Verena Gotta (1,2), Andrew Atkinson(1,3), Klervi Golhen(4), Olivera Marsenic(4) and Marc Pfister (1)
(1) University Children’s Hospital Basel, University of Basel, Basel, Switzerland, (2) University Hospital Basel, Basel, Switzerland (3) Washington University in St Louis School of Medicine, St Louis MO (5) Stanford University School of Medicine, Lucile Packard Children's Hospital, Stanford, CA
Objectives: Renal anemia is an important complication in hemodialysis (HD) patients requiring erythropoiesis stimulating agents (ESA) in about 90% of patients [1]. It is characterized by low hemoglobin (Hb) levels, which is an established correlate with morbidity and mortality, especially in adult HD patients. In children, anemia is defined as Hb <11-13.0 g/dL, depending on patient’s age and gender. Optimal Hb targets in pediatric HD patients are not well defined, a target of 11-12 g/dl under ESA therapy is currently proposed [2]. We aimed to characterize anemia control under chronic HD and association with long-term outcome (survival while remaining on maintenance HD) in pediatric and adolescent patients from real-world data.
Methods: A retrospective analysis was performed on a cohort of 1852 patients <30 years on chronic HD since childhood (≤18 years), having received outpatient HD 3x/week 2004-2016 [3]. The time-course of Hb control following HD treatment initiation was characterized with inter- and intra-individual variability by mixed effects modelling, investigating demographic (age, gender) and treatment-related factors (intensity of HD prescription: urea clearance in terms of spKt/V or Kt/BSA, and ultrafiltration rate, UFR) as covariates. For long-term outcome analysis, incidence plots of death on hemodialysis versus time-varying Hb up to 12 months into HD treatment were generated as a diagnostic tool to determine the time window of strongest predictive association between Hb control and survival. The derived predictor was subsequently included in a previously reported parametric time-to-event model (Weibull accelerated failure time model), adjusting for demographic characteristics (age at start of HD, etiology of kidney disease, ethnic origin) and intensity of HD prescription [4].
Results: A total of 1482 patients with 128’195 Hb measurements could be included in analysis of anemia control over time. The course of Hb over time on HD was described using a piece-wise linear model showing a “sharp” increase of Hb during the first 3 months on HD (slopeincrease=0.99 g/dl per month, 95%CI: 0.96-1.03 g/dl per month) from baseline (Hb0=9.4 g/dl, 95%CI: 9.35-9.56 g/dl), and a shallow decrease afterwards (slopedecrease=-0.15 g/dl per year, 95%CI: -0.146 to -0.153 g/dl per year). High between-subject and intra-individual variability were quantified (±1.68 g/dl and ±1.35 g/dl, respectively within first 3 months). Young age (<6 years) and female gender (in adolescent patients) were associated with lower Hb values (-1.2 g/dl and -0.6 g/dl respectively in initial model, -0.5 g/dl and -0.2 g/dl in long-term model). HD intensity was not associated with initial Hb time course, but with long-term Hb control (steeper decrease in patients treated with below target spkt/V of <1.2, and low UFR <25th percentile, corresponding to <9.8 ml/kg/h). Hb at start of hemodialysis treatment was not associated with incidence of death, the strongest correlation was apparent with mean individual Hb measured over 2-3 months into HD treatment (available for n=886 of patients). In the corresponding adjusted Weibull survival model a linear association with hazard for was characterized for those with Hb < 12 g/dl (adjusted HR=0.59 for each 1 g/dl Hb increase, p<0.001).
Conclusions: This real-world data analysis suggests that HD initiation significantly improves anemic control in pediatric HD patients, regardless of HD intensity. Longer-term however, adequate HD treatment may slow down further anemia progression, potentially due to reduced ESA resistance with better control of the uremic mileu. Anemic control achieved within the first 3 months of HD treatment initiation strongly correlates with survival on HD in pediatric maintenance HD patients, with suggested optimal Hb ≥12 g/dl.
References:
[1] McFarlane, et al. Kidney International (2010) 78, 215–223
[2] KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease (2012)
[3] Gotta V, et al. Nephrol Dial Transplant. 2018 Sep 1;33(9):1649-1660
[4] Gotta V, et al. Pediatr Nephrol. 2021 Aug;36(8):2421-2432
Reference: PAGE 32 (2024) Abstr 10894 [www.page-meeting.org/?abstract=10894]
Poster: Real-world data (RWD) in pharmacometrics