Comment on 'Allograft function and muscle mass evolution after kidney transplantation' by Gaillard et al.: The authors reply.

Abstract

We are very pleased by the comments raised by our study entitled ‘Allograft function and muscle mass evolution after kidney transplantation’. In their commentary, Thomas Stehlé et al. pinpoint a discrepancy between our finding that creatinine excretion rate (CER) is an independent risk factor for mortality after kidney transplantation and their previous report indicating that kidney transplant recipients with a skeletal muscle mass index below the 2.5th percentile of normal prior to transplantation had no increased risk of mortality.1 In their study, skeletal muscle mass index was calculated by dividing total lumbar muscle cross-sectional area (CSMA) through the middle of L3 by height squared. On the contrary, we did not normalize CER to body size, but instead adjust for height in multivariable analyses. We prioritized this approach to separately assess the association of muscle mass and height with transplantation outcome, as height is an independent predictor of mortality in patients with chronic kidney disease.2 Stehlé et al. therefore questioned whether indexing CER on height would have modified the association of CER with mortality. To answer this question, we performed additional analyses with CER adjusted to squared height (CERheight). Consistently with our findings with crude CER, we found a significant association of CERheight with mortality in univariable (Figure 1) and multivariable analysis (Table 1). One possible explanation for the discrepancy highlighted by Stehlé et al. is that adipocytes do not produce creatinine. Thus, CER is not solely a reflection of muscle volume but also impacted by the relative amount or muscle fibres and adipocytes within muscles. In their elegant study, Stehlé et al. found that, contrary to muscle cross section area, myosteatosis associated with mortality. The idea that myosteatosis decreases creatinine production is sustained by a recent study demonstrating that creatinine to cystatin C ratio predicts myosteatosis in older adults, independently of CSMA.3 CER and muscle area and density measurement by CT are complementary approaches to estimate muscle health from data collected for other purposes. These approaches have been helpful to unveil important aspects of muscle health in kidney transplant recipients. To our opinion, considering studies based on CER may have modified the conclusion of a recent meta-analysis, which did not demonstrate an impact of sarcopenia on clinical health after kidney transplantation.4 CER or CT-based approaches are however insufficient to guide or evaluate interventions targeting muscle health in kidney transplant recipients. In that perspective, we would like to highlight the study from Dienemann et al., which combined a longitudinal analysis of both muscle mass and performances after kidney transplantation.5 This observational study, which unfortunately included a limited number of patients, provides a rigorous framework for future studies in the field.