Combined podocyte, fibrotic and echocardiographic correlates of an operationally defined subclinical cardiorenal phenotype in chronic kidney disease: an exploratory study.

Although cardiovascular complications are the most common cause of morbidity and mortality in chronic kidney disease (CKD), the detection of subclinical cardiorenal remodeling is still limited. This is a single-center, exploratory observational study of 127 patients with CKD of various etiologies (hypertensive nephropathy, diabetic nephropathy and chronic glomerulonephritis) and 30 healthy controls. In addition to transthoracic echocardiography at rest and after exercise, biomarkers of podocyte injury (urinary nephrin), fibrosis (urinary type IV collagen and serum galectin-3), cardiac wall stress (serum NT-proBNP) and renal filtration/cardiovascular risk integration (serum cystatin C) were assessed. Biomarker abnormalities were consistent across all CKD groups, even in the absence of overt heart-failure symptoms and preserved ejection fraction. Urinary nephrin and type IV collagen were significantly increased, as were galectin-3 and NT-proBNP concentrations. All CKD groups had resting E/e' values above the normal range and these values were further elevated following exercise. Nephrin showed a strong positive correlation with E/e' and post-exercise echocardiography was associated with greater discrimination of an operationally defined subclinical cardiorenal phenotype than resting imaging. These exploratory findings indicate that a combined biomarker and echocardiographic profile is associated with an early cardiorenal phenotype and may assist in risk stratification of patients with CKD exhibiting early cardiorenal remodeling prior to the development of overt heart failure; they are hypothesis-generating and not intended to set diagnostic criteria. Prior to implementing this multimarker strategy clinically, larger, multicenter prospective studies with multivariable adjustment and external validation should be performed.