Aerobic exercise capacity in chronic kidney disease

Aerobic exercise capacity is impaired in chronic kidney disease (CKD) and it is associated with increased mortality and reduced quality of life. The mechanisms underlying reduced exercise capacity in CKD are complex and a comprehensive understanding is lacking, particularly in non-dialysis dependent CKD. The overreaching aim of this thesis was therefore to investigate factors influencing aerobic exercise capacity in individuals with non-dialysis CKD. This was done in a cross-sectional (study I and III), longitudinal (study II and III) and experimental design (study IV).

In study I, aerobic exercise capacity and related factors were assessed at different stages of CKD and compared with healthy controls. Exercise capacity, peak heart rate (HR), stroke volume and hemoglobin level were already reduced in CKD stages 2-3 and gradually decreased with increasing disease severity. Exercise capacity was independently associated with peak HR, stroke volume and hemoglobin levels, with peak HR showing the strongest association.

The aim of study II was to study the changes in aerobic exercise capacity over time. Over the course of five years, individuals with CKD 2-3 maintained their exercise capacity and peak HR, despite an average decline in renal function of 17%. However, exercise capacity decreased in a subgroup of patients who reported low physical activity at baseline.

The relationship between the uremic metabolites kyrunenine and kynurenic acid, both metabolites of tryptophan, and aerobic exercise capacity in CKD 2-5 was shown in study III. An increase in kyrunenine and the kyrunenine/tryptophan ratio over five years was associated with a decline in exercise capacity.

The effects of adding arm exercise to leg exercise, thereby increasing the active muscle mass, was investigated in CKD 3-5 in study IV. Peak oxygen uptake, but not peak HR, increased when arm exercise was added in the CKD group. This was in contrast to healthy controls in whom peak oxygen uptake did not increase. The results provide evidence for a peripheral/muscular limitation of aerobic capacity in CKD.

In summary, both central and peripheral factors influence aerobic exercise capacity in individuals with non-dialysis dependent CKD. Peak HR is an important determinant of exercise capacity in this population. The results also demonstrate that aerobic capacity in this population is dependent on active muscle mass, emphasizing the importance of peripheral factors.

List of scientific papers

I. Wallin H, Asp AM, Wallquist C, Jansson E, Caidahl K, Hylander Rössner B, Jacobson SH, Rickenlund A, Eriksson MJ. (2018). Gradual reduction in exercise capacity in chronic kidney disease is associated with systemic oxygen delivery factors. PLoS ONE. 13(12): e0209325.
https://doi.org/10.1371/journal.pone.0209325

II. Wallin, H, Jansson, E, Wallquist, C, Hylander Rössner B, Jacobson SH, Rickenlund A, Eriksson MJ. Aerobic exercise capacity is maintained over a 5-year period in mild-to-moderate chronic kidney disease: a longitudinal study. BMC Nephrol. 21, 475 (2020).
https://doi.org/10.1186/s12882-020-02110-2

III. Wallin H, Jansson E, Erhardt S, Wallquist C, Hylander Rössner B, Jacobson SH, Caidahl K, Rickenlund A, Eriksson MJ. (2023). Kynurenines and aerobic exercise capacity in chronic kidney disease: a cross-sectional and longitudinal study. [Manuscript]

IV. Wallin H, Jansson E, Said R, Lundberg S, Zolfaghardidani P, Eriksson MJ, Rickenlund A, Sundblad P. (2023). Exercise capacity is limited by peripheral rather than by central factors in chronic kidney disease. An experimental study with leg and arm exercise. [Manuscript]