Low Exercise Tolerance Before Kidney Transplant Signals Poor Muscle Recovery

Low exercise tolerance before kidney transplantation may predict impaired skeletal muscle recovery 1 year after transplant in patients with chronic kidney disease (CKD), according to new research.1

In a retrospective analysis, investigators reported a persistent risk of sarcopenia among living donor kidney transplant recipients, even as renal function improved.1

“Sarcopenia remains a significant concern among kidney transplant recipients even after renal function improves. However, the predictors of impaired muscle recovery are not well established,” wrote study investigator Masaaki Yanishi, MD, from the department of urology and andrology at Kansai Medical University, and colleagues.1

Patients with CKD who have reduced exercise tolerance are more likely to develop sarcopenia, a condition observed across all stages of the disease. Prior research has suggested sarcopenia is not exclusively age-related, despite its higher prevalence among older adults, and may be exacerbated by uremic toxin accumulation, inflammation, insulin resistance, malnutrition, oxidative stress, increased ubiquitination, and low physical activity. Investigators have also linked sarcopenia with higher risks of morbidity, mortality, and progression to end-stage renal disease in CKD.1,2

Mechanistically, sarcopenia is characterized by increased protein degradation and reduced protein synthesis, resulting in a negative protein balance. Among patients with end-stage kidney disease undergoing hemodialysis, low physical activity may further contribute to “muscle disuse,” an underrecognized driver of muscle loss. However, the relationship between pretransplant exercise tolerance and post-transplant skeletal muscle recovery has not been well studied.1,2

To address gaps in identifying predictors of post-transplant muscle recovery, investigators conducted a retrospective analysis of patients who underwent living donor kidney transplantation. They utilized preoperative cardiopulmonary exercise testing (CPX) to stratify participants into a low-tolerance (anaerobic threshold VO₂ < 11 mL/kg/min; peak VO₂ < 20 mL/kg/min) and normal groups. To identify sarcopenia, they measured skeletal muscle index using dual-energy x-ray absorptiometry from baseline to 3 years post-transplantation.1

The study included 40 adults who underwent living donor kidney transplantation at Kansai Medical University Hospital in Japan between January 2018 and December 2020. Overall, 12 patients fell under the criteria for the low-tolerance group (30%).1

At 6 months after transplantation, investigators observed a decline in median skeletal muscle index in both groups, followed by subsequent increases. At 1 year, however, skeletal muscle index was significantly higher in the normal-tolerance group compared with the low-tolerance group.1

By 3 years post-transplant, the median skeletal muscle index in the normal-tolerance group exceeded pretransplant levels and continued to increase. In contrast, investigators did not observe improvement or return to baseline in the low-tolerance group, despite improved renal function (P ≤.05).1

In multivariable analysis, low preoperative exercise tolerance emerged as an independent predictor of reduced skeletal muscle index recovery (P ≤.05). Correlation analyses demonstrated moderate but significant associations between preoperative anaerobic threshold VO₂ and peak VO₂ with 3-year skeletal muscle index improvement (r = 0.427 and r = 0.607, respectively).1

“Cardiopulmonary exercise testing-based risk assessment may help identify candidates who could benefit from tailored perioperative rehabilitation strategies to enhance functional outcomes,” concluded study investigators.1

References

1. Yanishi M, Kimura Y, Koito Y, et al. Low Preoperative Exercise Tolerance Predicts Impaired Skeletal Muscle Recovery After Kidney Transplantation. Transplantation Proceedings. Published online January 9, 2026. doi:https://doi.org/10.1016/j.transproceed.2025.11.013

2. Wang K, Liu Q, Tang M, et al. Chronic kidney disease-induced muscle atrophy: Molecular mechanisms and promising therapies. Biochemical Pharmacology. 2023;208:115407. doi:https://doi.org/10.1016/j.bcp.2022.115407