Decreased circulating klotho levels in patients undergoing dialysis and relationship to oxidative stress and inflammation.
BACKGROUND
It has been reported that klotho deficiency is associated with oxidative stress and inflammation in experimental kidney disease models. Patients with endstage renal disease (ESRD) are particularly characterized by increased oxidative stress and inflammation. However, little is known about the relationship between these features and klotho in patients with ESRD.


METHODS
We conducted a single-center, cross-sectional study of 78 patients receiving peritoneal dialysis (PD). Serum concentrations of klotho, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and 8-isoprostane were measured by enzyme-linked immunosorbent assay. To define factors independently associated with klotho, we determined Spearman's correlation coefficients for between co-variates and conducted multiple linear regression analyses.


RESULTS
Patients were classified by median concentration of klotho. In patients with klotho levels > 329.6 pg/mL, serum 8-isoprostane and IL-6 levels were significantly higher than in those with klotho levels < 329.6 pg/mL. In correlation analyses, log 8-isoprostane (γ = -0.310, p = 0.006) and log IL-6 (γ = -0.343, p = 0.002) were inversely correlated with log klotho. After adjustment for age, gender, mean arterial pressure, log intact parathyroid hormone, and log IL-6, log 8-isoprostane was independently associated with log klotho (β = -0.158, p = 0.040). However, the significant relationship between klotho and IL-6 was not seen in an adjusted model.


CONCLUSIONS
This study showed that circulating klotho levels were significantly associated with 8-isoprostane levels in patients undergoing PD, suggesting a potential link between klotho deficiency and enhanced oxidative stress in ESRD patients.
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Hyung Jung
HJ
Oh
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Bo Young
BY
Nam
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Mi Jung
MJ
Lee
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Chan Ho
CH
Kim
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Hyang Mo
HM
Koo
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Fa Mee
FM
Doh
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Jae Hyun
JH
Han
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Eun Jin
EJ
Kim
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Ji Suk
JS
Han
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Jung Tak
JT
Park
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Tae-Hyun
TH
Yoo
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Shin-Wook
SW
Kang
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Dae-Suk
DS
Han
Division of Nephrology, Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
Seung Hyeok
SH
Han
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000090265:Klotho Proteins; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010530:Peritoneal Dialysis / Q000009:adverse effects / Q000379:methods*; D011237:Predictive Value of Tests; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
D015415:Biomarkers; D015850:Interleukin-6; C075750:8-epi-prostaglandin F2alpha; D002097:C-Reactive Protein; D015237:Dinoprost; D005966:Glucuronidase; D000090265:Klotho Proteins
ESRD; inflammation; klotho; oxidative stress