Acute Renal Failure Trial Network Research Articles

Subgroups of Patients with Distinct Health Utility Profiles after AKI.

A large amount of inter-individual variability exists in health-related quality of life outcomes following acute kidney injury (AKI). This study aimed to determine if subgroups of early AKI survivors could be identified based on distinct health utility impairment profiles ascertained at 60 days after AKI and if these subgroups differed in clinical and biomarker characteristics at index hospitalization and outcomes at 1-year follow up. This retrospective analysis used data from the BioMaRK study, an observational subcohort of the Acute Renal Failure Trial Network study. Of 402 patients who survived to 60 days after AKI, 338 completed the Health Utility Index-3 survey which measures impairments in 8 health attributes. Latent class analysis was used to identify subgroups of patients with distinct health utility profiles. Three subgroups with distinct health utility impairment profiles were identified: Low (28% of participants), Moderate (58%) and High (14%) with a median of 1, 4, and 6 impairments across the 8 health attributes at 60 days after AKI, respectively. Patient subgroups differed in weight, history of cerebrovascular disease, intensity of dialysis, hospital length of stay, and dialysis dependence. Serum creatinine and blood urea nitrogen at index hospitalization did not differ among the 3 subgroups. The High impairment subgroup had higher levels of interleukin-6 and soluble tumor necrosis factor receptor-2 at study day 1. The 3 subgroups had different 1-year mortality rates: 5% in the Low, 21% in the Moderate, and 52% in the High impairment subgroup. Patient subgroups with distinct health utility impairment profiles can be identified 60 days after AKI. These subgroups have different characteristics at index hospitalization. A higher level of impairment at 60 days was associated with decreased survival.

Renal outcomes according to renal replacement therapy modality and treatment protocol in the ATN and RENAL trials

BackgroundIn critically ill patients with acute kidney injury, renal replacement therapy (RRT) modality and treatment protocols may affect kidney recovery. This study explored whether RRT modality and treatment protocol affected RRT dependence in the ‘Randomized Evaluation of Normal versus Augmented Level of RRT’ and the ‘Acute Renal Failure Trial Network’ (ATN) trials.MethodsPrimary outcome was 28-day RRT dependence. Secondary outcomes included RRT dependence among survivors and in different SOFA-based treatment protocol groups. We used the Fine-Gray competing-risk model sub-distribution hazard ratio (SHR) to assess the primary outcome. Analyses were adjusted for confounders.ResultsOf 2542 patients, 2175 (85.5%) received continuous RRT (CRRT) and 367 (14.4%) received intermittent hemodialysis (IHD) as first RRT modality. CRRT-first patients had greater illness severity. After adjustment, there was no between-group difference in 28-day RRT dependence (SHR, 0.96 [95% CI 0.84–1.10]; p = 0.570) or hospital mortality (odds ratio [OR], 1.14 [95% CI 0.86–1.52]; p = 0.361) However, among survivors, CRRT-first was associated with decreased 28-day RRT dependence (OR, 0.54 [95% CI 0.37–0.80]; p = 0.002) and more RRT-free days (common OR: 1.38 [95% CI 1.11–1.71]). Moreover, among CRRT-first patient, the ATN treatment protocol was associated with fewer RRT-free days, greater mortality, and a fourfold increase in RRT dependence at day 28.ConclusionsThere was no difference in RRT dependence at day 28 between IHD and CRRT. However, among survivors and after adjustment, both IHD-first and the ATN treatment protocol were strongly associated with greater risk of RRT dependence at 28 days after randomization.Trial registration NCT00221013 registered September 22, 2005, and NCT00076219 registered January 19, 2004.

