Indoxyl Sulfate Might Play a Role in Sarcopenia, While Myostatin Is an Indicator of Muscle Mass in Patients with Chronic Kidney Disease: Analysis from the RECOVERY Study

Abstract

Serum myostatin and indoxyl sulfate (IS) levels increase with kidney function decline and may function as uremic toxins in chronic kidney disease (CKD)-related sarcopenia. Herein, we analyzed the association between serum myostatin and IS levels and sarcopenia in patients with CKD, by performing a post hoc analysis of baseline data extracted from the RECOVERY study (clinicaltrials.gov: NCT03788252) of 150 patients with CKD. We stratified patients into two groups according to the median value of myostatin (cutoff 4.5 ng/mL) and IS levels (cutoff 0.365 mg/dL). The proportion of patients with sarcopenia was higher in those with high IS levels but lower in those with high myostatin levels. The skeletal muscle mass index (SMI) and handgrip strength (HGS) were significantly lower in patients with high IS levels but significantly higher in patients with high myostatin levels. IS levels showed a negative correlation with glomerular filtration rate (GFR), SMI, and HGS. However, myostatin levels were positively correlated with SMI and HGS, but not with GFR. Sarcopenia was independently associated with age and IS level after adjustment. Increased levels of serum total IS might play a role in sarcopenia, while increased levels of serum myostatin are associated with muscle mass in patients with CKD.

Indoxyl Sulfate-Induced Macrophage Toxicity and Therapeutic Strategies in Uremic Atherosclerosis

“…Vanholder et al ranked IS toxicity with the second highest evidence score in SPBMs, such as inflammation, CVD, CKD–MBD, fibrosis metabolic function, and thrombogenicity [ 28 ]. IS acts widely across various organs, tissues, and cells such as bones [ 29 , 30 , 31 , 32 , 33 ], skeletal muscles [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], and myocardium [ 45 , 46 , 47 , 48 , 49 , 50 , 51 ], causing dysfunction in their functions. A clinical study has shown that the serum levels of IS increased with CKD progression, and high levels of serum IS are independently associated with an increased all-cause mortality and cardiovascular mortality in CKD patients [ 25 ] and a trend towards increased cardiovascular events in hemodialysis patients [ 23 ].…”