Renal Replacement Therapy Dependence Research Articles

Initial renal replacement therapy (RRT) modality associates with 90-day postdischarge RRT dependence in critically ill AKI survivors

PurposeReal-world comparison of RRT modality on RRT dependence at 90 days postdischarge among ICU patients discharged alive after RRT for acute kidney injury (AKI). MethodsUsing claims-linked to US hospital discharge data (Premier PINC AI Healthcare Database [PHD]), we compared continuous renal replacement therapy (CRRT) vs. intermittent hemodialysis (IHD) for AKI in adult ICU patients discharged alive from January 1, 2018 to June 30, 2021. RRT dependence at 90 days postdischarge was defined as ≥2 RRT treatments in the last 8 days. Between-group differences were balanced using inverse probability treatment weighting (IPTW). ResultsOf 34,804 patients, 3804 patients (from 382 hospitals) had claims coverage for days 83–90 postdischarge. Compared to IHD-treated patients (n = 2740), CRRT-treated patients (n = 1064) were younger; had more admission to large teaching hospitals, surgery, sepsis, shock, mechanical ventilation, but lower prevalence of comorbidities (p < 0.05 for all). Compared to IHD-treated patients, CRRT-treated patients had lower RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and lower RRT dependence at 90 days postdischarge (4.9% vs. 7.4% p = 0.006) with weighted adjusted OR (95% CI): 0.68 (0.47–0.97), p = 0.03. Results persisted in sensitivity analyses including patients who died during days 1–90 postdischarge (n = 112) or excluding patients from hospitals with IHD patients only (n = 335), or when excluding patients who switched RRT modalities (n = 451). ConclusionsAdjusted for potential confounders, the odds of RRT dependence at 90 days postdischarge among survivors of RRT for AKI was 30% lower for those treated first with CRRT vs. IHD, overall and in several sensitivity analyses. SummaryCritically ill patients in intensive care units (ICU) may develop acute kidney injury (AKI) that requires renal replacement therapy (RRT) to temporarily replace the injured kidney function of cleaning the blood. Two main types of RRT in the ICU are called continuous renal replacement therapy (CRRT), which is performed almost continuously, i.e., for >18 h per day, and intermittent hemodialysis (IHD), which is a more rapid RRT that is usually completed in a little bit over 6 h, several times per week. The slower CRRT may be gentler on the kidneys and is more likely to be used in the sickest patients, who may not be able to tolerate IHD. We conducted a data-analysis study to evaluate whether long-term effects on kidney function (assessed by ongoing need for RRT, i.e., RRT dependence) differ depending on use of CRRT vs. IHD. In a very large US linked hospital-discharge/claims database we found that among ICU patients discharge alive after RRT for AKI, fewer CRRT-treated patients had RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and at 90 days after discharge (4.9% vs. 7.4% p = 0.006). In adjusted models, RRT dependence at 90 days postdischarge was >30% lower for CRRT than IHD-treated patients. These results from a non-randomized study suggest that among survivors of RRT for AKI, CRRT may result in less RRT dependence 90 days after hospital discharge.

Initiation of continuous renal replacement therapy versus intermittent hemodialysis in critically ill patients with severe acute kidney injury: a secondary analysis of STARRT-AKI trial.

There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.

Differential effect on mortality of the timing of initiation of renal replacement therapy according to the criteria used to diagnose acute kidney injury: an IDEAL-ICU substudy

