Initiation Of Requiring Renal Replacement Therapy Research Articles

Long-term outcomes of renal AL amyloidosis patients undergoing autologous stem cell transplantation: Validating the performance of the renal staging system.

Renal AL amyloidosis can be complicated by end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). In this study, we describe the long-term outcomes of renal AL amyloidosis patients undergoing autologous stem cell transplantation (ASCT) and assess the utility of the renal staging system. Retrospective study of renal AL patients (n = 697; Mayo Clinic, Boston University) who underwent ASCT between 2003 and 2020. Renal stage was assigned based on 24-h proteinuria and estimated glomerular filtration rate measurements. Renal survival was defined as the time from ASCT until initiation of RRT, while patients who were not placed on RRT were censored at their last follow-up. With a median follow-up of 10.4 years, RRT was required in 149 patients (21%). The median time from ASCT to ESRD was 3.4 years, with late events of progression to ESRD seen >10 years from ASCT. Pre-ASCT renal stage was significantly associated with the cumulative incidence of RRT: 3-year RRT rate was 3%, 10%, and 37% for renal stages I, II, and III, respectively. However, in the 2012-2020 period subset, a significant decrease in ESRD risk was noted across all renal stages (3-year RRT 0%, 5%, and 24%, respectively). In multivariate analysis, renal survival was independently associated with the pre-ASCT renal stage, lambda isotype, bone marrow plasmacytosis ≥20%, post-ASCT hematologic response, and year of ASCT. Long-term outcomes of renal AL amyloidosis treated with ASCT are presented. Renal stage reliably predicts renal outcomes in patients with AL undergoing ASCT, despite a reduction in the proportion of patients progressing to RRT in recent years.

#1708 Mortality and kidney function recovery in patients with sepsis-associated vs non-septic acute kidney injury treated with CRRT

Abstract Background and Aims It was recently suggested that sepsis-associated acute kidney injury (SA-AKI) is characterized by different pathogenesis and outcomes compared to non-Septic AKI (NS-AKI). However, limited data are available focusing on the clinical outcomes of SA-AKI versus NS-AKI. The aim of this study is to examine risk factors and outcomes of SA-AKI vs NS-AKI among critically ill patients who developed AKI requiring renal replacement therapy (RRT). Methods We performed a single-center retrospective analysis, examining all patients admitted to ICU who developed AKI requiring RRT at Policlinico of Bari, from January 2021 to July 2023. We classified patients in two groups based on the leading cause of AKI: NS-AKI and SA-AKI. We collected clinical and laboratory data, including maximum AKI stage reached during hospitalization, RRT indications, modality and duration. The primary outcome was to assess mortality rate between SA-AKI and NS-AKI groups. The cumulative 28-day survival probability was calculated using the Kaplan–Meier method. The analysis of the risk factors associated with in-hospital mortality was performed using Cox's proportional hazard regression models. Kidney Functional Recovery (KFR) from, RRT discontinuation and length of ICU and hospital stay were also analyzed. Results 320 patients were included in the study; 131 patients developed SA-AKI (40.9%), while the remaining 189 were classified as NS-AKI (59.1%). Median age was 67 years (IQR 57-73) with a predominance of male gender (67.8%), without significant differences between groups. A significant percentage of patients had an history of cardiovascular disease in NS-AKI group compared to SA-AKI group (54.5% vs 29%, p < 0.001). Conversely, the proportion of patients with a history of chronic respiratory disease was significantly higher in the SA-AKI group (23.7% vs 9.5%, p = 0.001). 268 patients (83.8%) developed AKI Stage 3 and 40 patients AKI stage 2 (12.5%) at RRT initiation. All patients were treated with continuous modalities (CRRT). There was no significant difference in CRRT duration between groups (median days 5, IQR 2-12) (Table 1). The timing of CRRT initiation from ICU admission was significant different and we reported a late CRRT initiation in the SA-AKI group (3 vs 1 days, p = 0.002). The median length of ICU stay was 12 days (IQR 4-25) and did not differ between groups. 184 patients (57.5%) died at 28 days, with a higher percentage in the SA-AKI (70.2 vs 48.6%, p < 0.001). Similarly, in-hospital mortality was reported in 221 patients (69%), with impressive percentages in the SA-AKI group (82.45 vs 69.3%, p < 0.001) (Fig. 1). KFR at 28 days from CRRT initiation was significantly higher in the NS-AKI (28.5%) compared to the SA-AKI group (13.7%, p = 0.002). Median time of KFR was similar between groups (p = 0.833). Multivariate Cox Regression analysis showed that only SA-AKI (HR 1.442, 95% CI 1.052-1.978, p = 0.023) was independently associated with increased risk of mortality. Conclusions Sepsis-associated AKI was associated with high mortality rate and lower likelihood of renal recovery compared to non-septic AKI in critically ill patients requiring RRT. These findings emphasize the importance of identifying specific AKI phenotypes characterized by different pathophysiology and clinical outcomes.

Practical considerations for individualizing drug dosing in critically ill adults receiving renal replacement therapy.

Critically ill patients with sepsis admitted to the intensive care unit (ICU) often present with or develop renal dysfunction requiring renal replacement therapy (RRT) in addition to antimicrobial therapy. While early and appropriate antimicrobials for sepsis have been associated with an increased probability of survival, adequate dosing is also required in these patients. Adequate dosing of antimicrobials refers to dosing strategies that achieve serum drug levels at the site of infection that are able to provide a microbiological and/or clinical response while avoiding toxicity from excessive antibiotic exposure. Therapeutic drug monitoring (TDM) is the recommended strategy to achieve this goal, however, TDM is not routinely available in all ICUs and for all antimicrobials. In the absence of TDM, clinicians are therefore required to make dosing decisions based on the clinical condition of the patient, the causative organism, the characteristics of RRT, and an understanding of the physicochemical properties of the antimicrobial. Pharmacokinetics (PK) of antimicrobials can be highly variable between critically ill patients and also within the same patient over the course of their ICU stay. The initiation of RRT, which can be in the form of intermittent hemodialysis, continuous, or prolonged intermittent therapy, further complicates the predictability of drug disposition. This variability highlights the need for individualized dosing. This review highlights the practical considerations for the clinician for antimicrobial dosing in critically ill patients receiving RRT.

Critically ill patients with acute kidney injury: clinical determinants and post-mortem histology.

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) in the intensive care unit (ICU) portends a poor prognosis. We aimed to better characterize predictors of survival and the mechanism of kidney failure in these patients. This was a retrospective observational study using clinical and radiological electronic health records, analysed by univariable and multivariable binary logistic regression. Histopathological examination of post-mortem renal tissue was performed. Among 157 patients with AKI requiring RRT, higher serum creatinine at RRT initiation associated with increased ICU survival [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.17-0.62, P=.001]; however, muscle mass (a marker of frailty) interacted with creatinine (P=.02) and superseded creatinine as a predictor of survival (OR 0.26, 95% CI 0.08-0.82; P=.02). Achieving lower cumulative fluid balance (mL/kg) predicted ICU survival (OR 1.01, 95% CI 1.00-1.01, P<.001), as supported by sensitivity analyses showing improved ICU survival with the use of furosemide (OR 0.40, 95% CI 0.18-0.87, P=.02) and increasing net ultrafiltration (OR 0.97, 95% CI 0.95-0.99, P=.02). A urine output of >500 mL/24 h strongly predicted successful liberation from RRT (OR 0.125, 95% CI 0.05-0.35, P<.001). Post-mortem reports were available for 32 patients; clinically unrecognized renal findings were described in 6 patients, 1 of whom had interstitial nephritis. Experimental staining of renal tissue from patients with sepsis-associated AKI (S-AKI) showed glomerular loss of synaptopodin (P=.02). Confounding of creatinine by muscle mass undermines its use as a marker of AKI severity in clinical studies. Volume management and urine output are key determinants of outcome. Loss of synaptopodin implicates glomerular injury in the pathogenesis of S-AKI.

Predictive factors for severe long-term chronic kidney disease after acute kidney injury requiring renal replacement therapy in critically ill patients: an ancillary study of the ELVIS randomized controlled trial

BackgroundAcute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown.MethodsWe performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD.ResultsOf the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02–1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77–0.93] per point).ConclusionSevere long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT.Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

One-Year Survival for Adult Venoarterial Extracorporeal Membrane Oxygenation Patients Requiring Renal-Replacement Therapy

Acute kidney injury (AKI) and chronic kidney disease (CKD) previously have been associated with in-hospital and long-term mortality of patients undergoing support with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Patient selection criteria and survival prediction scores for VA-ECMO often include AKI or CKD, but exclude patients requiring renal replacement therapy (RRT). The need for RRT in ECMO patients is associated with increased intensive unit care and in-hospital mortality. The effect RRT has on mortality beyond hospital survival is not well-reported. The authors hypothesized that the timing of initiation (pre-ECMO v during ECMO) of RRT can have a significant impact on short- and long-term mortality. The authors categorized patients into 3 groups: those receiving RRT before initiation of ECMO, those initiated on RRT while on ECMO, and those who did not need RRT while on ECMO. The authors compared survival to decannulation, 30 days and 1 year between the 3 groups. A multivariate survival analysis also was conducted. This was a single center retrospective review of all patients receiving VA-ECMO. A total of 347 adult VA-ECMO extracorporeal membrane oxygenation patients. None, retrospective. The authors' cohort included 347 total patients, 39 required RRT before ECMO, 139 while on ECMO, and 169 did not require RRT while on ECMO. If RRT was initiated before ECMO, survival to decannulation was 48.72%, 46.6% if RRT was initiated on ECMO, and 73.96% for patients who did not need RRT while on ECMO. One-year survival was 25.64%, 23.74%, and 46.75%, respectively. There was no significant difference in survival between patients initiated on RRT before ECMO and those who required RRT while on ECMO. The authors demonstrated that the need for RRT before or while on ECMO has reduced short- and long-term survival when compared with those who did not need RRT while on ECMO. The authors believe that RRT is a marker for severe multiorgan failure and that, despite the benefits of RRT, high mortality will occur. This lack of mortality difference between patients previously on RRT and those newly requiring RRT may help clinicians in deciding to initiate ECMO for patients previously on RRT. Further investigation into complication rates between the groups is required.

Clinical Predictors of Mortality of Patients with Acute Kidney Injury Requiring Renal Replacement Therapy

Objective: Acute kidney injury (AKI) is frequently encountered around 40% in critically ill patients and associate with a high mortality. The objective was to assess the clinical predictors for 28-day mortality in AKI patients requiring renal replacement therapy (RRT). Materials and Methods: This is a retrospective cohort study from prospectively collected data. AKI patients requiring RRT were included. We collected demographic and laboratory data within 24 hours before the initiation of RRT. We excluded patients with preexisting chronic kidney disease stage 5 and AKI patients requiring peritoneal dialysis. We compared clinical characteristics and analyzed the predictors of mortality of survivors and non-survivors according to 28-day mortality. Results: We included 122 AKI patients requiring RRT. Mortality rate at day 28 and 90 after AKI diagnosis were 59% (95% confidence interval [CI] 49.7 to 67.8) and 72.1% (95% CI 63.3 to 79.9). On multivariable analysis, clinical predictors for 28-day mortality were serum creatinine before RRT (hazard ratio [HR] 0.84, 95% CI 0.74 to 0.95), SOFA score before initiation of RRT (HR 1.10, 95% CI 1.03 to 1.18), presence of vasopressors before initiation of RRT (HR 2.80, 95% CI 1.03 to 7.64), serum lactate &gt;4 mmol/L before initiation of RRT affected the first 10 days of survival time (HR 2.17, 95% CI 1.03 to 4.57). However, serum lactate &gt;4 mmol/L before initiation of RRT did not affect the after 10 days of survival time (HR 0.99, 95% CI 0.37 to 2.66). Conclusion: AKI patients with shock and multiorgan failure had a lower chance of survival. In addition, a lower serum creatinine that represents a high fluid overload can predict death as well. Keywords: Acute kidney injury; Lactate; Mortality; Renal replacement therapy; Vasopressors

Continuous renal replacement therapy and extracorporeal membrane oxygenation: implications in the COVID-19 era.

The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%-70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19's pathophysiological impact.

The Current State of Renal Replacement Therapy in the Treatment of Sepsis

Of all cases of acute kidney injury (AKI), 45-70% are associated with sepsis. Lethality in sepsis-associated AKI requiring renal replacement therapy (RRT) ranges from 40 to 50%, and in AKI combined with other organ dysfunctions - 60-80%. In order to improve the results of treatment of sepsis and septic shock, various methods of extracorporeal detoxification (ECD) have been developed. The effectiveness of these methods is controversial. In the treatment of sepsis, RRT is used not only to replace the impaired detoxification function of kidneys, but also to remove excess cytokines from the systemic bloodstream. The literature describes mainly positive results of the use of dialyzers with an adsorbing membrane, however, these data do not have the necessary degree of evidence. Currently, there are no clear criteria for the initiation of RRT, its duration and doses, the choice of methodology determined by specific clinical and laboratory parameters, and staging of this therapy. All this highlights the need for further research in this field.

Prospective model for predicting renal recovery in cardiac surgery patients with acute kidney injury requiring renal replacement therapy.

AimTo develop a model for predicting renal recovery in cardiac surgery patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT).MethodsData from a prospective randomized controlled trial, conducted in a tertiary hospital to compare the survival effect of two dosages of hemofiltration for continuous RRT in cardiac surgery patients between 20 March 2012 and 9 August 2015, were used to develop the model. The outcome was renal recovery defined as alive and dialysis‐free 90 days after RRT initiation. Multivariate logistic regression with a stepwise backward selection of variables based on Akaike Information Criterion was applied to develop the model, which was internally validated using bootstrapping. Model discrimination, calibration and clinical value were assessed using the concordance index (C‐Index), calibration plots and decision curve analysis, respectively.ResultsTotally, 211 patients with AKI requiring RRT (66.8% male) with median age of 57 years were included. The incidence of renal recovery was 33.2% (n = 70). The model included six variables: body mass index stratification, baseline estimated glomerular filtration rate, hypertension, sepsis, mean arterial pressure and mechanical ventilation. The C‐Index for this model was 0.807 (95% CI, 0.744–0.870). After correction by the bootstrap, the C‐Index was 0.780 (95% CI, 0.720–0.845). The calibration plots indicated good consistency between actual observations and model prediction of renal recovery. Decision curve analysis demonstrated the model was clinical usefulness.ConclusionWe developed and validated a model to predict the chance of renal recovery in cardiac surgery patients with AKI requiring RRT.

Kidney failure after lung transplantation in systemic scleroderma: a case report with literature review

BackgroundSystemic scleroderma (SSc) involves multiple organs including the skin, the lung, the kidney, and the esophagus. Nowadays, patient life prognosis has substantially improved due to more appropriate management of lung complications, including lung transplantation. However, the extension of their survival may increase SSc patients with chronic kidney diseases and requiring renal replacement therapy (RRT).Case presentationA 51-year-old female with SSc who underwent unilateral deceased-donor lung transplantation was referred because of progressive renal dysfunction. Despite no episodes of scleroderma renal crisis, her renal function gradually deteriorated for 2 years with her serum creatinine level increasing from 0.5 mg/dL at transplantation to 4.3 mg/dL. Although we reinforced antihypertensive treatment and reduced calcineurin inhibitor dose, she thereafter developed symptomatic uremia. Due to impaired manual dexterity with contracture of the interphalangeal joints, no caregivers at home, and kidney transplantation donor unavailability, maintenance hemodialysis was chosen as RRT modality. Further, due to the narrowing of superficial vessels in the sclerotic forearm skin and post-transplant immunocompromised status, the native left brachiocephalic arteriovenous fistula was created. Post-operative course was uneventful while any sign of cutaneous infection and pulmonary hypertension was closely monitored. Our literature review also indicates several difficulties with initiating and maintaining RRT in patients with SSc although case reports of kidney failure after lung transplanation in SSc were not accumulated.ConclusionsWith respect to initiating RRT for post-lung transplant patients with SSc, the clinical course of our case exemplifies recent complex trends of renal management. The optimal modality with secured initiation of RRT should be carefully determined based on the severity and risk for the cardiopulmonary, peripheral vascular, cutaneous, and systemic or local infectious complications.

Early Initiation of Renal Replacement Therapy Among Burned Patients With Acute Kidney Injury.

