title: Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis.
abstract: BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). An immune-mediated damage and alteration of immune response have been postulated as potential mechanisms involved in CRS type 1. In this pilot study, we examined the possible role of the immune-mediated mechanisms in the pathogenesis of this syndrome. The main objective was to analyze in vitro that plasma of CRS type 1 patients was able to trigger a response in monocytes resulting in apoptosis. The secondary aim was to evaluate TNF-α and IL-6 plasma levels of CRS type 1 patients.  METHODS: Fifteen patients with acute heart failure (AHF) and CRS type 1 were enrolled and 20 healthy volunteers without AHF or AKI were recruited as control group. Plasma from these two groups was incubated with monocytes and, subsequently, cell apoptosis was evaluated. In addition, the activity of caspase-8 was assessed after 24 h incubation. Quantitative determination of TNF-α and IL-6 levels was performed.  RESULTS: Plasma-induced apoptosis was significantly higher in CRS type 1 patients compared with healthy controls at 72 h (78 vs. 11%) and 96 h (81 vs. 11%). At 24 h, the activity of caspase-8 was significantly higher in monocytes incubated with plasma from the CRS type 1 group. TNF-α (2.39 vs. 28.49 pg/ml) and IL-6 (4.8 vs. 16.5 pg/ml) levels were significantly elevated in the CRS type 1 group (p < 0.01).  CONCLUSIONS: In conclusion, there is a defective regulation of monocyte apoptosis in CRS type 1 patients, and inflammatory pathways may have a central role in the pathogenesis of CRS type 1 and may be fundamental in damage to distant organs.
authors.affiliation: Department of Nephrology, Dialysis and Transplant, Vicenza, Italy.
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Virzì
authors.forename: Rossella
authors.initials: R
authors.lastname: Torregrossa
authors.forename: Dinna N
authors.initials: DN
authors.lastname: Cruz
authors.forename: Chang Y
authors.initials: CY
authors.lastname: Chionh
authors.forename: Massimo
authors.initials: M
authors.lastname: de Cal
authors.forename: Sachin S
authors.initials: SS
authors.lastname: Soni
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.forename: Giorgio
authors.initials: G
authors.lastname: Vescovo
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Rosner
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco