Hypoxia-inducible factor prolyl hydroxylase domain inhibitors may mitigate loss of skeletal muscle mass in haemodialysis patients

Abstract

Background

Chronic kidney disease patients particularly with renal anaemia hyporesponsive to erythropoiesis-stimulating agents (ESAs) are at a greater risk of having skeletal muscle mass (SMM) loss. Hypoxia-inducible factor prolyl hydroxylase domain inhibitor (HIF-PHI), a novel therapeutic agent for renal anaemia, potentially promotes angiogenesis, muscle repair, and homeostasis. However, effects of HIF-PHIs on SMM remain unknown.

Methods

This retrospective observational cohort study enrolled 292 Japanese adults receiving maintenance haemodialysis at our dialysis centre. The dataset included 11 patients who received daprodustat for 6 months or longer during 1 December 2020 through 30 June 2022. From the previously published pooled cohort, we enrolled 281 participants from 1 August 2018 to 31 July 2019 prior to the approval of HIF-PHIs for renal anaemia. SMM was assessed using modified creatinine index (mg/kg/day) calculated by age, sex, serum creatinine, and single-pool Kt/V. Annual changes of SMM [ΔSMM (%)] were analysed with the least squares regression model and mixed-effects model during 6- to 12-month follow-up period.

Results

The median age of the participants was 63 years [interquartile range (IQR), 54–71 years], and 33% were female. The median ΔSMM levels (IQR) in the least squares regression model were 4.0% (−1.7% to 9.3%) in the HIF-PHI group, 0.20% (−2.1% to 2.1%) in the no ESA group, and −0.94% (−3.0% to 1.3%) in the high ESA group using darbepoetin equivalent to 20 μg or more per week. Those in the mixed-effects model were −1.7% (−1.2% to 3.8%), 0.09% (−1.4% to 1.3%), and −0.74% (−2.0% to 0.8%), respectively. The multivariable linear regression models revealed that HIF-PHI use was associated with greater ΔSMM compared with the high ESA group [coefficient, 3.737; 95% confidence interval (CI), 1.216–6.258 in the least squares regression model or coefficient, 1.635; 95% CI, 0.068–3.201 in the mixed-effects model, respectively].

Conclusions

HIF-PHI use led to greater ΔSMM in maintenance haemodialysis patients. HIF-PHIs may minimize loss of SMM in patients with end-stage kidney disease and renal anaemia.