Predictors of Change in Left-Ventricular Structure and Function in a Trial of Extended Hours Hemodialysis

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ABSTRACT

Background

Myocardial pathology is common in patients undergoing hemodialysis. To explore the effects of differing aspects of dialysis treatment on its evolution, we examined the impact of change in markers of volume status, hemodynamics and solute clearance on left ventricular (LV) parameters in a randomized trial of extended hours dialysis.

Methods and Results

A Clinical Trial of IntensiVE (ACTIVE) Dialysis randomized 200 patients undergoing hemodialysis to extended dialysis hours (≥ 24 hours/week) or standard hours (12–18 hours/week) for 12 months. In a prespecified substudy, 95 participants underwent cardiac magnetic resonance imaging (CMR) at baseline and at the study's end. Generalized linear regression was used to model the relationship between changes in LV parameters and markers of volume status (normalized ultrafiltration rate and total weekly interdialytic weight gain), hemodynamic changes (systolic and diastolic blood pressure) and solute control (urea clearance, dialysis hours and phosphate). Randomization to extended hours dialysis was not associated with change in any CMR parameter. Reduction in ultrafiltration rate was associated with reduction in LV mass index (P = 0.049) and improved ejection fraction (P = 0.024); reduction in systolic blood pressure was also associated with improvement in ejection fraction (P = 0.045); reduction in interdialytic weight gain was associated with reduced stroke volume (P = 0.038). There were no associations between change in urea clearance, phosphate or total hours per week and CMR parameters.

Conclusions

Reduction in ultrafiltration rate and blood pressure are associated with improved myocardial parameters in hemodialysis recipients independently of solute clearance or dialysis time. These findings underscore the importance of fluid status and related parameters as potential treatment targets in this population.

Section snippets

ACTIVE Dialysis MRI Substudy

The design and primary results of the ACTIVE Dialysis trial have been reported previously.9,10 Briefly, 200 patients undergoing hemodialysis, who were from 40 sites in China, Australia, New Zealand, and Canada, were randomized to 12 months of standard hours of dialysis (≤ 18 hours per week) or to extended hours of dialysis (≥ 24 hours per week). A minimum of 3 dialysis sessions per week was specified for both groups. Participants from 29 sites with access to CMR and no contraindication to this

Baseline characteristics and effect of randomized allocation

In the ACTIVE Dialysis study, 200 participants were enrolled, of whom 95 (51 extended hours, 44 standard hours) were included in the CMR substudy. At baseline, the substudy population was similar to the broader study cohort, and they experienced similar changes in dialysis schedules. Within the substudy, baseline characteristics were balanced between groups (Table 2), and participants in the extended hours dialysis group increased their total weekly dialysis time by a median of 12 hours (IQR

Discussion

In this exploratory analysis of participants in the ACTIVE Dialysis study, favorable changes in 2 myocardial parameters (LVMI and EF) were associated with reduction in the rate of ultrafiltration. Reduction in systolic blood pressure was associated with improvement in EF. These associations were independent of changes in dialysis time or Kt/V or phosphate levels. Collectively, these findings are consistent with a central role for volume overload and related stresses in the myocardial pathology

Conclusion

In conclusion, changes in volume status and hemodynamics (such as the rate of UF) may be more influential on myocardial pathology in hemodialysis recipients than solute clearance and dialysis time alone. Future studies should consider whether interventions specifically targeting these parameters can influence cardiac and clinical outcomes.

Authors’ contributions

Research inception, study design and leadership: MJ; Critical review of study design and oversight of study conduct: VP, MG, AC; Analysis plan: CC, BS, MJ, DH, LZ; Data acquisition: SMG, RP; Statistical analysis: AS, BS; Participant recruitment: MJ, LZ, NAG, JRdZ, CC; Manuscript preparation: BS; Drafting and revision of manuscript: VP, SMG, MG, NAG, RP, JRdZ, MJ, DH, CC. Each author contributed important intellectual content during manuscript drafting or revision, and has approved the final

Support

The ACTIVE Dialysis study was funded by National Health and Medical Research Council of Australia grants APP571045 and APP358395 and by an unrestricted grant from Baxter International. The funders had no role in the study's design, collection, analysis and interpretation of data, writing of the report, or the decision to submit it for publication. BS is supported by an Australian Government Research Training Program Scholarship via the University of Sydney. MJ is supported by a Medical Research

Financial disclosures

BS reports receiving travel support from Roche and Vimedimex Binh Duong; he serves as Associate Editor for Kidney Blood Pressure Research. CC reports receiving consulting fees and grant support from Medtronic. MG reports speaking fees from Astra-Zeneca. MJ reports consulting or serving on advisory board for Akebia, Baxter, and Vifor, she has received speaking fees from Vifor and Janssen and has received grant support from Merck Sharpe & Dohme and Eli Lilly, with all honoraria paid to her

Acknowledgments

Thank you to Dr. Rathika Krishnasamy for her critical review of the manuscript.

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