Discontinuation Of Renal Replacement Therapy Research Articles

Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury

Plain Language SummaryPatients with severe AKI require RRT. When we should stop RRT and what parameter predicts worse clinical outcome in long-term have still not been clear. In this prospective study, we confirmed that urine volume was the best predictor to determine when to stop RRT. Further, we found that urinary marker NGAL was predictive for worse clinical outcomes within 3 months after RRT.

Evaluation of Dosing Regimens of Vancomycin and Aminoglycosides in Pediatric Patients on Continuous Renal Replacement Therapy.

To determine the optimal empiric dosing regimen to achieve therapeutic serum concentrations of vancomycin and aminoglycosides in pediatric patients who are receiving continuous renal replacement therapy (CRRT). This retrospective study investigated pediatric patients (<18 years old) who received at least one dose of an aminoglycoside and/or vancomycin while on CRRT and who had at least one serum concentration assessed during the study period. Rates of culture clearance and discontinuation of renal replacement therapy, pharmacokinetic variables (i.e., volume of distribution [Vd], half-life [t½], rate of elimination [ke]), and correlations between patient's age and weight in regard to the empiric dosing regimen were evaluated. Forty-three patients were included in this study. The median dose required to reach therapeutic serum concentrations for vancomycin was 17.6 mg/kg (12.8-20.4 mg/kg) every 12 hours (6-30 hours) in continuous venovenous hemodialysis (CVVHD) patients and 16.3 mg/kg (13.9-21.4 mg/kg) every 12 hours (6-24 hours) in continuous venovenous hemodiafiltration (CVVHDF) patients. The median dose for aminoglycosides was unable to be determined. In CVVHD patients, the median vancomycin ke was 0.04 hr-1, t½ was 18 hours, and Vd was 1.6 L/kg. In CVVHDF patients, the median vancomycin ke was 0.05 hr-1, t½ was 14 hours, and Vd was 0.6 L/kg. No correlation was found between age and weight with regard to effective dosing regimen. To achieve therapeutic trough concentrations in pediatric patients on CRRT, vancomycin should be dosed at approximately 17.5 mg/kg administered every 12 hours.

A clinical model to predict successful renal replacement therapy (RRT) discontinuation in patients with Acute Kidney Injury (AKI)

IntroductionIdeal timing of Renal Replacement Therapy (RRT) discontinuation in Acute Kidney Injury (AKI) is still unknown. We aimed to study the role of creatinine-related variables in predicting RRT successful discontinuation and to propose a clinical predictive score. MethodsIn this single-centre retrospective study, we evaluated all AKI patients in whom RRT was interrupted for at least 48 hours. Patients who were still RRT-independent 7 days after initial RRT cessation were included in the “Success” group and opposed to the “Failure” group. We evaluated baseline characteristics and variables collected at the time of RRT interruption, as well as the Kinetic estimated Glomerular Filtration Rate (KeGFR), the simple variation in serum Creatinine (ΔsCr), and the incremental creatinine ratio on the first three days after RRT interruption. Multivariable analysis was performed to evaluate prediction of success. Internal validation using a simple binomial generalized regression model with Lasso estimation and 5-fold cross validation method was performed. ResultsWe included 124 patients, 49 in the “Failure” group and 75 in the “Success” group. All creatinine-related variables predicted success in simple and multiple logistic regression models. The best model generated a clinical score based on the odds ratio obtained for each variable and included urine output, non-renal SOFA score, fluid balance, serum urea, serum potassium, blood pH, and the variation in sCr values after RRT discontinuation. The score presented an area under the ROC of 0.86 (95% CI 0.76‒1.00). ConclusionCreatinine variation between the first 2 consecutive days after RRT discontinuation might predict success in RRT discontinuation. The developed clinical score based on these variables might be a useful clinical decision tool to guide hemodialysis catheter safe removal.

ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy.

Mishra RC, Sodhi K, Prakash KC, Tyagi N, Chanchalani G, Annigeri RA, et al. ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy. Indian J Crit Care Med 2022;26(S2):S13-S42.

