Mechanisms Of Acute Kidney Injury Research Articles

Folic acid-targeted pluronic F127 micelles improve oxidative stress and inhibit fibrosis for increasing AKI efficacy

The oxidative stress and activation of the fibrosis pathway are essential pathological mechanisms of acute kidney injury (AKI). In this article, we designed a drug delivery system that could effectively improve oxidative stress and relieve fibrosis by the combination of precise targeting, solubilization, and reducing the toxicity of nano-transport system to strengthen the efficacy of AKI. Folic acid (FA) was used as the targeting molecule, and curcumin (Cur) and resveratrol (Res), which are Chinese medicine monomers with anti-inflammatory and antioxidant effects, were used as model drugs. Here, the targeting nanosystem (Cur/Res@FA-F127/TPGS) co-loaded with Cur and Res was successfully synthesized. Finally, the comprehensive therapeutic effect of the nanosystem was evaluated through the targeted and pharmacodynamic researches on the AKI models induced by cisplatin (CDDP) in vitro and in vivo. The studies in vitro proved that the nanosystem could not only specifically target HK-2 cells and promote the effective accumulation of Cur and Res in the kidney, but also effectively improve oxidative stress by eliminating reactive oxygen species (ROS), stabilizing mitochondrial membrane potential (MMP), and reducing the expression of apoptosis-related proteins. The studies in vivo showed that the nanosystem could effectively play the role of anti-oxidation, anti-inflammatory and alleviate fibrosis to reduce the apoptosis and necrosis of renal tubular cells. The nanosystem could coordinately repair damaged HK-2 cells by improving oxidative stress, inhibiting inflammation and tissue fibrosis, which provided a new idea for the treatment of AKI.

Patulin Induces Acute Kidney Injury in Mice through Autophagy-Ferroptosis Pathway.

Patulin (PAT) is a common mycotoxin, widely found in cereals, seafood, nuts, and especially in fruits and their products. Exposure to this mycotoxin has been reported to induce kidney injury. However, the possible mechanism remains unclear. In our study, short-term high-dose intake of PAT caused acute kidney injury (AKI) in mice. We performed high-throughput transcriptional sequencing to identify differentially expressed genes (DEGs) between the treatment and control groups. The ferroptosis signaling pathway had the highest enrichment, suggesting ferroptosis is involved in PAT-induced AKI. Further, the existence of ferroptosis and autophagy was confirmed by observing the changes of mitochondria morphology and the formation of autophagosomes by electron microscopy. And the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), p62, nuclear receptor coactivator 4 (NCOA4), and ferritin heavy chain 1 (FTH1) were downregulated, whereas acyl-CoA synthase long-chain family member 4 (ACSL4), transferrin (TF), LC3, and ferritin light chain (FTL) expression were upregulated in PAT-exposed mice. These results suggested autophagy-dependent ferroptosis occurred in the animal model. This view has also been confirmed in the human renal tubular epithelial cell (HKC) experiments. Autophagy inhibitor 3-methyladenine (3MA) attenuated PAT-induced ferroptosis and the iron contents in HKC cells. Simultaneous autophagy-dependent ferroptosis can be inhibited by ferroptosis inhibitors ferrostatin-1 (Fer-1) and desferrioxamine (DFO). In general, this study provides a new perspective for exploring the new mechanism of acute kidney injury caused by PAT.

Maslinic Acid Attenuates Ischemia/Reperfusion-Induced Acute Kidney Injury by Suppressing Inflammation and Apoptosis Through Inhibiting NF-κB and MAPK Signaling Pathway.

