Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury.

BACKGROUND: Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. METHODS: We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days. RESULTS: Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001). CONCLUSIONS: Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).

Effect of kidney disease on all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

Artificial intelligence for the prediction of acute kidney injury during the perioperative period: systematic review and Meta-analysis of diagnostic test accuracy.

BACKGROUND: Acute kidney injury (AKI) is independently associated with morbidity and mortality in a wide range of surgical settings. Nowadays, with the increasing use of electronic health records (EHR), advances in patient information retrieval, and cost reduction in clinical informatics, artificial intelligence is increasingly being used to improve early recognition and management for perioperative AKI. However, there is no quantitative synthesis of the performance of these methods. We conducted this systematic review and meta-analysis to estimate the sensitivity and specificity of artificial intelligence for the prediction of acute kidney injury during the perioperative period. METHODS: Pubmed, Embase, and Cochrane Library were searched to 2nd October 2021. Studies presenting diagnostic performance of artificial intelligence in the early detection of perioperative acute kidney injury were included. True positives, false positives, true negatives and false negatives were pooled to collate specificity and sensitivity with 95% CIs and results were portrayed in forest plots. The risk of bias of eligible studies was assessed using the PROBAST tool. RESULTS: Nineteen studies involving 304,076 patients were included. Quantitative random-effects meta-analysis using the Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model revealed pooled sensitivity, specificity, and diagnostic odds ratio of 0.77 (95% CI: 0.73 to 0.81),0.75 (95% CI: 0.71 to 0.80), and 10.7 (95% CI 8.5 to 13.5), respectively. Threshold effect was found to be the only source of heterogeneity, and there was no evidence of publication bias. CONCLUSIONS: Our review demonstrates the promising performance of artificial intelligence for early prediction of perioperative AKI. The limitations of lacking external validation performance and being conducted only at a single center should be overcome. TRIAL REGISTRATION: This study was not registered with PROSPERO.

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole-trimethoprim and temozolomide.

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.

BACKGROUND: Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. METHODS/DESIGN: This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. DISCUSSION: The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. STUDY REGISTRATION: The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .

Effect of nephrology follow-up on long-term outcomes in patients with acute kidney injury: A systematic review and meta-analysis.

AIM: Acute kidney injury (AKI) is associated with poor short-term and long-term clinical outcomes. The role of nephrology follow-up in post-AKI management remains uncertain. METHODS: A systematic review and meta-analysis were performed examining all randomized controlled trials and observational studies assessing the effect of nephrology follow-up on patients' clinical outcomes. The primary outcome was all-cause mortality. The secondary outcomes were renal outcomes, which were defined as a composite of requirement of permanent dialysis and recurrent AKI. Pooled analysis was performed using a random-effect model. RESULTS: We identified six studies (8972 patients, mean follow-up of 49 months). Five were retrospective cohort studies and one was a prospective cohort study. Risk of bias was a concern with all studied. Only four studies reported primary and/or secondary outcomes and were included. Compared with patients without nephrology follow-up, patients with nephrology follow-up had significantly reduced mortality by 22% (three studies, 3240 patients, relative risk [RR] = 0.78, 95% confidence interval [CI] = 0.70-0.88, I2 = 0.0%). Nephrology follow-up did not improve composite renal outcomes with high heterogeneity due to significant differences in reported renal outcomes and follow-up period (two studies, 2537 patients, RR = 1.72, 95% CI = 0.49-6.05, I2 = 90.1%). CONCLUSION: Current evidence from observational studies is biased. It suggests long-term survival benefits with post-discharge nephrology follow-up in AKI patients. However, due to its low quality, such evidence is only hypothesis-generating. Nonetheless, it provides a rationale for future randomized controlled trials of nephrology follow-up in AKI patients. SUMMARY AT A GLANCE The present meta-analysis assessed the effect of nephrology follow-up on patients' clinical outcomes, and suggested long-term survival benefits in acute kidney injury (AKI) survivors. Although the study inherently comprises potential risks of bias due to paucity of available data, the results provide a rationale for future randomized controlled trials.

Understanding and managing intimate partner violence in the pediatric primary care setting: a review.

