AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients

Abstract

Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Role of skin autofluorescence in managing renal and cardiac diseases in outpatient dermatology

“…A positive correlation was also seen between the SAF and CACS in PD population when SAF correlated negatively with ultrasound elastography and muscle density, where the latter correlated negatively with CACS. 44 …”

Accelerated AGEing: The Impact of Advanced Glycation End Products on the Prognosis of Chronic Kidney Disease

“…AGEs induce arterial stiffness by reducing the expression and phosphorylation of endothelial nitric oxide synthases, which leads to endothelial dysfunction and activation of the proinflammatory response, which further leads to cross linking of the media collagen molecules and osteogenic differentiation of vascular smooth muscle cells [ 93 ]. Furthermore, AGEs have been correlated with markers of coronary artery calcifications in both CKD and ESRD patients [ 94 , 95 ].…”

Post‐translational regulation of muscle growth, muscle aging and sarcopenia

“…Activation of these signalling pathways can evoke DNA binding activity in a variety of nuclear transcription factors, such as NF‐κB, STAT1/3/5 and AP‐1 85 . The regulation of AGE–RAGE signalling is associated with an inflammatory state, ROS production, endothelial dysfunction, vascular calcification and pathological changes in skeletal muscle blood flow, which results in chronic muscle fibre damage 86 . RAGE‐induced NADPH oxidase is the major source of ROS, which activates NF‐κB through Ras/ERK‐ and Rac1/Mkk6‐dependent pathways.…”

“…85 The regulation of AGE-RAGE signalling is associated with an inflammatory state, ROS production, endothelial dysfunction, vascular calcification and pathological changes in skeletal muscle blood flow, which results in chronic muscle fibre damage. 86 RAGE-induced NADPH oxidase is the major source of ROS, which activates NF-κB through Ras/ERK-and Rac1/Mkk6-dependent pathways. ROS also activate AP-1 and STAT3 through the Rac1/Mkk4/7 and JAK-STAT pathways and accelerate muscle protein damage through a Ca 2+ -dependent pathway.…”