Renal Replacement Therapy in Special Situations: Heart Failure and Neurological Injury Roy O. Mathew and Jorge Cerda ´ Division of Nephrology, Department of Medicine, Stratton VA Medical Center, Albany Medical College, Albany, New York ABSTRACT The cardiorenal syndrome is a complicated and increasingly prevalent entity requiring a multidisciplinary approach. Renal replacement therapy (RRT) in the form of slow ultra- filtration (UF) demonstrates promise for the treatment of acutely decompensated heart failure. Despite the lack of evidence for decreased mortality, there is considerable short-term benefit in decreased rehospitalizations and a resto- ration of diuretic responsiveness. Given the potential for improvement in quality of life and cost if hospitalizations are minimized, slow UF should be considered in patients with repeated hospitalization for decompensated heart failure. Acute neurologic injury is a highly unstable state requiring strict adherence to evidence-based guidelines to achieve the best possible functional outcomes. With improved short-term survival, a greater burden of non-neurologic injury may hinder long-term functional recovery. Acute kidney injury is among such important considerations that can lead to wors- ened neurological injury. Careful application of continuous modalities of therapy, probably early in the course of illness to avoid intradialytic osmolar shifts and provide hemo- dynamic stability, will allow for unimpeded neurologic recovery. Newer evidence on dose and RRT modality on patients with acute and chronic brain injury will certainly add important knowledge to this field. Heart Failure The cardiorenal syndrome encompasses the complex interplay between cardiac and renal dysfunctions when attempting to compensate for dysfunction in either organ (1). Since then, the term has been expanded to include renal functional injury with added prognostic and therapeutic considerations; the evolving pathophysi- ologic concept has been extensively reviewed recently (1,2). Despite the leading role of diuretics to treat acutely decompensated heart failure (ADHF), resistance to diuretic therapy with worsening renal function is a hall- mark of advanced cardiac disease and the cardiorenal syndrome (3). Mullens et al. (4) examined the changes in hemody- namic parameters measured with pulmonary artery catheterization, including central venous filling pressure (CVP), cardiac output ⁄ cardiac index, systemic vascular resistance, and peripheral vascular resistance. The study revealed that CVP was most closely associated with the development of worsening renal function (defined as a ‡ 0.3 mg ⁄ dl rise in serum creatinine during the hospitalization): lowering of CVP throughout the course of treatment mitigated this association. The direct asso- ciation of CI with serum creatinine (and negatively with estimated glomerular filtration rate) suggests that com- promised renal perfusion may not be the main cause of declining renal function in ADHF. The implications of this study are that any increase over optimal venous filling pressures (through dietary or therapeutic non-adherence, acute illness, etc.) will result in the progressive inability of the kidneys to compensate by increasing urine output. In addition, this study pro- vides a physiologic basis for the all too common clinical scenario of patients presenting with congestive signs and symptoms, acute kidney injury (AKI) and preserved systemic pressures (5). Furthermore, it suggests that selective reduction in venous filling pressures (i.e., UF) may have greater efficacy than general extracellular fluid contraction with diuretics in ADHF. The reasons for the progressive resistance to as well as the worsening of renal function with loop diuretic therapy are not perfectly understood. In theory, loop diuretics (selective inhibitors of the thick ascending limb Na+ ⁄ K+ ⁄ 2Cl) channel) should inhibit the decline in glomerular filtration rate (GFR) that is seen with increased tubular flow, via the tubuloglomerular feed- back (6). Clinical evidence, however, demonstrates that diuretic therapy is limited in ADHF and that loop diuretics lead to further declines in GFR (7–9). Extracor- poreal ultrafiltration (UF), as mentioned, provides a means of directly reducing venous filling pressures. Marenzi et al. (10) examined the circulatory response to Address correspondence to: Dr. Jorge Cerda ´ , Division of Nephrology, Albany Medical College and Capital District Renal Physicians, 62 Hackett Boulevard, Albany, NY 12209, Tel.: 518-434-2244, Fax: 518-434-4659, or e-mail: cerdaj@ mail.amc.edu. Seminars in Dialysis—Vol 24, No 2 (March–April) 2011 pp. 192–196 DOI: 10.1111/j.1525-139X.2011.00872.x ª 2011 Wiley Periodicals, Inc. 192 RENAL REPLACEMENT THERAPY IN ACUTE KIDNEY INJURY: WHEN, HOW AND HOW MUCH?