PURPOSE OF REVIEW: To highlight the impact of intimate partner violence (IPV), also known as domestic violence, on children and families and to provide a framework for pediatricians in managing IPV-affected families. RECENT FINDINGS: Children living with a victim of IPV are at a much higher risk of being physically abused themselves. Exposure to IPV places children at high risk for multiple adverse childhood experiences, long-term health morbidity, and increased chance of intergenerational transmission of child abuse and future IPV. Exposure to a violent home environment alone is considered a form of child maltreatment. Furthermore, recent studies have proposed that maternal posttraumatic stress disorder and ineffective parenting styles by a victim of IPV mediate children's negative developmental outcomes, such as aggressive or internalizing behavior, mental health issues, and developmental delays. Trauma-informed care and a better understanding of the child abuse reporting process allow pediatricians to address specific needs of children and families exposed to IPV, to serve as mandated reporters with sensitivity and empathy, and to promote resiliency in families. SUMMARY: IPV is a public health issue that affects children in a variety of ways. Pediatricians can better manage this very serious and personal issue in their offices through an understanding of the unique healthcare needs of children and families impacted by IPV.

Interaction between PLA2R1 and HLA-DQA1 variants contributes to the increased genetic susceptibility to membranous nephropathy in Western China.

AIM: Recent studies showed that single nucleotide polymorphisms (SNP) within the phospholipase A2 receptor (PLA2R1) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) genes were associated with the susceptibility to patients with primary membranous nephropathy (PMN). However, the results of previous research have not been always consistent. METHODS: We performed a case-control study including 314 patients with PMN and 354 healthy subjects in Western China. Eight SNP in PLA2R1 and one SNP in HLA -DQA1 were genotyped and association between PLA2R1 and HLA-DQA1 was investigated. One hundred and twenty patients were detected anti-PLA2R antibodies to analyze the association between genotype and anti-PLA2R antibody. RESULTS: We found A allele of rs2715918 (odds ratio (OR) = 1.66, corrected P values (Pc) = 7.9 × 10-3 ), A allele of rs4665143 (OR = 1.76, Pc = 2.7 × 10-6 ) and A allele of rs2187668 (OR = 3.29, Pc = 8.0 × 10-11 ) were associated with PMN. Susceptibility of PMN was significantly increased with rs2715918 in dominant model (OR = 1.624, Pc = 5.0 × 10-2 ), rs4665143 in recessive model (OR = 2.134, Pc = 1.4 × 10-4 ) and rs2187668 in dominant model (OR = 3.961, Pc = 4.1 × 10-11 ). The haplotype ATAC of rs2715918, rs6757188, rs4665143, rs3749119 was associated with the high risk of PMN (OR = 1.453, P = 3.0 × 10-4 ). Interaction of rs2715918 GA/AA, rs4665143 GA/AA and rs2187668 GA/AA could significantly increase the 10.61-fold higher risk for the development of PMN (OR = 10.61, P = 4.0 × 10-10 ). Patients who carried with risk genotypes for both HLA-DQA1 and PLA2R1 (87.8%) had antibodies positivity. However, patients who carried low-risk genotypes (41.6%) had antibodies positivity (P = 0.001). CONCLUSION: There are some differences in PLA2R1 distributions in PMN patients between previous literature and our study. Our results showed that interactions between PLA2R1 and HLA-DQA1 alleles increased genetic susceptibility to PMN in Western China.

HMG-CoA reductase inhibitors (statins) and acute kidney injury: A secondary analysis of renal study outcomes.

BACKGROUND: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG-CoA reductase inhibitors (statins) with variable findings. METHODS: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all-cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all-cause mortality at 90 days. RESULTS: Of the 1462 participants with the available data on statin usage, 187 (12.8%) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95% confidence interval (CI) = 0.784-1.415, P = 0.730) and day 90 (HR = 1.091, 95% CI = 0.836-1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95% CI = 0.734-1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95% CI = 1.132-2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95% CI = 1.296-3.599, P = 0.003), compared with statin withdrawal. CONCLUSION: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005.

Acute kidney injury in critically ill surgical patients: Epidemiology, risk factors and outcomes.