BackgroundThis substudy of the randomized IDEAL-ICU trial assessed whether the timing of renal replacement therapy (RRT) initiation has a differential effect on 90-day mortality, according to the criteria used to diagnose acute kidney injury (AKI), in patients with early-stage septic shock.MethodsThree groups were considered according to the criterion defining AKI: creatinine elevation only (group 1), reduced urinary output only (group 2), creatinine elevation plus reduced urinary output (group 3). Primary outcome was 90-day all-cause death. Secondary endpoints were RRT-free days, RRT dependence and renal function at discharge. We assessed the interaction between RRT strategy (early vs. delayed) and group, and the association between RRT strategy and mortality in each group by logistic regression.ResultsOf 488 patients enrolled, 205 (42%) patients were in group 1, 174 (35%) in group 2, and 100 (20%) in group 3. The effect of RRT initiation strategy on 90-day mortality across groups showed significant heterogeneity (adjusted interaction p = 0.021). Mortality was 58% vs. 42% for early vs. late RRT initiation, respectively, in group 1 (p = 0.028); 57% vs. 67%, respectively, in group 2 (p = 0.18); and 58% vs. 55%, respectively, in group 3 (p = 0.79). There was no significant difference in secondary outcomes.ConclusionThe timing of RRT initiation has a differential impact on outcome according to AKI diagnostic criteria. In patients with elevated creatinine only, early RRT initiation was associated with significantly increased mortality. In patients with reduced urine output only, late RRT initiation was associated with a nonsignificant, 10% absolute increase in mortality.

Urinary neutrophil gelatinase-associated lipocalin and plasma IL-6 in discontinuation of continuous venovenous hemodiafiltration for severe acute kidney injury: a multicenter prospective observational study

BackgroundPatients with severe acute kidney injury (AKI) who require continuous venovenous hemodiafiltration (CVVHDF) in intensive care unit (ICU) are at high mortality risk. Little is known about clinical biomarkers for risk prediction, optimal initiation, and optimal discontinuation of CVVHDF.MethodsThis prospective observational study was conducted in seven university-affiliated ICUs. For urinary neutrophil gelatinase-associated lipocalin (NGAL) and plasma IL-6 measurements, samples were collected at initiation, 24 h, 48 h after, and CVVHDF discontinuation in adult patients with severe AKI. The outcomes were deaths during CVVHDF and CVVHDF dependence.ResultsA total number of 133 patients were included. Twenty-eight patients died without CVVHDF discontinuation (CVVHDF nonsurvivors). Urinary NGAL and plasma IL-6 at the CVVHDF initiation were significantly higher in CVVHDF nonsurvivors than in survivors. Among 105 CVVHDF survivors, 70 patients were free from renal replacement therapy (RRT) or death in the next 7 days after discontinuation (success group), whereas 35 patients died or needed RRT again (failure group). Urinary NGAL at CVVHDF discontinuation was significantly lower in the success group (93.8 ng/ml vs. 999 ng/ml, p < 0.01), whereas no significant difference was observed in plasma IL-6 between the groups. Temporal elevations of urinary NGAL levels during the first 48 h since CVVHDF initiation were observed in CVVHDF nonsurvivors and those who failed in CVVHDF discontinuation.ConclusionsUrinary NGAL at CVVHDF initiation and discontinuation was associated with mortality and RRT dependence, respectively. The serial changes of urinary NGAL might also help predict the prognosis of patients with AKI on CVVHDF.Graphical

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.

Timing of renal-replacement therapy in intensive care unit-related acute kidney injury.

The optimal timing of renal-replacement therapy (RRT) initiation for the management of acute kidney injury (AKI) in the intensive care unit (ICU) is frequently controversial. An earlier-strategy has biological rationale, even in the absence of urgent indications; however, a delayed-strategy may prevent selected patients from receiving RRT and avoid complications related to RRT. Previous studies assessing the optimal timing of RRT initiation found conflicting results, contributing to variation in clinical practice. The recent multinational trial, standard vs. accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI) found no survival benefit and a higher risk of RRT dependence with an accelerated compared to a standard RRT initiation strategy in critically ill patients with severe AKI. Nearly 40% of patients allocated to the standard-strategy group did not receive RRT. The Artificial Kidney Initiation in Kidney Injury-2 (AKIKI-2) trial further assessed delayed compared to more-delayed strategies for RRT initiation. The more-delayed strategy did not confer an increase in RRT-free days and was associated with a higher risk of death. Early preemptive initiation of RRT in critically ill patients with AKI does not confer clear clinical benefits. However, protracted delays in RRT initiation may be harmful.

Hyperoncotic Albumin Solution in Continuous Renal Replacement Therapy Patients

Aim: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT). Methods: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. Results: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was −288 mL (−904 to 261) with 20% HAS only versus 245 mL (−248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77–1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84–1.30; p = 0.70) compared to those who received 4% HAS only. Conclusions: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only.

The indications for and timing of haemodialysis in critically ill patients with acute kidney injury in Johannesburg, South Africa.

Background Acute kidney injury (AKI) is common among patients admitted to the intensive care unit (ICU). It is an independent risk factor for morbidity and mortality. The optimal timing of renal replacement therapy (RRT) remains unknown, resulting in a wide variation in observed current practices. There is a paucity of data on current practices within ICUs in South Africa. Objectives To describe current practices in the timing of RRT in patients with AKI admitted to the ICU. The secondary objectives were to describe the patient characteristics, severity of illness scores, staging at initiation of RRT, outcome at ICU discharge, and to estimate and describe delays in the initiation of RRT. Methods A retrospective, descriptive study was conducted in an adult academic ICU in Soweto from 1 January 2014 to 31 December 2015. Results There were 2 152 ICU admissions over the 2 years. Less than a tenth of the patients (3.5%; n=76) required RRT and the majority had sepsis (83%). The most common indication for RRT was oliguria/anuria (50%; n=38), followed by worsening urea/creatinine (29%; n=22), metabolic acidosis (11.8%; n=9), refractory hyperkalaemia (5.3%; n=4), fluid overload (2.6%; n=2) and other (1.3%; n=1). More than half of the patients (55%; n=42) had RRT instituted on admission day (D0 ), while 45% (n=34) had RRT initiated after D0 (D1-21). RRT was initiated at stage 3 AKI in 90% and 94% of D0 RRT group and D1-21 RRT group, respectively. The median (interquartile range (IQR)) time to starting RRT was 4 (4) hours once the decision to initiate RRT was made. The composite outcome of death, RRT dependence and diuretic dependence at ICU discharge was 21% and there was no difference between the two groups (p=0.22). The ICU mortality was 3%. Conclusion The sampled population was young, predominantly male and had post emergency surgery with a high burden of sepsis and HIV. The observed current threshold for RRT was late (stage 3 AKI with classic/emergent indications) with outcomes comparable with the reviewed literature. Contributions of the studyThe present study adds insight into the practice of initiating RRT in patients admitted to the ICU with AKI. These data have previously not been described in the South African context. The patient population differed from the literature in that they were young, predominantly male and had post-emergency surgery with a high burden of sepsis and HIV.

Time to Initiation of Renal Replacement Therapy Among Critically Ill Patients With Acute Kidney Injury: A Current Systematic Review and Meta-Analysis.

The optimal time to initiate renal replacement therapy in critically ill patients with acute kidney injury is controversial. We investigated the effect of such earlier versus later initiation of renal replacement therapy on the primary outcome of 28-day mortality and other patient-centered secondary outcomes. We searched MEDLINE (via PubMed), EMBASE, and Cochrane databases to July 17, 2020, and included randomized controlled trials comparing earlier versus later renal replacement therapy. Multiple centers involved in eight trials. Total of 4,588 trial participants. Two independents investigators screened and extracted data using a predefined form. We selected randomized controlled trials in critically ill adult patients with acute kidney injury and compared of earlier versus later initiation of renal replacement therapy regardless of modality. Overall, 28-day mortality was similar between earlier and later renal replacement therapy initiation (38.43% vs 38.06%, respectively; risk ratio, 1.01; [95% CI, 0.94-1.09]; I2 = 0%). Earlier renal replacement therapy, however, shortened hospital length of stay (mean difference, -2.14 d; [95% CI, -4.13 to -0.14]) and ICU length of stay (mean difference, -1.18 d; [95% CI, -1.95 to -0.42]). In contrast, later renal replacement therapy decreased the use of renal replacement therapy (relative risk, 0.69; [95% CI, 0.58-0.82]) and lowered the risk of catheter-related blood stream infection (risk ratio, 0.50, [95% CI, 0.29-0.86). Among survivors, renal replacement therapy dependence at day 28 was similar between earlier and later renal replacement therapy initiation (risk ratio, 0.98; [95% CI, 0.66-1.40]). Earlier or later initiation of renal replacement therapy did not affect mortality. However, earlier renal replacement therapy was associated with significantly shorter ICU and hospital length of stay, whereas later renal replacement therapy was associated with decreased use of renal replacement therapy and decreased risk of catheter-related blood stream infection. These findings can be used to guide the management of critically ill patients with acute kidney injury.

Relationship between the timing of initiation of continuous renal replacement therapy and the prognosis of patients with sepsis-associated acute kidney injury

To investigate the relationship between the timing of initiation of continuous renal replacement therapy (CRRT) and the prognosis of patients with sepsis associated-acute kidney injury (SA-AKI). The clinical data of SA-AKI patients undergoing CRRT in intensive care unit (ICU) of Ningbo First Hospital from January 2017 to November 2019 were retrospectively analyzed. According to the guidelines for Kidney Disease: Improving Global Outcomes (KDIGO), patients with AKI who started CRRT in stage 1 or 2 were included in the early treatment group, and those started CRRT in stage 3 were included in the late treatment group. The general clinical data, length of ICU stay, total length of hospital stay, 28-day and 90-day mortality, CRRT duration, 28-day and 90-day renal replacement therapy (RRT) disengagement rate, 28-day and 90-day RRT dependence rate in the survival patients were compared between the two groups. Kaplan-Meier survival analysis was performed to assess the 90-day cumulative survival rate of patients with SA-AKI between two groups. A total of 244 SA-AKI patients were enrolled in this study, including 71 patients in the early treatment group and 173 patients in the late treatment group. There were no significant differences in age, gender composition, acute physiology and chronic health evaluation II (APACHE II), proportion of surgical patients, infection site and anticoagulation program between the two groups. The CRRT duration in the early group was significantly shorter than that in the late group [hours: 26.0 (12.0, 49.0) vs. 41.0 (20.8, 87.0), P < 0.01], but there were no significant differences in the length of ICU stay [days: 9.0 (4.0, 15.0) vs. 10.0 (4.5, 18.0)], total length of hospital stay [days: 17.0 (10.0, 30.0) vs. 18.0 (10.0, 32.0)], 28-day mortality (45.1% vs. 48.0%), 90-day mortality (46.4% vs. 51.4%), 28-day RRT disengagement rate (49.3% vs. 45.1%) and 90-day RRT disengagement rate (52.1% vs. 47.4%) between the early treatment group and late treatment group (all P > 0.05). There were also no significant differences in 28-day RRT dependence rate [10.3% (4/39) vs. 13.3% (12/90)] and 90-day RRT dependence rate [2.6% (1/38) vs. 2.4% (2/84)] between early treatment group and late treatment group (both P > 0.05). Kaplan-Meier survival analysis suggested that there was no significant difference in the 90-day cumulative survival rate between two groups (Log-Rank test: χ2 = 0.791, P = 0.374). Early initiation of CRRT treatment in SA-AKI patients can reduce the duration of CRRT, but has no effect on length of ICU stay, total length of hospital stay, renal function recovery and mortality. At present, the optimal timing for initiation of CRRT in patients with SA-AKI remains unknown.

Early Treatment with Human Albumin Solution in Continuous Renal Replacement Patients

Aims: To study the impact of early human albumin solution (HAS) in continuous renal replacement therapy (RRT) patients. Methods: Analysis of Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. Results: Of 1,464 patients, 500 (34%) received early albumin. These patients had higher illness severity scores, greater use of mechanical ventilation, and 90-day mortality (51 vs. 41%; p < 0.001). However, early albumin carried similar RRT dependence risk among survivors at day 90 (4.9 vs. 5.8%; p = 0.62). On Cox proportional hazards regression, with standardized inverse probability of treatment weighting, early albumin was not associated with increased mortality (hazard ratio [HR]: 1.23, 95% CI: 0.97–1.55; p = 0.09) or recovery to RRT independence (HR: 0.92, 95% CI: 0.78–1.10; p = 0.38). Conclusions: Early albumin was administered to one-third of RENAL trial patients and in those with greater illness severity. Early albumin was not independently associated with mortality risk or rate of recovery to RRT independence.

Characteristics and Clinical Outcomes of Prolonged Continuous Renal Replacement Therapy in Critically Ill Pediatric Patients.

Paralleling improved outcomes in critically ill patients, survival for pediatric acute kidney injury has improved. Continuous renal replacement therapy is the preferred modality to optimize fluid and electrolyte management as well as nutritional support for children developing acute kidney injury in the PICU. However, some patients remain too fragile for transition to intermittent renal replacement therapies and require continuous renal replacement therapy for a prolonged period. Characteristics of this cohort and factors impacting outcomes are not well known. We aimed to describe the characteristics of pediatric patients requiring prolonged continuous renal replacement therapy and evaluate the factors impacting hospital survival. Retrospective chart review. Tertiary PICU. Children requiring prolonged continuous renal replacement therapy. Prolonged continuous renal replacement therapy was defined as continuous renal replacement therapy dependence greater than or equal to 28 days. Primary outcome was hospital mortality. None. From 2013 to 2016, 344 patients received continuous renal replacement therapy, 36 (10%) received continuous renal replacement therapy for greater than or equal to 28 days. Seventeen patients (47%) were female. Overall mortality was 44% (16/36); 69% (11/16) of nonsurvivors died of sepsis. Pediatric Logistic Organ Dysfunction score was significantly higher in nonsurvivors. Mortality rate was significantly higher in patients who were neutropenic at continuous renal replacement therapy start. Neutropenia (defined as absolute neutrophil count < 1,500/mm) at continuous renal replacement therapy start was the only independent predictor of mortality. One in four survivors did not recover renal function and remained dialysis dependent. Prolonged continuous renal replacement therapy patients are at high risk of nonrecovery of renal function and require close monitoring. The majority of nonsurvivors in the study group died from sepsis. Neutropenia at continuous renal replacement therapy initiation was associated with increased risk of mortality. Progression of underlying disease process could explain the higher death rate in patients with neutropenia; however, inadequate treatment of infectious complications could be another explanation to explore further in future studies.

Effect of low-dose atrial natriuretic peptide in critically ill patients with acute kidney injury: a retrospective, single-center study with propensity-score matching

BackgroundAcute kidney injury (AKI) is a major comorbidity in critically ill patients. Low-dose atrial natriuretic peptide (ANP) has been shown to effectively prevent acute kidney injury (AKI), especially in cardiovascular surgery patients. However, its treatment effects for AKI in critically ill patients are unclear.MethodsThis single-center, retrospective, observational study included patients with AKI diagnosed within 7 days after intensive care unit (ICU) admission during the period January 2010 to December 2017. We conducted a propensity-matched analysis to estimate the treatment effect of low-dose carperitide (a recombinant human ANP) on the clinical outcomes. The primary outcome was a composite of death, renal replacement therapy dependence, or no recovery from AKI (defined as an increase of the serum creatinine level to ≥200% of baseline) at hospital discharge.ResultsDuring the study period, 4479 adult patients were admitted to the ICU. We identified 1374 eligible patients with AKI diagnosed within 7 days after ICU admission. Among these patients, 346 (25.2%) were treated with low-dose carperitide, with an average dose of 0.019 μg kg− 1 min− 1. The primary outcome occurred more often in the treatment group than in the control group (29.7% versus 23.4%, respectively; p = 0.022). After propensity score matching, characteristics of 314 patients from each group were well- balanced. Significant difference of the primary outcome, as seen with the full cohort, was no longer obtained; no benefit of carperitide was detected in the matched cohort (29.0% versus 25.2%; p = 0.281).ConclusionsLow-dose ANP showed no treatment effect in general critically ill patients who developed AKI.