MO298: Predictors of Renal Function Recovery in Critically ill Patients With Acute Kidney Injury

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a frequent and serious complication in critically ill patients admitted in intensive care unit (ICU). The development of acute kidney damage is associated with various adverse outcomes, such as prolonged stay in the ICU, the development of chronic kidney disease (CKD), increased mortality and increased treatment costs. The aim of this study was to determine the predictors of renal function recovery in critically ill patients with AKI who were treated with continuous renal replacement therapy (CRRT). METHOD We performed a single-centre retrospective study of 440 adult surgical and non-surgical patients with AKI or AKI episode in CKD who were admitted to the ICU between 2014 and 2018 and treated with CRRT. Demographic, clinical and laboratory parameters [urea, creatinine, C-reactive protein (CRP), procalcitonin (PCT), quick sequential organ failure assessment (qSOFA) score], comorbidities, the need for vasopressor therapy and mechanical lung ventilation on the day of confirmed AKI, as well as CRRT modalities were analysed. Renal recovery was defined by renal replacement therapy discontinuation within 90 days of its start. Patients with the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 AKI and/or volume overload have had an ‘early’ start of CRRT within 24 h of the AKI diagnosis; patients with poor response to conservative treatment or evidence of clinical complications associated with AKI have had a ‘late’ start of CRRT. The patients were divided into two groups: patients with recovered renal function (RRF group) and patients who had not recovered renal function (NRRF group). RESULTS Out of a total of 440 patients, 242 (55%) recovered renal function. RRF versus NRRF group did not differ significantly by gender (males: 64.5% versus 69.7%) and age (mean age of 60.93 years versus 64.5 years). Cardiovascular diseases were the most common comorbidity in both groups of patients, and CKD was significantly more prevalent in the NRRF groups (88 versus 352, P &amp;lt; .001). There were no significant differences in examined laboratory parameters in the RRF and NRRF group (urea 27.28 versus 26.68 mmol/L; creatinine 401.43 versus 373.7 μmol/L; CRP 144.38 versus 143.52 mg/L; PCT 23.07 versus 22.44 ng/L). No significant difference was found in relation to mechanical lung ventilation (234 in the RRF group versus 206 in the NRRF group; P = .18) and vasopressor therapy (221 in the RRF group versus 219 in the NRRF group; P = 0.94). Values of the qSOFA score were significantly lower (P &amp;lt; .001) in patients with recovered renal function (Fig. 1). In the RRF group, the most commonly used CRRT modality was CVVHD (165; 37.6%), while in the NRRF group it was CVVHDF (181; 40.9%). Predictors of renal recovery in critically ill patients who were treated with CRRT were: age &amp;lt;65 years (P = .044), an ‘early’ start of RRT (P = .043), absence of mechanical ventilation (P = .044) and absence of earlier CKD (P = .005) (Table 1). Predictors of renal recovery in septic critically ill patients with AKI treated with CRRT were: age &amp;lt;65 years (P = .002), the absence of diabetes mellitus (P = .023) and previous CKD (P = .045) and CRP &amp;lt; 100 mg/L (P = .033), while in critically ill patients without sepsis, the predictor of renal function recovery was the absence of previous kidney disease (P = .035). CONCLUSION Previous kidney disease is the most significant factor for the prediction of renal function recovery in critically ill patients with AKI treated with CRRT. Individual consideration of potential predictors of renal recovery, as well as a timely decision to initiate continuous dialysis, will prevent complications and improve the outcome of critically ill patients with AKI.