AIM: Acute kidney injury (AKI) is one of the most serious complications seen in intensive care units (ICUs). However, its epidemiology, risk factors and clinical outcomes in surgical critically ill patients remains unclear. METHODS: A prospective cohort study was conducted in surgical intensive care unit (ICU) of the university hospital in Bangkok, Thailand. AKI was diagnosed according to the KDIGO 2012 criteria. RESULTS: A total of 189 of the 400 patients enrolled in our study developed AKI (47.3%). The severity was: stage 1 = 29.6% of all AKI (56 cases), stage 2 = 30.7% (58 cases), and stage 3 = 39.7% (75 cases). Risk factors of AKI development included a higher BMI, a greater APACHE-II score, septic shock, use of mechanical ventilation, acute medical complications during surgical admission, and pre-existing chronic kidney disease. After adjustment for covariates, only the most severe stage of AKI (stage 3) was associated with increasing 28-day ICU mortality compared with no AKI stage, HR = 7.75 (95% CI, 1.46-41.20, P = 0.02). CONCLUSION: Acute kidney injury is common and is associated with an increase in mortality in surgical ICU patients. There should be more focus on patients with AKI risk factors to prevent this deleterious event.

RNA-Seq profiling of circular RNAs in human laryngeal squamous cell carcinomas.

Abnormal expression of non-coding circular RNAs (circRNAs) have been reported in many types of tumors. circRNA have been suggested to be an ideal candidate biomarker for diagnostic and therapeutic implications in cancers. The aim of this study was to assess the circRNA expression profile of laryngeal squamous cell carcinomas (LSCC). The biopsy samples from patients with LSCC were obtained intra-operatively. The circRNA expression was performed using secondary sequencing. Among 10 patients with LSCC, 2 were well differentiated, 3 were moderately differentiated and 5 were adjunctive samples with normal and LSCC tissues. A total of 21,444 distinct circRNA candidates were detected. Among them, we defined the statistical criteria for selecting aberrant-expressed circRNA using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. A total of 29 circRNA were upregulated and 19 circRNA were downregulated significantly in the LSCC tissues. The intersection of these dysregulated circRNAs of normal-well differentiated set and normal-moderately differentiated set was then assessed to narrow the upregulated and downregulated circRNAs down to 18 and 5 respectively. Furthermore, an association of the circRNA-miRNA-mRNA was investigated, showing that 20 dysregulated circRNA successfully predicted an interaction with several cancer-related miRNAs. Finally, a further KEGG analysis showed that PPAR, Axon guidance, Wnt and Cell cycle signaling pathway were key putative pathways in the process of LSCC. hsa_circ:chr20:31876585-31,897,648 was found to be able to differentiate most of LSCC from the matching normal tissues. This observational study demonstrated dysregulation of circRNA in LSCC, which may have an impact on development of potential biomarkers in this disease. Validation of down-regulation of hsa_circ:chr20:31876585-31,897,648 in LSCC compared to each adjunctive tissue by Q-RT-PCR, indicating that hsa_circ:chr20:31876585-31,897,648 may be a novel promising tumor suppresser in LSCC.

Association of high body mass index with development of interstitial fibrosis in patients with IgA nephropathy.

BACKGROUND: The worldwide prevalence of obesity is increasing. Obesity is associated with a variety of chronic diseases, including chronic kidney disease. Several studies suggested that body mass index (BMI) could be an independent risk factor for progression of IgA nephropathy (IgAN). However, whether high BMI is associated with progression of IgAN remains uncertain. METHODS: This retrospective study included patients with biopsy proven IgAN from 2006 to 2017 in Sichuan Provincial People's Hospital. BMI was categorized according to the WHO Asian guideline: underweight (< 18.5 kg/m2), normal weight (18.5-25 kg/m2), overweight (25-28 kg/m2) and obese (≥28 kg/m2). The main outcome was development of end-stage renal disease (ESRD) or a decline in eGFR by at least 30%. The association of BMI and IgAN progression was determined by propensity-score-matched cohort analysis. RESULTS: Four hundred eighty one patients with IgAN were finally enrolled in this study. The mean age was 37 ± 11 years and 40.3% were men. There was no significant difference in clinical and pathological characteristics among the four-group patients categorized by BMI. After matching with propensity scores, no significant correlation between BMI and renal outcomes was seen. However, compared with the reference group (18.5≦BMI≦25 kg/m2), being overweight (odd ratio [OR], 2.28; 95%CI: 1.06-4.88; P = 0.034) and obese (OR, 3.43; 95%CI: 1.06-11.04; P = 0.039) was associated with a high risk of interstitial fibrosis. In the cross figure demonstrating the association of BMI subgroup and interstitial fibrosis on renal outcomes, ORs of interstitial fibrosis groups were higher than those of no interstitial fibrosis. Compared with other BMI subgroups, patients with 18.5-25 kg/m2 had lowest ORs. CONCLUSIONS: High BMI and interstitial fibrosis were associated with progression of IgAN. Interstitial fibrosis appears to be common in IgAN patients with elevated BMI.

An update on clinical significance of use of THSD7A in diagnosing idiopathic membranous nephropathy: a systematic review and meta-analysis of THSD7A in IMN.

BACKGROUND: THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients. METHODS: We searched English and Chinese database to 31 December 2017 with the term 'THSD7A' or 'thrombospondin type 1 domain-containing 7A'. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A. RESULTS: Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%-4%) in all patients and 10% (95% CI, 6%-15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%-4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%-4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%. CONCLUSIONS: The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended.

Muscle strength, mobility, quality of life and falls in patients on maintenance haemodialysis: A prospective study.

AIM: The aim is to explore (i) the relationship between quality of life and physical parameters (muscle strength and mobility) among people undergoing maintenance haemodialysis; (ii) changes in strength and mobility over time and predictors of changes; and (iii) whether strength and mobility were associated with falls. METHODS: We recruited 51 maintenance haemodialysis patients to a prospective longitudinal study. Baseline quality of life was assessed using the SF-36 physical component summary and mental component summary scores. Muscle strength (ankle dorsiflexion strength measured with a hand-held dynamometer), mobility (short physical performance battery) and falls history were assessed at baseline, 12 and 36 months. Associations between variables at baseline were assessed with linear regression models. Changes in physical parameters were evaluated with paired t-tests and prediction of falls assessed by negative binominal regression. RESULTS: Fifty and 34 patients completed 12 and 36 month follow-ups, respectively. Baseline mobility but not muscle strength correlated with physical component summary (P = 0.01 and P = 0.23, respectively). Neither baseline mobility nor muscle strength correlated with mental component summary. At 12 months, muscle strength and mobility had significantly deteriorated (mean ankle dorsiflexion strength 11.0 lb (SD 1.5) from 14.0 lb (SD 2.2), P < 0.01; short physical performance battery 8.5 (SD 2.8) from 9.3 (SD 2.6), P < 0.01). Falls at 12 and 36 months were predicted by baseline mobility (P = 0.06 and P = 0.02, respectively) but not muscle strength. CONCLUSION: Physical parameters appear to be associated with meaningful patient outcomes and showed measurable deterioration over relatively short time frames. Interventions, with the potential to slow physical decline in people receiving maintenance dialysis, such as exercise programmes, warrant further investigation.

Health-related quality of life in survivors of acute kidney injury: The Prolonged Outcomes Study of the Randomized Evaluation of Normal versus†Augmented Level Replacement Therapy study outcomes.

AIM: While patients with chronic kidney disease have reduced health-related quality of life (HRQOL), long-term HRQOL of survivors of severe acute kidney injury (AKI) remains unclear. METHODS: We analysed HRQOL from the Prolonged Outcomes Study of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (POST-RENAL) study and compared findings with those from a general Australian adult population enrolled in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. We used a multivariate analysis adjusted for baseline characteristics along with sensitivity analysis using age and sex-matched case controls. RESULTS: In the POST-RENAL study, 282 participants had HRQOL data collected using the SF-12 questionnaire. This was compared with 6330 participants from the AusDiab study. Unadjusted analyses showed that POST-RENAL participants had lower physical component scores (PCS, mean score 40.0 vs 49.8, P<0.0001) and lower mental component scores (MCS, mean score 49.8 vs 53.9, P<0.0001) than the AusDiab group. After age and sex matching, the difference in PCS and MCS remained statistically significant (P<0.0001). Advanced age, reduced renal function and albuminuria (all P ≤ 0.01) were all strongly associated with lower PCS values but not MCS values. After matching subsets of the cohorts on the basis of age, sex and renal function, PCS and MCS were lower in the POST-RENAL group (P<0.0001). CONCLUSION: Survivors of severe AKI in the POST-RENAL study had lower physical and mental components of HRQOL compared with general population, even after adjustment for their reduced renal function. Increasing age and reduced renal function were associated with poorer physical QOL.

