Assessment of the antioxidant status and markers of oxidative stress in patients with kidney failure: effects of a hemodialysis session.

Data about the impacts of hemodialysis on antioxidant status and markers of oxidative stress are controversial, probably due to the use of different methodological approaches. The aim of this study was to assess the changes in the oxidative damage markers and antioxidant enzymes, and the serum antioxidant capacity by using in vitro model systems of free radical generation before and after one hemodialysis session. Blood samples were collected from 40 patients with kidney failure before and after hemodialysis. In pre- and post-hemodialysis serum samples, concentrations of biomarkers of oxidative damage and the activities of antioxidant enzymes were measured, as well as the in vitro antioxidant potential. The high concentrations of oxidative stress markers in serum of kidney failure patients were decreased after one hemodialysis session. In pre-hemodialysis, low activities of antioxidant enzymes were observed, including paraoxonase-1, however paraoxonase-1 activity was partially recovered after hemodialysis. Crocin bleaching and radical scavenging assays showed that serum antioxidant potential was decreased after hemodialysis. Although one hemodialysis session increased paraoxonase-1 activity and decreased oxidative stress markers, it caused a decrease in the serum antioxidant potential. Future research is needed to prospect strategies to mitigate the impacts of oxidative stress in the scenario of hemodialysis repetitions.

A comparative study on the haemostatic changes in kidney failure patients: Pre- and post- haemodialysis and haemodiafiltration.

BACKGROUND: Individuals with kidney failure have a compromised haemostatic system making them susceptible to both thrombosis and bleeding. OBJECTIVES: Assessment of primary haemostasis in patients treated with either haemodialysis (HD) or haemodiafiltration (HDF) was performed through the measurement of several coagulation-based tests, both pre- and post-dialysis. PATIENTS/METHODS: 41 renal failure patients and 40 controls were recruited. Platelet aggregometry, Factor XIII (FXIII), Fibrinogen, Von Willebrand Factor (VWF) and Soluble P-Selectin (sP-Sel) levels were measured. RESULTS: Maximum platelet aggregation was diminished in renal patients irrespective of aspirin intake. Post-dialysis, platelet function was exacerbated. Pre-dialysis FXIII levels were similar to the healthy cohort and became elevated post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. Fibrinogen levels were already elevated pre-dialysis and further increased post-dialysis. This elevation was associated with the relative decrease of water by dialysis. VWF levels in males were similar to the healthy cohort and became elevated post-dialysis. This elevation was associated with dialysis-related water loss. VWF antigen and activity in female patients were already elevated pre-dialysis and further increased post-dialysis with the exception of VWF activity in HDF treated female patients. sP-Sel levels were lower than those of the healthy cohort and became similar to the healthy cohort post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. CONCLUSIONS: Whilst platelet aggregometry was diminished, we noted elevated clotting factors such as fibrinogen, FXIII and VWF with no significant differences between HD and HDF-treated patients.

Association between Low Serum Creatinine Levels and Knee Osteoarthritis in Koreans without Renal Insufficiency.

PURPOSE: This study aimed to investigate the correlation between serum creatinine levels and the presence and severity of radiographic knee osteoarthritis (OA) in individuals aged ≥50 years while adjusting for potential confounders. MATERIALS AND METHODS: Cross-sectional data from the 2009-2011 Korea National Health and Nutrition Examination Survey comprising 3428 individuals aged ≥50 years were utilized. The Kellgren-Lawrence (K-L) grading scale was used to assess the radiographic presence and severity of knee OA. Logistic regression and receiver operating characteristic analyses were used to investigate the association between serum creatinine levels and the presence of knee OA, whereas ordinal regression was used to assess the impact of creatinine levels on knee OA severity. RESULTS: The presence of radiographic knee OA conferred by low serum creatinine levels was found to be significant in both sexes [odds ratio (OR), 0.118; 95% confidence interval (CI), 0.045-0.314, p<0.001 for men; OR, 0.148; 95% CI, 0.040-0.549, p=0.004 for women]. Low serum creatinine was significantly associated with knee OA-graded K-L severity in each sex-based group [ß, -1.923; standard error, 0.478; p<0.001 for men and ß, -1.532; SE, 0.575; p=0.008 for women]. CONCLUSION: Low serum creatinine level was associated with a higher presence of knee OA in both men and women, and was also linked to the severity of the disease. These findings suggest that the serum creatinine level may be a potential biomarker for assessing the presence and severity of knee OA.