Inflammation and apoptosis are the major contributors to the mechanisms of acute kidney injury (AKI) due to renal ischemia-reperfusion injury (IRI). Maslinic acid (MA), a pentacyclic triterpene acid mostly found in dietary plants, the current study was to demonstrate the renoprotective effect of MA on IRI-induced AKI, and to investigate the role of inflammation and apoptosis-related signaling pathways as a molecular mechanism. C57BL/6J mice were subjected to IRI for 72 h, and MA was daily administered by intraperitoneal injection during this period. In parallel, rat renal proximal tubule cells (NRK52E) were prophylactically treated with MA and then exposed to hydrogen peroxide (H2O2). MA treatment significantly inhibited the mRNA expression of interleukin (IL-1β), tumor necrosis factor-α (TGF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1(ICAM-1). Also, MA reduced the expression of Bax/Bcl2 ratio and cleaved caspase-3. In NRK52 cells, MA inhibited the IκBα degradation, blocked NF-κB/p65 phosphorylation, and nuclear translocation. The phosphorylation of ERK, JNK, and p38 was attenuated by MA in IRI-induced kidney injury and H2O2-stimulated NRK52 cells. The expression levels of IL-1β, MCP-1, and ICAM-1 were upregulated in H2O2-stimulated NRK52E cells, which was attenuated by NF-κB inhibitor. H2O2 treatment increased the Bax/Bcl2 ratio and cleaved caspase-3 in NRK52E cells, which was counteracted by MAPK inhibitors. Together, our data demonstrate that MA suppresses IR-induced AKI injury through NF-κB and MAPK signaling pathways and that MA is a promising agent in the treatment of kidney diseases.

331 Dual Pathologic Mechanism of Acute Kidney Injury in a Patient Following Percutaneous Renal Biopsy

331 Dual Pathologic Mechanism of Acute Kidney Injury in a Patient Following Percutaneous Renal Biopsy

A Stepwise Targeting Curcumin Derivative, Ser@TPP@CUR, for Acute Kidney Injury.

Based on the pathological mechanisms of acute kidney injury (AKI), a stepwise targeting curcumin derivative, Ser@TPP@CUR, was developed in this study. Ser@TPP@CUR can be specifically internalized by renal tubular epithelial cells via KIM-1 receptor-mediated endocytosis and then actively distributed in mitochondria under the effect of TPP, a mitochondrial targeting molecule. Both in vitro and in vivo results showed that Ser@TPP@CUR effectively ameliorated injured renal tubular epithelial cells and improved renal functions of AKI mice.

Serum Myoglobin Is Associated With Postoperative Acute Kidney Injury in Stanford Type A Aortic Dissection.

BackgroundThe correlation between rhabdomyolysis and postoperative acute kidney injury has been reported in several surgical procedures. As a good predictor of rhabdomyolysis-related acute kidney injury, an elevated serum myoglobin level was often observed after total aortic arch replacement combined with frozen elephant trunk implantation. However, the correlation between serum myoglobin and acute kidney injury in such patients had not been established.MethodsTotally 398 stanford type A aortic dissection patients who underwent total aortic arch replacement combined with frozen elephant trunk implantation were enrolled in this retrospective study. The correlations between serum myoglobin and acute kidney injury as well as the 30-day mortality were assessed.ResultsOverall, 268(67.3%) patients had acute kidney injury (KDIGO stage 1 or higher) and 75(18.8%) had severe acute kidney injury (KDIGO stage 2&3). Patients who developed acute kidney injury had higher level of perioperative serum myoglobin than patients without acute kidney injury. After adjusting for known acute kidney injury risk factors, logarithmically transformed preoperative serum myoglobin [OR = 1.58 (95% CI, 1.26–1.95), P < 0.001] and postoperative day 1 serum myoglobin [OR = 3.47 (95%CI, 2.27–5.29), P < 0.001] were associated with severe acute kidney injury. These correlation persisted after adjustment for decline in filtration via change in serum creatinine (ΔCr) and biomarkers of cardiac and kidney injury, including N-terminal prohormone of brain natriuretic peptide, cardiac troponin I, creatine kinase-MB, serum creatinine and Cystatin C. Compared with the clinical model, sMb considerably improved the risk discrimination and reclassification for AKI.ConclusionFor stanford type A aortic dissection patients underwent total aortic arch replacement with frozen elephant trunk implantation, serum myoglobin can improve postoperative acute kidney injury risk classification. Rhabdomyolysis may be an important supplement to the existing knowledge on the mechanism of acute kidney injury.