Effect of hemodiafiltration or hemofiltration compared with hemodialysis on mortality and cardiovascular disease in chronic kidney failure: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Whether convective modalities of dialysis, including hemofiltration (HF) and hemodiafiltration (HDF), improve cardiovascular outcomes and mortality is unclear. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Patients receiving HDF, HF, or standard hemodialysis (HD). SELECTION CRITERIA FOR STUDIES: Randomized controlled trials. INTERVENTION: Convective modalities of dialysis (HDF and HF) versus standard HD. OUTCOMES: The primary outcome was clinical cardiovascular outcomes. Secondary outcomes were all-cause mortality, episodes of symptomatic hypotension, dialysis adequacy, and ß2-microglobulin level. Relative risks (RRs) or weighted mean differences with 95% CIs for individual trials were pooled using random-effects models. RESULTS: The search yielded 16 trials including 3,220 patients. Therapies assessed were convective modalities (HDF or HF) compared with standard HD. Compared with HD, convective modalities did not significantly reduce the risk of cardiovascular events (RR, 0.85; 95% CI, 0.66-1.10) or all-cause mortality (RR, 0.83; 95% CI, 0.65-1.05). Convective modalities reduced symptomatic hypotension (RR, 0.49; 95% CI, 0.30-0.81) and improved serum ß2-microglobulin levels (-5.95 mg/L; 95% CI, -10.27 to -1.64), but had no impact on small-molecule clearance (weighted mean difference in Kt/V, 0.04; 95% CI, -0.04 to 0.12). There was a nonsignificant trend to a greater likelihood of receiving a kidney transplant for participants allocated to filtration therapies (RR, 1.19; 95% CI, 0.99-1.42). LIMITATIONS: The trials were predominantly of suboptimal quality and underpowered, with imbalance in some prognostic variables at baseline. Intention-to-treat analysis was not used in some trials. Our analysis was limited to published outcomes. CONCLUSIONS: The potential benefits of convective modalities over standard HD for cardiovascular outcomes and mortality remain unproved. Further high-quality randomized trials are needed to define the impact of these modalities on clinically important outcomes.

Angiotensin-converting enzyme inhibitor usage and acute kidney injury: a secondary analysis of RENAL study outcomes.

AIM: Acute kidney injury (AKI) is associated with increased mortality. While angiotensin-converting enzyme inhibitors (ACEI) are known to slow progression of chronic kidney disease, their role in AKI remains unclear. METHODS: The Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy (RENAL) study data were analysed according to ACEI use over time. The primary outcome was all-cause mortality at 90 days following randomisation. Analyses used a multivariate Cox model adjusted for either baseline or for time-dependent covariates, and a sensitivity analysis of patients surviving to at least the median time to ACEI initiation. RESULTS: Of the 1463 participants with available data on ACE inhibitors usage, 142 (9.7%) received ACEI at least once during study data collection. Participants treated with ACEI were older (P = 0.02) and had less sepsis at baseline (P < 0.001). ACEI use was significantly associated with lower mortality at 90 days (HR 0.46, 95% CI 0.30-0.71, P < 0.001), and an increase in renal replacement therapy-free days (P < 0.001), intensive care unit-free days (P < 0.001) and hospital free-days (P < 0.001) after adjusting for baseline covariates. Using the time-dependent analysis, however, the effect of ACEI administration was not significant (HR 0.78, 95% CI 0.51-1.21, P = 0.3). The sensitivity analysis in day 8 survivors produced similar results. CONCLUSION: In the RENAL study cohort, the use of ACEI during the study was not common and, after adjustment for time-dependent covariates, was not significantly associated with reductions in mortality. Further assessment of the effect of ACEI use in AKI patients is needed.

