Increased extracellular water measured by bioimpedance and by increased serum levels of atrial natriuretic peptide in RA patients—signs of volume overload
The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.
KeywordsHypertension Inflammation Rheumatoid arthritis Volume overload
Rainer H Straub contributed to the development of hypothesis and concept, analyses of data, generating draft figures, drafting the paper, and final approval; Boris Ehrenstein to the generation of data, revising the draft paper, and final approval; Florian Günther to the generation of data, revising the draft paper, and final approval; Luise Rauch to the generation of data, writing parts of the paper, revising the draft paper, and final approval; Nadezhda Trendafilova to the generation of data, revising the draft paper, and final approval; Dario Boschiero to the development of the BIA-ACC technique, coordinating patient recruitment in Italy (first study arm), writing the part on BIA methods, revising the draft paper, and final approval; Joachim Grifka to providing patient material, revising the draft paper, and final approval; and Martin Fleck to the generation of data, revising the draft paper, and final approval.
Compliance with ethical standards
The study was supported by the institutions. Dario Boschiero is the Director of the Research and Development at BioTekna Biomedical Technologies, Marcon, Italy. Dario Boschiero coordinated patient recruitment of the Italian patients (first study arm), but he was not involved in data analyses, and writing of the draft paper. All authors had access to the data and a role in writing the manuscript.
- 8.Giordano R, Di VL, Lanfranco F, Broglio F, Benso A, Gianotti L et al (2001) Elderly subjects show severe impairment of dehydroepiandrosterone sulphate and reduced sensitivity of cortisol and aldosterone response to the stimulatory effect of ACTH(1–24). Clin Endocrinol (Oxf) 55:259–265CrossRefGoogle Scholar
- 13.Peters MJ, Welsh P, McInnes IB, Wolbink G, Dijkmans BA, Sattar N et al (2010) Tumour necrosis factor blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study. Ann Rheum Dis 69:1281–1285CrossRefPubMedGoogle Scholar
- 38.Kotyla PJ, Owczarek A, Rakoczy J, Lewicki M, Kucharz EJ, Emery P (2012) Infliximab treatment increases left ventricular ejection fraction in patients with rheumatoid arthritis: assessment of heart function by echocardiography, endothelin 1, interleukin 6, and NT-pro brain natriuretic peptide. J Rheumatol 39:701–706CrossRefPubMedGoogle Scholar