Association of Physiological Reserve Obtained from Cardiopulmonary Exercise Testing and Frailty with All-Cause Mortality in Hemodialysis Patients

Naoto Usui; Junichiro Nakata; Akimi Uehata; Sho Kojima; Shuji Ando; Masakazu Saitoh; Akihito Inatsu; Hideki Hisadome; Yuki Nishiyama; Yusuke Suzuki

doi:10.2215/CJN.0000000621

Association of Physiological Reserve Obtained from Cardiopulmonary Exercise Testing and Frailty with All-Cause Mortality in Hemodialysis Patients

Clin J Am Soc Nephrol. 2024 Dec 18. doi: 10.2215/CJN.0000000621. Online ahead of print.

Authors

Naoto Usui^{1

2}, Junichiro Nakata², Akimi Uehata³, Sho Kojima^{1

4}, Shuji Ando⁵, Masakazu Saitoh⁶, Akihito Inatsu⁷, Hideki Hisadome³, Yuki Nishiyama¹, Yusuke Suzuki²

Affiliations

¹ Department of Rehabilitation, Kisen Hospital, Tokyo, Japan.
² Department of Nephrology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
³ Division of Cardiology, Kisen Hospital, Tokyo, Japan.
⁴ Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, Niigata, Japan.
⁵ Department of Information Sciences, Tokyo University of Science, Chiba, Japan.
⁶ Department of Physical Therapy, Faculty of Health Science, Juntendo University, Tokyo, Japan.
⁷ Division of Nephrology, Kisen Hospital, Tokyo, Japan.

PMID: 39693148
DOI: 10.2215/CJN.0000000621

Abstract

Background: Potential impairment of exercise capacity is prevalent even in patients undergoing hemodialysis without frailty. Cardiopulmonary exercise testing (CPET) can detect physiological reserves such as cardiopulmonary, muscle, and autonomic function. We hypothesized that these indices could accurately determine the prognosis of patients on hemodialysis and analyzed them based on their relationship to frailty.

Methods: In this two-center prospective cohort study hemodialysis patients from Japan, participants underwent CPET and physical assessment to evaluate peak oxygen uptake (peak VO2, indicator of exercise capacity), peak work rate (WR, indicator of muscle function), ventilatory equivalent for carbon dioxide (VE/VCO2) slope (indicator of cardiac reserve), heart rate reserve (indicator of chronotropic incompetence), and frailty phenotype. Survival was followed-up for up to 5 years.

Results: Data from 189 patients (median [IQR] age: 71 [62, 77] years) were analyzed. All CPET indicators showed a consistent nonlinear relationship with all-cause mortality after adjustment: for peak VO2, hazard ratio [HR] 0.79 [95% CI: 0.71, 0.88], P <0.001; for peak WR, HR 0.95 [95% CI: 0.93, 0.97], P <0.001; for VE/VCO2 slope, HR 1.09 [95% CI: 1.05, 1.13], P <0.001; for heart rate reserve, HR 0.96 [95% CI: 0.93, 0.99], P=0.02). Frailty phenotype was associated with mortality after adjustment (HR 1.73 [95% CI: 1.06, 2.81], P=0.03); however, this association was not statistically significant in the model after adding peak VO2 (P=0.41). Furthermore, in both subgroups with and without frailty, CPET measures were significantly associated with mortality risk (peak VO2, peak WR, and VE/VCO2 slope: P <0.05). The peak VO2 (Δ area under the curve [AUC] 0.09, 95% CI: 0.02, 0.16) or the peak WR (ΔAUC 0.09, 95% CI: 0.02, 0.15) most significantly improved the prognostic accuracy.

Conclusions: Results showed the fragile aspect of the frailty phenotype in the hemodialysis population and the superior ability of CPET to indicate death risk complementing that aspect.