Sepsis-associated acute kidney injury

Acute kidney injury (AKI) is a condition that develops as a result of a rapid decrease in the glomerular filtration rate, which leads to the accumulation of nitrogenous, including urea and creatinine, and non-nitrogenous metabolic products with electrolytic disorders, impairment of the acid-base balance, and the volume of fluid excreted by the kidneys. Objective: to provide a review of the literature concerning sepsis-associated acute kidney injury. We presented the problems of diagnosis, risk factors, the pathogenesis of sepsis-associated acute kidney injury, as well as to outline terminologically the clinical form of sepsis-associated acute kidney injury: the paradigm shifts from ischemia and vasoconstriction to hyperemia and vasodilation, from acute tubular necrosis to acute tubular apoptosis. Sepsis contributes significantly to the development of AKI: in sepsis, it occurs in 19 % of patients; nevertheless, it is much more frequent in septic shock (45 % of cases), the mortality of individuals with AKI is especially high in non-septic and septic conditions (45 and 73 %, respectively). To effectively diagnose the functional state of the kidneys and conduct nephroprotective therapy, stratification scales for assessing the severity of acute kidney damage are applied, which are based on the determination of plasma creatinine level and urine output: RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure), AKIN (Acute Kidney Injury Network), KDIGO (Kidney Disease Improving Global Outcomes); the experts considered KDIGO scale more modern and perfect. It has been found that plasma creatinine is not an early biomarker of AKI that indicates the advisability of using other integral indicators. AKI biomarkers are substances that either participate in the pathological process or witness it allowing diagnose AKI even before an increase in plasma creatinine level. The characteristics of the structure, role of functions of such biomarkers as neutrophil gelatinase-associated lipocalin, cystatin C, interleukin-18, kidney injury molecule-1 and others are given. Intensive care for sepsis-associated acute kidney injury includes the standard therapy corresponding to 2016 Surviving Sepsis Campaign and KDIGO guidelines. Also, the paper focuses on renal replacement therapy (RRT): renal and extrarenal indications for the initiation, factors affecting the initiation of RRT, the timing of initiation, ways of optimization, the timing of RRT discontinuation, recommendations for the dose of RRT, the dose of renal replacement therapy in sepsis-associated AKI, choice of method, advantages and disadvantages of continuous RRT and intermittent hemodialysis, medication support for continuous therapy, the role of hemodialysis machine in the intensive care unit.

SAT-023 SURVIVAL OF SOUTH AFRICAN PATIENTS ON RENAL REPLACEMENT THERAPY

In South Africa, 84% of the population rely on public sector healthcare and 16% use mainly private facilities. Since 2012, the South African Renal Registry (SARR) has reported on the treatment of end-stage renal disease (ESRD) in South Africa. Overall rates of renal replacement therapy (RRT) are low, with a prevalence of 183 per million population (pmp). Large disparities exist between the private and public sectors (798 versus 68 pmp), between provinces and between ethnic groups. Private sector patients on RRT are approximately 10 years older, have more diabetes and other comorbid illnesses, and are less likely to be transplanted or use peritoneal dialysis. The aim of this analysis was to explore, for the first time, survival of all incident and prevalent patients on RRT in South Africa. SARR data were used to estimate 1-year survival in patients on RRT by the Kaplan Meier method. The incident cohort included patients who started treatment between 1 January 2013 and 30 September 2016 and survived 90 days; the prevalent cohort included all those on RRT on 31 December 2015. Data were collected on potential risk factors, including ethnicity, renal diagnosis, first RRT modality, HIV status and public/private sector provision of RRT. Failure events included death and discontinuation of RRT without recovery of function. Patients were censored if they recovered renal function, emigrated or were lost to follow-up. Multivariable Cox regression was used to estimate adjusted hazard ratios. In the incident cohort (n=6187), the mean age was 51.8 years, 54% were Black, 44% were diabetic, 10% were HIV positive and 82% had haemodialysis as their first modality. Overall 1-year survival from day 90 was 90.4% (95%CI 89.6-91.2%). On multivariable analysis, survival was associated with age, renal diagnosis, diabetes and province. The 18-40-year age group and non-diabetics had improved survival. There was no association with ethnicity, first modality or healthcare sector. HIV status was missing in 20% of the cohort and was therefore omitted from the multivariable analysis. The crude 1-year survival rates of HIV-positive and negative patients were 95.7% and 93.8%, respectively, and much lower at 74.8% in patients without data on HIV. The absence of this optional data element seemed to identify sicker patients; those who survived for longer would be more likely to have their virological status captured by the registry. In the December 2015 prevalent cohort (n=10155), the mean age was 51.5 years, 52% were Black, 37% were diabetic, 8% were HIV positive, and 74% were on haemodialysis as their treatment modality. The overall 1-year survival was 90.1% (CI 89.4-90.6%). The crude survival rates of public and private sector patients were 93.4% and 88.4%, respectively. This was not significant on multivariable analysis, where survival was associated with age, diabetes, RRT vintage, and province. The 18-40-year age group, non-diabetics and those with RRT vintage >2.5 years had improved survival. The survival rates of South African patients who access RRT services are comparable to those in better resourced countries. Although access to government-supported, public sector RRT is limited, the patients who are accommodated have good survival rates as compared to patients at private facilities, even after adjusting for factors such as age and comorbid illnesses.