Efectos histológicos hepático y renal relacionados con la hiperglicemia producida por el extracto de Angostura trifoliata (Willd) T.S. Elías. Rutaceae / Hepatic and renal histological effects related to hyperglycemia produced by the extract of Angostura trifoliata (Willd) T.S. Elías. Rutaceae

Angostura trifoliata (Willd) T.S. Elías (Rutaceae) es una planta, cuya corteza es empleada en Venezuela para el tratamiento de la diabetes mellitus, la malaria y la disminución de peso. Sin embargo, se ha demostrado que altas dosis de su extracto administrados en forma aguda producen hiperglicemia y alteraciones neurológicas. El objetivo de este estudio fue correlacionar los efectos histológicos a nivel hepático y renal en ratones sanos con la hiperglicemia aguda producida por el extracto de la corteza de esta planta. Métodos: Se realizó un estudio experimental in vivo utilizando el extracto diluido en agua y administrado vía ip a dosis de 452 y 700 mg/kg; se determinó la glicemia utilizando un glucómetro comercial; los efectos histológicos con hematoxilina eosina previa fijación de los órganos con formaldehído al 10%. En todos los casos, se comparó con el grupo control. Resultados: el extracto produjo hiperglicemia significativamente P<0,05. En el tejido hepático causó: pérdida parcial de su arquitectura, binucleación, vasos congestivos con elementos inflamatorios, núcleos hipercromáticos, espacios de Disse dilatados con hematíes y áreas de necrosis. En el riñón originó congestión vascular en los tubos contorneados proximales y distales, concomitante con ruptura y necrosis de la membrana basal. Conclusión: el extracto produce toxicidad hepática y renal que se correlacionan con hiperglicemia, por lo que podría ser considerado como un agente hepatotóxico y nefrotóxico. (AU)

Angostura trifoliata (Willd) T.S. Elías (Rutaceae) is a plant, whose bark is used in Venezuela for the treatment of diabetes mellitus, malaria and weight loss. However, it has been shown that high doses of its extract administered acutely produce hyperglycemia and neurological alterations. The objective of this study was to correlate the histological effects at the liver and kidney level in healthy mice with the acute hyperglycemia produced by the bark extract of this plant. Methods: An in vivo experimental study was carried out using the extract diluted in water and administered ip at doses of 452 and 700 mg/kg; blood glucose was determined using a commercial glucometer; the histological effects with hematoxylin eosin after fixation of the organs with 10% formaldehyde. In all cases, it was compared with the control group. Results: the extract produced hyperglycemia significantly P<0.05. In the liver tissue it caused: partial loss of its architecture, binucleation, congested vessels with inflammatory elements, hyperchromatic nuclei, dilated spaces of Disse with red blood cells and areas of necrosis. In the kidney, it caused vascular congestion in the proximal and distal convoluted tubes, concomitant with rupture and necrosis of the basement membrane. Conclusion: the extract produces liver and kidney toxicity that correlates with hyperglycemia, so it could be considered a hepatotoxic and nephrotoxic agent. (AU)

Kidney Function Biomarkers During Extreme Heat Exposure in Young and Older Adults.

This study investigates the effects of extreme heat exposure on kidney function using plasma-based biomarkers in young and older adults.

Associations of Urine and Plasma Metabolites With Kidney Failure and Death in a Chronic Kidney Disease Cohort.

