Nephrol Dial Transplant (2004) 19: 797-804
Nephrol Dial Transplant Vol. 19 No. 4 © ERA-EDTA 2004; all rights reserved
Original Article
Counter-regulatory effects of procalcitonin and indoxyl sulphate on net albumin secretion by cultured rat hepatocytes
1Department of Clinical Nutrition, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, 2Division of Nephrology, Endocrinology and Metabolism, Shizuoka Cancer Center Hospital, Nagaizumi-cho and 3First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Correspondence and offprint requests to: Mari Odamaki, PhD, Department of Clinical Nutrition, School of Food and Nutritional Sciences, University of Shizuoka, 521 Yada, Shizuoka, 422-8526, Japan. Email: odamari{at}u-shizuoka-ken.ac.jp
Background. Although hypoalbuminaemia is a significant predictor of mortality in haemodialysis (HD) patients, the pathophysiological mechanisms involved remain to be determined. Albumin is a negative acute-phase reactant and many proinflammatory substances are elevated in HD patients. We investigated factors that may affect liver albumin synthesis.
Methods. Hepatocytes were isolated from rat livers and were cultured with interleukin (IL)-4, IL-6, IL-12, tumor necrosis factor (TNF)-
, procalcitonin (PCT), a sensitive marker of infection, and indoxyl sulphate (IS), a uraemic toxin. Albumin levels in the supernatant were measured by enzyme-linked immunosorbent assay. Albumin mRNA expression was determined by reverse transcriptase polymerase chain reaction.
Results. IL-6 and TNF-
significantly decreased albumin levels in a dose-dependent manner (P<0.01 and P<0.05, respectively). In contrast, IL-4 and IL-12 did not modulate albumin production. PCT and IS significantly and dose-dependently increased albumin levels (both P<0.01). PCT increased albumin mRNA expression in the hepatocytes (P = 0.05) and dose-dependently abrogated IL-6-induced suppression of albumin synthesis (P<0.01). IS also blocked the IL-6-induced decrease in net albumin secretion (P<0.01).
Conclusion. Our findings indicate that PCT and IS protect against suppression of hepatic albumin synthesis caused by proinflammatory cytokines, suggesting their potential role in preventing hypoalbuminaemia in HD patients.
Keywords: albumin; haemodialysis; IL-6; indoxyl sulphate; procalcitonin