Serum metabolite profiles predict outcomes in critically ill patients receiving renal replacement therapy

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with increased incidence of dialysis dependence and portends high mortality in critically ill patients. At the early stage of RRT, serum metabolic biomarkers might differntiate patients with a high risk of mortality or permanent kidney injury from those who can recover. Serum samples from participants enrolled in the Veteran’s Affairs/National Institutes of Health Acute Renal Failure Trial Network study were collected on day 1 (n = 97) and day 8 (n = 105) of randomized RRT. The samples were further evaluated using LC/MS-based metabolic profiling. A model predicting mortality by day 8 was built from samples collected on day 1 and based on four metabolites with an area under the curve (AUC) of 0.641. A model most predictive of mortality by day 28 was built from the levels of 11 serum metabolites from day 8 with an AUC of 0.789. Both day 1 and day 8 samples had lower serum levels of 1-arachidonoyl-lysoPC and 1-eicosatetraenoyl-lysoPC (involved in anti-inflammatory processes) in the critically ill patients who died by day 8 or day 28. Higher levels of amino acids and amino acid metabolites in the day 8 model predicting < day 28 mortality may be indicative of muscle wasting. A kidney recovery biomarker panel based on the serum levels of three metabolites from day 8 samples with an AUC of 0.70 was devised. Serum metabolic profiling of AKI critically ill patients requiring RRT revealed predictive models of mortality based on observed differences in four serum metabolites at day 1 and 11 metabolites at day 8 which were predictive of mortality. Significant changes in the levels of these metabolites suggest links to inflammatory processes and/or muscle wasting.

Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients.

AKI requiring dialysis (AKI-D) is associated with prolonged hospitalization, mortality, and progressive CKD among survivors. Previous studies have examined only select urine or serum biomarkers for predicting kidney recovery from AKI. Serum samples collected on day 8 of randomized RRT from 72 patients enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the SOMAscan proteomic platform to profile 1305 proteins in each sample. Of these patients, 38 recovered kidney function and dialysis was discontinued, whereas another 34 patients remained on dialysis by day 28. Differential serum levels of 119 proteins, with 53 higher and 66 lower, were detected in samples from patients who discontinued dialysis, compared with patients who remained on dialysis by day 28. Patients were classified into tertiles on the basis of SOMAscan protein measurements for the 25 proteins most differentially expressed. The association of serum levels of each protein with kidney recovery was further evaluated using logistic regression analysis. Higher serum levels of CXCL11, CXCL2/CXCL3, CD86, Wnt-7a, BTK, c-Myc, TIMP-3, CCL5, ghrelin, PDGF-C, survivin, CA2, IL-9, EGF, and neuregulin-1, and lower levels of soluble CXCL16, IL1RL1, stanniocalcin-1, IL-6, and FGF23 when classified in tertiles were significantly associated with better kidney recovery. This significant association persisted for each of these proteins after adjusting for potential confounding risk factors including age, sex, cardiovascular SOFA score, congestive heart failure, diabetes, modality of intensive dialysis treatment, cause of AKI, baseline serum creatinine, day 8 urine volume, and estimated 60-day mortality risk. These results suggest concerted changes between survival-related proteins and immune-regulatory chemokines in regulating angiogenesis, endothelial and epithelial remodeling, and kidney cell regeneration, illustrating potential mechanisms of kidney recovery. Thus, this study identifies potential novel predictive biomarkers of kidney recovery in patients with AKI-D.

Intensity of Renal Replacement Therapy and Duration of Mechanical Ventilation: Secondary Analysis of the Acute Renal Failure Trial Network Study