Effects of early dialysis on the outcomes of critically ill patients with acute kidney injury: a systematic review and meta-analysis of randomized controlled trials

The appropriate timing for initiating renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) remains unknown. This meta-analysis aims to assess the efficacy of early initiation of RRT in critically ill patients with AKI. The Pubmed, Embase and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) comparing the effects of early and late RRT on AKI patients were included. The primary outcome was 28-day mortality. Eleven RCTs including 1131 and 1111 AKI patients assigned to early and late RRT strategies, respectively, were enrolled in this meta-analysis. The pooled 28-day mortality was 38.1% (431/1131) and 40.7% (453/1111) in the patients assigned to early and late RRT, respectively, with no significant difference between groups (risk ratio (RR), 0.95; 95% CI, 0.78–1.15, I2 = 63%). No significant difference was found between groups in terms of RRT dependence in survivors on day 28 (RR, 0.90; 95% CI, 0.67–1.25, I2 = 0%), and recovery of renal function (RR, 1.03; 95% CI, 0.89–1.19, I2 = 56%). The early RRT group had higher risks of catheter-related infection (RR, 1.7, 95% CI, 1.01–2.97, I2 = 0%) and hypophosphatemia (RR, 2.5, 95% CI, 1.25–4.99, I2 = 77%) than the late RRT group. In conclusion, an early RRT strategy does not improve survival, RRT dependence, or renal function recovery in critically ill patients with AKI in comparison with a late RRT strategy. However, clinicians should be vigilant because early RRT can carry higher risks of catheter-related infection and hypophosphatemia during dialysis than late RRT.

Early versus late initiation of renal replacement therapy for acute kidney injury in critically ill patients: A systematic review and meta-analysis.

BackgroundAcute kidney injury is associated with high mortality, and is the most frequent complication encountered in patients residing in the intensive care unit. Although renal replacement therapy (RRT) is the standard of care for acute kidney injury, the optimal timing for initiation is still unknown.MethodsWe conducted a systemic review and meta-analysis of randomized controlled trials evaluating early versus late initiation of RRT in critically ill patients with acute kidney injury. We searched MEDLINE, Embase, and CENTRAL databases from inception to October 15, 2018. We screened studies and extracted data from published reported independently. The primary outcome was short-term mortality.ResultsA total of 2242 patients were included from 11 trials. No statistically significant effect was found for early versus late initiation of RRT on short-term mortality (risk ratio [RR] 0.99, 95% CI 0.84–1.17, p = 0.93) or long-term mortality (RR 0.98, 95% CI 0.85–1.13, p = 0.76). There were also no statistically significant effects on ICU length of stay, hospital length of stay, recovery of renal function, and renal replacement therapy dependence. Early initiation of RRT decreased the risk of metabolic acidosis (RR 0.65, 95% CI 0.43–0.99, p = 0.04), but increased the risk of hypotension (RR 1.24, 95% CI 1.08–1.43, p = 0.003).ConclusionsIn critically ill patients with acute kidney injury, early compared with late initiation of RRT is not associated with favorable mortality outcomes, although it appears to reduce the risk of metabolic acidosis.

Fluid Overload Associates With Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

We examined the association between fluid overload and major adverse kidney events in critically ill patients requiring continuous renal replacement therapy for acute kidney injury. Retrospective cohort study. ICU in a tertiary medical center. Four-hundred eighty-one critically ill adults requiring continuous renal replacement therapy for acute kidney injury. None. Fluid overload was assessed as fluid balance from admission to continuous renal replacement therapy initiation, adjusted for body weight. Major adverse kidney events were defined as a composite of mortality, renal replacement therapy-dependence or inability to recover 50% of baseline estimated glomerular filtration rate (if not on renal replacement therapy) evaluated up to 90 days after discharge. Patients with fluid overload less than or equal to 10% were less likely to experience major adverse kidney events than those with fluid overload greater than 10% (71.6% vs 79.4%; p = 0.047). Multivariable logistic regression showed that fluid overload greater than 10% was associated with a 58% increased odds of major adverse kidney events (p = 0.046), even after adjusting for timing of continuous renal replacement therapy initiation. There was also a 2.7% increased odds of major adverse kidney events for every 1 day increase from ICU admission to continuous renal replacement therapy initiation (p = 0.024). Fluid overload greater than 10% was also found to be independently associated with an 82% increased odds of hospital mortality (p = 0.004) and 2.5 fewer ventilator-free days (p = 0.044), compared with fluid overload less than or equal to 10%. In critically ill patients with acute kidney injury requiring continuous renal replacement therapy, greater than 10% fluid overload was associated with higher risk of 90-day major adverse kidney events, including mortality and decreased renal recovery. Increased time between ICU admission and continuous renal replacement therapy initiation was also associated with decreased renal recovery. Fluid overload represents a potentially modifiable risk factor, independent of timing of continuous renal replacement therapy initiation, that should be further examined in interventional studies.

