INTRODUCTION:Calcium supplementation is one of the most important factors in maintaining the safety and efficacy of regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). The aims of this study were to assess the determinants of calcium requirements in RCA-CVVH and to simplify the calcium supplementation approach.METHODS:Our study consisted of two parts. The first part was a discovery phase to determine the key factors of calcium supplementation. Twenty critically ill patients who required RCA-CVVH were enrolled in this part. Systemic citrate, total calcium, protein-bound calcium, and ionized calcium concentrations were serially measured using the traditional RCA protocol. A two-phase calcium supplementation protocol was then proposed, and algorithms were developed for calcium supplementation. The second part of the study was the validation phase. Another 97 critically ill patients were enrolled and were treated with RCA-CVVH using the new version of the calcium supplementation protocol.FINDINGS:The loss of calcium flux in the extracorporeal circuit and the increase in citrate-calcium complexes in vivo were the main determinants of the required calcium supplementation. In the CVVH mode, the rate of calcium infusion had to be reduced after systemic citrate level reached a steady state. With the aid of mathematical models, systemic calcium levels could be stably maintained in the normal range, and the frequencies of calcium monitoring were reduced.DISCUSSION:Calcium supplementation during RCA-CVVH undergoes two phases. We propose mathematical models to quantify the need for calcium supplementation, which enable individualization of the RCA prescription and simplify the management of RCA in the CVVH mode.

Introduction Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA. Methods Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients’ CVVH sessions with citrate anticoagulation. Results Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements. Conclusions Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation. Trial Registration ClinicalTrials.gov Identifier NCT00948558

Background and aims: Outcome prediction is important in clinical practice. Despite significant improvements in therapeutics, the mortality associated with acute kidney injury (AKI) in elderly patients remains high. Several severity scoring systems have been used in hospital mortality prediction of patients, but little is known of their significance in elderly patients with AKI. The aim of this study is to evaluate the ability of version II of Acute Physiology and Chronic Health Evaluation (APACHE II) and Acute Tubular Necrosis Individual Severity Index (ATN-ISI) on predicting the hospital mortality of elderly patients with AKI. Methods: A consecutive sample of 99 elderly patients (age≥65) with AKI in a university hospital was enrolled. Receiver operating characteristic analyses were used to assess the discriminative power for hospital mortality prediction. The McNemar and Kappa tests were also applied. Results: The areas under the receiver operating characteristic curve of APACHE II and ATN-ISI were 0.895 (95% CI 0.829–0.960) and 0.858 (95% CI 0.783–0.934), respectively. The sensitivity of the hospital mortality prediction of the two scoring systems was 87.72% and 89.47%, respectively, and the specificity of hospital mortality prediction was 76.19% and 66.67%, respectively. No significant differences were found between the predicted and real mortality rates. Conclusions: APACHE II and ATN-ISI scoring systems can predict the hospital mortality of elderly AKI patients. However, APACHE II performs better than ATN-ISI.

Objective To elucidate the malnutrition in patients with hospital-acquired acute kidney injury (AKI), and to examine the association between subjective global assessment (SGA) and prognosis. Methods Adult patients with hospital-acquired AKI were prospectively enrolled in this cohort study.Nutritional evaluations, including SGA, anthropometric and serum nutritional markers were conducted at enrollment.Overall survival at 90 days among different SGA scores was analyzed using Kaplan-Meier methods, and differences were tested using the log-rank test.The Cox model was used to analyze the relationship between SGA scores and all-cause mortality after adjusting for confounders.Results A total of 170 patients were enrolled.The prevalence of moderate malnutrition (SGA B) and severe malnutrition (SGA C) was 51.8％ and 22.9％ respectively, while patients with normal nutrition (SGA A) accounted for 25.3％.After 90 days follow-up, all-cause mortality was 9.8％ in SGA A group, 34.9％ in SGA B group and 56.8％ in SGA C group respectively. After adjusting for age, sex, dialysis, ventilation, hemoglobin, platelets and bilirubin, the hazard ratio (HR) of 90 days all-cause mortality was 4.0(95％ CI 1.42-11.22, P=0.008) in malnutrition group (SGA B group and SGA C group) compared with SGA A group.The Kaplan-Meier curve also revealed that the worse the SGA score was, the lower the cumulative survival became (P＜0.01). Conclusion SGA score is an independent risk factor for all-cause mortality within 90 days in patients with hospital-acquired acute kidney injury.

Objectives To evaluate the effect of the selective cytopheretic device (SCD) on outcome of severe acute kidney injury (AKI) requiring renal replacement therapy, and to observe the occurrence of adverse events from application of the device. Methods In this study, acute kidney injury was defined as ischemic or nephrotoxic acute tubular necrosis by clinic diagnosis, with at least one nonrenal organ failure or presence of sepsis at the same time. All subjects received standard intensive care treatment with continuous veno-venous hemofiltration (CVVH) in addition to the SCD treatment. Patients enrolled in the trial were compared with the historical casematched controls from PICARD study with respect to age and Sequential Organ Failure Assessment (SOFA) score. The primary endpoint was in-hospital all cause mortality. Other observation index included urine output change and the occurrence of adverse events. After adjusting for confounders, the Cox model was used to analyze whether SCD combined with CVVH treatment was better than routine CVVH. Results A total of 9 patients were enrolled. In-hospital all cause mortality of SCD combined with CVVH treatment group was 22.2%, significantly lower than historical case-matched control group (77.8%) (x2=5.247,P=0.027). Multiple regression analysis identified treatment with SCD as the only significant variable affecting mortality among age, SOFA score, and average change in urine output (SCD vs. CVVH historical cohort,(T=-2.596,P=0.0222). Mean total urine output in the 9 subjects receiving SCD treatment increased from a baseline of approximately 500 ml/d to more than 2,000 ml/d by day 7 of treatment. In this study, only a few mild adverse events occurred, and no serious adverse events were reported.Conclusion SCD can regulate the immune response by deactivating leukocytes, and therefore improve in-hospital mortality of patients with AKI. The safety of SCD is favorable.

Background: Animal and human studies suggest that inflammation and malnutrition are common in acute kidney injury (AKI) patients. However, only a few studies reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol, markers of nutritional status were associated with the prognosis of AKI patients. No study examined whether the combination of inflammatory and nutritional markers could predict the mortality of AKI patients.Methods: 155 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. C-reactive protein (CRP), and the nutritional markers (albumin, prealbumin and cholesterol) measured at nephrology consultation were analyzed in relation to all cause mortality of these patients. In addition, CRP and prealbumin were also measured in healthy controls (n = 45), maintenance hemodialysis (n = 70) and peritoneal dialysis patients (n = 50) and then compared with AKI patients.Results: Compared with healthy controls and end-stage renal disease patients on maintenance hemodialysis or peritoneal dialysis, patients with AKI had significantly higher levels of CRP/prealbumin (p < 0.001). Higher level of serum CRP and lower levels of albumin, prealbumin and cholesterol were found to be significant in the patients with AKI who died within 28 days than those who survived >28 days. Similarly, the combined factors including the ratio of CRP to albumin (CRP/albumin), CRP/prealbumin and CRP/cholesterol were also significantly higher in the former group (p < 0.001 for all). Multivariate analysis (Cox regression) revealed that CRP/prealbumin was independently associated with mortality after adjustment for age, gender, sepsis and sequential organ failure assessment (SOFA, p = 0.027) while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and CRP/cholesterol) became non-significantly associated. The hazard ratio was 1.00 (reference), 1.85, 2.25 and 3.89 for CRP/prealbumin increasing according to quartiles (p = 0.01 for the trend).Conclusions: Inflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to independent of the severity of illness and it may be a valuable addition to SOFA score to predict the prognosis of AKI patients.

<正>自20世纪90年代,局部枸橼酸抗凝(regional citrate anticoagulation,RCA)最早被应用于持续动静脉血液滤过治疗[1],目前对于伴有出凝血功能

We retrospectively studied a random cohort of patients with cerebral trauma to investigate the risk factors of acute kidney injury (AKI) following cerebral trauma. AKI was determined using the RIFLE (risk, injury, failure, loss, or end-stage kidney) staging criteria. About 171 patients were chosen in the study, with 53 patients in AKI group and 118 patients without AKI in non-AKI group. By logistic regression analysis, univariate analysis revealed that age, hypertension, emergent surgery, systemic inflammatory response syndrome (SIRS), Glasgow coma score (GCS), sequential organ failure assessment (SOFA) score, the respiration, coagulation, and cardiovascular components of the SOFA score, mechanical ventilation time, red blood cell transfusion, plasma transfusion, and the accumulative doses of furosemide, torsemide, and mannitol were significantly related to AKI after cerebral trauma. Logistic multivariate regression analysis showed that SOFA score [odds ratio (OR) = 1.516, 95% confidence interval (CI) 1.222-1.881, p < 0.001], the accumulative doses of torsemide (OR = 0.016, 95% CI 1.002-1.031, p = 0.016), and the accumulative doses of mannitol (OR = 2.687, 95% CI 1.062-6.800, p = 0.037) were independent risk factors of AKI. This model had a good discrimination for AKI with an area under the receiver operating characteristic (ROC) curve of 0.901 (p < 0.001). The accumulative doses of mannitol as a risk factor of AKI were identified by propensity score match (PSM) method. We concluded that AKI was a common complication in patients with cerebral trauma. SOFA score and the accumulative doses of torsemide and mannitol were independent risk factors of AKI following cerebral trauma.

Objective To evaluate the value of the three general scoring systems (SOFA, APACHE Ⅱ and SAPS Ⅱ), the AKI-specific scoring system (Liano), and the RILFE criteria for predicting prognosis in acute kidney injury (AKI) patients. Methods In this prospective and single center study, AKI patients with different causes and hospitalized in this hospital from December 2008 to November 2009 were enrolled. AKI was diagnosed based on the serum creatinine of RIFLE criteria. Patients were excluded from this study if the AKI was due to obstructive uropathy, interstitial nephritis, primary or secondary glomerulonephritis. The primary end point of the study was the mortality after 28 days. Scores from RIFLE classification, SOFA, APACHE Ⅱ, SAPS Ⅱ and Liano scoring systems were compared between the survival and non-survival patients. Receiver operating characteristic (ROC) curve for predict- ing death was used for the evaluation of scoring systems with and without stratification based on RIFLE classification. Results A total of 194 AKI patients were enrolled in this study. No significant differences were found in RIFLE classification, cause of AKI and dialysis between survivor and death groups. However, ventilation therapy, and scores from SOFA, APACHE Ⅱ, SAPS Ⅱ and Liano systems were significantly different between survivors and non-survivors. Area under ROC (AUROC) curves for predicting death by SOFA, APACHE Ⅱ, SAPS Ⅱ and Liano scores were 0.900, 0.885, 0.888 and 0.875, respectively (P<0.001), which were all higher than the AUROC of RIFLE (0.566, P > 0.05). Stratification of AKI based on RIFLE classification revealed that patients in the failure group had higher AUROC of the 4 scoring systems, especially the AUROC of Liano scoring system. Conclusions General or AKI-specific scoring systems including SOFA, APACHE Ⅱ, SAPS Ⅱ and Liano systems are superior to RIFLE criteria for predicting prognosis in AKI patients.

Objective To establish a citrate pharmacokinetics model which is applied to evaluate the risk of citrate accumulation in patients with liver dysfunction in the continuous renal replacement treatment (CRRT) with regional citrate anticoagulation (RCA). Methods The source of citrate for extracorporeal anticoagulation, the body clearance and filter elimination of citrate, which were the three major citrate fluxes of systemic citrate level, were combined into a single-pool, first order kinetic equation. The data from a published clinical study of systemic citrate kinetics in the intensive care unit patients with or without liver cirrhosis were adapted and the citrate kinetic equation was applied to predict the risk of systemic citrate accumulation in patients with normal, impaired and absent liver clearance while different RCA-CRRT protocols were carried out. Results The single pool, first order citrate kinetic modeling equation was as follows:Csys=C(0)·e-[(clb+clf)·t/V]+G/CLb+CLf×(1-e-[(clb+clf)·t/V])There was excellent agreement between published citrate measurements and our predictions. Kinetic modeling showed that the plasma citrate concentration of patients with normal citrate body clearance was no more than 1 mmol/L during common RCA-CRRT. The model predicted that when the single pass fractional extraction of citrate on the artificial kidney was above 66％, systemic steady citrate concentration would be among the safe range even in patients of impaired body metabolism of citrate.Conclusions The citrate kinetic model of RCA-CRRT can predict the risk of systemic citrate accumulation and provide the basis for designing the safe RCA-protocols for the patients with impaired body clearance of citrate.

Objective To explore the risk factors of acute kidney injury(AKI)in patients with brain trauma and to investigate the role of mannitol.Methods A random cohort of traumatic brain injury patients who were admitted to Neurosurgical Emergency Center of Huashan Hospital,Fudan University from January 2006 to December 2008 was studied.AKI was determined using RIFLE staging criteria for changes in serum creatinine(Scr).By means of Logistic regression analysis,the risk factors of AKI were investigated,and a predictive model was established.Discrimination of the model was assessed using the receiver operating characteristic(ROC)curve.Association between single independent risk factor and AKI was depicted with ROC curve.Adjustment for selection bias was further assessed using propensity score match(PSM)to evaluate the role of mannitol in the development of AKI.Results A total of selected 171 patients were enrolled in the study,including 53 patients in AKI group and 118 patients without AKI as control group.The average age of these 171 patients was(45.92±16.50)years old.Univariate analysis revealed that age,hypertension,emergent surgery,systemic inflammatory response syndrome(SIRS),Glasgow coma score(GCS),sequential organ failure assessment(SOFA)score,respiration component of the SOFA score,coagulation component of the SOFA score,cardiovascular component of the SOFA score,mechanical ventilation time,red blood cell transfusion,plasma transfusion,accumulative dose of furosemide,accumulative dose of terasemide and accumulative dose of mannitol were significantly associated to AKI in patients with brain trauma.Logistic multivariate regression analysis showed that SOFA score(OR =1.516,95% CI 1.222-1.881,P<0.01),accumulative dose of tomsemide(OR=0.016,95%CI 1.002-1.031,P=0.016)and accumulative dose of mannitol(OR=2.687,95%CI 1.062-6.800,P=0.037)were independent risk factors of AKI.This model had a good discrimination for AKI with an area under the ROC curve of 0.901(P<0.01).The accumulative dose of mannitol was identified as a risk factor of AKI by PSM test.Conclusions AKI is a common complication in patients with traumatic brain injury.SOFA score,accumulative dose of torasemide and accumulative dose of mannitol are independent risk factors of AKI following traumatic brain injury.

利尿剂从开始使用至今已有40多年的历史,目前仍广泛地用于临床.当今对利尿剂的临床评价已逐步走上循证医学轨道,以大量的临床试验、荟萃分析评价利尿剂的效果以及对疾病发展、预后的影响和不良反应.