Estimated GFR at Dialysis Initiation and Mortality in Children and Adolescents.

RATIONALE & OBJECTIVE: The association of estimated glomerular filtration rate (eGFR) at dialysis therapy initiation with mortality among adult dialysis patients has been greatly debated, with some studies showing no benefit from early dialysis therapy initiation. However, this association has not been well investigated in pediatric dialysis patients. The objective of this study was to evaluate the mortality risk associated with eGFR at dialysis therapy initiation in children and adolescents with kidney failure. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 9,963 incident dialysis patients aged 1 to 17 years in the US Renal Data System registry (1995-2016). PREDICTOR: eGFRs at dialysis therapy initiation calculated using the pediatric-specific bedside Schwartz equation (<5, 5-<7, 7-<9, 9-<12, and ≥12mL/min/1.73m2). OUTCOME: Time to all-cause death. ANALYTICAL APPROACH: Cox proportional hazards regression adjusted for case-mix variables, height, body mass index, hemoglobin level, and serum albumin level. RESULTS: Median eGFR was 7.8 (IQR, 5.6-10.5) mL/min/1.73m2 and median age was 13 (IQR, 9-16) years. 696 deaths were observed during the median follow-up of 1.4 (IQR, 0.7-2.7) years, and overall crude mortality rate was 31 per 1,000 patient-years. There appeared to be a trend toward higher mortality risk across higher eGFRs at dialysis therapy initiation. Compared with eGFRs of 7 to <9mL/min/1.73m2, eGFRs <5 and ≥12mL/min/1.73m2 were associated with lower and higher mortality, with adjusted HRs of 0.57 (95% CI, 0.43-0.74) and 1.31 (95% CI, 1.05-1.65), respectively. In age-stratified analysis, there were consistent relationships among patients 6 years and older while the eGFR-mortality association was attenuated among patients younger than 6 years (Pinteraction = 0.002). LIMITATIONS: Possible errors in eGFRs due to methods for serum creatinine measurement. Unmeasured confounders related to eGFR at dialysis therapy initiation. CONCLUSIONS: Higher eGFR at dialysis therapy initiation was associated with higher mortality risk. Further studies of eGFR at initiation are needed in pediatric dialysis patients, especially among those younger than 6 years.

Early Renal Replacement Therapy Versus Standard Care in the ICU: A Systematic Review, Meta-Analysis, and Cost Analysis.

OBJECTIVE:: Renal replacement therapy (RRT) is the treatment of choice for severe acute kidney injury, but there are no firm guidelines as to the time of initiation of RRT in the critically ill. The primary objective of this study is to determine 1-month mortality rates of early versus late dialysis in critical care. As secondary end points, we provide a cost analysis of early versus late RRT initiation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and number of patients on dialysis at day 60 postrandomization. DATA SOURCES:: We identified all randomized controlled trials (RCTs) through EMLINE and MEDBASE that examined adult patients admitted to critical care who were randomized to receiving early dialysis versus standard of care. STUDY SELECTION:: Inclusion criteria: (1) RCTs conducted after the year 2000, (2) the population evaluated had to be adults admitted to ICU, (3) the intervention had to be early RRT versus standard care, and (4) outcomes had to measure patient mortality. DATA EXTRACTION:: Two independent investigators reviewed search results and identified appropriate studies. Information was extracted using standardized case report forms. DATA SYNTHESIS:: Overall, 7 RCTs were included with a total of 1400 patients. Early RRT showed no survival benefit when compared to standard treatment (odds ratio [OR], 0.90 95% confidence interval [95% CI] 0.70-1.15, P = .39). There was no significant difference in length of hospital stay in patients with early RRT (-1.55 days [95% CI -4.75 to 1.65, P = .34]), in length of ICU stay (-0.79 days [95% CI -2.09 to 0.52], P = .24), or proportion of patients on dialysis at day 60 (OR 0.93 [95% CI 0.62 to 1.43], P = .79). Per patient, there is likely a small increase in costs (

Effect of the timing of dialysis initiation on left ventricular hypertrophy and inflammation in pediatric patients.

BACKGROUND: The optimal time for dialysis initiation in adults and children with chronic kidney disease remains unclear. The aim of this study was to evaluate the impact of dialysis timing on different outcome parameters, in particular left ventricular (LV) morphology and inflammation, in pediatric patients receiving peritoneal dialysis and hemodialysis. METHODS: The medical records of pediatric dialysis patients who were followed-up in nine pediatric nephrology centers in Turkey between 2008 and 2013 were retrospectively reviewed. In addition to demographic data, we retrieved anthropometric measurements, data on dialysis treatment modalities, routine biochemical parameters, complete blood count, serum ferritin, parathormone, C-reactive protein (CRP), and albumin levels, as well as echocardiographic data and hospitalization records. The patients were divided into two groups based on their estimated glomerular filtration rate (eGFR) levels at dialysis initiation, namely, an early-start group, characterized by an eGFR of >10 ml/min/1.73 m2, and a late-start group, with an eGFR of < 7 ml/min/1.73 m2. The collected data were compared between these groups. RESULTS: A total of 245 pediatric dialysis patients (mean age ± standard deviation 12.3 ± 5.1 years, range 0.5-21 years) were enrolled in this study. Echocardiographic data were available for 137 patients, and the mean LV mass index (LVMI) was 58 ± 31 (range 21-215) g/m2.7. The LVMI was 75 ± 30 g/m2.7(n = 81) and 34 ± 6 g/m2.7(n = 56) in patients with or without LV hypertrophy (LVH) (p < 0.001). Early-start (eGFR >10 ml/min/1.73 m2) versus late-start dialysis (eGFR < 7 ml/min/1.73 m2) groups did not significantly differ in LVMI and LVH status (p > 0.05) nor in number of hospitalizations. Serum albumin levels were significantly higher in the early-dialysis group compared with the late-dialysis group (3.3 ± 0.7 vs. 3.1 ± 0.7 g/dl, respectively; p < 0.05). The early-start group had relatively higher time-averaged albumin levels (3.2 ± 0.5 vs. 3.1 ± 0.5 g/dl; p = > 0.05) and relatively lower CRP levels (3.64 ± 2.00 vs. 4.37 ± 3.28 mg/L, p > 0.05) than the late-start group, but these differences did not reach statistical significance. CONCLUSION: Although early dialysis initiation did not have a significant effect on important clinical outcome parameters, including LVH, inflammatory state, and hospitalization, in our pediatric dialysis patients, this area of study deserves further attention.

Early Dialysis and Adverse Outcomes After Hurricane Sandy.

BACKGROUND: Hemodialysis patients have historically experienced diminished access to care and increased adverse outcomes after natural disasters. Although "early dialysis" in advance of a storm is promoted as a best practice, evidence for its effectiveness as a protective measure is lacking. Building on prior work, we examined the relationship between the receipt of dialysis ahead of schedule before the storm (also known as early dialysis) and adverse outcomes of patients with end-stage renal disease in the areas most affected by Hurricane Sandy. STUDY DESIGN: Retrospective cohort analysis, using claims data from the Centers for Medicare & Medicaid Services Datalink Project. SETTING & PARTICIPANTS: Patients receiving long-term hemodialysis in New York City and the state of New Jersey, the areas most affected by Hurricane Sandy. FACTOR: Receipt of early dialysis compared to their usual treatment pattern in the week prior to the storm. OUTCOMES: Emergency department (ED) visits, hospitalizations, and 30-day mortality following the storm. RESULTS: Of 13,836 study patients, 8,256 (60%) received early dialysis. In unadjusted logistic regression models, patients who received early dialysis were found to have lower odds of ED visits (OR, 0.75; 95% CI, 0.63-0.89; P=0.001) and hospitalizations (OR, 0.77; 95% CI, 0.65-0.92; P=0.004) in the week of the storm and similar odds of 30-day mortality (OR, 0.80; 95% CI, 0.58-1.09; P=0.2). In adjusted multivariable logistic regression models, receipt of early dialysis was associated with lower odds of ED visits (OR, 0.80; 95% CI, 0.67-0.96; P=0.01) and hospitalizations (OR, 0.79; 95% CI, 0.66-0.94; P=0.01) in the week of the storm and 30-day mortality (OR, 0.72; 95% CI, 0.52-0.997; P=0.048). LIMITATIONS: Inability to determine which patients were offered early dialysis and declined and whether important unmeasured patient characteristics are associated with receipt of early dialysis. CONCLUSIONS: Patients who received early dialysis had significantly lower odds of having an ED visit and hospitalization in the week of the storm and of dying within 30 days.

Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.

BACKGROUND: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. DESIGN: This study is a multicenter, 2-arm parallel, cluster randomized trial. SETTING: The study involves 55 advanced chronic kidney disease clinics across Canada. PATIENTS: Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. MEASUREMENTS: Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. METHODS: We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in-person medical detailing visit. Control clinics are only exposed to guideline release without active dissemination. We hypothesize that the clinics randomized to the intervention group will have a lower proportion of early dialysis starts. LIMITATIONS: Limitations include passive dissemination of the guideline through publication, and lead-time and survivor bias, which favors delayed dialysis initiation. CONCLUSIONS: If successful, this active knowledge translation intervention will reduce early dialysis starts, lead to health and economic benefits, and provide a successful framework for evaluating and disseminating future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02183987.

MISE EN CONTEXTE: Malgré l'absence d'avantages probants pour la santé des patients et en dépit de coûts plus élevés liés à la dialyse, la décision d'amorcer un tel traitement au moment où la fonction rénale du patient est encore relativement élevée (dialyse hâtive) est en forte hausse depuis une vingtaine d'années au Canada et partout dans le monde. Toutefois, les lignes directrices canadiennes publiées en 2014 à ce sujet recommandent plutôt de retarder le démarrage de la dialyse. OBJECTIFS DE L'ÉTUDE: Cette étude a pour but d'évaluer l'efficacité et la sécurité d'une intervention au niveau de l'application des connaissances qui favoriserait le démarrage tardif de la dialyse chronique dans la pratique. CADRE ET TYPE D'ÉTUDE: Il s'agit d'un essai clinique randomisé en deux groupes parallèles avec échantillonnage par grappes (clusters). Cinquante-cinq cliniques multidisciplinaires traitant des patients en insuffisance rénale chronique et provenant de partout au Canada participent à l'étude. PATIENTS: L'étude porte sur des patients adultes suivis par un néphrologue depuis plus de trois mois et ayant démarré la dialyse au cours de la période de suivi. MESURES: Les données recueillies seront mesurées au niveau des patients et analysées par regroupement (clusters). Les paramètres de démarrage pour chaque début de dialyse seront établis par la consultation du registre canadien des insuffisances et des transplantations d'organes (RCITO). Les issues primaires sont i) la proportion de patients qui auront démarré la dialyse avec un débit de filtration glomérulaire estimé de plus de 10,5 mL/min/1,73 m2 (dialyse hâtive); ii) la proportion de patients pour lesquels l'amorce aura été faite au cours d'une hospitalisation ou lors d'une admission aux urgences. Les issues secondaires qui seront mesurées incluent : le taux de variation dans le moment du démarrage de la dialyse, le taux d'hospitalisations, le nombre de décès et les coûts associés aux soins prédialyse (lorsque l'évaluation est possible). On voudra également établir un rapport trimestriel des nouveaux cas de démarrages de dialyses, et savoir à quel point les éléments de transmission des connaissances seront acceptés dans la pratique. MÉTHODOLOGIE: Nous avons randomisé 55 cliniques multidisciplinaires en traitement de l'insuffisance rénale (clusters) au Canada à recevoir, ou non, une intervention de transmission des connaissances portant sur les lignes directrices Canadiennes du démarrage de la dialyse. L'intervention consiste en une visite médicale individuelle où l'information pertinente et des outils pédagogiques, tant pour le patient que pour le médecin traitant, sont distribués. Le suivi est assuré par rétroaction et par des vérifications ponctuelles (audits). Les groupes contrôles sont quant à eux mis au fait des nouvelles recommandations sans toutefois recevoir d'outils pédagogiques ni être soumis à la diffusion active de l'information. Nous émettons l'hypothèse que la proportion de dialyses hâtives diminuera au sein des cliniques ayant été randomisées dans le groupe où une intervention sera effectuée. LIMITES DE L'ÉTUDE: La première limite consiste en la possible diffusion passive des nouvelles lignes directrices uniquement par voie de publication. En outre, les biais liés à la survie et au délai d'exécution favorisent les démarrages tardifs de dialyse. CONCLUSION: Une intervention réussie au niveau de la transmission des connaissances contribuera à réduire le nombre d'amorces de dialyse hâtives. Dès lors, on peut penser que cela aura une incidence sur les coûts reliés à cette procédure et des avantages pour la santé des patients. Enfin, cette étude pourrait constituer un cadre favorable pour procéder à l'évaluation et à la diffusion de futures lignes directrices.

Risk factors for an early dialysis start in patients with diabetic nephropathy end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have symptoms related to severe anemia, edema, and heart failure. Although dialysis improves ESRD syndromes, the optimum timing for initiation of dialysis is unclear. Recent observational studies have suggested that early commencement of dialysis can be harmful. Given that early dialysis may increase the risk of death, avoiding an early start to dialysis is recommended. Patients with diabetic nephropathy (DN) may have risk factors for early dialysis. However, the risk factors for early dialysis are unclear in ESRD patients with DN. The aim of this study was to elucidate the risk factors for early initiation of dialysis in patients with DN and ESRD. METHODS: From April 2009 to December 2012, we identified Japanese DN patients with an estimated glomerular filtration rate of less than 15 mL/minute/1.73 m(2). The patients were divided into late or early dialysis groups based on the timing of start of dialysis. RESULTS: We evaluated 52 patients who commenced dialysis during the observation period, including 33 in the late dialysis group and 19 in the early dialysis group. There was a significant association between early dialysis and age ≥65 years (odds ratio 4.59). The incidence of pneumonia before starting dialysis was significantly higher in elderly patients than in nonelderly patients. CONCLUSION: Our findings suggest that elderly patients with DN and ESRD have an increased risk of early initiation of dialysis, and occurrence of pneumonia is also associated with early dialysis. To avoid early commencement of dialysis, booster pneumococcal vaccination could be useful in elderly DN patients with ESRD.

Early, Frequent, and Efficient Hemodialysis: A New Trend or Déjà Vu From the 1970s?

After more than a quarter century of dialysis, two factors are still present in dialysis treatment of chronic renal failure patients: inadequacy of technology (the artificial kidney acts as an artificial glomerulus) and inadequate use of technology in terms of dialysis initiation and frequency. This paper presents the results of two less unphysiological dialysis programs, introduced in Bologna at the beginning of the 1960s, which proved their clinical value and are now becoming trendy, at the end of this century. Features of these programs are twofold: (1) daily dialysis, which aims at making treatment more biologically suited to the patient; its validity relies on lower intra- and interdialytic osmotic fluctuations; (2) early dialysis, which aims at making the patient more biologically suited to the treatment. After more than 25 years it is evident that this treatment has fulfilled its original expectations versus late dialysis. There is a 40% improvement in survival, a 35% decrease in morbidity, and a 24% improvement in the cost/benefit ratio. This report is based on a retrospective analysis of our overall experience and clinical results of chronic hemodialysis carried out in 224 patients on early dialysis and 1210 patients on late dialysis in Bologna from 1967 to 1997. Based on this experience, the following should be regarded as particularly important indications for early dialysis: adequate dialysis facilities; symptomatic patients despite renal creatinine clearances between 15 and 20 mL/min; patients unable to comply with dietary measures; children, to allow for adequate development; patients with diabetes mellitus; candidates for renal transplantation.