RATIONALE & OBJECTIVE: Biomarkers that enable better identification of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease. STUDY DESIGN: Prospective metabolome-wide association study. SETTING & PARTICIPANTS: Persons with CKD enrolled in the GCKD (German CKD) study with metabolite measurements, with external validation within the ARIC (Atherosclerosis Risk in Communities) Study. EXPOSURES: 1,513 urine and 1,416 plasma metabolites (Metabolon Inc) measured at study entry using untargeted mass spectrometry. OUTCOMES: Main end points were kidney failure (KF) and a composite kidney end point (CKE) of KF, estimated glomerular filtration rate<15mL/min/1.73m2, or a 40% decrease in estimated glomerular filtration rate. Death from any cause was a secondary end point. After a median of 6.5 years of follow-up, 500 persons had experienced KF, 1,083 had experienced the CKE, and 680 had died. ANALYTICAL APPROACH: Time-to-event analyses using multivariable proportional hazard regression models in a discovery-replication design with external validation. RESULTS: 5,088 GCKD study participants were included in analyses of urine metabolites, and 5,144 were included in analyses of plasma metabolites. Among 182 unique metabolites, 30 were significantly associated with KF, 49 with the CKE, and 163 with death. The strongest association with KF was observed for plasma hydroxyasparagine (HR, 1.95; 95% CI, 1.68-2.25). An unnamed metabolite measured in plasma and urine was significantly associated with KF, the CKE, and death. External validation of the identified associations of metabolites with KF or the CKE revealed directional consistency for 88% of observed associations. Selected associations of 18 metabolites with study outcomes have not been previously reported. LIMITATIONS: Use of observational data and semiquantitative metabolite measurements at a single time point. CONCLUSIONS: The observed associations between metabolites and KF, the CKE, or death in persons with CKD confirmed previously reported findings and also revealed several associations not previously described. These findings warrant confirmatory research in other study cohorts. PLAIN-LANGUAGE SUMMARY: Incomplete understanding of the variability of chronic kidney disease (CKD) progression motivated the search for new biomarkers that would help identify people at increased risk. We explored metabolites in plasma and urine for their association with unfavorable kidney outcomes or death in persons with CKD. Metabolomic analyses revealed 182 metabolites significantly associated with CKD progression or death. Many of these associations confirmed previously reported findings or were validated by analysis in an external study population. Our comprehensive screen of the metabolome serves as a valuable foundation for future investigations into biomarkers associated with CKD progression.

Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant.

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.

Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes.

Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.

GC × GC-TOFMS metabolomics analysis identifies elevated levels of plasma sugars and sugar alcohols in diabetic mellitus patients with kidney failure.

Two dimensional GC (GC × GC)-time-of-flight mass spectrometry (TOFMS) has been used to improve accurate metabolite identification in the chemical industry, but this method has not been applied as readily in biomedical research. Here, we evaluated and validated the performance of high resolution GC × GC-TOFMS against that of GC-TOFMS for metabolomics analysis of two different plasma matrices, from healthy controls (CON) and diabetes mellitus (DM) patients with kidney failure (DM with KF). We found GC × GC-TOFMS outperformed traditional GC-TOFMS in terms of separation performance and metabolite coverage. Several metabolites from both the CON and DM with KF matrices, such as carbohydrates and carbohydrate-conjugate metabolites, were exclusively detected using GC × GC-TOFMS. Additionally, we applied this method to characterize significant metabolites in the DM with KF group, with focused analysis of four metabolite groups: sugars, sugar alcohols, amino acids, and free fatty acids. Our plasma metabolomics results revealed 35 significant metabolites (12 unique and 23 concentration-dependent metabolites) in the DM with KF group, as compared with those in the CON and DM groups (N = 20 for each group). Interestingly, we determined 17 of the 35 (14/17 verified with reference standards) significant metabolites identified from both the analyses were metabolites from the sugar and sugar alcohol groups, with significantly higher concentrations in the DM with KF group than in the CON and DM groups. Enrichment analysis of these 14 metabolites also revealed that alterations in galactose metabolism and the polyol pathway are related to DM with KF. Overall, our application of GC × GC-TOFMS identified key metabolites in complex plasma matrices.

