The use of NPs for diagnosis and prognosis of CVD comes at a time of great interest pertaining to the important interaction between cardiac and renal dysfunction. Although it is clear that BNP and NT-proBNP are metabolized by the kidney and their levels are increased in patients who have renal dysfunction even in the absence of clinical HF, a precise understanding of their metabolic pathways is not clear at this time. Current data indicate that there are important differences in metabolism and clearance of BNP and NT-proBNP. Although BNP and NT-proBNP perform reasonably well in the diagnosis of acute heart failure in patients who have concomitant renal insufficiency (eGFR <60 mL/min) being evaluated for acute dyspnea, both markers require an adjustment in the clinical cut-point greater than the accepted levels used for patients who have preserved renal function. Even less is known regarding the diagnostic performance of these markers in the acute setting in patients who have more severe CKD and ESRD. Clinicians caring for patients who have ESRD should not use NPs to reliably predict or rule out the presence of underlying ventricular dysfunction. Further testing is required in patients who have less severe forms of CKD to ascertain whether NP levels can serve as markers of clinically important cardiac disease before symptoms or geometric changes of the LV occur. Although NP levels correlate with underlying heart disease and mortality in patients receiving dialysis, current data do not support the use of these markers as a surrogate marker of volume status.