Burned patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have exceedingly high mortality rates of 73% to 100%. Since January 2011, we have been adopting an early RRT approach in managing burned patients with AKI. Our hypothesis was that early initiation of RRT leads to improved outcome and survival among burned patients with AKI. We conducted a retrospective analysis of Burns Database in Singapore General Hospital from January 2011 to February 2016. Indications for dialysis included serum creatinine of greater than 1.5 times baseline or urine output of less than 0.5 mL/kg per hour for at least 6 consecutive hours. Patients with similar condition from January 2006 to December 2010 were recruited for comparison. A total of 27 patients with burns and AKI were recruited from January 2011 to February 2016. The mean age was 45.4 years and 88.9% were male. The mean total burn surface area (TBSA) was 54.8%. The total volume of fluid resuscitation was 2.7 mL/kg per TBSA. The time from onset of burn to RRT was 6.4 days. Most patients presented with stage 1 AKI (51.9%), whereas 22.2% and 25.9% had stage 2 and stage 3 AKI, respectively. Most patients (74.1%) received CRRT and 18.5% received SLED. The mortality rate was 37.0% with majority of death (70%) due to sepsis/multiorgan failure. Only 1 patient required long-term RRT after discharge, and there was no occurrence of abdominal compartment syndrome. The mean age of 15 patients from 2006 to 2010 was 47.8 years. The mean TBSA was 49.5%. Only 26.7% of patients were started on RRT. The mortality rate was 66.7%, which was higher than that of subjects from 2011 to 2016 (37.0%) (P = 0.039). Optimal timing of RRT for burned patients with AKI has not been established and data on early RRT approach are scarce. The findings of our study suggested that early RRT was associated with lower mortality rates among burned victims with AKI.

Performance of Fluid Balance as A Marker of Acute Kidney Injury in Children after Open Heart Surgery

Abstract Acute kidney injury (AKI) is a serious complication in the perioperative period and is consistently associated with increased morbidity and case fatality rate. This has been best studied in the cardiac surgery setting where it has been shown that up to 11.5–86.0% of patients exposed to cardiopulmonary bypass (CPB) will develop AKI, with 2.0–18.9% requiring renal replacement therapy (RRT). A prospective uncontrolled cohort study was conducted between 2011 and 2015, in which 93 children with various congenital heart lesions undergoing CPB were enrolled. Serum creatinine (SCr) level was determined by Jaffé’s method (Cobas 6000 analyser, Roche). Postoperative fluid balance was estimated as the difference between fluid intake and output. Data for further processing were retrieved from anaesthesia and intensive care data management system flowsheets (IntelliView, Philips). AKI developed in 42 patients (45.6%) by meeting at least KDIGO (Kidney Disease: Improving Global Outcomes) stage I criteria (with SCr rise by more than 50% from the baseline). Thirty eight patients complied with the 1st stage of AKI, three with 2nd stage and two with 3rd stage, according the KDIGO classification and staging system. One patient having severity stage II and two patients having severity stage III of AKI required initiation of RRT using peritoneal dialysis. Two patients from the RRT group survived, one died. The median intraoperative urine output was 2.32 ml/kg/h, (range from 0.42–5.87 ml/kg/h). Median CPB time was 163 min., median aortic cross-clamping time was 97.9 min., cooling during CPB to 29.5 °C. The diagnosis of AKI using SCr was delayed by 48 hours after CPB. Median fluid balance (FB) on the first postoperative day in non-AKI patients was 13.58 ml/kg (IQR 0–37.02) vs 49.38 ml/kg (IQR 13.20–69.32) in AKI patients, p &lt; 0.001. AKI is a frequent complication after open heart surgery in children with congenital heart lesions. From 93 patients included in the study, 42 (45.2%) met at least KDIGO Stage I criteria for AKI. FB is a sensitive marker of kidney dysfunction. Median FB in the 1st postoperative day significantly differed between AKI patients: 49.38 ml/kg (13.20–69.32) versus 13.58 ml/kg in patients with intact kidney function (AUC = 0.84; p = 0.001). Thus it can be used as a marker of AKI.

Endogenous Erythropoietin and Hepatic Dysfunction in Acute Kidney Injury Requiring Renal Replacement Therapy

Backgrounds/Objectives: Elevated erythropoietin (EPO) is observed in human acute kidney injury (AKI). Whether blood EPO level is associated with mortality or other organ dysfunction in critically ill patients is unknown. Methods: A prospective observational cohort study of 162 AKI patients requiring renal replacement therapy (RRT) was conducted in our intensive care unit (ICU) during October 2013 through October 2016. We evaluated the relation with plasma EPO at RRT initiation and 90-day mortality, hemoglobin, urine output, and sequential organ failure assessment (SOFA) score until day 7 or discharge from the ICU. Results: The analysis revealed that EPO was significantly associated with 90-day mortality with an adjusted hazard ratio of 2.13 (95% CI 1.11–5.78). Hemoglobin levels, RRT dependence, and daily urine output on days 1 through 7 did not differ between the high EPO group (≥56.2 mIU/mL) and low EPO groups (< 56.2 mIU/mL). As for organ dysfunction, hyperbilirubinemia patients (≥2.0 mg/dL; hepatic SOFA ≥2) were more frequent in the high EPO group (62.1 vs. 37.9%; p < 0.05), while other SOFA scores did not differ between both groups. Exacerbation of hepatic dysfunction was observed more frequently in the high EPO than the low EPO group (49.3 vs. 27.2%; p < 0.05). Conclusion: Elevated EPO was not associated with anemia or RRT dependence. However, higher rates of mortality and hepatic dysfunction were observed in high EPO patients than in low EPO patients.

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.

Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry

Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and2013. Scleroderma as the identified cause of ESRD. Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both P<0.001), though timerequired to achieve recovery was longer. The 5-year survival probability from day 91 of RRT among patients with scleroderma was 38.9% (95% CI, 32.0%-45.8%), whereas 5-year posttransplantation patient survival and 5-year allograft survival were 88.2% (95% CI, 75.3%-94.6%) and 72.4% (95% CI, 55.0%-84.0%), respectively. Adjusted mortality from day 91 on RRT was higher among patients with scleroderma than observed in both control groups (HRs of 1.25 [95% CI, 1.05-1.48] and 2.00 [95% CI, 1.69-2.39]). In contrast, patient and graft survival after kidney transplantation did not differ between patients with scleroderma and control groups. No data for extrarenal manifestations, treatment, or recurrence. Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation wassimilar to that observed among patients withESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.

Fluid balance-adjusted creatinine at initiation of continuous venovenous hemofiltration and mortality. A post-hoc analysis of a multicenter randomized controlled trial.

IntroductionAcute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high mortality. The creatinine-based stage of AKI is considered when deciding to start or delay RRT. However, creatinine is not only determined by renal function (excretion), but also by dilution (fluid balance) and creatinine generation (muscle mass). The aim of this study was to explore whether fluid balance-adjusted creatinine at initiation of RRT is related to 28-day mortality independent of other markers of AKI, surrogates of muscle mass and severity of disease.MethodsWe performed a post-hoc analysis on data from the multicentre CASH trial comparing citrate to heparin anticoagulation during continuous venovenous hemofiltration (CVVH). To determine whether fluid balance-adjusted creatinine was associated with 28-day mortality, we performed a logistic regression analysis adjusting for confounders of creatinine generation (age, gender, body weight), other markers of AKI (creatinine, urine output) and severity of disease.ResultsOf the 139 patients, 32 patients were excluded. Of the 107 included patients, 36 died at 28 days (34%). Non-survivors were older, had higher APACHE II and inclusion SOFA scores, lower pH and bicarbonate, lower creatinine and fluid balance-adjusted creatinine at CVVH initiation. In multivariate analysis lower fluid balance-adjusted creatinine (OR 0.996, 95% CI 0.993–0.999, p = 0.019), but not unadjusted creatinine, remained associated with 28-day mortality together with bicarbonate (OR 0.869, 95% CI 0.769–0.982, P = 0.024), while the APACHE II score non-significantly contributed to the model.ConclusionIn this post-hoc analysis of a multicentre trial, low fluid balance-adjusted creatinine at CVVH initiation was associated with 28-day mortality, independent of other markers of AKI, organ failure, and surrogates of muscle mass, while unadjusted creatinine was not. More tools are needed for better understanding of the complex determinants of “AKI classification”, “CVVH initiation” and their relation with mortality, fluid balance is only one.