SAP130 released by damaged tubule drives necroinflammation via miRNA-219c/Mincle signaling in acute kidney injury

Tubules injury and immune cell activation are the common pathogenic mechanisms in acute kidney injury (AKI). However, the exact modes of immune cell activation following tubule damage are not fully understood. Here we uncovered that the release of cytoplasmic spliceosome associated protein 130 (SAP130) from the damaged tubular cells mediated necroinflammation by triggering macrophage activation via miRNA-219c(miR-219c)/Mincle-dependent mechanism in unilateral ureteral obstruction (UUO) and cisplatin-induced AKI mouse models, and in patients with acute tubule necrosis (ATN). In the AKI kidneys, we found that Mincle expression was tightly correlated to the necrotic tubular epithelial cells (TECs) with higher expression of SAP130, a damaged associated molecule pattern (DAMP), suggesting that SAP130 released from damaged tubular cells may trigger macrophage activation and necroinflammation. This was confirmed in vivo in which administration of SAP130-rich supernatant from dead TECs or recombinant SAP130 promoted Mincle expression and macrophage accumulation which became worsen with profound tubulointerstitial inflammation in LPS-primed Mincle WT mice but not in Mincle deficient mice. Further studies identified that Mincle was negatively regulated via miR-219c-3p in macrophages as miR-219c-3p bound Mincle 3′-UTR to inhibit Mincle translation. Besides, lentivirus-mediated renal miR-219c-3p overexpression blunted Mincle and proinflammatory cytokine expression as well as macrophage infiltration in the inflamed kidney of UUO mice. In conclusion, SAP130 is released by damaged tubules which elicit Mincle activation on macrophages and renal necroinflammation via the miR-219c-3p-dependent mechanism. Results from this study suggest that targeting miR-219c-3p/Mincle signaling may represent a novel therapy for AKI.

A Metabolic Profiling Study of Realgar-Induced Acute Kidney Injury in Mice.

Realgar has been used as a type of mineral drug that contains arsenic for thousands of years. Previous studies have shown that Realgar-induced acute kidney injury is associated with abnormal metabolism, but the underlying mechanism is poorly understood. The aim of this study is to investigate the metabolic changes in serum and kidney tissues of mice exposed to Realgar by using a metabolomic approach and explore the molecular mechanisms of acute kidney injury induced by Realgar. Forty mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After 1 week, the body weight and kidney weight of the mice were measured. The serum and kidney samples were used for LC-MS spectroscopic metabolic profiling. Principal component analysis (PCA), correlation analysis, and pathway analysis were used to detect the nephrotoxic effects of Realgar. Body weight decreased significantly in the 2.0 g/kg group, and the kidney weight index also showed a dose-dependent increase in Realgar. The PCA score plot showed the serum and kidney tissue metabolic profile of mice exposed to 2.0 g/kg Realgar separated from the control group, while the lower-doses of 0.5 g/kg and 1.0 g/kg Realgar shown a similar view to the Control group. Thirty-three metabolites and seventeen metabolites were screened and identified in the serum and kidney of mice in a dose-dependent manner. respectively. Correlation analysis showed a strong correlation among these metabolites. Amino acid metabolism, lipid metabolism, glutathione metabolism, and purine metabolism pathways were found to be mainly associated with Realgar nephrotoxicity. This work illustrated the metabolic alterations in Realgar-induced nephrotoxic mice through a metabolomic approach.

An acute phase protein \u03b11-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action

The molecular mechanism for acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) continues to be unclear. In this study, we investigated the pathophysiological role of the acute phase protein α1-acid glycoprotein (AGP) in AKI and its progression to CKD using AGP KO mice. Plasma AGP levels in WT mice were increased by about 3.5-fold on day 1–2 after renal ischemia–reperfusion (IR), and these values then gradually decreased to the level before renal IR on day 7–14. On day 1 after renal IR, the AGP KO showed higher renal dysfunction, tubular injury and renal inflammation as compared with WT. On day 14, renal function, tubular injury and renal inflammation in WT had recovered, but the recovery was delayed, and renal fibrosis continued to progress in AGP KO. These results obtained from AGP KO were rescued by the administration of human-derived AGP (hAGP) simultaneously with renal IR. In vitro experiments using RAW264.7 cells showed hAGP treatment suppressed the LPS-induced macrophage inflammatory response. These data suggest that endogenously induced AGP in early renal IR functions as a renoprotective molecule via its anti-inflammatory action. Thus, AGP represents a potential target molecule for therapeutic development in AKI and its progression CKD.