Kinetic estimated glomerular filtration rate as a predictor of successful continuous renal replacement therapy discontinuation.

No standardized criteria for continuous renal replacement therapy (CRRT) discontinuation have been established. Kinetic estimated glomerular filtration rate (eGFR) is a newly developed estimation method based on dynamic changes of serum creatinine expected to reflect the true GFR. This study aimed to evaluate the predictive role of kinetic eGFR for CRRT discontinuation. A retrospective single-centre cohort study was conducted. Acute kidney injury (AKI) patients who received CRRT between May 2015 and April 2016 were enrolled. Successful CRRT discontinuation was defined as neither resuming CRRT for the next 48 h nor receiving intermittent haemodialysis 7 days from the CRRT discontinuation. Clinical factors associated with CRRT discontinuation were evaluated by receiver operating characteristic (ROC) curve analysis. Of 52 AKI patients treated with CRRT, 38 could discontinue CRRT while 14 could not. Urine volume, regular and kinetic eGFR of days 0 (day of CRRT discontinuation) and 1 were all good predictive parameters (area under the ROC curve (AUC) > 0.7). Kinetic eGFR of day 1 showed the AUC of 0.87 [95% confidence interval 0.73-0.94]). Combining kinetic eGFR of day 1 and urine volume of day 0 gave a high AUC of 0.93 [95% confidence interval 0.82-0.97]. The combination was significantly greater than urine volume of day 0 (P = 0.008). Kinetic eGFR combined with urine volume was a better predictor for CRRT discontinuation. Evaluation of kinetic eGFR utility in other clinical settings will be necessary.

Timing of renal replacement therapy initiation for acute kidney injury.

Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs), and is associated with high death. Renal replacement therapy (RRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate RRT so as to improve clinical outcomes remains uncertain.This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury. To assess the effects of different timing (early and standard) of RRT initiation on death and recovery of kidney function in critically ill patients with AKI. We searched the Cochrane Kidney and Transplant's Specialised Register to 23 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 11 September 2017. We included all randomised controlled trials (RCTs). We included all patients with AKI in ICU regardless of age, comparing early versus standard RRT initiation. For safety and cost outcomes we planned to include cohort studies and non-RCTs. Data were extracted independently by two authors. The random-effects model was used and results were reported as risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included five studies enrolling 1084 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early initiation may reduce the risk of death at day 30, although the 95% CI does not rule out an increased risk (5 studies, 1084 participants: RR 0.83, 95% CI 0.61 to 1.13; I2 = 52%; low certainty evidence); and probably reduces the death after 30 days post randomisation (4 studies, 1056 participants: RR 0.92, 95% CI 0.76 to 1.10; I2= 29%; moderate certainty evidence); however in both results the CIs included a reduction and an increase of death. Earlier start may reduce the risk of death or non-recovery kidney function (5 studies, 1076 participants: RR 0.83, 95% CI 0.66 to 1.05; I2= 54%; low certainty evidence). Early strategy may increase the number of patients who were free of RRT after RRT discontinuation (5 studies, 1084 participants: RR 1.13, 95% CI 0.91 to 1.40; I2= 58%; low certainty evidence) and probably slightly increases the recovery of kidney function among survivors who discontinued RRT after day 30 (5 studies, 572 participants: RR 1.03, 95% CI 1.00 to 1.06; I2= 0%; moderate certainty evidence) compared to standard; however the lower limit of CI includes the null effect. Early RRT initiation increased the number of patients who experienced adverse events (4 studies, 899 participants: RR 1.10, 95% CI 1.03 to 1.16; I2 = 0%; high certainty evidence). Compared to standard, earlier RRT start may reduce the number of days in ICU (4 studies, 1056 participants: MD -1.78 days, 95% CI -3.70 to 0.13; I2 = 90%; low certainty evidence), but the CI included benefit and harm. Based mainly on low quality of evidence identified, early RRT may reduce the risk of death and may improve the recovery of kidney function in critically patients with AKI, however the 95% CI indicates that early RRT might worsen these outcomes. There was an increased risk of adverse events with early RRT. Further adequate-powered RCTs using appropriate criteria to define the optimal time of RRT are needed to reduce the imprecision of the results.

