of Acute Kidney Injury.

Acute kidney injury (AKI), a common condition associated with a high mortality rate, is characterized by declined glomerular filtration rate, retention of nitrogen products, and disturbances in balance of water, electrolyte, and acid-base. Up to date, there is no effective treatment for AKI. Despite the continuous improvement in blood purification techniques, a considerable proportion of patients with AKI still progress to end-stage renal disease. These patients with advanced stage of end-stage renal disease will require long-term renal replacement therapy, which places a heavy burden on the family and the society. In recent years, the use of traditional Chinese medicine (TCM) in AKI management has been gradually increasing. Clinical evidence has demonstrated that three-month treatment with TCM produced better clinical outcomes in terms of clinical effectiveness rate and improvement in renal function (serum creatinine, neutrophil gelatinase-associated lipocalin, and cystatin C) compared with Western medicine. Rhubarb is a commonly used herb in TCM for the treatment of AKI. The main active component of rhubarb is emodin, which was first recorded in Shennong's Classic of Materia Medica. It has been shown that emodin has a variety of pharmacological activities including antibacterial, anti-inflammatory, antiulcer, and immunosuppressive effects. Emodin has been found to be effective against renal fibrosis and has been widely studied for its effects on kidney diseases such as diabetic nephropathy, renal fibrosis, and AKI. Moreover, promising results have been obtained from these studies. In this study, the results obtained from research on the use of emodin for AKI treatment has been reviewed.

Nucleic Acid Nanotechnology for Diagnostics and Therapeutics in Acute Kidney Injury.

Acute kidney injury (AKI) has impacted a heavy burden on global healthcare system with a high morbidity and mortality in both hospitalized and critically ill patients. However, there are still some shortcomings in clinical approaches for the disease to date, appealing for an earlier recognition and specific intervention to improve long-term outcomes. In the past decades, owing to the predictable base-pairing rule and highly modifiable characteristics, nucleic acids have already become significant biomaterials for nanostructure and nanodevice fabrication, which is known as nucleic acid nanotechnology. In particular, its excellent programmability and biocompatibility have further promoted its intersection with medical challenges. Lately, there have been an influx of research connecting nucleic acid nanotechnology with the clinical needs for renal diseases, especially AKI. In this review, we begin with the diagnostics of AKI based on nucleic acid nanotechnology with a highlight on aptamer- and probe-functionalized detection. Then, recently developed nanoscale nucleic acid therapeutics towards AKI will be fully elucidated. Furthermore, the strengths and limitations will be summarized, envisioning a wiser and wider application of nucleic acid nanotechnology in the future of AKI.

Predictive Value of Urinary Aquaporin 2 for Acute Kidney Injury in Patients with Acute Decompensated Heart Failure.

Acute kidney injury (AKI) is frequently encountered in people with acute decompensated heart failure (ADHF) and is associated with increased morbidity and mortality. Early detection of a urinary biomarker of kidney injury might allow a prompt diagnosis and improve outcomes. Levels of urinary aquaporin 2 (UAQP2), which is also associated with several renal diseases, are increased with ADHF. We aimed to determine whether UAQP2 predicted AKI in patients with ADHF. We conducted a prospective observation study in the coronary care unit (CCU) in a tertiary care university hospital in Taiwan. Individuals with ADHF admitted to the CCU between November 2009 and November 2014 were enrolled, and serum and urinary samples were collected. AKI was diagnosed in 69 (36.5%) of 189 adult patients (mean age: 68 years). Area under the receiver operating characteristic curve (AUROC) of biomarkers was evaluated to evaluate the diagnostic power for AKI. Both brain natriuretic peptide and UAQP2 demonstrated acceptable AUROCs (0.759 and 0.795, respectively). A combination of the markers had an AUROC of 0.802. UAQP2 is a potential biomarker of AKI in CCU patients with ADHF. Additional research on this novel biomarker is required.

In hospital risk factors for acute kidney injury and its burden in patients with Sars-Cov-2 infection: a longitudinal multinational study

Acute kidney injury (AKI) is associated with increased mortality in most critical settings. However, it is unclear whether its mild form (i.e. AKI stage 1) is associated with increased mortality also in non-critical settings. Here we conducted an international study in patients hospitalized with SARS-CoV-2 infection aiming 1. to estimate the incidence of AKI at each stage and its impact on mortality 2. to identify AKI risk factors at admission (susceptibility) and during hospitalization (exposures) and factors contributing to AKI-associated mortality. We included 939 patients from medical departments in Moscow (Russia) and Padua (Italy). In-hospital AKI onset was identified in 140 (14.9%) patients, mainly with stage 1 (65%). Mortality was remarkably higher in patients with AKI compared to those without AKI (55 [39.3%] vs. 34 [4.3%], respectively). Such association remained significant after adjustment for other clinical conditions at admission (relative risk [RR] 5.6; CI 3.5- 8.8) or restricting to AKI stage 1 (RR 3.2; CI 1.8–5.5) or to subjects with AKI onset preceding deterioration of clinical conditions. After hospital admission, worsening of hypoxic damage, inflammation, hyperglycemia, and coagulopathy were identified as hospital-acquired risk factors predicting AKI onset. Following AKI onset, the AKI-associated worsening of respiratory function was identified as the main contributor to AKI-induced increase in mortality risk. In conclusion, AKI is a common complication of Sars-CoV2 infection in non-intensive care settings where it markedly increases mortality risk also at stage 1. The identification of hospital-acquired risk factors and exposures might help prevention of AKI onset and of its complications.