Nuciferine protects against folic acid-induced acute kidney injury by inhibiting ferroptosis.

Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid-induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury. The effects of nuciferine on folic acid-induced acute kidney injury in mice were investigated. HK-2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3-induced ferroptosis. Nuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid-induced acute kidney injury. In HK-2 and HEK293T cells, nuciferine significantly prevented RSL3-induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis. Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.

Severe Acute Respiratory Syndrome Coronavirus-2-Associated Acute Kidney Injury: A Narrative Review Focused Upon Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 acute kidney injury is a condition that in many ways resembles classical acute kidney injury. The pathophysiology appears to be multifactorial, and accordingly, our main objective was to review possible components of this form of acute kidney injury. Literature review. Our principal observation was that the various components of severe acute respiratory syndrome coronavirus-2 acute kidney injury appear to be relatively similar to the classical forms. Temporality of injury is an important factor but is not specific to severe acute respiratory syndrome coronavirus-2 acute kidney injury. Several insults hit the kidney at different moments in the course of disease, some occurring prior to hospital admission, whereas others take place at various stages during hospitalization. Treatment of severe acute respiratory syndrome coronavirus-2 acute kidney injury cannot be approached in a "one-size-fits-all" manner. The numerous mechanisms involved do not occur simultaneously, leading to a multiple hit model that may contribute to the prevalence and severity of acute kidney injury. A personalized approach to each patient with acute kidney injury based on the timing and severity of disease is necessary in order to provide appropriate treatment. Although data from the literature regarding the previous coronavirus infections can give some insights, more studies are needed to explore the different mechanisms of acute kidney injury occurring as a result of severe acute respiratory syndrome coronavirus-2.

An Ultrasmall RuO2 Nanozyme Exhibiting Multienzyme-like Activity for the Prevention of Acute Kidney Injury.

Oxidative stress induced by reactive oxygen species (ROS) is one of the major pathological mechanisms of acute kidney injury (AKI). Inorganic nanomaterial-mediated antioxidant therapy is considered a promising method for the prevention of AKI; however, currently available antioxidants for AKI exhibit limited clinical efficacy due to the glomerular filtration threshold (∼6 nm). To address this issue, we developed ultrasmall RuO2 nanoparticles (RuO2NPs) (average size ≈ 2 nm). The NPs show excellent antioxidant activity and low biological toxicity. In addition, they can pass through the glomerulus to be excreted. These properties in combination make the ultrasmall RuO2NPs promising as a nanozyme for the prevention of AKI. The NP catalytic properties mimic the activity of catalase, peroxidase, superoxide dismutase, and glutathione peroxidase. The nanozyme can be efficiently and rapidly absorbed by human embryonic kidney cells while significantly reducing ROS-induced apoptosis by eliminating excess ROS. After intravenous injection, the ultrasmall RuO2NPs significantly inhibit the development of AKI in mice. In vivo toxicity experiments demonstrate the biosafety of the NPs after long-term preventing. The multienzyme-like activity and biocompatibility of the ultrasmall RuO2NPs makes them of great interest for applications in the fields of biomedicine and biocatalysis.

Long-term complications of acute kidney injury in children.