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.

Anticoagulant therapies for the prevention of intravascular catheters malfunction in patients undergoing haemodialysis: systematic review and meta-analysis of randomized, controlled trials.

BACKGROUND: Catheter malfunction (CM), including thrombosis, is associated with reduced dialysis adequacy, as well as an increased risk of catheter-related bacteraemia (CRB) and mortality. The role of alternative anticoagulant regimens for CM prevention remains uncertain. METHODS: A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) assessing interventions acting via an anticoagulant mechanism compared with conventional care for the prevention of CM in adult patients receiving haemodialysis for end-stage kidney disease. Medline, EMBASE and the Cochrane Register were searched to November 2012. The primary outcome was CM. Secondary outcomes were CRB, all-cause mortality and bleeding events (all bleeding events reported or as defined by authors). Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using random effects models for treatment classes. RESULTS: The search yielded 28 trials including 3081 patients. Therapies assessed were alternative anticoagulant locking solutions (ALSs), systemic warfarin and low/no dose heparin locking solutions (normal saline locks). No significant effect on CM (18 trials, 1579 participants) was observed for alternative ALSs (9 trials, 887 participants, RR 0.85, 95% CI 0.68-1.07), or low/no dose heparin (4 trials, 231 participants, RR 0.99, CI 0.60-1.62), compared with heparin locking solutions (5000 units). Similarly, no significant effect was observed for warfarin (5 trials, 479 participants, RR 0.59, 95% CI 0.28-1.22) compared with placebo. No significant effect on CRB was observed (15 trials, 2367 participants) for alternative ALSs (11 trials, 2010 participants, RR 0.57, 95% CI 0.30-1.10), warfarin (1 trial, 174 participants, RR 2.40, 95% CI 0.88-6.52) or low/no dose heparin (3 trials, 183 participants, RR 0.76, 95% CI 0.35-1.64). All-cause mortality was not affected by alternative ALSs (9 trials, 1719 participants, RR 0.83, 95% CI 0.56-1.24) or warfarin (3 trials, 403 participants, RR 0.78, 95% CI 0.37-1.65). Bleeding events were only reported in seven trials, including only two trials of warfarin, with no clear effect demonstrated. Within the alternative ALSs group, the only agent with a reduction in CM was recombinant tissue plasminogen activator (rt-PA)-locking solution (RR 0.52, 95% CI 0.32-0.86) based on the results of a single trial. Trials were mainly of high risk of bias. CONCLUSIONS: There is uncertainty on the benefits and harms of anticoagulant therapies over conventional care for prevention of CM. Further high-quality randomized trials, including safety outcomes, are needed.

Clinical Manifestations and Risk Factors Associated with 14 Deaths following Swarm Wasp Stings in a Chinese Tertiary Grade A General Hospital: A Retrospective Database Analysis Study.

INTRODUCTION: The objective was to evaluate the poisoning severity score (PSS) as an early prognostic predictor in patients with wasp stings and identify associated clinical characteristics and risk factors for mortality. METHODS: A total of 363 patients with wasp stings at Suining Central Hospital between January 2016 and December 2018 were enrolled. Within the first 24 h of admission, the poisoning severity score (PSS) and the Chinese expert consensus on standardized diagnosis and treatment of wasp stings (CECC) were utilized for severity classification, and their correlation was examined. Patients were then divided into survival and death groups based on discharge status. Logistic regression analysis was employed to analyze factors influencing patients' outcomes. RESULTS: The mortality of wasp sting patients was 3.9%. The PSS and CECC were found to correlate for severity classification. Additionally, female gender, age, number of stings, and PSS were identified as independent risk factors for mortality in wasp sting patients. Combining these four factors yielded an AUC of 0.962 for predicting death. CONCLUSIONS: PSS aids in early severity classification of wasp stings. Female gender, age, number of stings, and PSS were independent mortality risk factors in these patients.