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Elevated Plasma Cyclophillin A in Hemodialysis and Peritoneal Dialysis Patients: a Novel Link to Systemic
Kyubok Jin1, Nosratola D Vaziri
1Division of Nephrology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea. mdjin922@gmail.com.
Insights
Circulating cyclophilin A is significantly elevated in patients undergoing hemodialysis and peritoneal dialysis. This elevation correlates with key markers of systemic inflammation, suggesting its role in kidney disease complications.
Area of Science:
- Biochemistry
- Nephrology
- Immunology
Background:
- Cyclophilin A (CypA) is implicated in oxidative stress and inflammation, relevant to cardiovascular disease, diabetes, and infections.
- Conditions common in end-stage renal disease (ESRD) can trigger CypA release, potentially worsening systemic inflammation.
- The impact of ESRD and dialysis on circulating CypA levels remains largely uninvestigated.
Purpose of the Study:
- To investigate whether extracellular cyclophilin A levels are elevated in patients with end-stage renal disease undergoing different dialysis modalities.
- To compare CypA levels in hemodialysis and peritoneal dialysis patients against healthy controls.
Main Methods:
- Plasma concentrations of cyclophilin A, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured.
- Lipid profiles were also assessed in fasting plasma samples.
- The study included 20 hemodialysis patients, 20 peritoneal dialysis patients, and 20 age- and sex-matched controls.
Main Results:
- Plasma CypA levels were significantly higher in both hemodialysis (105.3 ± 6.2 ng/mL) and peritoneal dialysis (106.8 ± 9.0 ng/mL) patients compared to controls (29.7 ± 4.1 ng/mL).
- Elevated hs-CRP, IL-6, and TNF-α were observed in dialysis patients.
- CypA concentrations positively correlated with hs-CRP, IL-6, and TNF-α, and inversely with high-density lipoprotein (HDL) cholesterol.
Conclusions:
- Plasma cyclophilin A is markedly elevated in patients on hemodialysis and peritoneal dialysis.
- Elevated CypA levels are associated with increased systemic inflammation markers in these patients.
- These findings highlight CypA's potential role in the inflammatory state associated with ESRD and dialysis.
Introduction:
Cyclophillin A has emerged as a novel mediator of oxidative stress and inflammation and a major player in cardiovascular disease, diabetes mellitus, viral infections, and neurodegenerative and thrombotic disorders. Cyclophillin A is released by certain cell types spontaneously or in response to inflammatory mediators, hypoxia, oxidative stress, and hyperglycemia. Many of these conditions are either present or frequently occur in patients with end-stage renal disease and can stimulate release of cyclophillin A, thereby amplifying systemic inflammation. To our knowledge, the effect of end-stage renal disease and dialysis modalities on circulating cyclophillin A has not been previously investigated. This study tested the hypothesis that extracellular cyclophillin A is elevated in patients maintained on hemodialysis and peritoneal dialysis.
Materials And Methods:
Cyclophillin A, high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and lipid levels were measured in the fasting plasma samples from 20 hemodialysis and 20 peritoneal dialysis patients, and 20 age- and sex-matched controls.
Results:
Plasma cyclophillin A concentration in the patients on hemodialysis (105.3 ± 6.2 ng/mL) and peritoneal dialysis (106.8 ± 9.0 ng/mL) were significantly higher than that in the control group (29.7 ± 4.1 ng/mL). This was associated with significant elevation of high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α. Plasma cyclophillin A concentration showed direct correlations with high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α, and an inverse correlation with high-density lipoprotein cholesterol concentration.
Conclusions:
Plasma cyclophillin A concentration is markedly elevated and positively correlates with the markers of systemic inflammation in hemodialysis and peritoneal dialysis patients.
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