Association between intravenous contrast media exposure and non-recovery from dialysis-requiring septic acute kidney injury: a nationwide observational study.

This study aimed to examine the association between the use of intravenous contrast and non-recovery from dialysis-requiring acute kidney injury (AKI-D) and in-hospital mortality among patients with sepsis. This was a retrospective observational study using the Japanese Diagnosis Procedure Combination inpatient database between January 2011 and December 2016. We identified patients with septic AKI who began continuous renal replacement therapy (RRT) within 2-days of admission and underwent computed tomography. We compared patients with AKI-D with and without the use of intravenous contrast for computed tomography and performed propensity score matching to adjust for confounders for the association between exposure to intravenous contrast and outcomes, including a composite outcome of in-hospital mortality and RRT dependence at discharge and RRT duration. From 3782 and 6619 patients with septic AKI-D with and without intravenous contrast exposure, respectively, 3485 propensity score-matched pairs were generated. No significant differences were found in the outcomes between the propensity score-matched groups: a composite outcome of in-hospital mortality and RRT dependence, 49.6% vs. 50.2% (odds ratio (OR) 0.98; 95% CI (confidence interval) 0.88, 1.07); in-hospital mortality, 45.3% vs. 46.1% (OR 0.97; 95% CI 0.87, 1.06); RRT dependence, 4.4% vs 4.1% (OR 1.08; 95% CI 0.85, 1.31); and median (interquartile range) of RRT duration, 4 [2-11]days vs. 4 [2-11]days (P = 0.58). This large observational study did not support an association between intravenous contrast media and adverse in-hospital outcomes in patients with septic AKI-D. Further studies are warranted to assess the generalizability.

Earlier start versus standard start dialysis in patients with acute kidney injury: systematic review and meta-analysis

Objectives The aim of the present review is to synthesize evidence from the published literature about the effect of early versus late initiation of renal replacement therapy (RRT) on the outcomes of patients with acute kidney injury (AKI). Backgrounds AKI is a serious clinical disorder with significant increase in risk of mortality and morbidity, especially among hospitalized patients. Data sources A computer literature search of Medline via PubMed, Cochrane CENTRAL Register of Controlled Trials, SCOPUS, and Web of science was conducted. Study selection Records were screened for eligible studies according to the predetermined inclusion and exclusion criteria. Data extraction Data were extracted and synthesized using standardized tables. Data synthesis Dichotomous data were pooled as relative risk (RR) in a random-effect model using Mantel–Haenszel method. Continuous data were pooled as standardized mean difference (SMD) in generic-variance model. We used Review Manager 5.3 for Windows. Findings The present review included nine studies. Our pooled effect estimates did not favor early initiation of RRT versus late intuition in terms of all-causes mortality (RR = 0.88; 95% confidence interval (CI), 0.68, 1.14; P = 0.33), RRT dependence (RR = 0.81; 95% CI, 0.46, 1.42; P = 0.46), length of stay in ICU (SMD, −0.28; 95% CI, −0.58, 0.03; P = 0.08), and length of stay in hospital (SMD, −0.40; 95% CI, −0.83, 0.03; P = 0.07). Conclusion The present systematic review and meta-analysis shows that early initiation of RRT does not improve survival outcomes and hospital stay among patients with AKI, in comparison with late initiation of RRT.

STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury: Study Protocol for a Multi-National, Multi-Center, Randomized Controlled Trial.

