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Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. CRS type 1 most commonly occurs in the setting of acutely decompensated heart failure where approximately 25% of patients develop a rise in serum creatinine and a reduction of urine output after the first several doses of intravenous diuretics. Altered cardiac and renal hemodynamics are believed to be the most important determinants of CRS type 1. CRS type 2 is the hastened progression of chronic kidney disease (CKD) in the setting of chronic heart failure. Accelerated renal cell apoptosis and replacement fibrosis is considered to be the dominant mechanism. CRS type 3 is acutely decompensated heart failure after acute kidney injury from inflammatory, toxic, or ischemic insults. This syndrome is precipitated by salt and water overload, acute uremic myocyte dysfunction, and neurohormonal dysregulation. CRS type 4 is manifested by the acceleration of the progression of chronic heart failure in the setting of CKD. Cardiac myocyte dysfunction and fibrosis, so-called 'CKD cardiomyopathy', is believed to be the predominant pathophysiologic mechanism. Type 5 CRS is simultaneous acute cardiac and renal injury in the setting of an overwhelming systemic insult such as sepsis. In this scenario, the predominant pathophysiological disturbance is microcirculatory dysfunction as a result of acutely abnormal immune cell signaling, catecholamine cellular toxicity, and enzymatic activation which result in simultaneous organ injury often extending beyond both the heart and the kidneys. This paper will summarize these and other key findings from an international consensus conference on the spectrum of pathophysiologic mechanisms at work in the CRS. (C) 2013 S. Karger AG, Basel

Acute kidney injury (AKI) remains a major clinical challenge, especially in combination with acute lung injury (ALI). Clinical as well as experimental studies have provided evidence for clinically relevant kidney-lung interactions, ultimately leading to a drastic reduction in survival. The crosstalk between AKI and ALI is a consequence of both direct loss of normal organ function and inflammatory dysregulation resulting from each organ failure. Cellular (e.g. neutrophils) as well as soluble mediators (cytokines) contribute to the inflammatory dysregulation under these circumstances. Clinical interventions are currently limited to general, unspecific preventive or supportive measures. With respect to AKI, these strategies include adequate volume control, correction of acid-base/electrolyte abnormalities and elimination of uremic substances by renal replacement therapy. Lung protective ventilation, including low tidal volume ventilation, is a cornerstone in the management of ALI. This approach has been shown to attenuate both the direct mechanical effects of ventilation and the inflammatory response arising from ALI and mechanical ventilation, ultimately reducing the incidence of extrapulmonary organ failure. The fact that multiorgan failure is not only the sum of organ functions lost, but also includes inflammatory dysregulation together with a lack of treatment options greatly emphasizes the need for future research in this area.

Predicting recovery of renal function following acute kidney injury (AKI) is one of the top ten questions in the field of AKI research. Accurate prediction would help physicians distinguish patients with poor renal prognosis in whom further therapy is likely to be futile from those who are likely to have good renal prognosis. Proper stratification of patients with AKI is also critical to design clinical trials to target patients with poor prognosis. Unfortunately, current general clinical severity scores (APACHE, SOFA, etc.) and AKI-specific severity scores (Mehta's score, Liano's score, Chertow's score, etc.) are not the good predictors of renal recovery. Recent progress on the pathophysiology of renal injury and recovery is encouraging. Repopulation of surviving renal tubular epithelial cell with the assistance of certain renal epithelial cell and specific growth factors such as neutrophil gelatinase-associated lipocalin (NGAL), hepatocyte growth factor (HGF), epidermal growth factor, and insulin-like growth factor-1, etc., play a major role in the recovery process. Such findings provide a great opportunity to test and validate these potential biomarkers as candidate markers of renal recovery. This review will describe the current understanding of the renal recovery process, and the role of clinical severity scores and novel biomarkers such as NGAL, HGF, and cystatin C in predicting renal recovery.

Sepsis is one of the main causes of death in critically ill patients. The pathophysiology of sepsis is complex and not completely understood. The proinflammatory and anti-inflammatory response leads to cell and organ dysfunction and, in many cases, death. Thus, the goal of the intervention is to restore the homeostasis of circulating mediators rather than to inhibit selectively the proinflammatory or anti-inflammatory mediators. Blood purification has been reported to remove a wide array of inflammatory mediators. The effects are broad-spectrum and auto-regulating. Blood purification has also been demonstrated to restore immune function through improving antigen-presenting capability, adjusting leukocyte recruitment, oxidative burst and phagocytosis, and improving leukocyte responsiveness. A great deal of work has to be done in order to find and optimize the best extracorporeal blood purification therapy for sepsis. New devices specifically target the pathophysiological mechanisms involved in these conditions. High-volume hemofiltration, hemoadsorption, coupled plasma filtration adsorption, and high cutoff membrane are now being tested in septic patients. Preliminary data indicate the feasibility of these modified techniques in sepsis. Their impact on patient prognosis, however, still needs proof by large randomized clinical trials. Finally, the emerging paradigm of sepsis-induced immune suppression provides additional rationale for the development of extracorporeal blood purification therapy for sepsis.