Continuous Veno-Venous Hemodialysis Using the Cardio-Renal Pediatric Dialysis Emergency MachineTM: First Clinical Experiences

We report the first worldwide experience with continuous veno-venous hemodialysis (CVVHD) in children using the last generation Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)^TM device. Thirteen children received 1,008 h of CVVHD during 95 sessions, using a 0.15 (n = 7) or a 0.25 m² (n = 6) hemofilter. The median weight was 3 kg (interquartile range [IQR] 2.5–6.2). In 10 patients, CVVHD was conducted using a 5 Fr double-lumen central vascular access, whereas in 3 children, bigger sizes were used (6.5 and 8 Ch). The median prescribed Qb was 17 mL/min (IQR 10–29.5), with a median Qd of 10 mL/min. Circuits were primed with 5% albumin in 12 out of 13 patients, using anticoagulation with heparin in all 13 cases. The median delivered/prescribed time ratio yielded a 100% result (95–100%). The most common cause for “downtime” was clotting that however occurred in only 3% of all treatments. Survivals at continuous renal replacement therapy discontinuation and ICU discharge were 100 and 69% respectively. The CARPEDIEM^TM machine allowed successful delivery of diffusive blood purification modality to very small patients, using small catheters, no blood primes, and excellent concordance between delivered and prescribed treatment duration.

Discontinuation of renal replacement therapy in critically ill patients with severe acute kidney injury: predictive factors of renal function recovery.

Severe acute kidney injury (AKI-D) is common in critically ill patients and contributes substantially to short- and long-term morbidity and mortality. Acute renal replacement therapy (RRT) is an increasingly widely utilized life-sustaining support strategy for AKI-D patients, providing a bridge to renal recovery in many survivors of AKI. However, key aspects (when and how) of this therapy's appropriate cessation remain unclear. Today, wide variation in clinical practice exists regarding the indication for and the timing of RTT discontinuation, likely due to the poor current evidence base. Few studies have evaluated the process of weaning or ideal markers (clinical factorsor parameters that may suggest renal recovery, such as urine output, urine chemistry, and creatinine clearance) to predict sufficient recovery of renal function following AKI and to avoid re-institution of RRT. However, translation of the current evidence to clinical practice is hampered by considerable limitations of the retrospective, post hoc secondary design of cohort studies, small sample sizes, heterogeneity across study populations and illness severity, variations of the thresholds of predictive markers and conflicting results for given markers. Currently, 24-h creatinine clearance greater than 20ml/min combined with spontaneously decreasing serum creatinine concentrations in the context of fixed RRT and a clinically stable intensive care unit (ICU) patient may be the best predictor of recovery of excretory renal function. The decision regarding the appropriate time to wean acute RRT is complex, integrating numerous clinical variables and renal functional parameters. Cessation of RRT should largely be individualized in critically ill patients. Large randomized multicentre trials are needed to definitively answer the vitally important question of whether inappropriate discontinuation of RRT in ICU patients with AKI-D impacts patient outcomes. Future work should integrate novel kidney damage and repair biomarkers and techniques to measure real-time glomerular filtration rates.

Timing of initiation and discontinuation of renal replacement therapy in children with acute kidney injury

Renal replacement therapy(RRT) is the most effective treatment for patient with severe acute kidney injury(AKI). But the timing of initiation of RRT remains controversial.In recent years, there has been an ongoing trend in clinical practice to initiate RRT for AKI earlier especially for patient with AKI stage 2 and severe fluid accumulation.There is no single target can predict the timing of discontinuation of RRT, combined use biomarker and urine volume may be a better choice in future. Key words: Acute kidney injury; Renal replacement therapy; Initiation timing; Discontinuation timing; Child

ICU Patients Requiring Renal Replacement Therapy Initiation: Fewer Survivors and More Dialysis Dependents From 80 Years Old.

