Impaired K+ regulation contributes to exercise limitation in end-stage renal failure

Background. Patients with end-stage renal failure (ESRF) exhibit grossly impaired maximal exercise performance. This study investigated whether K+ regulation during exercise is impaired in ESRF and whether this is related to reduced exercise performance. Methods. Nine stable hemodialysis patients and eight controls (CON) performed incremental cycling exercise to volitional fatigue, with measurement of peak oxygen consumption (V O2 peak). Arterial blood was sampled during and following exercise and analyzed for plasma [K+] (PK). Results. The V O2 peak was approximately 44% less in ESRF than in CON (P < 0.001), whereas peak exercise PK was greater (7.23 ± 0.38 vs. 6.23 ± 0.14 mmol · L-1, respectively, P < 0.001). In ESRF, the rate of rise in PK during exercise was twofold greater (0.43 ± 0.05 vs. 0.23 ± 0.03 mmol · L-1 ·min-1, P < 0.005) and the ratio of rise in PK relative to work performed was 3.7-fold higher (90.1 ± 13.5 vs. 24.7 ± 3.3 nmol · L-1 · J-1, P < 0.001). A strong inverse relationship was found between V O2 peak and the DeltaPK · work-1 ratio (r = -0.80, N = 17, P < 0.001). Conclusions. Patients with ESRF exhibit grossly impaired extrarenal K+ regulation during exercise, demonstrated by an excessive rise in PK relative to work performed. We further show that K+ regulation during exercise was correlated with aerobic exercise performance. These results suggest that disturbed K+ regulation in ESRF contributes to early muscle fatigue during exercise, thus causing reduced exercise performance.