Oxidative stress: dual pathway induction in cardiorenal syndrome type 1 pathogenesis.

Grazia Maria Virzì,Alessandra Brocca,Sonya Day,Massimo De Cal,Giorgio Vescovo,Anna Clementi,Chiara Bolin,Silvia Pastori,Claudio Ronco

doi:10.1155/2015/391790

Abstract

Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P < 0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis.

Highlights

Heart performance and kidney function are strictly interconnected and communication between these two organs occurs through a variety of pathways, including hemodynamic and nonhemodynamic mechanisms [1,2,3,4,5,6]
Our results demonstrate the significantly heightened presence of dual reactive oxygen species imbalance in patients with cardiorenal syndromes (CRS) Type 1 compared to acute heart failure (AHF) patients: ROS/ reactive nitrogen species (RNS) production involving NADPH oxidase and MPO; SOD production of hydrogen peroxide; and nitric oxide (NO) upregulation of proinflammatory mediators via peroxynitrite (Figure 1)
Our results demonstrate a significant increase in both ROS and RNS redox disequilibrium in patients with CRS Type 1 compared to patients with acute heart failure and control subjects

Summary

Introduction

Heart performance and kidney function are strictly interconnected and communication between these two organs occurs through a variety of pathways, including hemodynamic and nonhemodynamic mechanisms [1,2,3,4,5,6]. Clinical trial data have demonstrated that cardiac disease can directly contribute to worsening kidney function and vice versa. These critical, dynamic, and bidirectional connections between both acute and chronic cardiac dysfunction and acute and chronic kidney disease are well recognized and have been defined as cardiorenal syndromes (CRS) by the consensus conference of Acute Dialysis Quality Initiative (ADQI) [3, 4]. A large body of data indicates that the bidirectionality and the temporal pattern of cellular and humoral signaling between these two organs occurs through a variety of mechanisms [6], including oxidative damage, sustained cell activation, metabolic dysregulation and inflammation leading

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