To assess the role of advanced age on survival and dialysis dependency after initiation of renal replacement therapy for acute kidney injury. Retrospective pooled analysis of prospectively collected data. ICUs of two teaching hospitals in Paris area, France. One thousand five hundred thirty adult patients who required renal replacement therapy initiation in the ICU. None. Survival and post acute kidney injury chronic dialysis dependency were assessed at hospital discharge according to the quintile (Q) of age. The oldest quintile included 289 patients 80 years old and over. Seventy-three percent of included patients had respiratory and hemodynamic supports at renal replacement therapy initiation, similarly distributed across quintiles. Mortality increased with age strata from 63% in Q1 (≤ 52 yr) to 76% in Q5 (≥ 80 yr) (p < 0.001). After adjustment, age did not increase the risk of death up to 80 years. The oldest patients (≥ 80 yr) had a significant higher risk of dying (adjusted odds ratio, 2.59; 95% CI, 1.66-4.03). Dialysis dependency was more frequent among survivors 80 years old or older (30% vs 14%; p = 0.001). Age 80 years old or older was an independent risk for dialysis dependency only for patients with prior advanced chronic kidney disease (p = 0.04). Baseline estimated glomerular filtration rate was the only one predictor of dialysis dependency identified. Patients with advanced age represent a substantial subgroup of patients requiring renal replacement therapy in the ICU. From 80 years, age should be considered as an additional risk of dying over the severity of organ failures. Patients 80 years old or older are likely to recover sufficient renal function allowing renal replacement therapy discontinuation when baseline estimated glomerular filtration rate is above 44 mL/min/1.73 m. At 3 months, only 6% were living at home, dialysis independent.

Predictive Factors Upon Discontinuation of Renal Replacement Therapy for Long-Term Chronic Dialysis and Death in Acute Kidney Injury Patients.

The specific timing for discontinuing renal replacement therapy (RRT) in acute kidney injury (AKI) patients is debatable. The predictive abilities of variables at the time of discontinuation of RRT for the long-term prognoses of patients have not been explored. This study aimed to explore the prognostic factors upon discontinuation of RRT for long-term chronic dialysis and death of patients with acute RRT-requiring AKI, thus improving decision making regarding the discontinuation of RRT and the follow-up of patients thereafter. A cohort of 302 AKI patients who required acute RRT and remained alive and free of dialysis for at least 30 days after discharge from January 2009 to December 2012 were followed up. The predictive abilities of general characteristics, RRT details, and variables upon discontinuation of RRT for long-term chronic dialysis and all-cause death were evaluated using Cox proportional hazards models. Kaplan-Meier analysis with a log-rank test was used to compare the survival curves between the strata of levels of good predictors upon discontinuation of RRT. After a median follow-up time of 4.1 years, 20 (6.6%) patients initiated chronic dialysis and 56 (18.5%) patients died. A higher CysC level upon discontinuation of RRT (HR 1.520, 95% CI 1.082-2.135; P = 0.016), comorbid chronic kidney disease, and a higher non-renal Charlson comorbidity index (CCI) were independently predictive for chronic dialysis. The hemoglobin level upon discontinuation of RRT was inversely predictive of death (HR 0.986, 95% CI 0.973-0.999; P = 0.035), and comorbid malignancy, the presence of multiple organ dysfunction syndrome, and a higher non-renal CCI also predicted death. Urine output upon discontinuation of RRT was marginally inversely predictive of death (HR 0.997, 95% CI 0.994-1.000; P = 0.056). Patients who discontinued RRT with CysC levels <2.97 mg/L, hemoglobin levels >85 g/L, and urine output >1130 mL/24 h showed significantly higher non-chronic dialysis and survival rates according to a log-rank test. Our study suggested that upon discontinuation of RRT, higher serum CysC levels had the most promising predictive value for long-term chronic dialysis, and lower hemoglobin levels predicted long-term death; lower urine output also marginally predicted long-term death. Based on the remission of the comprehensive condition, lower CysC levels and higher hemoglobin levels and urine output should be considered in the decision to stop RRT. Patients showing worse levels of these indices upon discontinuation of RRT should undergo stricter follow-up and treatment to improve long-term outcomes.

High Cut-Off Hemodialysis for Myeloma Cast Nephropathy – Do We Finally Have An Answer?