Patient and transplant outcome in infants starting renal replacement therapy before 2 years of age

Despite major technical improvements in the care of children requiring renal replacement therapy (RRT) before 2 years of age, the management of those patients remains challenging and transplantation is generally delayed until the child weighs 10 kg or is 2 years old. In this national cohort study, we studied patient and graft survival in children starting RRT before 2 years of age to help clinicians and parents when deciding on RRT initiation and transplantation management. All children starting RRT before 24 months of age between 1992 and 2012 in France were included through the national Renal Epidemiology and Information Network (REIN) registry. The primary endpoints were patient survival on dialysis and 10-year graft survival. A total of 224 patients were included {62% boys, median age 10.5 months [interquartile range (IQR) 5.8-15.6]}. The 10-year survival rate was 84% (IQR 77-89). Suffering from extrarenal comorbidities was the only factor significantly associated with both an increased risk of death on dialysis [hazard ratio 5.9 (95% confidence interval 1.8-19.3)] and a decreased probability of being transplanted. During follow-up, 174 renal transplantations were performed in 171 patients [median age at first transplantation 30.2 (IQR 21.8-40.7) months]. The 10-year graft survival was 74% (IQR 67-81). Factors associated with graft loss in multivariate analysis were the time spent on dialysis before transplantation, donor/recipient height ratio with an increased risk for both small and tall donors and presenting two human leucocyte antigen-antigen D-related mismatches. This study confirms the good outcome of children starting RRT before 2 years of age. The main question remains when and how to transplant those children. Our study provides data on the optimal morphological and immunological matching in order to help clinicians in their decisions.

Perioperative body weight change is associated with in-hospital mortality in cardiac surgical patients with postoperative acute kidney injury.

BackgroundPostoperative acute kidney injury (AKI) is common following cardiac surgery (CS). Body weight (BW) may be an amenable variable by representing the summation of the nutritional and the fluid status. However, the predictive role of perioperative BW changes in CS patients with severe postoperative AKI is never explored. This study aimed to evaluate this association.MethodsThis study was conducted using a prospectively collected multicenter cohort, NSARF (National Taiwan University Hospital Study Group on Acute Renal Failure) database. The adult CS patients with postoperative AKI requiring renal replacement therapy (RRT), who had clear initial consciousness, received CS within 14 days of hospitalization, and underwent RRT within seven days after CS in intensive care units from January 2001 to January 2014 were enrolled. With the endpoint of 30-day postoperative mortality, we evaluated the association between the clinical factors denoting fluid status and patients outcomes.ResultsA total of 188 patients (70 female, mean age 63.7 ± 15.2 years) were enrolled. Comparing with the survivors (n = 124), the non-survivors (n = 64) had a significantly higher perioperative BW change [3.6 ± 6.1% versus 0.1 ± 8.3%, p = 0.003] but not the postoperative and pre-RRT BW changes. By using multivariate Cox proportional hazards model, the independent indicators of 30-day postoperative mortality included perioperative BW change (p = 0.026) and packed red blood cells transfusion (p = 0.007), postoperative intra-aortic balloon pump (p = 0.001) and central venous pressure level (p = 0.005), as well as heart rate (p = 0.022), sequential organ failure assessment score (p < 0.001), logistic organ dysfunction score (p = 0.001), and blood total bilirubin level (p = 0.044) at RRT initiation. The generalized additive models further demonstrated, in a multivariate manner, that the mortality risk rose significantly during a perioperative BW change of 2% to 15%.ConclusionsPerioperative BW change was independently associated with an increased risk for 30-day postoperative mortality in CS patients with RRT-requiring AKI.

Renal replacement therapy for AKI: When? How much? When to stop?

Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a significant proportion of critically ill patients. However, many questions remain about the optimal administration of RRT with regard to several important considerations, including treatment dose, timing of treatment initiation and cessation, therapy mode, type of anticoagulation, and management of fluid overload. While Level 1 evidence exists for RRT dosing in AKI, all the studies contributing to this evidence base employed fixed-dose regimens throughout a patient's continuous RRT (CRRT) course, without regard for the possibility of individualizing treatment dose according to the clinical status of a given patient at a specific time. As opposed to CRRT dose, no consensus about the timing of RRT in critically ill AKI patients exists currently. While numerous clinical trials over the past 40 years have attempted to assess "early" versus "late" initiation of RRT, they have been plagued by a myriad of methodological problems, including their largely observational nature and the widely varying definitions of early and late initiation. Although questions about the appropriate timing of CRRT discontinuation arise very frequently in clinical practice, even less information is available in the literature to guide this important decision. The aim of this review is to provide a comprehensive update on RRT delivery to critically ill AKI patients, with specific attention paid to treatment dose and timing and emphasis on addressing the practical questions that arise in daily clinical practice.