Randomized clinical trials have failed to show benefit from increasing intensity of renal replacement therapy (RRT) for acute kidney injury, but continue to be frequently used. In addition, intensive RRT is associated with an increase in adverse events potentially secondary to small solute losses, such as phosphate. We hypothesized that, compared with less-intensive RRT, intensive RRT would lead to longer duration of mechanical ventilation. Does more-intensive renal replacement therapy in critically ill patients with acute kidney injury increase time to extubation from mechanical ventilation when compared with less-intensive therapy? The Acute Renal Failure Trial Network study was a randomized multicenter trial of more-intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35mL/kg per hour) vsless-intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20mL/kg per hour) RRT in critically ill patients with acute kidney injury. Of 1124 patients, 907 who were supported by mechanical ventilation on study initiation were included in this Cox-proportional hazards analysis. The primary outcome was the time to first successful extubation off mechanical ventilation. Patients who were assigned randomly to more-intensive RRT had a 33.3%lower hazard rate of successful extubation (hazard ratio, 0.67; 95%CI, 0.52-0.88; P< .001) when compared with patients who were assigned to less-intensive RRT. Patients who were assigned to more-intensive RRT had, on average, 2.07 ventilator-free days, compared with 3.08days inthose who were assigned to less-intensive RRT (P< .001) over 14days from start of thestudy. Critically ill mechanically ventilated patients who were assigned randomly to more-intensive RRT had longer duration of mechanical ventilation compared with those who were assigned to less-intensive RRT. The reasons for this, such as excessive phosphate loss from more-intensive RRT, deserve further study to optimize the safety and effectiveness of CRRT delivery. This was a post hoc analysis of the Acute Renal Failure Trial Network study; clinical trial registration of the original trial is NCT00076219.

Evaluation of five different renal recovery definitions for estimation of long-term outcomes of cardiac surgery associated acute kidney injury

BackgroundThe commonly used recommended criteria for renal recovery are not unequivocal. This study compared five different definitions of renal recovery in order to evaluate long-term outcomes of cardiac surgery associated acute kidney injury (CSA-AKI).MethodsPatients who underwent cardiac surgery between April 2009 and April 2013 were enrolled and divided into acute kidney injury (AKI) and non-AKI groups. The primary endpoint was 3-year major adverse events (MAEs) including death, new dialysis and progressive chronic kidney disease (CKD). We compared five criteria for complete renal recovery: Acute Renal Failure Trial Network (ATN): serum creatinine (SCr) at discharge returned to within baseline SCr + 0.5 mg/dL; Acute Dialysis Quality Initiative (ADQI): returned to within 50% above baseline SCr; Pannu: returned to within 25% above baseline SCr; Kidney Disease: Improving Global Outcomes (KDIGO): eGFR at discharge ≥60 mL/min/1.73 m2; Bucaloiu: returned to ≥90% baseline estimated glomerular filtration rate (eGFR). Multivariate regression analysis was used to compare risk factors for 3-year MAEs.ResultsThe rate of complete recovery for ATN, ADQI, Pannu, KDIGO and Bucaloiu were 84.60% (n = 1242), 82.49% (n = 1211), 60.49% (n = 888), 68.60% (n = 1007) and 46.32% (n = 680). After adjusting for confounding factors, AKI with complete renal recovery was a risk factor for 3-year MAEs (OR: 1.69, 95% CI: 1.20–2.38, P < 0.05; OR: 1.45, 95% CI: 1.03–2.04, P < 0.05) according to ATN and ADQI criteria, but not for KDIGO, Pannu and Bucaloiu criteria. We found that relative to patients who recovered to within 0% baseline SCr or recovered to ≥100% baseline eGFR, the threshold values at which significant differences in 3-year MAEs were observed were > 30% or > 0.4 mg/dL above baseline SCr or < 70% of baseline eGFR.ConclusionsADQI or ATN-equivalent criteria may overestimate the extent of renal recovery, while KDIGO, Pannu and Bucaloiu equivalent criteria may be more appropriate for clinical use. Our analyses revealed that SCr at discharge > 30% or > 0.4 mg/dL of baseline, or eGFR < 70% of baseline led to significant 3-year MAE incidence differences, which may serve as hints for new definitions of renal recovery.

Antibiotic Exposure Profiles in Trials Comparing Intensity of Continuous Renal Replacement Therapy.

To determine whether the probability of target attainment over 72 hours of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, meropenem) antibiotics were substantially influenced between intensive and less-intensive continuous renal replacement therapy groups in the Acute Renal Failure Trial Network trial and The RENAL Replacement Therapy Study trial. The probability of target attainment was calculated using pharmacodynamic targets of percentage of time that free serum concentrations (fT): 1) were above the target organism's minimum inhibitory concentration (≥ fT > 1 × minimum inhibitory concentration); 2) were above four times the minimum inhibitory concentration (≥ % fT > 4 × minimum inhibitory concentration); and 3) were always above the minimum inhibitory concentration (≥ 100% fT > minimum inhibitory concentration) for the first 72 hours of antibiotic therapy. Demographic data and effluent rates from the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials were used. Optimal doses were defined as the dose achieving greater than or equal to 90% probability of target attainment. Monte Carlo simulations using demographic data from Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials. Virtual critically ill patients requiring continuous renal replacement therapy. None. The pharmacodynamic target of fT greater than 1 × minimum inhibitory concentration led to similarly high rates of predicted response with antibiotic doses often used in continuous renal replacement therapy. Achieving 100% fT greater than minimum inhibitory concentration is a more stringent benchmark compared with T greater than 4 × minimum inhibitory concentration with standard antibiotic dosing. The intensity of effluent flow rates (less intensive vs intensive) did not substantially influence the probability of target attainment of antibiotic dosing regimens regardless of pharmacodynamic target. Antibiotic pharmacodynamic target attainment rates likely were not meaningfully different in the low- and high-intensity treatment arms of the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study Investigators trials.

Plasma Biomarkers in Predicting Renal Recovery from Acute Kidney Injury in Critically Ill Patients

Background: Numerous studies have suggested a possible role for acute kidney injury (AKI) biomarkers in predicting renal recovery both before and after renal replacement therapy (RRT). However, definitions for recovery and whether to include patients dying but free of RRT may influence results. Objectives: To validate plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a useful biomarker for predicting or improving the ability of clinical predictors alone to predict recovery following AKI, including in our model plasma B-type natriuretic peptide (pBNP) to account for cardiovascular events. Methods: We analyzed 69 patients enrolled in the Acute Renal Failure Trial Network study. pNGAL and pBNP were measured on days 2, 7, and 14. We analyzed their predictive ability for subsequent recovery, defined as alive and independent from dialysis in 60 days. In sensitivity analyses, we explored changes in results with alternative definitions of recovery. Results: Twenty-nine patients (42%) recovered from AKI. Neither pNGAL nor pBNP, alone or in combination, was accurate predictors of renal recovery-the best area under the receiver-operating characteristics curve (AUC) was for pNGAL using the largest relative change (AUC 0.59, 95% CI 0.45–0.74). The best clinical model achieved superior performance to biomarkers (AUC 0.69, 95% CI 0.56–0.81). The AUC was greatest (0.75, 95% CI 0.60–0.91) when pNGAL + pBNP on day 14 were added to the clinical model but this increase did not achieve statistical significance. However, integrated discrimination improvement analysis showed that the addition of pNGAL and pBNP on day 14 to the clinical model significantly improved the prediction of renal recovery (p = 0.008). Conclusions: pNGAL and pBNP can improve the accuracy of clinical parameters in predicting AKI recovery and a full model using biomarkers together with age achieved adequate discrimination.

Effects of Baseline Thrombocytopenia and Platelet Decrease Following Renal Replacement Therapy Initiation in Patients With Severe Acute Kidney Injury*

Thrombocytopenia is common in critically ill patients with severe acute kidney injury and may be worsened by the use of renal replacement therapy. In this study, we evaluate the effects of renal replacement therapy on subsequent platelet values, the prognostic significance of a decrease in platelets, and potential risk factors for platelet decreases. Post hoc analysis of the Acute Renal Failure Trial Network Study. The Acute Renal Failure Trial Network study was a multicenter, prospective, randomized, parallel-group trial of two strategies for renal replacement therapy in critically ill patients with acute kidney injury conducted between November 2003 and July 2007 at 27 Veterans Affairs and university-affiliated medical centers. The Acute Renal Failure Trial Network study evaluated 1,124 patients with severe acute kidney injury requiring renal replacement therapy. Predictor variables were thrombocytopenia at initiation of renal replacement therapy and platelet decrease following renal replacement therapy initiation. Outcomes were mortality at 28 days, 60 days, and 1 year, renal recovery, renal replacement therapy free days, ICU-free days, and hospital-free days. Baseline thrombocytopenia in patients requiring renal replacement therapy was associated with increased mortality and was also associated with lower rates of renal recovery. A decrease in platelet values following renal replacement therapy initiation was associated with increased mortality. Continuous renal replacement therapy was not an independent predictor of worsening thrombocytopenia compared with those treated with intermittent hemodialysis. Baseline thrombocytopenia and platelet decrease following renal replacement therapy initiation were associated with increased mortality, and baseline thrombocytopenia was associated with decreased rates of renal recovery. Continuous renal replacement therapy did not decrease platelets compared with hemodialysis.

Urea reduction ratio may be a simpler approach for measurement of adequacy of intermittent hemodialysis in acute kidney injury

BackgroundAssessment of adequacy of intermittent hemodialysis (IHD) is conventionally based upon urea kinetic models for calculation of single pool Kt/Vurea (Kt/V), with 1.2 accepted as minimum adequate clearance for thrice weekly IHD. In the Acute Renal Failure Trial Network (ATN) Study, adequacy of IHD in patients with acute kidney injury (AKI) was assessed using Kt/V. However, equations for Kt/V require volume of distribution of urea, which is highly variable in AKI. Therefore, simpler methods are needed to assess adequacy of IHD in AKI. We assessed correlation of urea reduction ratio (URR) with Kt/V and determined URR thresholds corresponding to Kt/V values to determine if URR could be a simpler means to assess the delivered dose of IHD.MethodsUsing patients who received IHD for 2.5–6 h and with pre-dialysis BUN ≥20 mg/dL, we plotted URR against Kt/V. We determined URR thresholds (0.60 to 0.75) corresponding to Kt/V ≥ 1.2, 1.3, and 1.4. We generated receiver operating characteristic (ROC) curves for increasing URR values for each level of Kt/V to identify the corresponding thresholds of URR.ResultsThere was strong correlation between URR and Kt/V. ROC curves comparing URR with Kt/V ≥ 1.2, 1.3, and 1.4 had area under the curves (AUC) of 0.99. Sensitivity and specificity of URR ≥0.67 for corresponding values of Kt/V ≥ 1.2 were 0.769 (95% CI: 0.745 to 0.793) and 0.999 (95% CI: 0.997 to 1.000), respectively and the sensitivity and specificity of URR ≥0.67 for corresponding values of Kt/V ≥ 1.4 were 0.998 (95% CI: 0.995 to 1.000) and 0.791 (95% CI: 0.771 to 0.811), respectively.ConclusionsTargeting a URR ≥0.67 provides a simplified means of assessing adequacy of IHD in patients with AKI. Use of URR will enhance ability to assess delivery of small solute clearance and improve adherence with clinical practice guidelines in AKI.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Uric Acid and Acute Kidney Injury in the Critically Ill

Rationale & ObjectiveUric acid is excreted by the kidney and accumulates in acute kidney injury (AKI). Whether higher plasma uric acid level predisposes to AKI or its complications is not known.Study DesignProspective observational cohort study.Setting & Participants2 independent cohorts of critically ill patients: (1) 208 patients without AKI admitted to the intensive care unit (ICU) at Brigham & Women’s Hospital between October 2008 and December 2016; and (2) 250 participants with AKI requiring renal replacement therapy (RRT) who had not yet initiated RRT enrolled in the Acute Renal Failure Trial Network (ATN) Study.ExposurePlasma uric acid level upon ICU admission and before RRT initiation in the ICU and ATN Study cohorts, respectively.OutcomesIncident AKI and 60-day mortality in the ICU and ATN Study cohorts, respectively.Analytical ApproachLogistic regression models were used to test the association of plasma uric acid level with incident AKI and 60-day mortality.ResultsIn the ICU cohort, median plasma uric acid level was 4.7 (interquartile range [IQR], 3.6-6.4) mg/dL, and 40 patients (19.2%) developed AKI. Higher plasma uric acid levels associated with incident AKI, but this association was confounded by serum creatinine level and was not significant after multivariable adjustment (adjusted OR per doubling of uric acid, 1.50; 95% CI, 0.80-2.81). In the ATN Study cohort, median plasma uric acid level was 11.1 (IQR, 8.6–14.2) mg/dL, and 125 participants (50.0%) died within 60 days. There was no statistically significant association between plasma uric acid levels and 60-day mortality in either unadjusted models or after multivariable adjustment for demographic, severity-of-illness, and kidney-specific covariates (adjusted OR per doubling of uric acid, 1.15; 95% CI, 0.71-1.86).LimitationsHeterogeneity of ICU patients.ConclusionsPlasma uric acid levels upon ICU admission or before RRT initiation are not independently associated with adverse clinical outcomes in critically ill patients.

Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy: External Validation of a Prediction Model.

A recent prognostic model, predicting 60-day case fatality in critically ill patients requiring renal replacement therapy (RRT), has been developed (Acute Renal Failure Trial Network [ATN] study). Because many prognostic models are suggested in literature, but just a few have found its way into clinical practice, we aimed to externally validate this prediction model in an independent cohort. A total of 1,053 critically ill patients requiring RRT from the MIMIC-III database were analyzed. The models' discrimination was evaluated using c-statistics. Calibration was evaluated by Hosmer-Lemeshow (H-L) test and GiViTi calibration belt. In a case-mix population, including patients with normal or altered serum creatinine (sCr) at intensive care unit admission, discrimination was moderate, with a c-statistic of 0.71 in the nonintegerized risk model. In patients with altered baseline sCr, better discrimination was achieved with the integer risk model (0.76, 95% confidence interval, 0.71-0.81). As for the calibration, although the H-L test was good only in patients with normal/slightly altered sCr at admission, the calibration belt disclosed no significant deviations from the bisector line for any of the models in patients, regardless of admission sCr. Of note, a refitted model had a c-statistics of 0.85, similar to the derivation cohort. The ATN prognostic model can be useful in a broad cohort of critically ill patients. Although it showed only moderate discrimination capacity when patients with elevated admission sCr were included, using a refitted model improved it, illustrating the need for continuous external validation and updating of prognostic models over time before their implementation in clinical practice.

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

IntroductionCurrently, no effective therapies exist to reduce the high mortality associated with dialysis-dependent acute kidney injury (AKI-D). Serum biomarkers may be useful in understanding the pathophysiological processes involved with AKI and the severity of injury, and point to novel therapeutic targets.MethodsStudy day 1 serum samples from 100 patients and day 8 samples from 107 patients enrolled in the Veteran’s Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the slow off-rate modified aptamers scan proteomic platform to profile 1305 proteins in each sample. Patients in each cohort were classified into tertiles based on baseline biomarker measurements. Cox regression analyses were performed to examine the relationships between serum levels of each biomarker and mortality.ResultsChanges in the serum levels of 54 proteins, 33 of which increased and 21 of which decreased, were detected when comparing samples of patients who died in the first 8 days versus patients who survived >8 days. Among the 33 proteins that increased, higher serum levels of fibroblast growth factor-23 (FGF23), tissue plasminogen activator (tPA), neutrophil collagenase (matrix metalloproteinase-8), and soluble urokinase plasminogen activator receptor, when stratified by tertiles, were associated with higher mortality. The association with mortality persisted for each of these proteins after adjusting for other potential risk factors, including age, sex, cardiovascular sequential organ failure assessment score, congestive heart failure, and presence of diabetes. Upper tertile levels of FGF23, tPA, and interleukin-6 on day 8 were associated with increased mortality; however, FGF23 barely lost significance after multivariable adjustment.ConclusionsOur results underscore an emerging proteomics tool capable of identifying low-abundance serum proteins important not only in the pathogenesis of AKI-D, but which is also helpful in discriminating AKI-D patients with high mortality.

Effect of Frequent Dialysis on Renal Recovery: Results From the Acute Renal Failure Trial Network Study

IntroductionThe optimal frequency of intermittent hemodialysis (IHD) in the treatment of acute kidney injury (AKI) remains unclear. Increasing the frequency of IHD, while offering the possible advantage of reduced ultrafiltration requirement and less hemodynamic instability per session, amplifies patient contact with an extracorporeal circuit with possible deleterious cardiovascular and immunological consequences. A recent study suggested that intensive renal replacement therapy (RRT) is associated with a decrease in urine output during AKI. We hypothesized that increased frequency of IHD may be associated with delayed renal recovery.MethodsThis is a post hoc analysis of the Acute Renal Failure Trial Network (ATN) study. The ATN study was a large randomized multicenter trial of intensive versus less-intensive RRT in critically ill patients with AKI. This study used either continuous RRT or IHD, depending on the hemodynamic status of the patient. Of 1124 patients, 246 were treated solely with IHD during the study period and were included in this analysis. The participants were randomized to receive IHD 3 days per week (L-IntRRT) or 6 days per week (IntRRT). The primary outcome of interest was renal recovery at day 28.ResultsL-IntRRT was associated with higher number of RRT-free days through day 28 than IntRRT (mean difference 2.5 days; 95% confidence interval [CI]: −4.79 to −0.27 days; P = 0.028). The likelihood for renal recovery at day 28 was lower in the IntRRT group (OR: 0.49; 95% CI: 0.28–0.87; P = 0.016).ConclusionIn hemodynamically stable patients with AKI, intensifying the frequency of IHD from 3 to 6 days per week may be associated with impaired renal recovery.

Vascular Access Site for Renal Replacement Therapy in Acute Kidney Injury: A Post hoc Analysis of the ATN Study.

Acute kidney injury requiring renal replacement therapy (RRT) in the intensive care unit portends a poor prognosis. The decisions regarding dialysis catheter placement is based mainly on physician discretion with little evidence to support the choice of dialysis catheter location. The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was a multicenter, prospective, randomized trial of intensive vs. less intensive RRT in critically ill patients with AKI. We assessed the association of dialysis catheter location with dialysis catheter-related outcomes including catheter-related complications, mortality, dialysis dependence, and dialysis dose delivered. Of the 1,124 patients enrolled in the ATN study, catheter data were available in 1,016 (90.39%) patients. A total of 91 (8.96%) subclavian, 387 (38.09%) internal jugular, and 538 (52.95%) femoral dialysis catheters were inserted. The femoral group was younger (58.39 ± 16.27), had greater bleeding tendency [lower platelet count (96.00 ± 109.35) with higher INR (2.01 ± 2.19)], and had a higher baseline sequential organ failure assessment score on admission (14.59 ± 3.61) compared to the other two groups. Dialysis catheter-related complications were low in this study with no significant difference in the rates of complications among all catheter locations. Mortality and dialysis dependence was lowest in the subclavian group, while the dose of dialysis delivered (Kt/V) remained lowest in the femoral group, after propensity score and center adjustments. Patient characteristics influence the choice of dialysis catheter location with a tendency to place femoral catheters in younger, sicker, and more coagulopathic patients. There were no statistically significant differences in complication rates among the three catheter locations, although femoral catheters may be associated with a lower delivered dose of dialysis during intermittent hemodialysis. www.ClinicalTrials.gov, identifier NCT00076219.

Validity of low-efficacy continuous renal replacement therapy in critically ill patients.