The most common kidney presentation in patients with multiple myeloma (MM) is acute kidney injury (AKI) from cast nephropathy. Patients have a poorer 1 year survival compared to patients free of kidney involvement. The key to treating cast nephropathy is rapid reduction of free light chain (FLC) levels. The modern era of MM treatment was ushered in by the introduction of newer chemotherapeutic agents, such as bortezomib. Also, there is interest in the application of extracorporeal removal of FLCs with high cut-off hemodialysis (HCO-HD) using a dialysis membrane with a higher molecular weight cut-off pore size compared to conventional high-flux (HF) dialyzers. Does the use of HCO-HD provide additional benefit to bortezomib-based chemotherapy alone? Two trials have now been completed and the results were published in abstract form and orally presented at the 2016 American Society Nephrology Annual Scientific Meeting in Chicago, Illinois, USA. Both the MYRE and the EuLITE trials randomized patients with dialysis-dependent AKI due to biopsy-confirmed cast nephropathy to bortezomib-based chemotherapy, and either conventional high-flux hemodialysis (HF-HD) or HCO-HD with a primary end point of the discontinuation of renal replacement therapy. In the MYRE study, more patients in the HCO-HD arm were independent of dialysis at 6 months. In the EuLITE study, there was no difference in kidney recovery at 3 months. Both studies were small, which makes any firm conclusions on the benefit of HCO-HD tenuous. Based on the current knowledge, without more robust data, the routine use of HCO-HD cannot be recommended.

Épuration extrarénale et insuffisance rénale aiguë en soins intensifs

Renal replacement therapy for acute kidney injury has been used for more than 60 years. Except when life-threatening metabolic complications such as severe hyperkalaemia are present, renal replacement therapy initiation criteria are the subject of intense debate. Significant progress has been made with the publication of the AKIKI multicenter trial, which showed that a delayed renal replacement therapy initiation strategy (in the absence of life-threatening metabolic complications) was not associated with a difference in mortality compared to an early renal replacement therapy initiation strategy. In addition, this delayed strategy obviated the need for renal replacement therapy in almost 50% of cases was associated with a more rapid renal function recovery and with a lower incidence of catheter-bloodstream related infections. Research on renal replacement therapy modalities (continuous vs. intermittent renal replacement therapy, citrate vs. heparin anticoagulation, jugular vs. femoral catheterization) did not show any obvious superiority of one modality over another. Thus, the choice depends mainly on local considerations (patient recruitment, availability of modalities, staff experience). The criteria for renal replacement therapy discontinuation are still unclear due to difficulties in assessing renal function recovery. Urine output remains the main criteria in the decision to wean from renal replacement therapy. Pending the confirmation of AKIKI trial by similar studies in progress, it seems reasonable to choose a delayed renal replacement therapy initiation strategy under watchful surveillance in case of severe acute kidney injury in the absence of life-threatening metabolic complications.

Biomarkers upon discontinuation of renal replacement therapy predict 60-day survival and renal recovery in critically ill patients with acute kidney injury.

There is no consensus on the specific indications for weaning critically ill patients with acute kidney injury (AKI) off renal replacement therapy (RRT). This study aimed to explore the prognostic value of several biomarkers measured upon discontinuation of RRT for their value in predicting 60-day survival and renal recovery in an effort to add knowledge to the decision-making process regarding RRT withdrawal. We prospectively enrolled 102 patients with AKI who required RRT from the intensive care unit. Serum osteopontin (sOPN), serum interleukin 6 (sIL-6), serum cystatin C (sCysC), sIL-18, serum neutrophil gelatinase-associated lipocalin and urinary IL-18 and urinary neutrophil gelatinase-associated lipocalin were measured upon discontinuation of RRT. Patients were followed up at 60 days for survival and renal recovery. Patients who survived showed lower levels of all serum and urinary biomarkers. Serum OPN (OR 1.029, 95% CI 1.013-1.047, P = 0.001), diabetes (OR 23.157, 95% CI 4.507-118.981, P < 0.001) and APACHE II score (OR 1.308, 95% CI 1.121-1.527, P = 0.001) were independent predictors of 60-day mortality. Patients whose sOPN values fell within the highest and middle tertiles showed 5.25- and 2.31-fold increased risks of mortality, respectively, compared with that of patients in the lowest tertile. The addition of sOPN to the clinical model resulted in significant net reclassification improvement of 0.453 (P = 0.026) and an integrated discriminative index of 0.155 (P = 0.032). Lower levels of sOPN and sIL-6 were associated with greater odds of 60-day survival (AUC 0.812 and 0.741). The AUC value for predicting survival reached its highest level when all biomarkers were combined with urine output (UO) and urinary and serum creatinine upon discontinuation of RRT (0.882). Lower sCysC performed as well as higher UO in predicting 60-day renal recovery with the greatest AUC of 0.743. Upon discontinuation of RRT, serum and urinary biomarkers, particularly sOPN, may predict 60-day survival and renal recovery in critically ill patients with AKI. The serum levels of OPN, IL-6 and CysC may be useful when considering withdrawal of RRT on the basis of conventional indicators.