Instrument’s Reliability and Validity for Evaluating the Nursing Risk Assessment of Acute Kidney Injury tools for the Surgical Department: A Pilot Study

Acute Kidney Injury (AKI) is common but is often under-recognized. Delayed diagnosis may lead to patients’ increased morbidity and mortality. AKI is fully established with various guideline but remained lacking in early detection through knowledge, understanding, assessment, and poor identification. High incidence and mortality rate of AKI in Malaysia could be assumed to be due to inadequate early nursing assessment and intervention. Hence an education programme for nurses with valid and reliable tools need to be developed. The aim of this study to develop a valid and reliable research tools for nursing risk assessment education programme in the detection of AKI from surgical patients. The tools were developed within four phases. Phase 1, the development of instruments through research and literature review. Phase 2, the validity process. The tools were submitted for relevancy and validation by expert panels. Phase 3, a pilot study conducted to test the instruments and phase 4 involved analyzing the tools. Two types of research tools developed in the study. Type 1: The Knowledge, Attitude and Practice (KAP) of AKI questionnaire and Type 2: The Nursing Risk Assessment AKI form. Overall Content Validity Index value for type 1 instrument was 0.96 and type 2 instrument was 0.95 indicating adequate standard of acceptability. Overall Cronbach’s Alpha value was at 0.81. KAP of AKI questionnaire and the Nursing Risk Assessment AKI form are valid tools to assess nurses KAP level and the early detection of patients at risk of AKI respectively.

Prevention and Treatment of AKI during Various Disasters

Acute kidney injury (AKI) is frequent, and shows wide variation with regards to the spectrum, etio-pathogenesis and management strategies after natural (e.g., earthquakes) and man-made disasters (e.g., wars). The most important pathogenetic mechanisms in AKI during earthquakes are crush injury-related hypovolemia and myoglobinuria. Therefore, the most effective preventive measures are early and energetic fluid resuscitation (especially isotonic saline due to medical and logistic advantages) and also avoiding nephrotoxic medications. When preventive measures fail and intrarenal AKI develops, dialysis is lifesaving, with a preference towards intermittent hemodialysis due to medical and logistic advantages during disasters. During wars, the most important man-made disaster, prerenal, intrarenal and postrenal AKI may develop both at the battlefield and also in the field- or tertiary care-hospital setting. Overall, pathogenesis and management strategies of AKI in war victims are similar with those of AKI in general and in natural disasters. Logistic planning after disasters is vital for providing the most effective treatment. If patients cannot be coped with locally, either help should be asked from, or, alternatively, patients should be referred to, other regions or countries. Importantly, nephrology units in and around disaster-prone areas should be prepared for disasters for a sudden influx of AKI victims after disasters.

Oligosaccharides Ameliorate Acute Kidney Injury by Alleviating Cluster of Differentiation 44-Mediated Immune Responses in Renal Tubular Cells.

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1β, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia–reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1β, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI.

Reflections on the KDIGO Definition of Acute Kidney Injury and Its Integration in the Concept of Acute Diseases and Disorders and Chronic Kidney Diseases

Acute kidney injury (AKI) describes a heterogeneous group of conditions, without specification of their etiology and diagnosed only by indirect markers of glomerular filtration rate (GFR), such as serum creatinine and urine output. Bedside estimation of GFR and detection of structural alterations with novel biomarkers, and stress tests have more recently been developed. These novel findings should probably be included in future AKI definitions. Chronic kidney disease (CKD) is defined by abnormalities in kidney function and structure that persist over >3 months and is classified according to cause, GFR, and albuminuria. Acute kidney disease (AKD) is the term representing patients with abnormalities of function and structure with a duration of ≤3 months that fall outside the definitions of AKI or CKD. Since AKI is by definition also AKD, 2 types of AKD have been proposed, one with and one without AKI. AKD without AKI is common, often undetected, occurs frequently in the outpatient population and shows increased risk of CKD, ESKD and mortality. Alternatively, AKD has also been defined as the period of incomplete recovery following an AKI episode, the latter limited for the duration of 7 days. This contribution discusses the pros and cons of the existence of these 2 definitions of AKD.

A clarion call for follow-up of acute kidney injury survivors: perspective from a developing country.

Acute kidney injury (AKI) is associated with long term adverse renal outcomes. Since AKI is a risk factor for chronic kidney disease (CKD), follow up of AKI survivors assumes significance. Currently, follow up rates of AKI survivors are poor. Universally acceptable definition for AKI recovery is lacking. The epidemiology and clinical profile of AKI are different in developing countrieswhere patients are often referred lateto healthcare facilities and initiation of renal replacement therapy is often delayed. Recently, proposals for defining AKI recovery and indications forAKI follow-up care have been published; while interesting, these suggestions are complex, and difficult to follow. Developing countries require simple definitions of AKI recovery and manageablefollow-up care models, thatcould be applicable in scarcelyresourced healthcare settings.