The current review will describe the current evidence and mechanisms of acute kidney injury (AKI) as a risk factor for long-term kidney complications, summarize the rationale for AKI follow-up and present an approach to monitoring children with AKI. Despite emerging evidence linking AKI with risk for long-term kidney and cardiovascular outcomes, many children who develop AKI are not followed for kidney disease development after hospital discharge. Better understanding of long-term complications after AKI and practical algorithms for follow-up will hopefully increase the rate and quality of post-AKI monitoring. Recent evidence shows that pediatric AKI is associated with long-term renal outcomes such as chronic kidney disease (CKD) and hypertension, both known to increase cardiovascular risk. The mechanism of AKI progression to CKD involves maladaptive regeneration of tubular epithelial and endothelial cells, inflammation, fibrosis and glomerulosclerosis. Many AKI survivors are not followed, and no guidelines for pediatric AKI follow-up have been published. Children who had AKI are at increased risk of long-term renal complications but many of them are not monitored for these complications. Recognizing long-term outcomes post-AKI and integration of follow-up programs may have a long-lasting positive impact on patient health.

SAT-433 RENAL CORTICAL NECROSIS IN NON-HEMORRHAGIC DENGUE FEVER- A RARE CASE REPORT

Dengue fever is a tropical febrile illness caused by one of the 4 genotypes of dengue virus. Acute Kidney Injury (AKI) is a rare complication of Dengue Fever and is usually associated with severe forms of the disease as in Dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). We present a patient diagnosed as a case of Dengue fever without Shock or any Hemorrhagic manifestation, developing Acute Cortical Necrosis and requiring maintenance Haemodialysis. Patient was admitted with Acute febrile illness, diagnosis of Dengue Fever was confirmed by positive IgM for Dengue. He underwent extensive diagnostic workup to rule out other causes of Acute Kidney Injury. 30 year old married, male, patient was admitted complaints of Abdominal pain and fever since 3 days with history of decreased urine output since one day. There was no history of any Malena or hematemesis or any chronic illness like Hypertension or Diabetes. Blood pressure was within normal limit. His blood investigations revealed Hb 12.7g/dl, Total Leucocyte count-10860/cumm, Platelet counts-3,65000/cumm, Hematocrit-37.3%, Reticulocyte count-1%, ESR-02, APTT-26, INR was 1.20, Peripheral Smear showed Normocytic Normochromic RBCS with no schistocytes. SGPT-92, SGOT-94, Total bilirubin-0.8, Total Serum Proteins-6.2g/dl, Serum Albumin-3.5g/dl, Serum Globulin-2.7g/dl, Lipase-65, Amylase-73, LDH-1297, TSH-1.67, RBS-102, Blood urea-111mg/dl, Serum Creatinine-6.27mg/dl, Na-138, K-4.3, Bicarbonate-18.1mmol/L, Creatinine Phosphokinase-193, C3 level was normal, Calcium-8.4mg/dl, iPTH-75 pg/ml, Dengue Serology showed positive IgM for Dengue, Malaria antigen was negative. His Direct coombs test, Antinuclear Antibody, ANCA c & p, Lupus anticoagulant, Antiphospholipid antibody, Anticardiolipin antibodies, Protein C and S deficiency were negative.G6PD quantitative was within normal limits and Sickling test was negative. His heavy metal screening was also negative. Urine RM showed Protein 3+, WBCs-03, RBCs-02(isomorphic type). Patient was initially managed with Intravenous fluids and later Haemodialysis was started in view of severe acidosis and fluid overload. He underwent extensive radiological evaluation with Ultrasonography of Abdomen showing normal liver echoes with bilateral normal sized kidney and intact corticomedullary differentiation with decreased cortical blood flow on power doppler, CT Contrast study of Abdomen confirmed poor renal cortical blood flow. Renal Biopsy was done which showed Cortical Necrosis with near complete thrombotic occlusion in medium sized vessels. In view of persistent Anuria, the patient was put on maintenance Haemodialysis. Irreversible Kidney Injury is an extremely rare complication of Dengue fever as most of the patients of AKI recover with supportive treatment. In our case a young patient with a short clinical history of Dengue Fever presented with AKI. Renal Biopsy showed Renal Cortical Necrosis with medium sized vessels showing near complete occlusion of vascular lamina by thrombi suggesting Thrombotic Microangiopathy. Hence, delay in recovery of AKI in Dengue patients presenting without Hemorrhage or shock should prompt the clinician to evaluate further regarding the underlying pathological mechanisms of Acute Kidney Injury.