High-sensitivity cardiac troponin and the diagnosis of myocardial infarction in patients with kidney impairment.

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients with suspected acute coronary syndrome enrolled in a stepped-wedge, cluster-randomized controlled trial were included in this pre-specified secondary analysis. Kidney impairment was defined as an eGFR under 60mL/min/1.73m2. The index diagnosis and primary outcome of type 1 and type 4b myocardial infarction or cardiovascular death at one year were compared in patients with and without kidney impairment following implementation of hs-cTnI assay with 99th centile sex-specific diagnostic thresholds. Serum creatinine concentrations were available in 46,927 patients (mean age 61 years; 47% women), of whom 9,080 (19%) had kidney impairment. hs-cTnIs were over 99th centile in 46% and 16% of patients with and without kidney impairment. Implementation increased the diagnosis of type 1 infarction from 12.4% to 17.8%, and from 7.5% to 9.4% in patients with and without kidney impairment (both significant). Patients with kidney impairment and type 1 myocardial infarction were less likely to undergo coronary revascularization (26% versus 53%) or receive dual anti-platelets (40% versus 68%) than those without kidney impairment, and this did not change post-implementation. In patients with hs-cTnI above the 99th centile, the primary outcome occurred twice as often in those with kidney impairment compared to those without (24% versus 12%, hazard ratio 1.53, 95% confidence interval 1.31 to 1.78). Thus, hs-cTnI testing increased the identification of myocardial injury and infarction but failed to address disparities in management and outcomes between those with and without kidney impairment.

Europium (III) chelate nanoparticle-based lateral flow immunoassay strips for rapid and quantitative detection of cystatin C in serum.

The concentration of Cys C in the patient's serum can reflect the level of glomerular filtration rate and indicate the occurrence of renal failure. The establishment of a simple and rapid analytical method to quantitatively monitor the concentration of Cys C in serum could help timely detection of renal failure. In this study, we have developed an Eu (III) chelate nanoparticles based lateral flow immunoassay to fulfill real-time monitoring of Cys C concentration in serum within 15 min. This method was performed as a sandwich immunoassay with a wide detection range (0.05-10 µg/mL) and a low limit of detection (24.54 ng/mL). The intra and inter-assay coefficients of variation were 8.31-8.61% and 8.92-9.95%, respectively. Furthermore, the application of this method was evaluated by comparing the determined results with those obtained by chemiluminescence immunoassay, exhibiting a satisfactory correlation (R2 = 0.9830). The developed LFIA method with satisfactory analytical performance has great potential for real-time monitoring of renal failure and self-detection for the high-risk population.

Circulating Cystatin C Is an Independent Risk Marker for Cardiovascular Outcomes, Development of Renal Impairment, and Long-Term Mortality in Patients With Stable Coronary Heart Disease: The LIPID Study.

Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; P=0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; P<0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each P<0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471.

Favorable therapeutic efficacy of low-density lipoprotein apheresis for nephrotic syndrome with impaired renal function.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m2 ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m2 ), and severely impaired (S) (<30 ml/min/1.73 m2 ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m2 .

Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial.

INTRODUCTION: Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. AIMS: Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. METHODS: WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR <15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. RESULTS: 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06-7.96), p value <0.0001. CONCLUSION: Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.

Effects of High-Flux Dialysis Combined with Hemoperfusion on Serum GRP78 and miR-495-3p in Renal Failure Patients.