Background:The optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) remains controversial.Objective:In critically ill patients with AKI, to determine whether the accelerated initiation of RRT reduces mortality compared to a strategy of standard RRT initiation whereby RRT is initiated if urgent complications of AKI arise or based on clinician judgment.Design:Pragmatic allocation-concealed open-label randomized controlled trial.Setting:Up to 170 centers in Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Ireland, Italy, Finland, New Zealand, Switzerland, the United Kingdom, and the United States.Patients:We will enroll at least 2,866 critically ill patients with AKI stages 2 or 3 (defined as doubling of serum creatinine from baseline or serum creatinine ≥354 µmol/L with increase of ≥27 µmol/L from baseline or urine output <6 mL/kg in preceding 12 hours). Patients will be excluded if 1 or more of the following is/are present: potassium >5.5 mmol/L; bicarbonate <15 mmol/L; concomitant intoxication necessitating RRT; philosophy of care precluding escalation to RRT; any RRT in preceding 2 months; kidney transplant within the past year; preexisting estimated glomerular filtration rate <20 mL/min/1.73 m2; AKI etiology attributable to obstruction, glomerulonephritis, vasculitis, microangiopathy, or acute interstitial nephritis; clinician opinion that urgent RRT is mandated; or clinician opinion that RRT must be deferred.Methods:Participants will be randomized to one of two strategies: accelerated RRT initiation, which entails the initiation of RRT within 12 hours of the patient fulfilling all eligibility criteria, or standard RRT initiation, whereby clinicians would be discouraged from initiating RRT unless a conventional trigger for RRT initiation arises or if AKI persists for ≥72 hours.Measurements:The primary outcome is all-cause mortality at 90 days following randomization. Key secondary outcomes include RRT dependence, residual kidney function, health services use, and health-related quality of life, all assessed at 90 days after randomization. In jurisdictions where it is feasible, participants will be followed through day 365 using linked administrative data.Results:Through March 18, 2019, we have recruited 2623 (92% of target) participants.Limitations:Reliance on physician declaration of equipoise may create heterogeneity across the trial population; open-label design may introduce bias and uneven postrandomization cointerventions; variations in practice (eg, choice of RRT modality and RRT prescription) likely exist across sites.Conclusions:Once complete, the STARRT-AKI trial will provide the most robust evidence to date to guide clinical practice on the optimal timing of RRT initiation among critically ill patients with AKI.Trial registration:Clinicaltrials.gov NCT02568722.

Outcome Prediction of Acute Kidney Injury Biomarkers at Initiation of Dialysis in Critical Units.

The ideal circumstances for whether and when to start RRT remain unclear. The outcome predictive ability of acute kidney injury (AKI) biomarkers measuring at dialysis initializing need more validation. This prospective, multi-center observational cohort study enrolled 257 patients with AKI undergoing renal replacement therapy (RRT) shortly after admission. At the start of RRT, blood and urine samples were collected for relevant biomarker measurement. RRT dependence and all-cause mortality were recorded up to 90 days after discharge. Areas under the receiver operator characteristic (AUROC) curves and a multivariate generalized additive model were applied to predict outcomes. One hundred and thirty-five (52.5%) patients died within 90 days of hospital discharge. Plasma c-terminal FGF-23 (cFGF-23) had the best discriminative ability (AUROC, 0.687) as compared with intact FGF-23 (iFGF-23) (AUROC, 0.504), creatinine-adjusted urine neutrophil gelatinase-associated lipocalin (AUROC, 0.599), and adjusted urine cFGF-23 (AUROC, 0.653) regardless whether patients were alive or not on day 90. Plasma cFGF-23 levels above 2050 RU/mL were independently associated with higher 90-day mortality (HR 1.76, p = 0.020). Higher cFGF-23 levels predicted less weaning from dialysis in survivors (HR, 0.62, p = 0.032), taking mortality as a competing risk. Adding cFGF-23 measurement to the AKI risk predicting score significantly improved risk stratification and 90-day mortality prediction (total net reclassification improvement = 0.148; p = 0.002). In patients with AKI who required RRT, increased plasma cFGF-23 levels correlated with higher 90-day overall mortality after discharge and predicted worse kidney recovery in survivors. When coupled to the AKI risk predicting score, cFGF-23 significantly improved mortality risk prediction. This observation adds evidence that cFGF-23 could be used as an optimal timing biomarker to initiate RRT.