Traditional and novel reference index for the withdrawal of renal replacement therapy in patients with acute kidney injury

Acute kidney injury (AKI) is a serious clinical problem with high morbidity and mortality. Renal replacement therapy (RRT) is an important tool for treating patients with AKI. The 2011 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI points out that RRT should be discontinued when renal function has recovered enough to meet the body needs or when RRT is no longer consistent with treatment goals. However, the specific reference index of weaning RRT is unclear. The guiding roles of traditional indicators such as urine output (> 400 mL/24 h), serum creatinine (SCr, decreasing trend), creatinine clearance (CCr, > 20 mL/min), and novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), hepatocyte growth factor (HGF), interleukins (IL-6, IL-10), kidney injury molecule-1 (KIM-1), kynurenic acid, etc. for discontinuation of RRT in AKI patients were reviewed. Particularly, the importance of biomarkers for this purpose was highlighted.

Prognostics factors for mortality and renal recovery in critically ill patients with acute kidney injury and renal replacement therapy.

ObjectiveIdentify prognostic factors related to mortality and non-recovery of renal function.MethodsA prospective single-center study was conducted at the intensive care medicine department of a university hospital between 2012 and 2015. Patients with acute kidney injury receiving continuous renal replacement therapy were included in the study. Clinical and analytical parameters were collected, and the reasons for initiation and discontinuation of renal replacement therapy were examined.ResultsA total of 41 patients were included in the study, of whom 43.9% had sepsis. The median Simplified Acute Physiology Score II (SAPSII) was 56 and the mortality was 53.7%, with a predicted mortality of 59.8%. The etiology of acute kidney injury was often multifactorial (56.1%). Survivors had lower cumulative fluid balance (median = 3,600mL, interquartile range [IQR] = 1,175 - 8,025) than non-survivors (median = 12,000mL, IQR = 6,625 - 17,875; p = 0.004). Patients who recovered renal function (median = 51.0, IQR = 45.8 - 56.2) had lower SAPS II than those who do not recover renal function (median = 73, IQR = 54 - 85; p = 0.005) as well as lower fluid balance (median = 3,850, IQR = 1,425 - 8,025 versus median = 11,500, IQR = 6,625 - 16,275; p = 0.004).ConclusionsSAPS II at admission and cumulative fluid balance during renal support therapy were risk factors for mortality and non-recovery of renal function among critically ill patients with acute kidney injury needing renal replacement therapy.

Direct Reversible Kidney Injury in Familial Hemophagocytic Lymphohistiocytosis Type 3

Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder resulting from primary or secondary immune dysfunction. AKI is frequent in severe hemophagocytic lymphohistiocytosis and has been attributed to multiorgan failure or the use of nephrotoxic drugs, but AKI is rarely considered a direct consequence of the disease process. We describe a child with familial hemophagocytic lymphohistiocytosis type 3 who developed AKI requiring prolonged renal replacement therapy because of severe renal inflammation. There was massive infiltration of the renal parenchyma by activated macrophages and cytotoxic T cells, and acute tubular injury. The patient responded to high-dose intravenous methylprednisolone, which resulted in improvement of renal function and discontinuation of renal replacement therapy. This case confirms the occurrence of reversible AKI due to hemophagocytic lymphohistiocytosis-induced activated macrophage infiltration of the renal parenchyma and inflammation.