OBJECTIVE: This study was designed to probe into the changes and clinical significance of GRP78 and miR-495-3p in renal failure (RF) patients during high-flux dialysis (HFD) combined with hemoperfusion (HP). METHODS: Sixty-five RF patients and 74 health check-ups who were admitted in our hospital from March 2015 to February 2017 were prospectively selected, and the related characteristics were retrospectively collected for analysis. GRP78 and miR-495-3p were detected in RF patients at admission (before treatment), 12 weeks after treatment (during treatment), 24 weeks after treatment (after treatment), and the control group at admission, and the relationship between the two and the occurrence, efficacy, and recurrence of RF was analyzed. RESULTS: Before treatment, the GRP78 mRNA level in RF patients was higher than that in health check-ups, while the miR-495-3p level was lower (P < 0.05). GRP78 mRNA in RF patients was lower than that before treatment and was the lowest after treatment. On the contrary, miR-495-3p was higher than that before treatment and was the highest after treatment (P < 0.05). The two had a significant effect on predicting RF before treatment, efficacy of patients, and their recurrence after treatment (all P < 0.001). CONCLUSION: GRP78 decreased during the treatment of high-flux hemodialysis (HF-HD) combined with systemic HP in RF patients, while miR-495-3p increased. Both of them have a good reference value for RF occurrence, treatment results, and recurrence.

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis.

The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.

Hydrogel-coated needles prevent puncture site bleeding in arteriovenous fistula and arteriovenous grafts in rats.

INTRODUCTION: Imperfect hemostasis after arteriovenous fistula (AVF) and arteriovenous graft (AVG) cannulation can cause a hematoma or pseudoaneurysm and leads to poor satisfaction. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation in a rat AVF and AVG model. METHOD: A hydrogel comprised of sodium alginate (SA), hyaluronic acid (HA), and calcium carbonate was coated onto the surface of suture needles using a rotating system. The needles were observed using scanning electron microscopy (SEM) and immunofluorescence. Rat AVF with or without renal failure and AVG were punctured using bare and hydrogel-coated needles. The tissues were examined by histology. RESULT: The hydrogel was successfully coated onto the surface of 30 G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after AVF and AVG cannulation in rat. CONCLUSION: In this preliminary animal research, hydrogel-coated needles can stop AVF and AVG puncture-site bleeding; but additional clinical studies are needed to justify whether it is still effective in clinical.

Soluble urokinase plasminogen activator receptor (suPAR) predicts critical illness and kidney failure in patients admitted to the intensive care unit.

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker and risk factor for kidney diseases, with a potential prognostic value in critically ill patients. In this monocentric prospective study, we measured plasma suPAR levels immediately after ICU admission in unselected 237 consecutive patients using a turbidimetric assay. Primary objective was the prognostic value for ICU- and 28-day mortality. Secondary objectives were association with sequential organ failure assessment (SOFA) score, coagulation and inflammation markers, AKI-3 and differences in prespecified subgroups. Median suPAR levels were 8.0 ng/mL [25th-75th percentile 4.3-14.4], with lower levels in ICU survivors than non-survivors (6.7 vs. 11.6 ng/mL, p < 0.001). SuPAR levels were higher in COVID-19, kidney disease, moderate-to-severe liver disease, and sepsis. ICU mortality increased by an odds ratio (OR) of 4.7 in patients with the highest compared to lowest quartile suPAR. Kaplan-Meier overall survival estimates at 3 months were 63% and 49%, in patients with suPAR below/above 12 ng/mL (log-rank p = 0.027). Due to an observed interaction between SOFA score and suPAR, we performed a random forest method identifying cutoffs. ICU mortality was 53%, 17% and 2% in patients with a SOFA score > 7, SOFA ≤ 7 & suPAR > 8 ng/mL, and SOFA score ≤ 7 & suPAR ≤ 8 ng/mL, respectively. suPAR was a significant predictor for AKI-3 occurrence (OR per doubling 1.89, 95% CI: 1.20-2.98; p = 0.006). suPAR levels at ICU admission may offer additional value for risk stratification especially in ICU patients with moderate organ dysfunction as reflected by a SOFA score ≤ 7.