Search

Background: Acute kidney injury (AKI) and chronic kidney disease (CKD) are common syndromes associated with significant morbidity, mortality and cost. The extent to which repeated AKI episodes may cumulatively affect the rate of progression of all-cause CKD has not previously been investigated. In this study, we explored the hypothesis that repeated episodes of AKI increase the rate of renal functional deterioration loss in patients recruited to a large, all-cause CKD cohort., Methods: Patients from the Salford Kidney Study (SKS) were considered. Application of KDIGO criteria to all available laboratory measurements of renal function identified episodes of AKI. A competing risks model was specified for four survival events: Stage 1 AKI; stage 2 or 3 AKI; dialysis initiation or transplant before AKI event; death before AKI event. The model was adjusted for patient age, gender, smoking status, alcohol intake, diabetic status, cardiovascular co-morbidities, and primary renal disease. Analyses were performed for patients' first, second, and third or more AKI episodes., Results: A total of 48,338 creatinine measurements were available for 2287 patients (median 13 measures per patient [IQR 6-26]). There was a median age of 66.8years, median eGFR of 28.4 and 31.6% had type 1 or 2 diabetes. Six hundred and forty three (28.1%) patients suffered one or more AKI events; 1000 AKI events (58% AKI 1) in total were observed over a median follow-up of 2.6 years [IQR 1.1-3.2]. In patients who suffered an AKI, a second AKI was more likely to be a stage 2 or 3 AKI than stage 1 [HR 2.04, p 0.01]. AKI events were associated with progression to RRT, with multiple episodes of AKI progressively increasing likelihood of progression to RRT [HR 14.4 after 1 episode of AKI, HR 28.4 after 2 episodes of AKI]. However, suffering one or more AKI events was not associated with an increased risk of mortality., Conclusions: AKI events are associated with more rapid CKD deterioration as hypothesised, and also with a greater severity of subsequent AKI. However, our study did not find an association of AKI with increased mortality risk in this CKD cohort., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute Kidney Injury (AKI) is common and associated with increased morbidity and mortality. This retrospective analysis quantified and compared the association between AKI and the risk of death and admission to critical care in acute admissions of different aetiology., Methods: Data were extracted anonymously from the Trust 'data warehouse' for admissions between 2011and 2017. We applied KDIGO AKI criteria to establish AKI stage. Odds ratios (OR) for death and critical care admission were calculated for patients with AKI stage 3 (compared to all other patients), and patients with any stage AKI (compared to non-AKI admissions). Analyses were performed using logistic regression, adjusted for age, pre-existing CKD, co-morbid index, and gender., Results: There were 26,052 medical and 12,560 surgical patient episodes within sixteen common diagnoses with 3823 medical and 1520 surgical patients with AKI events. The likelihood of AKI was highest in sepsis (31.8%), and the likelihood of death in AKI 3 highest in femoral neck fracture (54.5%). AKI 3 has a OR for death for acute coronary syndrome of 12.8 and a OR of 24.6 in femoral neck fracture. Admission to critical care for any AKI in medical patients has a OR of 9.6, but increases to OR 37.2 for heart failure., Conclusion: The clinical impact of AKI differs across medical and surgical diagnoses, but is a significant contributor to the risk for death and critical care admission. This body of work may indicate a benefit to a more diagnosis-specific stratified approach to AKI care., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.1371/journal.pone.0206329.].

Background: This study examined the short-term reproducibility of non-invasive estimates of central and peripheral blood pressure and markers of central systolic loading (augmentation index [AIx; a measure of central systolic loading] and AIx75 [AIx standardised to 75 b·min-1 heart rate]) and the effect of posture and fasting state on these variables in patients with acute stroke., Methods: Twenty-two acute stroke patients (72 ± 10y) had blood pressure measured using the SphygmoCor XCEL in supine and seated postures and whilst fasted and non-fasted., Results: Acceptable short-term reproducibility (ICC >0.75) was reported for all peripheral and central variables in all conditions (ICC = 0.77-0.90) and for AIx and AIx75 in both fasted postures (ICC = 0.78-0.81). Food consumption significantly lowered all blood pressures (p <0.05; η2p = 0.20-0.55). The seated posture resulted in a significantly greater AIx than supine (p <0.05; η2p = 0.22). Fasting state had significant main effects on AIx and AIx75 (p <0.05; η2p = 0.14-0.22)., Conslusions: Oscillometric estimates of central blood pressure have high short-term reproducibility in different postures and fasting states but markers of systolic load should be assessed whilst fasted. Fasting state has a large effect on central and peripheral blood pressures and on measures of systolic loading. It is important for clinicians to be aware of optimal assessment conditions without this impacting on patient wellbeing., Trial Registration: Clinical trial registry name: NCT02537652., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objectives were to assess whether anatomical location of ultrasound (USS) indicated cervical cerclage and/or the degree of cervical shortening (cervical length; CL) prior to and following cerclage affects the risk of preterm birth (PTB)., Method: A retrospective cohort study of 179 women receiving cerclage for short cervix (≤25mm) was performed. Demographic data, CL before and after cerclage insertion, height of cerclage (distance from external os) and gestation at delivery were collected. Relative risk (RR) and odds ratio (OR) of preterm delivery were calculated according to the anatomical location of the cerclage within the cervix and the CL before and after cerclage as categorical and continuous variables. Partition tree analysis was used to identify the threshold cerclage height that best predicts PTB., Results: 25% (n = 45) delivered <34 weeks and 36% (n = 65) delivered <37 weeks. Risk of PTB was greater with cerclage in the distal 10mm (RR2.37, 95% CI 1.45-3.87) or the distal half of a closed cervix (RR2.16, 95% CI 1.45-3.87). Increasing absolute cerclage height was associated with a reduction in PTB (OR 0.87, 95% CI 0.82-0.94). A cerclage height <14.5 mm best predicts PTB (70.8%). Increasing CL following cerclage was associated with a reduction in PTB (OR0.87, 95% CI 0.82-0.94). Conversely, the risk of PTB was increased where CL remained static or shortened further following cerclage (RR2.34, 95% CI 1.04-5.25)., Conclusion: The higher a cerclage was placed within a shortened cervix, the lower the subsequent odds of PTB. Women whose cerclage is placed in the distal 10mm of closed cervix or whose cervix fails to elongate subsequently, should remain under close surveillance as they have the highest risk of PTB.

Background: 15-deoxy-Δ 12,14- Prostaglandin J2 (15dPGJ2) inhibits Nuclear factor kappa B (NF-κB) in human myocytes and amniocytes and delays inflammation induced preterm labour in the mouse. 15dPGJ2 is a ligand for the Chemoattractant Receptor Homologous to the T helper 2 cell (CRTH2), a G protein-coupled receptor, present on a subset of T helper 2 (Th2) cells, eosinophils and basophils. It is the second receptor for Prostaglandin D2, whose activation leads to chemotaxis and the production of Th2-type interleukins. The cellular distribution of CRTH2 in non-immune cells has not been extensively researched, and its identification at the protein level has been limited by the lack of specific antibodies. In this study we explored the possibility that CRTH2 plays a role in 15dPGJ2-mediated inhibition of NF-κB and would therefore represent a novel small molecule therapeutic target for the prevention of inflammation induced preterm labour., Methods: The effect of a small molecule CRTH2 agonist on NF-κB activity in human cultured amniocytes and myocytes was assessed by detection of p65 and phospho-p65 by immunoblot. Endogenous CRTH2 expression in amniocytes, myocytes and peripheral blood mononuclear cells (PBMCs) was examined by PCR, western analysis and flow cytometry, with amniocytes and myocytes transfected with CRTH2 acting as a positive control in flow cytometry studies., Results: The CRTH2 agonist had no effect on NF-κB activity in amniocytes and myocytes. Although CRTH2 mRNA was detected in amniocytes and myocytes, CRTH2 was not detectable at the protein level, as demonstrated by western analysis and flow cytometry. 15dPGJ2 inhibited phospho-65 in PBMC'S, however the CRTH2 antagonist was not able to attenuate this effect. In conclusion, CRTH2 is not expressed on human amniocytes or myocytes and plays no role in the mechanism of 15dPGJ2-mediated inhibition of NF-κB.