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Procalcitonin and the inflammatory response to salt in essential hypertension: a randomized cross-over clinical trial

Mallamaci, Francescaa,b; Leonardis, Danielaa,b; Pizzini, Patriziaa,b; Cutrupi, Sebastianoa,b; Tripepi, Giovannia,b; Zoccali, Carminea,b

doi: 10.1097/HJH.0b013e328360ddd5

Objectives: Inflammation is considered as a major effector of arterial damage brought about by salt excess in animal models. In a randomized, single masked, cross-over study in 32 uncomplicated essential hypertensive patients, we assessed the effect of a short-term low-salt diet on biomarkers of innate immunity [procalcitonin (PCT), interleukin-6, C-reactive protein, and tumor necrosis factor-α (TNF-α)], adiponectin (ADPN, an anti-inflammatory cytokine), and leptin.

Methods: Patients were randomized to either a 10–20 mmol sodium diet and sodium tablets (180 mEq/day) to achieve a 200 mmol intake per day or the same diet and identical placebo tablets, each for 2 weeks. At the end of each of these periods, all patients underwent a 24-h urine collection, a fasting blood sampling, and a 24 h ambulatory blood pressure monitoring.

Results: In parallel with expected increase in plasma renin activity and aldosterone (P <0.001), both PCT (+33%) and TNF-α (9%) rose at low salt intake (P ≤0.007) while ADPN underwent an opposite change (− 17%, P <0.001). In a linear regression analysis for repeated measurements, PCT was significantly and inversely related to urinary salt (weighted r = −0.27, P = 0.03). Changes in inflammation biomarkers did not differ in salt-sensitive (n = 7) and salt-resistant (n = 25) patients.

Conclusion: In essential hypertensive patients, a very low salt diet generates a pro-inflammatory phenotype characterized by an increase in PCT and TNF-α and an opposite effect on an anti-inflammatory cytokine like ADPN.

aCNR-IBIM Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension

bNephrology, Dialysis and Transplantation Unit of Reggio Calabria, Reggio Calabria, Italy

Correspondence to Professor Carmine Zoccali, CNR-IBIM and Nephrology, Dialysis and Transplantation Unit, Ospedali Riuniti, 89124 Reggio Calabria, Italy. Tel: +39 0965 397 010; fax: +39 0965 26879; e-mail:

Abbreviations: CGRP, calcitonin gene-related peptide; CKD, chronic kidney disease; CRP, C-reactive protein; GIP, glucose-dependent insulinotropic polypeptide; IL-6, interleukin-6; MCP1, monocyte chemoattractant protein; PCT, procalcitonin; PRA, plasma renin activity; TNF-α, tumor necrosis factor α

Received 16 October, 2012

Revised 14 December, 2012

Accepted 4 March, 2013

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins