Early versus late initiation of dialysis in end-stage kidney disease: nutritional and functional outcomes - An analysis of Auckland participants in the IDEAL nutritional substudy

Abstract

Introduction: Chronic kidney disease (CKD) is a progressive disease associated with development of comorbidities and increased risk of mortality. Protein energy wasting (PEW) is a key nutritional complication of CKD promoted by factors that include appetite suppression, increased energy expenditure, inflammation, protein catabolism and oxidative stress. Previous observational studies have investigated the impact of maintenance dialysis on PEW and PEWrelated complications (Jager et al., 2001; Mehrotra, Berman, Alistwani, & Kopple, 2002; Pupim et al., 2002). However, no randomised study has investigated the impact of early versus late initiation of dialysis on the nutritional status of end-stage CKD (stages 4 to 5). Aims: The primary aim of this thesis was to determine the impact of early versus late initiation of dialysis on the nutritional status of end-stage CKD patients as determined by total body protein (TBP), over a 3-year follow up period. The secondary aim was to determine the impact on secondary markers of nutritional status, body composition and functional outcomes over the same study period. Methods: This thesis analysed the data of Auckland participants (n=75) involved in the nutritional substudy of the Initiating Dialysis Early and Late (IDEAL) multi-centred randomised trial. TBP was measured by in vivo neutron activation analysis (IVNAA). Nutritional status was also assessed by subjective global assessment (SGA) and body compositional analysis was carried out using dualenergy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and anthropometry. Resting energy expenditure was measured by indirect calorimetry and functional status measures included handgrip strength, peak flow and fatigue score. All measurements were performed at baseline, soon after randomisation and at 3 follow up visits (12, 24 and 36 months). The early group (n=37) started dialysis at an estimated glomerular filtration rate (eGFR) between 10 and 14 ml/min/1.73m2 and the late group (n=38) between 5 and 7 ml/min/1.73m2. Repeated measures analysis of variance was used to assess the changes in each variable from baseline to 12, 24 and 36 months. Results: Loss to follow up included 7 deaths and 1 transplant in the early group and 5 deaths and 3 transplants in the late group. The median time from randomisation to dialysis was 6.35 (range 0.00-51.4) months for the late group and 2.22 (range 0.00-43.13) months for the early group (p<0.0002). The majority of participants in both the early and late dialysis groups had started dialysis at or before the 12-month follow up visit. Changes in TBP from baseline to 12, 24 and 36 months did not differ significantly between the two groups. However, for the total cohort, significant reductions in TBP of 0.4 to 0.6kg were seen at each of these time points (p<0.001). Similarly, for secondary measures, analysis showed no significant differences between the groups, except for the resting energy expenditure at the 36 month follow up, where a significant increase from baseline to 36 months was measured (109kcal/d, p=0.005) for the early dialysis group. For the total cohort of Auckland participants, fat free mass measured by DXA significantly decreased from baseline to 12 (p=0.010) and 24 months (p=0.013) but not for 36 months. Handgrip strength and peak flow for the total cohort of participants decreased from baseline to 24 and 36 months. Conclusions and recommendations: This study was unable to support a benefit of initiating dialysis early on nutritional status. A limitation of this study was at the follow-up time points most patients had started dialysis. However, this study highlighted significant deterioration in TBP stores and functional status of the participants over the duration of the study. Future randomised studies designed with larger sample sizes to address the limitations of this nutritional substudy are needed to inform future clinical practice for dialysis initiation and dietary recommendations for PEW.