The 1980s saw the use of continuous arteriovenous hemofiltration whose intensity hemofiltration rate was only 3 or 4 mL kg⁻¹ h⁻¹. With the installation of a blood pump, this dose went up to 8 or 10 mL kg⁻¹ h⁻1, and continued to increase, reaching about 20 mL kg⁻¹ h⁻¹ by the year 2000. Some studies found that a higher dose could be beneficial, and the world rapidly followed the trend, increasing the dose up to 35 mL kg⁻¹ h⁻¹. Then, two randomized control trials, namely the VA/NIH Acute Renal Failure Trial Network study and the RENAL study, came along in succession which changed the Kidney Disease: Improving Global Outcomes (KDIGO) recommendation to 20 to 25 mL kg⁻¹ h⁻¹. However, no good evidence exists to support this. Our recent multicenter retrospective studies from the JSEPTIC CRRT database show that the Japanese continuous renal replacement therapy dose of (14.3 mL kg⁻¹ h⁻¹) does not seem to have worse outcomes when compared with a higher dose.

Findings from two large randomized controlled trials on renal replacement therapy in acute kidney injury

Many issues regarding the management of renal replacement therapy (RRT) in acute kidney injury (AKI) including timing of initiation, selection of RRT modality, and optimal dosing remain to be resolved. Two major randomized controlled trials, the Veterans Affairs/National Institutes of Health (VA/NIH) Acute Renal Failure Trial Network (ATN) and the Randomized Evaluation of Normal versus Augmented Level (RENAL) studies, which were elaborately designed to evaluate the benefit for delivering RRT of higher intensity in critically ill patients, were characterized by their sophisticated design, large sample sizes, and comprehensive data collection. Although no beneficial effect of higher intensity RRT was demonstrated by these studies, many ancillary studies conducted subanalyses which provided additional findings on other important clinical questions that remained unsolved. This review aims to overview the useful information obtained by the VA/NIH ATN and the RENAL studies to gain useful insights for optimal RRT in AKI.

Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network Study

Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network Study

Outcomes After Post-Traumatic AKI Requiring RRT in United States Military Service Members.

Mortality and CKD risk have not been described in military casualties with post-traumatic AKI requiring RRT suffered in the Iraq and Afghanistan wars. This is a retrospective case series of post-traumatic AKI requiring RRT in 51 military health care beneficiaries (October 7, 2001-December 1, 2013), evacuated to the National Capital Region, documenting in-hospital mortality and subsequent CKD. Participants were identified using electronic medical and procedure records. Age at injury was 26±6 years; of the participants, 50 were men, 16% were black, 67% were white, and 88% of injuries were caused by blast or projectiles. Presumed AKI cause was acute tubular necrosis in 98%, with rhabdomyolysis in 72%. Sixty-day all-cause mortality was 22% (95% confidence interval [95% CI], 12% to 35%), significantly less than the 50% predicted historical mortality (P<0.001). The VA/NIH Acute Renal Failure Trial Network AKI integer score predicted 60-day mortality risk was 33% (range, 6%-96%) (n=49). Of these, nine died (mortality, 18%; 95% CI, 10% to 32%), with predicted risks significantly miscalibrated (P<0.001). The area under the receiver operator characteristic curve for the AKI integer score was 0.72 (95% CI, 0.56 to 0.88), not significantly different than the AKI integer score model cohort (P=0.27). Of the 40 survivors, one had ESRD caused by cortical necrosis. Of the remaining 39, median time to last follow-up serum creatinine was 1158 days (range, 99-3316 days), serum creatinine was 0.85±0.24 mg/dl, and eGFR was 118±23 ml/min per 1.73 m(2). No eGFR was <60 ml/min per 1.73 m(2), but it may be overestimated because of large/medium amputations in 54%. Twenty-five percent (n=36) had proteinuria; one was diagnosed with CKD stage 2. Despite severe injuries, participants had better in-hospital survival than predicted historically and by AKI integer score. No patient who recovered renal function had an eGFR<60 ml/min per 1.73 m(2) at last follow-up, but 23% had proteinuria, suggesting CKD burden.