Intradialytic hypotension (IDH) is a common complication of hemodialysis, but there is no data about the time of onset during treatment. Here we describe the incidence of IDH throughout hemodialysis and associations of time of hypotension with clinical parameters and survival by analyzing data from 21 dialysis clinics in the United States to include 785682 treatments from 4348 patients. IDH was defined as a systolic blood pressure of 90 mmHg or under while IDH incidence was calculated in 30-minute intervals throughout the hemodialysis session. Associations of time of IDH with clinical and treatment parameters were explored using logistic regression and with survival using Cox-regression. Sensitivity analysis considered further IDH definitions. IDH occurred in 12% of sessions at a median time interval of 120-149 minutes. There was no notable change in IDH incidence across hemodialysis intervals (range: 2.6-3.2 episodes per 100 session-intervals). Relative blood volume and ultrafiltration volume did not notably associate with IDH in the first 90 minutes but did thereafter. Associations between central venous but not arterial oxygen saturation and IDH were present throughout hemodialysis. Patients prone to IDH early as compared to late in a session had worse survival. Sensitivity analyses suggested IDH definition affects time of onset but other analyses were comparable. Thus, our study highlights the incidence of IDH during the early part of hemodialysis which, when compared to later episodes, associates with clinical parameters and mortality.

Significance Statement: SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived “Fluid Overload” at recruitment. Empagliflozin induced a prompt and sustained reduction in “Fluid Overload,” irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk. Background: CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived “Fluid Overload” and adiposity in a CKD population. Methods: EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute “Fluid Overload” (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach. Results: The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute “Fluid Overload” was 0.4±1.7 L. Compared with placebo, the overall mean absolute “Fluid Overload” difference among those allocated empagliflozin was −0.24 L (95% confidence interval [CI], −0.38 to −0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of −0.49 L (95% CI, −0.69 to −0.30, including the −0.24 L “Fluid Overload” difference) and a −0.30 L (95% CI, −0.57 to −0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (−0.28 kg [95% CI, −1.41 to 0.85]). The between-group difference in weight was −0.7 kg (95% CI, −1.3 to −0.1). Conclusions: In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass. Trial Registration: Clinicaltrials.gov: NCT03594110; EuDRACT: 2017-002971-24 (https://eudract.ema.europa.eu/).

Bioimpedance measurements with the Body Composition Monitor (BCM) have been shown to improve fluid management in haemodialysis. However, there is a lack of a sufficiently robust evidence-base for use of the BCM outside of standard protocols. This study aims to define the error associated with BCM measurement using alternate paths and timings to allow the use of BCM with confidence in a range of clinical scenarios. BCM measurements were made in 48 healthy controls and in 48 stable haemodialysis patients before and immediately after dialysis. The effect of utilising alternative measurement paths was assessed using mixed effects models and the effect of measuring post-dialysis was assessed by comparing changes in BCM-measured overhydration (OH) with weight changes over dialysis. The data from healthy controls suggest that there is no difference in BCM-measured OH between all the whole-body paths other than the ankle-to-ankle measurement. Dialysis patients showed similar results other than having higher BCM-measured OH when measured across the site of a vascular access. There was good agreement between BCM-measured OH from the standard path and change in weight, suggesting post-dialysis measurements can be utilised. These results suggest BCM protocols can be flexible regarding measurement paths and timing of measurement to ensure as many patients as possible can benefit from the technology.

Malnutrition is common in haemodialysis (HD) and is linked to poor outcomes. This study aimed to describe changes in body composition after the initiation of HD and investigate whether any routinely collected parameters were associated with these changes. The study cohort came from the HD population of a single centre between 2009 and 2014. Body composition measurements were obtained from a database of bioimpedance results using the Body Composition Monitor (BCM), while demographics and laboratory values came from the renal unit database. Primary outcomes were changes in normohydration weight, lean tissue mass and adipose tissue mass over the two years after HD initiation. A total of 299 patients were included in the primary analyses, showing an increase in adipose tissue, loss of lean tissue and no significant change in normohydration weight. None of the routinely collected parameters were associated with the lean tissue changes. Loss of lean tissue over the first year of dialysis was associated with increased mortality. The results showing loss of lean tissue that is not limited to those traditionally assumed to be at high risk supports interventions to maintain or improve lean tissue as soon as possible after the initiation of HD. It highlights the importance of monitoring nutrition and the potential for routine use of bioimpedance.