Cell-free hemoglobin augments acute kidney injury during experimental sepsis.

Acute kidney injury is a common complication of severe sepsis and contributes to high mortality. The molecular mechanisms of acute kidney injury during sepsis are not fully understood. Because hemoproteins, including myoglobin and hemoglobin, are known to mediate kidney injury during rhabdomyolysis, we hypothesized that cell-free hemoglobin (CFH) would exacerbate acute kidney injury during sepsis. Sepsis was induced in mice by intraperitoneal injection of cecal slurry (CS). To mimic elevated levels of CFH observed during human sepsis, mice also received a retroorbital injection of CFH or dextrose control. Four groups of mice were analyzed: sham treated (sham), CFH alone, CS alone, and CS + CFH. The addition of CFH to CS reduced 48-h survival compared with CS alone (67% vs. 97%, P = 0.001) and increased the severity of illness. After 24 and 48 h, CS + CFH mice had a reduced glomerular filtration rate from baseline, whereas sham, CFH, and CS mice maintained baseline glomerular filtration rate. Biomarkers of acute kidney injury, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), were markedly elevated in CS+CFH compared with CS (8-fold for NGAL and 2.4-fold for KIM-1, P < 0.002 for each) after 48 h. Histological examination showed a trend toward increased tubular injury in CS + CFH-exposed kidneys compared with CS-exposed kidneys. However, there were similar levels of renal oxidative injury and apoptosis in the CS + CFH group compared with the CS group. Kidney levels of multiple proinflammatory cytokines were similar between CS and CS + CFH groups. Human renal tubule cells (HK-2) exposed to CFH demonstrated increased cytotoxicity. Together, these results show that CFH exacerbates acute kidney injury in a mouse model of experimental sepsis, potentially through increased renal tubular injury.

Pathogenesis and Management of Acute Kidney Injury in Patients with Nephrotic Syndrome Due to Primary Glomerulopathies.

Acute kidney injury in the context of nephrotic syndrome is a serious and alarming clinical problem. Largely, acute kidney injury is a relatively frequent complication among patients with comorbidities while it has been independently associated with an increased risk of adverse outcomes, including death and chronic kidney disease. Nephrotic syndrome, without hematuria or with minimal hematuria, includes a list of certain glomerulopathies; minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy. In the light of primary nephrotic syndrome, pathophysiology of acute kidney injury is differentiated by the nature of the primary disease and the severity of the nephrotic state. This review aims to explore the clinical circumstances and pathogenetic mechanisms of acute kidney injury in patients with nephrotic syndrome due to primary glomerulopathies, focusing on newer perceptions regarding the pathogenesis and management of this complicated condition, for the prompt recognition and timely initiation of appropriate treatment in order to restore renal function to its baseline level. Prompt recognition of the precise cause of acute kidney injury is crucial for renal recovery. Clinical characteristics, laboratory and serological findings along with histopathological findings, if required, will reveal the implicated pathway leading to individualized approach and management.

Nephrocheck after cardiac surgery: Does it play a role in daily practice? A sequel of "Nephrocheck results should be corrected for dilution".

Acute kidney injury is a well-recognized complication after cardiac surgery and significantly affects morbidity and mortality. Although the mechanisms of acute kidney injury are not fully understood, Nephrocheck (Astute Medical, San Diego, CA, USA) is a meter for early detection of acute kidney injury based on bedside urinalysis of two cell-cycle arrest biomarkers. However, considerable overlap in the AKIRiskTM score of different RIFLE groups makes interpretation of the score uncertain. A possible reason for the overlap in the AKIRisk score between different RIFLE groups could be that the score is not corrected for dilution. We performed a pilot study to explore the applicability of the test in our daily practice. A total of 68 patients electively scheduled for cardiac surgery with at least two of the following inclusion criteria: age > 70 years, glomerular filtration rate <60 mL/min, left ventricular ejection fraction <41%, redo procedure and combined procedures have been enrolled in the study, and 25 of them developed acute kidney injury. We described the correlation between urine creatinine and Nephrocheck, all the samples with low Nephrocheck (<0.2) also have low urine creatinine, less than 50 mg/dL, detecting a potential diluted sample. In conclusion, in our daily practice AKIRisk score, together with an assessment of whether urine is diluted or concentrated can better discriminate between various degrees of acute kidney injury.

