Changes In Uremic Toxins And Skeletal Muscle Function Across Stages Of Chronic Kidney Disease

PURPOSE: To examine differences in uremic toxins (UT) and skeletal muscle function in individuals across stages of CKD compared to age-matched healthy controls (HC). METHODS: Thirty-nine individuals with either CKD stage 3 (n = 10), stage 4 (n = 10), or stage 5 (n = 9) or age-matched HC (n = 10) were recruited for this study. After obtaining approval from a physician, participants came to the lab on two occasions. The first visit consisted of the completion of an informed consent form, a health screening and medical history questionnaire. After completing these forms, anthropometric measurements were taken, as well as a venipuncture blood sample. Next, participants completed a familiarization trial of maximum voluntary isometric contractions (MVIC) of the knee extensors, a six-minute walk test (6MWT), and a short physical performance battery (SPPB). Participants returned to the lab 72 hours later for completion of three MVICs while force was recorded via load cell. Concentrations of UT indoxyl sulfate (IS) and p-cresyl sulfate (pCS), along with inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-⍺) were analyzed using commercially available enzyme-linked immunosorbent assays. RESULTS: Results of the study are presented in Table 1. UT IS and pCS, and inflammatory marker IL-6 all showed significantly greater values for each successive CKD severity group. TNF-⍺ had a significantly greater value for CKD stage 3 compared to HC, but no differences were detected between CKD stage 3 and CKD stage 4 or 5. SPPB, MVIC, and 6MWT performance was significantly lower for the CKD stage 3 group compared to HC, and the CKD stage 4 group was significantly lower than the CKD stage 3 group. No significant differences were found between CKD stage 4 and CKD stage 5 for SPPB, MVIC, or 6MWT. CONCLUSION: As CKD progresses, the levels of UT increase along with markers of inflammation. These changes in biomarkers seem to be linked to worsened SM function.Table 1: - Healthy Control(n = 10) CKD Stage 3(n = 10) CKD Stage 4(n = 10) CKD Stage 5(n = 9) IS (mg/dL) 0.56 0.91 2.44 6.94 pCS (mg/dL) 0.68 2.02 3.57 8.19 TNF-⍺ (pg/mL) 5.50 12.25 9.31 12.13 IL-6 (pg/mL) 3.40 5.05 7.02 8.69 SPPB 11.50 9.30 9.10 8.22 MVIC (N) 863.65 708.63 394.05 490.27 6MWT (feet) 525.62 402.16 305.92 320.81