Assessment of circulating extracellular vesicles from calorie-restricted mice and humans in ischaemic injury models.

Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. The cargo and function of circulating extracellular vesicles (EV) respond to changes in host physiology, including exercise, injury, and other interventions. Thus, we hypothesised that EVs induced following CR may reflect some of the beneficial properties of CR itself. In a pilot study, EVs were isolated from mice following 21 days of 30 % CR, and from eight human donors after 72 h water-only fasting. EV size, concentration and morphology were profiled by NTA, western blot and cryoEM, and their function was assessed using multiple assays related to ischaemic diseases. We found that EVs from post-fasting samples better protected cardiac cells from hypoxia/reperfusion (H/R) injury compared to pre-fasting EVs. However, there was no difference when used to treat H/R-injured kidney epithelial cells. Post-fasting derived EVs slowed the rate of fibroblast migration and slightly reduced macrophage inflammatory gene expression compared to pre-fasting derived EVs. Lastly, we compared miRNA cargos of pre- and post-fasting human serum EVs and found significant changes in a small number of miRNAs. We conclude that fasting appears to influence EV cargo and function, with varied effects worthy of further exploration.

Association between regional economic status and renal recovery of dialysis-requiring acute kidney injury among critically ill patients.

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022-1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

Multidisciplinary care program for advanced chronic kidney disease: reduces renal replacement and medical costs.

BACKGROUND: Multidisciplinary care is advocated as an effective chronic kidney disease treatment program in a few, but not all, studies. Our study aimed to evaluate the effect of multidisciplinary care on renal outcome and patient survival using a larger cohort. METHOD: A total 1382 chronic kidney disease patients, ages 18-80 years, with chronic kidney disease stage 3B-5, in nephrology outpatient clinics were enrolled. Using age, sex, chronic kidney disease stage, and diabetes mellitus as variables, 592 multidisciplinary care program participants were matched with 614 nonmultidisciplinary care patients. The primary outcomes were long-term renal replacement therapy and mortality. Secondary outcomes included changes of biochemical markers and blood pressure, infection hospitalization, cardiovascular events, and emergent start of long-term dialysis. Annual medical costs were compared. RESULTS: There were no between-group differences regarding mortality. In the multivariate competing-risk regression model, the multidisciplinary care group had a better renal survival (hazard ratio 0.640; 95% confidence interval, 0.484-0.847; P = .002). This effect was most prominent in stage 4 (hazard ratio 0.375; 95% confidence interval, 0.219-0.640; P < .001), but not in stage 3B and 5 patients. The multidisciplinary care group showed a slower estimated glomerular filtration rate decline (-2.57 vs -3.74 mL/min/1.73 m(2), P = .021), and a smaller increase in phosphate (+ 0.03 vs + 0.33 mg/dL, P = .013). Cardiovascular and infection events were both decreased in the multidisciplinary care group (P < .001). There was also less requirement of emergent start dialysis (39.6% vs 54.5%, P = .001). The annual cost for the multidisciplinary care group was lower than the nonmultidisciplinary care group (US $2372 vs $3794, P < .001). In addition, considering the reduction of patients requiring renal replacement therapy, the multidisciplinary care program saved a total US $1931 per patient annually. CONCLUSIONS: Our analysis demonstrated that the multidisciplinary care program provided better health care and reduced renal replacement therapy in patients with advanced chronic kidney disease. By decreasing hospitalizations, emergent start, and the need for renal replacement therapy, the multidisciplinary care program was cost-effective.

Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury.

INTRODUCTION: Sepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients. METHODS: Patient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT. RESULTS: Among the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patient's propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05). CONCLUSIONS: Use of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.

A modified sequential organ failure assessment score to predict hospital mortality of postoperative acute renal failure patients requiring renal replacement therapy.

BACKGROUND: A predictive model for hospital mortality in postoperative acute renal failure (ARF) patients requiring renal replacement therapy (RRT) may aid clinicians' therapeutic decision-making and research design. METHODS: A prospective observational study of 398 postoperative ARF patients requiring RRT was conducted in four hospitals. The derivation cohort consisted of 334 patients recruited between January 2002 and December 2005. The validation cohort consisted of 64 patients recruited between January 2006 and December 2006. RESULTS: The hospital mortality rates for the derivation and validation cohorts were 65.6 and 62.5%, respectively. A modified Sequential Organ Failure Assessment (SOFA) score was constructed at the commencement of RRT by a formula of serum lactate level (mM) + 2 x (generic SOFA score) + 3 x (age per decade) + 8 (if mechanical circulatory support required) + 10 (if total parenteral nutrition required) + 11 (if status postcardiopulmonary resuscitation) + 13 (if positive sepsis sign). The area under the receiver operating characteristic curve of the model for the derivation and validation cohorts was 0.804 and 0.839, respectively. CONCLUSION: This validated score at dialysis commencement might assist clinicians in estimating hospital mortality, planning future clinical trials, and providing quantitative guidance for decision making in postoperative ARF patients requiring RRT.