Enhanced efficiency of mitochondria-targeted peptide SS-31 for acute kidney injury by pH-responsive and AKI-kidney targeted nanopolyplexes

Oxidative stress is an important pathological mechanism for acute kidney injury (AKI). SS-31, as a mitochondria-targeted peptide with strong antioxidant activity, is a good candidate for the treatment of AKI. However, an efficient treatment of AKI requires frequent administration of SS-31, which is due to its poor specific biodistribution and low delivery efficiency. To overcome these deficiencies, we designed pH-responsive and AKI-kidney targeted nanopolyplexes (NPs) for effectively delivering SS-31, which is new frontier for formulation of HA and CS. NPs are electrostatically complexed using anionic hyaluronic acid and cationic chitosan as materials, which could increase the accumulation in injured areas and uptake into CD44-overexpressed cells. Electrostatic balance of NPs is broken in low pH environment of lysosomes to allow SS-31 releasing and subsequently targeting to mitochondria to represent therapeutic effect. In vitro studies indicate that NPs exhibited higher antioxidative and antiapoptotic effects as compared with free SS-31. AKI mouse model suggests that NPs have significantly higher therapeutic efficiency than bare SS-31. It was found that NPs had excellent ability to decrease oxidative stress, protect mitochondrial structure, reduce inflammatory response, reduce apoptosis and necrosis of tubular cells after intravenious administration. Overall, the results suggest that the NPs have significant potential to enhance the specific biodistribution and delivery of SS-31, therefore have good effects on reducing oxidative stress and inflammation, preventing tubular apoptosis and necrosis. We believe NPs are effective delivery system for AKI treatment in clinical application.

The Changing Face of Human Immunodeficiency Virus-Mediated Kidney Disease.

In nearly 40years since human immunodeficiency virus (HIV) first emerged, much has changed. Our understanding of the pathogenesis of HIV infection and its effect on the cells within each kidney compartment has progressed, and the natural history of the disease has been transformed. What was once an acutely fatal illness is now a chronic disease managed with oral medications. This change is largely due to the advent of antiretroviral drugs, which have dramatically altered the prognosis and progression of HIV infection. However, the success of antiretroviral therapy has brought with it new challenges for the nephrologist caring for patients with HIV/acquired immune deficiency syndrome, including antiretroviral therapy-induced nephrotoxicity, development of non-HIV chronic kidney disease, and rising incidence of immune-mediated kidney injury. In this review, we discuss the pathogenesis of HIV infection and how it causes pathologic changes in the kidney, review the nephrotoxic effects of select antiretroviral medications, and touch upon other causes of kidney injury in HIV cases, including mechanisms of acute kidney injury, HIV-related immune complex glomerular disease, and thrombotic microangiopathy.

Risk Factors and Mechanisms Underlying Cross-Shift Decline in Kidney Function in Guatemalan Sugarcane Workers.

Identify early biomarkers and mechanisms of acute kidney injury in workers at risk of developing chronic kidney disease of unknown origin (CKDu). We assessed cross-shift changes in kidney function and biomarkers of injury in 105 healthy sugarcane workers. We obtained pre-harvest clinical data as well as daily environmental, clinical, and productivity data for each worker. The average percent decline in cross-shift estimated glomerular filtration rate (eGFR) was 21.8% (standard deviation [SD] 13.6%). Increasing wet bulb globe temperature (WBGT), high uric acid, decreased urine pH, urinary leukocyte esterase, and serum hyperosmolality were risk factors for decline in kidney function. Sugarcane workers with normal kidney function experience recurrent subclinical kidney injury, associated with elevations in biomarkers of injury that suggest exposure to high temperatures and extreme physical demands.