1. Date of download: 6/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardio-Pulmonary-Renal Interactions: A Multidisciplinary Approach J Am Coll Cardiol. 2015;65(22):2433-2448. doi:10.1016/j.jacc.2015.04.024 Cardio-Pulmonary-Renal Interactions Multiple dependent inflammatory pathways promote injury and elevate the risk for chronic disease of the heart, lung, and kidney, including increased expression of soluble pro-inflammatory mediators, innate and adaptive immunity, physiological derangements, and cellular apoptosis. The figure illustrates the cellular and molecular crosstalk and potential biomarkers in acute and chronic cardio-pulmonary-renal interactions. BNP = B-type natriuretic peptide; ENaC = epithelial sodium channel; FGF = fibroblast growth factor; GST = glutathione S-transferase; hs-cTnT = high-sensitivity cardiac troponin T; ICAM = intercellular adhesion molecule; IGFBP = insulin-like growth factor binding protein; IL = interleukin; KIM = kidney injury molecule; L-FABP = L-type fatty acid binding protein; NAG = N-acetyl-β-D-glucosaminidase; NGAL = neutrophil gelatinase-associated lipocalin; NKCC1 = sodium-potassium chloride cotransporter 1; TIMP = tissue inhibitor of metalloproteinase; TGF = transforming growth factor; TNF = tumor necrosis factor. Figure Legend:

2. Date of download: 6/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardio-Pulmonary-Renal Interactions: A Multidisciplinary Approach J Am Coll Cardiol. 2015;65(22):2433-2448. doi:10.1016/j.jacc.2015.04.024 The Lung in Cardio-Pulmonary-Renal Interactions The primary involvement and acuity of organ failure leads to pathophysiological interactions and contributing factors in organ crosstalk. (A) The vicious circle of kidney and heart injury, reserve capacity and chronic organ failure, and its clinical features. (B) The cellular pattern of lung injury, repair, and fibrosis. Klotho may be an intermediate mediator that attenuates acute and chronic injury in all 3 organs. AKI = acute kidney injury; ARDS = acute respiratory distress syndrome; CKD = chronic kidney disease; ECM = extracellular matrix; ESRD = end stage renal disease; HF = heart failure; IL = interleukin; LV = left ventricular; PEEP = positive end- expiratory pressure; PH = pulmonary hypertension; RAAS = renin-angiotensin-aldosterone system; RFR = renal functional reserve; ROS = reactive oxygen species; RV = right ventricular; TGF = transforming growth factor; TNF = tumor necrosis factor. Figure Legend:

3. Date of download: 6/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardio-Pulmonary-Renal Interactions: A Multidisciplinary Approach J Am Coll Cardiol. 2015;65(22):2433-2448. doi:10.1016/j.jacc.2015.04.024 The Heart in Cardio-Pulmonary-Renal Interactions (A) The vicious circle of heart and lung injury, reserve capacity, and chronic organ failure, and its clinical features. (B) The cellular pattern of renal injury, repair, and fibrosis. FGF23 may contribute to cardiac remodeling in concert with Klotho deficiency. FGF = fibroblast growth factor; ICAM = intercellular adhesion molecule; IGFBP = insulin-like growth factor binding protein; PVR = pulmonary vascular resistance; RVR = renal vascular resistance; other abbreviations as in Figure 1. Figure Legend:

4. Date of download: 6/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardio-Pulmonary-Renal Interactions: A Multidisciplinary Approach J Am Coll Cardiol. 2015;65(22):2433-2448. doi:10.1016/j.jacc.2015.04.024 The Kidney in Cardio-Pulmonary-Renal Interactions (A) The vicious circle of heart and lung injury, reserve capacity, and chronic organ failure, and its clinical features. (B) The cellular pattern of renal injury, repair, and fibrosis. Activation of RAAS may contribute to renal fibrosis by diminishing the cytoprotective effects of Klotho. HF = heart failure; LV = left ventricular; RV = right ventricular; VCAM = vascular cell adhesion molecule; other abbreviations as in Figure 1. Figure Legend: